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Sample records for blocking chemically induced

  1. Chemical encapsulation of rocuronium by synthetic cyclodextrin derivatives: reversal of neuromuscular block in anaesthetized Rhesus monkeys.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: At present, reversal of neuromuscular block induced by steroidal neuromuscular blocking agents (NMBAs) is achieved by administration of cholinesterase inhibitors. Chemical encapsulation of steroidal NMBAs, such as rocuronium, by a cyclodextrin is a new concept in neuromuscular block

  2. Does the recommended lymphocyte cytokinesis-block micronucleus assay for human biomonitoring actually detect DNA damage induced by occupational and environmental exposure to genotoxic chemicals?

    Science.gov (United States)

    Speit, Günter

    2013-07-01

    This commentary challenges the paradigm that the cytokinesis-block micronucleus assay (CBMN assay) with cultured human lymphocytes, as it is performed currently, is a sensitive and useful tool for detecting genotoxic effects in populations exposed occupationally or environmentally to genotoxic chemicals. Based on the principle of the assay and the available data, increased micronucleus (MN) frequencies in binucleated cells (BNC) are mainly due to MN produced in vitro during the cultivation period (i.e. MN produced in vivo do not substantially contribute to the MN frequency measured in BNC). The sensitivity of the assay for the detection of induced MN in BNC after an in vivo exposure to a genotoxic chemical is limited because cytochalasin B (Cyt-B) is added relatively late during the culture period and, therefore, the BNC that are scored do not always represent cells that have completed one cell cycle only. Furthermore, this delay means that damaged cells can be eliminated by apoptosis and/or that DNA damage induced in vivo can be repaired prior to the production of a MN in the presence of Cyt-B. A comparison with the in vitro CBMN assay used for genotoxicity testing leads to the conclusion that it is highly unlikely that DNA damage induced in vivo is the cause for increased MN frequencies in BNC after occupational or environmental exposure to genotoxic chemicals. This commentary casts doubt on the usefulness of the CBMN assay as an indicator of genotoxicity in human biomonitoring and questions the relevance of many published data for hazard identification and risk assessment. Thus, it seems worthwhile to reconsider the use of the CBMN assay as presently conducted for the detection of genotoxic exposure in human biomonitoring.

  3. Laughter-induced left bundle branch block.

    Science.gov (United States)

    Chow, Grant V; Desai, Dipan; Spragg, David D; Zakaria, Sammy

    2012-10-01

    We present the case of a patient with ischemic heart disease and intermittent left bundle branch block, reproducibly induced by laughter. Following treatment of ischemia with successful deployment of a drug-eluting stent, no further episodes of inducible LBBB were seen. Transient ischemia, exacerbated by elevated intrathoracic pressure during laughter, may have contributed to onset of this phenomenon. © 2012 Wiley Periodicals, Inc.

  4. Chemical-induced Vitiligo

    Science.gov (United States)

    Harris, John E.

    2016-01-01

    Synopsis Chemical-induced depigmentation of the skin has been recognized for over 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. The importance of recognizing this phenomenon was highlighted during an outbreak of vitiligo in Japan during the summer of 2013, when over 16,000 users of a new skin lightening cosmetic cream developed skin depigmentation at the site of contact with the cream and many in remote areas as well. Depigmenting chemicals appear to be analogs of the amino acid tyrosine that disrupt melanogenesis and result in autoimmunity and melanocyte destruction. Because chemical-induced depigmentation is clinically and histologically indistinguishable from non-chemically induced vitiligo, and because these chemicals appear to induce melanocyte autoimmunity, this phenomenon should be known as “chemical-induced vitiligo”, rather than less accurate terms that have been previously used. PMID:28317525

  5. Photo-Induced Micellization of Block Copolymers

    Directory of Open Access Journals (Sweden)

    Satoshi Kuwayama

    2010-11-01

    Full Text Available We found novel photo-induced micellizations through photolysis, photoelectron transfer, and photo-Claisen rearrangement. The photolysis-induced micellization was attained using poly(4-tert-butoxystyrene-block-polystyrene diblock copolymer (PBSt-b-PSt. BSt-b-PSt showed no self-assembly in dichloromethane and existed as isolated copolymers. Dynamic light scattering demonstrated that the copolymer produced spherical micelles in this solvent due to irradiation with a high-pressure mercury lamp in the presence of photo-acid generators, such as bis(alkylphenyliodonium hexafluorophosphate, diphenyliodonium hexafluorophosphate, and triphenylsulfonium triflate. The 1H NMR analysis confirmed that PBSt-b-PSt was converted into poly(4-vinylphenol-block-PSt by the irradiation, resulting in self-assembly into micelles. The irradiation in the presence of the photo-acid generator also induced the micellization of poly(4-pyridinemethoxymethylstyrene-block-polystyrene diblock copolymer (PPySt-b-PSt. Micellization occurred by electron transfer from the pyridine to the photo-acid generator in their excited states and provided monodispersed spherical micelles with cores of PPySt blocks. Further, the photo-Claisen rearrangement caused the micellization of poly(4-allyloxystyrene-block-polystyrene diblock copolymer (PASt-b-PSt. Micellization was promoted in cyclohexane at room temperature without a catalyst. During micellization, the elimination of the allyl groups competitively occurred along with the photorearrangement of the 4-allyloxystyrene units into the 3-allyl-4-hydroxystyrene units.

  6. Comparative transcriptome analysis reveals carbohydrate and lipid metabolism blocks in Brassica napus L. male sterility induced by the chemical hybridization agent monosulfuron ester sodium.

    Science.gov (United States)

    Li, Zhanjie; Cheng, Yufeng; Cui, Jianmin; Zhang, Peipei; Zhao, Huixian; Hu, Shengwu

    2015-03-17

    Chemical hybridization agents (CHAs) are often used to induce male sterility for the production of hybrid seeds. We previously discovered that monosulfuron ester sodium (MES), an acetolactate synthase (ALS) inhibitor of the herbicide sulfonylurea family, can induce rapeseed (Brassica napus L.) male sterility at approximately 1% concentration required for its herbicidal activity. To find some clues to the mechanism of MES inducing male sterility, the ultrastructural cytology observations, comparative transcriptome analysis, and physiological analysis on carbohydrate content were carried out in leaves and anthers at different developmental stages between the MES-treated and mock-treated rapeseed plants. Cytological analysis revealed that the plastid ultrastructure was abnormal in pollen mother cells and tapetal cells in male sterility anthers induced by MES treatment, with less material accumulation in it. However, starch granules were observed in chloroplastids of the epidermis cells in male sterility anthers. Comparative transcriptome analysis identified 1501 differentially expressed transcripts (DETs) in leaves and anthers at different developmental stages, most of these DETs being localized in plastid and mitochondrion. Transcripts involved in metabolism, especially in carbohydrate and lipid metabolism, and cellular transport were differentially expressed. Pathway visualization showed that the tightly regulated gene network for metabolism was reprogrammed to respond to MES treatment. The results of cytological observation and transcriptome analysis in the MES-treated rapeseed plants were mirrored by carbohydrate content analysis. MES treatment led to decrease in soluble sugars content in leaves and early stage buds, but increase in soluble sugars content and decrease in starch content in middle stage buds. Our integrative results suggested that carbohydrate and lipid metabolism were influenced by CHA-MES treatment during rapeseed anther development, which might

  7. Hyperkalemia-induced complete heart block

    Directory of Open Access Journals (Sweden)

    Alireza Baratloo

    2015-05-01

    Full Text Available Background: Potassium, as an extracellular ion, plays an important role in the electrophysiologic function of the myocardium and any change in extracellular concentration of this ion might have a marked impression upon myocyte electrophysiologic gain. High serum potassium levels are thought to impair pulse conduction in Purkinje fibers and ventricles more than that in the Atrioventricular (AV node. Therefore, although complete AV block can occur, it is a rare initial presentation. Case Report: We describe a 62-year-old man with a history of diabetes mellitus, ischemic heart disease and previous Coronary Artery Bypass Graft (CABG, who came to our emergency department due to generalized weakness starting 2 days before admission. The patient also had decreased force in lower limbs, exacerbating from the morning, and was finally diagnosed as a hyperkalemia-induced Complete Heart Block (CHB. It should also be noted that the patient responded dramatically to the administration of 10 mL of 10% calcium gluconate along with external pacing until potassium level correction became effective. Conclusion: In spite of the fact that Hyperkalemia can be associated with frequent Electrocardiogram (ECG abnormality, advanced heart blocks (second- and third-degree AV blocks are usually found only in patients with pre-existing heart failure, conduction abnormalities, or other cardiac diseases. Institution of effective treatment rapidly and forgiveness of traditional non-effective, time consumptive and sometimes risking full-adjustment modalities, such as sodium bicarbonate infusion or exchange resins that prevent their use in the emergent phase, can help minimize patient morbidity and mortality.

  8. Microbial production of building block chemicals and polymers.

    Science.gov (United States)

    Lee, Jeong Wook; Kim, Hyun Uk; Choi, Sol; Yi, Jongho; Lee, Sang Yup

    2011-12-01

    Owing to our increasing concerns on the environment, climate change, and limited natural resources, there has recently been considerable effort exerted to produce chemicals and materials from renewable biomass. Polymers we use everyday can also be produced either by direct fermentation or by polymerization of monomers that are produced by fermentation. Recent advances in metabolic engineering combined with systems biology and synthetic biology are allowing us to more systematically develop superior strains and bioprocesses for the efficient production of polymers and monomers. Here, we review recent trends in microbial production of building block chemicals that can be subsequently used for the synthesis of polymers. Also, recent successful cases of direct one-step production of polymers are reviewed. General strategies for the production of natural and unnatural platform chemicals are described together with representative examples. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Electrocardiographic characteristics of atrioventricular block induced by tilt testing.

    Science.gov (United States)

    Zyśko, Dorota; Gajek, Jacek; Koźluk, Edward; Mazurek, Walentyna

    2009-02-01

    The electrocardiographic (ECG) characteristics of atrioventricular (AV) block during reflex syncope may be unique due to the presence of hypervagotonia. The aim of the present study was to define the ECG characteristics of the AV block induced by neurocardiogenic reflex provoked by tilt testing (TT). A series of 31 patients with presumed vasovagal syncope and AV block provoked by TT was studied. The duration of PP and PR interval, AV block grade and type, concomitant arrhythmias, and timing of the AV block occurrence were assessed. The AV block occurred at TT termination in 26 patients, in the recovery in 4 patients, and in both periods in 1 patient. Atrioventricular block was preceded by sinus slowing, and sinus rhythm during AV block was slow and instable. Mobitz I, 2:1 second-degree AV block, and advanced second-degree AV block were recognized in 35.5, 48.4, and 67.8% of patients, respectively. Third-degree AV block was diagnosed in 41.9% of patients. Twenty-one patients had at least two AV block forms. The most prevalent concomitant arrhythmia was junctional escape rhythm (61.3%). (i) The occurrence of the AV block during neurocardiogenic reaction induced by TT is always preceded by sinus rhythm slowing and usually by PR interval prolongation. (ii) The AV block provoked by TT usually occurs at TT termination, but may occur even in the recovery period in a supine position. Sometimes the AV block may be present both at TT termination and during the recovery period.

  10. MECs: "Building Blocks" for Creating Biological and Chemical Instruments.

    Directory of Open Access Journals (Sweden)

    Douglas A Hill

    Full Text Available The development of new biological and chemical instruments for research and diagnostic applications is often slowed by the cost, specialization, and custom nature of these instruments. New instruments are built from components that are drawn from a host of different disciplines and not designed to integrate together, and once built, an instrument typically performs a limited number of tasks and cannot be easily adapted for new applications. Consequently, the process of inventing new instruments is very inefficient, especially for researchers or clinicians in resource-limited settings. To improve this situation, we propose that a family of standardized multidisciplinary components is needed, a set of "building blocks" that perform a wide array of different tasks and are designed to integrate together. Using these components, scientists, engineers, and clinicians would be able to build custom instruments for their own unique needs quickly and easily. In this work we present the foundation of this set of components, a system we call Multifluidic Evolutionary Components (MECs. "Multifluidic" conveys the wide range of fluid volumes MECs operate upon (from nanoliters to milliliters and beyond; "multi" also reflects the multiple disciplines supported by the system (not only fluidics but also electronics, optics, and mechanics. "Evolutionary" refers to the design principles that enable the library of MEC parts to easily grow and adapt to new applications. Each MEC "building block" performs a fundamental function that is commonly found in biological or chemical instruments, functions like valving, pumping, mixing, controlling, and sensing. Each MEC also has a unique symbol linked to a physical definition, which enables instruments to be designed rapidly and efficiently using schematics. As a proof-of-concept, we use MECs to build a variety of instruments, including a fluidic routing and mixing system capable of manipulating fluid volumes over five orders

  11. Blocking of conditioned taste avoidance induced by wheel running.

    Science.gov (United States)

    Pierce, W David; Heth, C Donald

    2010-01-01

    In Experiment 1, compared to non-reinforced presentation of a food stimulus (A-->no US), the association of a food stimulus with wheel running (A-->US) blocked subsequent avoidance of a distinctive flavor (X), when both the food and flavor were followed by wheel running (AX-->US). Experiment 2 replicated and extended the blocking effect, demonstrating that the amount of avoidance of X after AX-->wheel training depended on the correlation between A-alone trials and wheel running-the predictiveness of the A stimulus. The present study is the first to demonstrate associative blocking of conditioned taste avoidance (CTA) induced by wheel running and strongly implicates associative learning as the basis for this kind of avoidance. 2009 Elsevier B.V. All rights reserved.

  12. The testing of thermal-mechanical-hydrological-chemical processes using a large block

    International Nuclear Information System (INIS)

    Lin, W.; Wilder, D.G.; Blink, J.A.; Blair, S.C.; Buscheck, T.A.; Chesnut, D.A.; Glassley, W.E.; Lee, K.; Roberts, J.J.

    1994-01-01

    The radioactive decay heat from nuclear waste packages may, depending on the thermal load, create coupled thermal-mechanical-hydrological-chemical (TMHC) processes in the near-field environment of a repository. A group of tests on a large block (LBT) are planned to provide a timely opportunity to test and calibrate some of the TMHC model concepts. The LBT is advantageous for testing and verifying model concepts because the boundary conditions are controlled, and the block can be characterized before and after the experiment. A block of Topopah Spring tuff of about 3 x 3 x 4.5 m will be sawed and isolated at Fran Ridge, Nevada Test Site. Small blocks of the rock adjacent to the large block will be collected for laboratory testing of some individual thermal-mechanical, hydrological, and chemical processes. A constant load of about 4 MPa will be applied to the top and sides of the large block. The sides will be sealed with moisture and thermal barriers. The large block will be heated with one heater in each borehole and guard heaters on the sides so that a dry-out zone and a condensate zone will exist simultaneously. Temperature, moisture content, pore pressure, chemical composition, stress and displacement will be measured throughout the block during the heating and cool-down phases. The results from the experiments on small blocks and the tests on the large block will provide a better understanding of some concepts of the coupled TMHC processes

  13. Induced radioactivity in Bevatron concrete radiation shielding blocks

    International Nuclear Information System (INIS)

    Moeller, G.C.; Donahue, R.J.

    1994-07-01

    The Bevatron accelerated protons up to 6.2 GeV and heavy ions up to 2.1 GeV/amu. It operated from 1954 to 1993. Radioactivity was induced in some concrete radiation shielding blocks by prompt radiation. Prompt radiation is primarily neutrons and protons that were generated by the Bevatron's primary beam interactions with targets and other materials. The goal was to identify the gamma-ray emitting nuclides (t 1/2 > 0.5 yr) that could be present in the concrete blocks and estimate the depth at which the maximum radioactivity presently occurs. It is shown that the majority of radioactivity was produced via thermal neutron capture by trace elements present in concrete. The depth of maximum thermal neutron flux, in theory, corresponds with the depth of maximum induced activity. To estimate the depth at which maximum activity occurs in the concrete blocks, the LAHET Code System was used to calculate the depth of maximum thermal neutron flux. The primary beam interactions that generate the neutrons are also modeled by the LAHET Code System

  14. Identifying the nature of surface chemical modification for directed self-assembly of block copolymers

    Directory of Open Access Journals (Sweden)

    Laura Evangelio

    2017-09-01

    Full Text Available In recent years, block copolymer lithography has emerged as a viable alternative technology for advanced lithography. In chemical-epitaxy-directed self-assembly, the interfacial energy between the substrate and each block copolymer domain plays a key role on the final ordering. Here, we focus on the experimental characterization of the chemical interactions that occur at the interface built between different chemical guiding patterns and the domains of the block copolymers. We have chosen hard X-ray high kinetic energy photoelectron spectroscopy as an exploration technique because it provides information on the electronic structure of buried interfaces. The outcome of the characterization sheds light onto key aspects of directed self-assembly: grafted brush layer, chemical pattern creation and brush/block co-polymer interface.

  15. Simultaneous tuning of chemical composition and topography of copolymer surfaces: micelles as building blocks.

    Science.gov (United States)

    Zhao, Ning; Zhang, Xiaoyan; Zhang, Xiaoli; Xu, Jian

    2007-05-14

    A simple method is described for controlling the surface chemical composition and topography of the diblock copolymer poly(styrene)-b-poly(dimethylsiloxane)(PS-b-PDMS) by casting the copolymer solutions from solvents with different selectivities. The surface morphology and chemical composition were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), respectively, and the wetting behavior was studied by water contact angle (CA) and sliding angle (SA) and by CA hysteresis. Chemical composition and morphology of the surface depend on solvent properties, humidity of the air, solution concentration, and block lengths. If the copolymer is cast from a common solvent, the resultant surface is hydrophobic, with a flat morphology, and dominated by PDMS on the air side. From a PDMS-selective solvent, the surface topography depends on the morphology of the micelles. Starlike micelles give rise to a featureless surface nearly completely covered by PDMS, while crew-cut-like micelles lead to a rough surface with a hierarchical structure that consists partly of PDMS. From a PS-selective solvent, however, surface segregation of PDMS was restricted, and the surface morphology can be controlled by vapor-induced phase separation. On the basis of the tunable surface roughness and PDMS concentration on the air side, water repellency of the copolymer surface could be tailored from hydrophobic to superhydrophobic. In addition, reversible switching behavior between hydrophobic and superhydrophobic can be achieved by exposing the surface to solvents with different selectivities.

  16. Understanding Chemical Reaction Kinetics and Equilibrium with Interlocking Building Blocks

    Science.gov (United States)

    Cloonan, Carrie A.; Nichol, Carolyn A.; Hutchinson, John S.

    2011-01-01

    Chemical reaction kinetics and equilibrium are essential core concepts of chemistry but are challenging topics for many students, both at the high school and undergraduate university level. Visualization at the molecular level is valuable to aid understanding of reaction kinetics and equilibrium. This activity provides a discovery-based method to…

  17. ChemCalc: a building block for tomorrow's chemical infrastructure.

    Science.gov (United States)

    Patiny, Luc; Borel, Alain

    2013-05-24

    Web services, as an aspect of cloud computing, are becoming an important part of the general IT infrastructure, and scientific computing is no exception to this trend. We propose a simple approach to develop chemical Web services, through which servers could expose the essential data manipulation functionality that students and researchers need for chemical calculations. These services return their results as JSON (JavaScript Object Notation) objects, which facilitates their use for Web applications. The ChemCalc project http://www.chemcalc.org demonstrates this approach: we present three Web services related with mass spectrometry, namely isotopic distribution simulation, peptide fragmentation simulation, and molecular formula determination. We also developed a complete Web application based on these three Web services, taking advantage of modern HTML5 and JavaScript libraries (ChemDoodle and jQuery).

  18. Time course of action of sugammadex (Org 25969) on rocuronium-induced block in the Rhesus monkey, using a simple model of equilibration of complex formation.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Driessen, J.J.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Reversal of neuromuscular block can be accomplished by chemical encapsulation of rocuronium by sugammadex (Org 25969), a synthetic gamma-cyclodextrin derivative. The present study determined the time course of the reversal action of sugammadex on rocuronium-induced block in the

  19. Clonidine blocks stress-induced craving in cocaine users.

    Science.gov (United States)

    Jobes, Michelle L; Ghitza, Udi E; Epstein, David H; Phillips, Karran A; Heishman, Stephen J; Preston, Kenzie L

    2011-11-01

    Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement. The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users. Healthy, non-treatment-seeking cocaine users (n = 59) were randomly assigned to three groups receiving clonidine 0, 0.1, or 0.2 mg orally under double-blind conditions. In a single test session, each participant received clonidine or placebo followed 3 h later by exposure to two pairs of standardized auditory-imagery scripts (neutral/stress and neutral/drug). Subjective measures of craving were collected. Subjective responsivity ("crave cocaine" Visual Analog Scale) to stress scripts was significantly attenuated in the 0.1- and 0.2-mg clonidine groups; for drug-cue scripts, this attenuation occurred only in the 0.2-mg group. Other subjective measures of craving showed similar patterns of effects but Dose × Script interactions were not significant. Clonidine was effective in reducing stress-induced (and, at a higher dose, cue-induced) craving in a pattern consistent with preclinical findings, although this was significant on only one of several measures. Our results, though modest and preliminary, converge with other evidence to suggest that alpha-2 adrenergic agonists may help prevent relapse in drug abusers experiencing stress or situations that remind them of drug use.

  20. Infrared laser-induced chemical reactions

    International Nuclear Information System (INIS)

    Katayama, Mikio

    1978-01-01

    The experimental means which clearly distinguishes between infrared ray-induced reactions and thermal reactions has been furnished for the first time when an intense monochromatic light source has been obtained by the development of infrared laser. Consequently, infrared laser-induced chemical reactions have started to develop as one field of chemical reaction researches. Researches of laser-induced chemical reactions have become new means for the researches of chemical reactions since they were highlighted as a new promising technique for isotope separation. Specifically, since the success has been reported in 235 U separation using laser in 1974, comparison of this method with conventional separation techniques from the economic point of view has been conducted, and it was estimated by some people that the laser isotope separation is cheaper. This report briefly describes on the excitation of oscillation and reaction rate, and introduces the chemical reactions induced by CW laser and TEA CO 2 laser. Dependence of reaction yield on laser power, measurement of the absorbed quantity of infrared ray and excitation mechanism are explained. Next, isomerizing reactions are reported, and finally, isotope separation is explained. It was found that infrared laser-induced chemical reactions have the selectivity for isotopes. Since it is evident that there are many examples different from thermal and photo-chemical reactions, future collection of the data is expected. (Wakatsuki, Y.)

  1. Blocked inverted indices for exact clustering of large chemical spaces.

    Science.gov (United States)

    Thiel, Philipp; Sach-Peltason, Lisa; Ottmann, Christian; Kohlbacher, Oliver

    2014-09-22

    The calculation of pairwise compound similarities based on fingerprints is one of the fundamental tasks in chemoinformatics. Methods for efficient calculation of compound similarities are of the utmost importance for various applications like similarity searching or library clustering. With the increasing size of public compound databases, exact clustering of these databases is desirable, but often computationally prohibitively expensive. We present an optimized inverted index algorithm for the calculation of all pairwise similarities on 2D fingerprints of a given data set. In contrast to other algorithms, it neither requires GPU computing nor yields a stochastic approximation of the clustering. The algorithm has been designed to work well with multicore architectures and shows excellent parallel speedup. As an application example of this algorithm, we implemented a deterministic clustering application, which has been designed to decompose virtual libraries comprising tens of millions of compounds in a short time on current hardware. Our results show that our implementation achieves more than 400 million Tanimoto similarity calculations per second on a common desktop CPU. Deterministic clustering of the available chemical space thus can be done on modern multicore machines within a few days.

  2. Engineering cell factories for producing building block chemicals for bio-polymer synthesis

    OpenAIRE

    Tsuge, Yota; Kawaguchi, Hideo; Sasaki, Kengo; Kondo, Akihiko

    2016-01-01

    Synthetic polymers are widely used in daily life. Due to increasing environmental concerns related to global warming and the depletion of oil reserves, the development of microbial-based fermentation processes for the production of polymer building block chemicals from renewable resources is desirable to replace current petroleum-based methods. To this end, strains that efficiently produce the target chemicals at high yields and productivity are needed. Recent advances in metabolic engineerin...

  3. Chemical Interactions and Their Role in the Microphase Separation of Block Copolymer Thin Films

    Directory of Open Access Journals (Sweden)

    Richard A. Farrell

    2009-08-01

    Full Text Available The thermodynamics of self-assembling systems are discussed in terms of the chemical interactions and the intermolecular forces between species. It is clear that there are both theoretical and practical limitations on the dimensions and the structural regularity of these systems. These considerations are made with reference to the microphase separation that occurs in block copolymer (BCP systems. BCP systems self-assemble via a thermodynamic driven process where chemical dis-affinity between the blocks driving them part is balanced by a restorative force deriving from the chemical bond between the blocks. These systems are attracting much interest because of their possible role in nanoelectronic fabrication. This form of self-assembly can obtain highly regular nanopatterns in certain circumstances where the orientation and alignment of chemically distinct blocks can be guided through molecular interactions between the polymer and the surrounding interfaces. However, for this to be possible, great care must be taken to properly engineer the interactions between the surfaces and the polymer blocks. The optimum methods of structure directing are chemical pre-patterning (defining regions on the substrate of different chemistry and graphoepitaxy (topographical alignment but both centre on generating alignment through favourable chemical interactions. As in all self-assembling systems, the problems of defect formation must be considered and the origin of defects in these systems is explored. It is argued that in these nanostructures equilibrium defects are relatively few and largely originate from kinetic effects arising during film growth. Many defects also arise from the confinement of the systems when they are ‘directed’ by topography. The potential applications of these materials in electronics are discussed.

  4. Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis.

    Science.gov (United States)

    Halder, Sunil K; Beauchamp, R Daniel; Datta, Pran K

    2005-07-01

    Smad proteins play a key role in the intracellular signaling of the transforming growth factor beta (TGF-beta) superfamily of extracellular polypeptides that initiate signaling to regulate a wide variety of biological processes. The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in several cancers. To determine the effect of Smad7-mediated blockade of TGF-beta signaling, we have stably expressed Smad7 in a TGF-beta-sensitive, well-differentiated, and non-tumorigenic cell line, FET, that was derived from human colon adenocarcinoma. Smad7 inhibits TGF-beta-induced transcriptional responses by blocking complex formation between Smad 2/3 and Smad4. While Smad7 has no effect on TGF-beta-induced activation of p38 MAPK and ERK, it blocks the phosphorylation of Akt by TGF-beta and enhances TGF-beta-induced phosphorylation of c-Jun. FET cells expressing Smad7 show anchorage-independent growth and enhance tumorigenicity in athymic nude mice. Smad7 blocks TGF-beta-induced growth inhibition by preventing TGF-beta-induced G1 arrest. Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1). As a result, Smad7 inhibits TGF-beta-mediated downregulation of Rb phosphorylation. Furthermore, Smad7 inhibits the apoptosis of these cells. Together, Smad7 may increase the tumorigenicity of FET cells by blocking TGF-beta-induced growth inhibition and by inhibiting apoptosis. Thus, this study provides a mechanism by which a portion of human colorectal tumors may become refractory to tumor-suppressive actions of TGF-beta that might result in increased tumorigenicity.

  5. Chemical lumbar sympathetic plexus block in Buerger′s disease: Current scenario

    Directory of Open Access Journals (Sweden)

    Rampal Singh

    2014-01-01

    Full Text Available Introduction: High incidences of Buerger′s disease (43-62% in India draw our attention towards available treatment modalities in such patients. Patients with this disease are in severe pain and agony. Pain relief by any means remains first and foremost priority in such patients and if patient is able to sleep even one pain free night it is a boon for the patients. The purpose of study was to test the hypothesis that lumber sympathetic block relieves the pain of ischemic limb in Buerger′s disease. Aims and Objectives: To study the effect of chemical lumber sympathetic block on visual analog score (VAS score and walking distance of the patients. Materials and Methods: Lumber sympathetic block was given under C-arm guidance with 17.5 cm long 22 G spinal needle at L3 and L4 level. Diagnostic block was given initially with plain bupivacaine 0.25% with two needle technique. Total seven blocks series were given in all patients. Final block was given with phenol 8%, 8 ml at L3 and L4 level. In postoperative period, VAS score was observed. Effect of block on walking distance was assessed on 3 rd day before giving next block. Statistical analysis: Software Statistical Package for Social Sciences (SPSS version 11.5 was used for statistical analysis. Data were analyzed by paired t-test and P-value < 0.05 was considered as significant. Results: Both VAS and walking distance improved significantly after each successive block. Healing of ulcers of foot is also noted. Conclusion: Despite advances in treatment modalities in such patients, lumber sympathetic block is still very cost-effective, safe, and least-invasive technique in treating painful ischemic legs.

  6. Kinetics of directed self-assembly of block copolymers on chemically patterned substrates

    International Nuclear Information System (INIS)

    Müller, Marcus; Li, Weihua; Rey, Juan Carlos Orozco; Welling, Ulrich

    2015-01-01

    Chemically patterned surfaces have been successfully employed to direct the kinetics of self-assembly of block copolymers into dense, periodic morphologies (”chemoepitaxy”). Significant efforts have been directed towards understanding the kinetics of structure formation and, particularly, the formation and annihilation of defects. In the present manuscript we use computer simulations of a soft, coarse-grained polymer model to study the kinetics of structure formation of lamellar-forming block copolymer thin films on a chemical pattern of lines and spaces. The case where the copolymer material replicates the surface pattern and the more subtle scenario of sparse guiding patterns are considered. Our simulation results highlight (1) the importance of the early stages of pattern-directed self-assembly that template the subsequent morphology and (2) the dependence of the free-energy landscape on the incompatibility between the two blocks of the copolymer. (paper)

  7. A synthetic peptide blocking TRPV1 activation inhibits UV-induced skin responses.

    Science.gov (United States)

    Kang, So Min; Han, Sangbum; Oh, Jang-Hee; Lee, Young Mee; Park, Chi-Hyun; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

    2017-10-01

    Transient receptor potential type 1 (TRPV1) can be activated by ultraviolet (UV) irradiation, and mediates UV-induced matrix metalloproteinase (MMP)-1 and proinflammatory cytokines in keratinocytes. Various chemicals and compounds targeting TRPV1 activation have been developed, but are not in clinical use mostly due to their safety issues. We aimed to develop a novel TRPV1-targeting peptide to inhibit UV-induced responses in human skin. We designed and generated a novel TRPV1 inhibitory peptide (TIP) which mimics the specific site in TRPV1 (aa 701-709: Gln-Arg-Ala-Ile-Thr-Ile-Leu-Asp-Thr, QRAITILDT), Thr 705 , and tested its efficacy of blocking UV-induced responses in HaCaT, mouse, and human skin. TIP effectively inhibited capsaicin-induced calcium influx and TRPV1 activation. Treatment of HaCaT with TIP prevented UV-induced increases of MMP-1 and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-α. In mouse skin in vivo, TIP inhibited UV-induced skin thickening and prevented UV-induced expression of MMP-13 and MMP-9. Moreover, TIP attenuated UV-induced erythema and the expression of MMP-1, MMP-2, IL-6, and IL-8 in human skin in vivo. The novel synthetic peptide targeting TRPV1 can ameliorate UV-induced skin responses in vitro and in vivo, providing a promising therapeutic approach against UV-induced inflammation and photoaging. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  8. Molecular building blocks and their architecture in biologically/environmentally compatible soft matter chemical machinery.

    Science.gov (United States)

    Toyota, Taro; Banno, Taisuke; Nitta, Sachiko; Takinoue, Masahiro; Nomoto, Tomonori; Natsume, Yuno; Matsumura, Shuichi; Fujinami, Masanori

    2014-01-01

    This review briefly summarizes recent developments in the construction of biologically/environmentally compatible chemical machinery composed of soft matter. Since environmental and living systems are open systems, chemical machinery must continuously fulfill its functions not only through the influx and generation of molecules but also via the degradation and dissipation of molecules. If the degradation or dissipation of soft matter molecular building blocks and biomaterial molecules/polymers can be achieved, soft matter particles composed of them can be used to realize chemical machinery such as selfpropelled droplets, drug delivery carriers, tissue regeneration scaffolds, protocell models, cell-/tissuemarkers, and molecular computing systems.

  9. Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Booij, L.H.D.J.; Driessen, J.J.

    2009-01-01

    A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and

  10. Chemical-induced allergy and autoimmunity

    NARCIS (Netherlands)

    Wulferink, Marty Bernardus Franciscus

    2001-01-01

    This thesis aims towards a better understanding of the mechanisms that lead to chemical-induced adverse immune effects. We focussed thereby on the initial induction stage of the immune reaction that consists of three major steps: (i) formation of neoantigen, (ii) processing and presentation of the

  11. The understanding of the R7T7 glass blocks long term behavior: chemical and transport coupling in fractured media

    International Nuclear Information System (INIS)

    Chomat, L.

    2008-04-01

    The long term behavior of nuclear waste glass blocks depends highly on chemical reactions which occur at the surface in contact with water. Studies carried out on inactive fractured glass blocks show that fracture networks play a significant part in reactive surface area. Nevertheless, the complexity of results interpretation, due to a weak knowledge of fracture networks and local lixiviation conditions, does not allow us to comprehend the physical and chemical mechanisms involved. Model cracks are a key step to study chemical and transport coupling in fractured media. Crack lixiviation in aggressive conditions (pH≥11) show that the crack's position (horizontal or vertical) determines the dominant transport mechanism (respectively diffusion or convection induced by gravity). This gravity driven flow seems to be negligible in lower pH conditions. The convective velocity is estimated by a 1D model of reactive transport. Two other parameters are studied: the influence of thermal gradient and the influence of interconnected cracks on alteration. A strong retroactive effect of convection, due to thermal gradient, on the alteration kinetic is observed inside the crack. These works lead to a complete alteration experiment of a 163 crack network subject to a thermal gradient. The use of the geochemical software, HYTEC, within the framework of this study shows the potential of the software which is however limited by the kinetics law used. (author)

  12. Oleic acid blocks EGF-induced [Ca2+]i release without altering cellular metabolism in fibroblast EGFR T17.

    Science.gov (United States)

    Zugaza, J L; Casabiell, X A; Bokser, L; Casanueva, F F

    1995-02-06

    EGFR-T17 cells were pretreated with oleic acid and 5-10 minutes later stimulated with EGF, to study if early ionic signals are instrumental in inducing metabolic cellular response. Oleic acid blocks EGF-induced [Ca2+]i rise and Ca2+ influx without altering 2-deoxyglucose and 2-aminobutiryc acid uptake nor acute, nor chronically. Oleic acid it is shown, in the first minutes favors the entrance of both molecules to modify the physico-chemical membrane state. On the other hand, oleic acid is unable to block protein synthesis. The results suggest that EGF-induced Ins(1,4,5)P3/Ca2+ pathway does not seem to be decisive in the control of cellular metabolic activity.

  13. Contribution of orientational effects into radiation-chemical properties of segregated block copolymers

    International Nuclear Information System (INIS)

    Bol'bit, N.M.; Korneev, Yu.N.

    1992-01-01

    Model of radiolysis of microphase-separated block copolymers of PS with PB is proposed. According this scheme the radiation-chemical yields of paramagnetic centres and crosslinks in PB domains differ from those for the PB homopolymer by the value proportional to the fraction of ordered chain segments. This orientational small-scale order arises as a result of the deformation of chains in a domain in the direction perpendicular to the interphase

  14. Synthesis and Characterization of Block Copolymers with Unique Chemical Functionalities and Entropically-Hindering Moieties

    Science.gov (United States)

    2017-08-14

    methanol as a function of chemistry , morphology and hydration levels. Accomplishments: This section is included in the "upload" section. Training...Copolymer Blend Membranes.” In Press, Polymer Engineering and Science, DOI: 10.1002 /pen.24508, 2017. 5. M. Pérez-Pérez and D. Suleiman. “Synthesis and...Synthesis and Characterization of Sulfonated Amine Block Copolymers for Energy Efficient Applications". Chemical Engineering Symposium, University of

  15. Engineering cell factories for producing building block chemicals for bio-polymer synthesis.

    Science.gov (United States)

    Tsuge, Yota; Kawaguchi, Hideo; Sasaki, Kengo; Kondo, Akihiko

    2016-01-21

    Synthetic polymers are widely used in daily life. Due to increasing environmental concerns related to global warming and the depletion of oil reserves, the development of microbial-based fermentation processes for the production of polymer building block chemicals from renewable resources is desirable to replace current petroleum-based methods. To this end, strains that efficiently produce the target chemicals at high yields and productivity are needed. Recent advances in metabolic engineering have enabled the biosynthesis of polymer compounds at high yield and productivities by governing the carbon flux towards the target chemicals. Using these methods, microbial strains have been engineered to produce monomer chemicals for replacing traditional petroleum-derived aliphatic polymers. These developments also raise the possibility of microbial production of aromatic chemicals for synthesizing high-performance polymers with desirable properties, such as ultraviolet absorbance, high thermal resistance, and mechanical strength. In the present review, we summarize recent progress in metabolic engineering approaches to optimize microbial strains for producing building blocks to synthesize aliphatic and high-performance aromatic polymers.

  16. Emulsion Solvent Evaporation-Induced Self-Assembly of Block Copolymers Containing pH-Sensitive Block.

    Science.gov (United States)

    Wu, Yuqing; Wang, Ke; Tan, Haiying; Xu, Jiangping; Zhu, Jintao

    2017-09-26

    A simple yet efficient method is developed to manipulate the self-assembly of pH-sensitive block copolymers (BCPs) confined in emulsion droplets. Addition of acid induces significant variation in morphological transition (e.g., structure and surface composition changes) of the polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) assemblies, due to the hydrophobic-hydrophilic transition of the pH-sensitive P4VP block via protonation. In the case of pH > pKa (P4VP) (pKa (P4VP) = 4.8), the BCPs can self-assemble into pupa-like particles because of the nearly neutral wetting of PS and P4VP blocks at the oil/water interface. As expected, onion-like particles obtained when pH is slightly lower than pKa (P4VP) (e.g., pH = 3.00), due to the interfacial affinity to the weakly hydrophilic P4VP block. Interestingly, when pH was further decreased to ∼2.5, interfacial instability of the emulsion droplets was observed, and each emulsion droplet generated nanoscale assemblies including vesicles, worm-like and/or spherical micelles rather than a nanostructured microparticle. Furthermore, homopolymer with different molecular weights and addition ratio are employed to adjust the interactions among copolymer blocks. By this means, particles with hierarchical structures can be obtained. Moreover, owing to the kinetically controlled processing, we found that temperature and stirring speed, which can significantly affect the kinetics of the evaporation of organic solvent and the formation of particles, played a key role in the morphology of the assemblies. We believe that manipulation of the property for the aqueous phase is a promising strategy to rationally design and fabricate polymeric assemblies with desirable shapes and internal structures.

  17. Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced

  18. General Syntheses of Nanotubes Induced by Block Copolymer Self-Assembly

    DEFF Research Database (Denmark)

    Zhao, Jianming; Huang, Wei; Si, Pengchao

    2018-01-01

    Amphiphilic block copolymer templating strategies are extensively used for syntheses of mesoporous materials. However, monodisperse tubular nanostructures are limited. Here, a general method is developed to synthesize monodisperse nanotubes with narrow diameter distribution induced by self...

  19. Are lesions induced by ionizing radiation direct blocks to DNA chain elongation

    International Nuclear Information System (INIS)

    Painter, R.B.

    1983-01-01

    Ionizing radiation blocks DNA chain elongation in normal diploid fibroblasts but not in fibroblasts from patients with ataxia-telangiectasia, even though there are no differences in the damage induced between the two cell types. This difference suggests that radiation-induced lesions in DNA are not themselves blocks to chain elongation in ataxia cells and raises the possibility that in normal cells a mediator exists between DNA damage and chain termination

  20. Quantitative NMR Approach to Optimize the Formation of Chemical Building Blocks from Abundant Carbohydrates.

    Science.gov (United States)

    Elliot, Samuel G; Tolborg, Søren; Sádaba, Irantzu; Taarning, Esben; Meier, Sebastian

    2017-07-21

    The future role of biomass-derived chemicals relies on the formation of diverse functional monomers in high yields from carbohydrates. Recently, it has become clear that a series of α-hydroxy acids, esters, and lactones can be formed from carbohydrates in alcohol and water solvents using tin-containing catalysts such as Sn-Beta. These compounds are potential building blocks for polyesters bearing additional olefin and alcohol functionalities. An NMR approach was used to identify, quantify, and optimize the formation of these building blocks in the Sn-Beta-catalyzed transformation of abundant carbohydrates. Record yields of the target molecules can be achieved by obstructing competing reactions through solvent selection. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Color changing block copolymer films for chemical sensing of simple sugars.

    Science.gov (United States)

    Ayyub, Omar B; Sekowski, Jennifer W; Yang, Ta-I; Zhang, Xin; Briber, Robert M; Kofinas, Peter

    2011-10-15

    We investigated the use of functionalized photonic block copolymer films for the detection of glucose. Polystyrene-b-poly(2-vinyl pyridine) (PS-b-P2VP) block copolymers were chemically functionalized with 2-(bromomethyl)phenylboronic acid and cast into films that reflect a visible color when exposed to aqueous media. The 2-(bromomethyl)phenylboronic acid functionality can reversibly bind to glucose. When exposed to high concentrations of glucose the polymer responded with a red shift in color. Low concentration exposure of glucose caused the polymer films to blue shift in color. The BCP films also exhibited a selective response to fructose, mannose or galactose, giving a different response depending on which sugar is present. The color of the polymer was tuned to blue, green, yellow or orange by varying the film's crosslink density. The color change can be visually observed without the use of equipment such as a spectrometer. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Medial septal dysfunction by Aβ-induced KCNQ channel-block in glutamatergic neurons

    DEFF Research Database (Denmark)

    Leão, Richardson N.; Colom, Luis V.; Borgius, Lotta

    2012-01-01

    (MS) neurons in mice. In glutamatergic neurons Aβ increases firing frequency and blocks the A- and the M-current (IA and IM, respectively). While the IA block is similar in other MS neuron classes, the block of IM is specific to glutamatergic neurons. IM block and a simulated Aβ block mimic the Aβ......-induced increase in spontaneous firing in glutamatergic neurons. Calcium imaging shows that under control conditions glutamatergic neurons rarely fire while nonglutamatergic neurons fire coherently at theta frequencies. Aβ increases the firing rate of glutamatergic neurons while nonglutamatergic neurons lose theta...... firing coherence. Our results demonstrate that Aβ-induced dysfunction of glutamatergic neurons via IM decrease diminishes MS rhythmicity, which may negatively affect hippocampal rhythmogenesis and underlie the memory loss observed in Alzheimer's disease....

  3. High-strain-induced deformation mechanisms in block-graft and multigraft copolymers

    KAUST Repository

    Schlegel, Ralf

    2011-12-13

    The molecular orientation behavior and structural changes of morphology at high strains for multigraft and block-graft copolymers based on polystyrene (PS) and polyisoprene (PI) were investigated during uniaxial monotonic loading via FT-IR and synchrotron SAXS. Results from FT-IR revealed specific orientations of PS and PI segments depending on molecular architecture and on the morphology, while structural investigations revealed a typical decrease in long-range order with increasing strain. This decrease was interpreted as strain-induced dissolution of the glassy blocks in the soft matrix, which is assumed to affect an additional enthalpic contribution (strain-induced mixing of polymer chains) and stronger retracting forces of the network chains during elongation. Our interpretation is supported by FT-IR measurements showing similar orientation of rubbery and glassy segments up to high strains. It also points to highly deformable PS domains. By synchrotron SAXS, we observed in the neo-Hookean region an approach of glassy domains, while at higher elongations the intensity of the primary reflection peak was significantly decreasing. The latter clearly verifies the assumption that the glassy chains are pulled out from the domains and are partly mixed in the PI matrix. Results obtained by applying models of rubber elasticity to stress-strain and hysteresis data revealed similar correlations between the softening behavior and molecular and morphological parameters. Further, an influence of the network modality was observed (random grafted branches). For sphere forming multigraft copolymers the domain functionality was found to be less important to achieve improved mechanical properties but rather size and distribution of the domains. © 2011 American Chemical Society.

  4. Biorefineries for the production of top building block chemicals and their derivatives.

    Science.gov (United States)

    Choi, Sol; Song, Chan Woo; Shin, Jae Ho; Lee, Sang Yup

    2015-03-01

    Due to the growing concerns on the climate change and sustainability on petrochemical resources, DOE selected and announced the bio-based top 12 building blocks and discussed the needs for developing biorefinery technologies to replace the current petroleum based industry in 2004. Over the last 10 years after its announcement, many studies have been performed for the development of efficient technologies for the bio-based production of these chemicals and derivatives. Now, ten chemicals among these top 12 chemicals, excluding the l-aspartic acid and 3-hydroxybutyrolactone, have already been commercialized or are close to commercialization. In this paper, we review the current status of biorefinery development for the production of these platform chemicals and their derivatives. In addition, current technological advances on industrial strain development for the production of platform chemicals using micro-organisms will be covered in detail with case studies on succinic acid and 3-hydroxypropionic acid as examples. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  5. Doxorubicin-induced second degree and complete atrioventricular block.

    Science.gov (United States)

    Kilickap, Saadettin; Akgul, Ebru; Aksoy, Sercan; Aytemir, Kudret; Barista, Ibrahim

    2005-05-01

    Doxorubicin is one of the most effective chemotherapeutic agents used in the treatment of malignancies. Cardiotoxicity is the most important dose-limiting toxicity of doxorubicin. Although cardiomyopathy is the most well known side effect of doxorubicin, it usually occurs many years after the treatment and relates to cumulative doxorubicin dosage. Another form of doxorubicin cardiotoxicity is arrhythmia which may occur at any time and after any dosage. However, doxorubicin-induced arrhythmia is rarely a life-threatening side effect. In this report, we present a case in which there were doxorubicin-induced life-threatening arrhythmias.

  6. Madecassoside Inhibits Melanin Synthesis by Blocking Ultraviolet-Induced Inflammation

    Directory of Open Access Journals (Sweden)

    Eunsun Jung

    2013-12-01

    Full Text Available Madecassoside (MA, a pentacyclic triterpene isolated from Centella asitica (L., is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to investigate the effects of MA on ultraviolet (UV-induced melanogenesis and mechanisms in a co-culture system of keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin synthesis and melanosome transfer in the co-culture system. These effects were further demonstrated by the MA-induced inhibition of protease-activated receptor-2 expression and its signaling pathway, cyclooxygenase-2, prostaglandin E2 and prostaglandin F2 alpha in keratinocytes. The clinical efficacy of MA was confirmed on artificially tanned human skin. MA significantly reduced UV-induced melanin index at 8 weeks after topical application. Overall, the study demonstrated significant benefits of MA use in the inhibition of hyperpigmentation caused by UV irradiation.

  7. The One-Pot Directed Assembly of Cylinder-Forming Block Copolymer on Adjacent Chemical Patterns for Bimodal Patterning.

    Science.gov (United States)

    Chang, Tzu-Hsuan; Xiong, Shisheng; Liu, Chi-Chun; Liu, Dong; Nealey, Paul F; Ma, Zhenqiang

    2017-09-01

    The direct self-assembly of cylinder-forming poly(styrene-block-methyl-methacrylate) (PS-b-PMMA) block copolymer is successfully assembled into two orientations, according to the underlying guiding pattern in different areas. Lying-down and perpendicular cylinders are formed, respectively, depending on the design of chemical pattern: sparse line/space pattern or hexagonal dot array. The first chemical pattern composed of prepatterned cross-linked polystyrene (XPS) line/space structure has a period (L S ) equal to twice the intercylinder period of the block copolymer (L 0 ). The PS-b-PMMA thin film on the prepared chemical template after thermal annealing forms a lying-down cylinder morphology when the width of the PS strips is less than the width of PS block in the PS-b-PMMA block copolymer. The morphology is only applicable at the discrete thickness of the PS-b-PMMA film. In addition to forming the lying-down cylinders directly on the XPS guiding pattern, the cylinder-forming block copolymer can also be assembled in a perpendicular way on the second guiding pattern (the hexagonal dot array). The block copolymer films are registered into two orientations in a single directed self-assembly process. The features of the assembled patterns are successfully transferred down to the silicon oxide substrate. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Chemical reactions induced by fast neutron irradiation

    International Nuclear Information System (INIS)

    Katsumura, Y.

    1989-01-01

    Here, several studies on fast neutron irradiation effects carried out at the reactor 'YAYOI' are presented. Some indicate a significant difference in the effect from those by γ-ray irradiation but others do not, and the difference changes from subject to subject which we observed. In general, chemical reactions induced by fast neutron irradiation expand in space and time, and there are many aspects. In the time region just after the deposition of neutron energy in the system, intermediates are formed densely and locally reflecting high LET of fast neutrons and, with time, successive reactions proceed parallel to dissipation of localized energy and to diffusion of the intermediates. Finally the reactions are completed in longer time region. If we pick up the effects which reserve the locality of the initial processes, a significant different effect between in fast neutron radiolysis and in γ-ray radiolysis would be derived. If we observe the products generated after dissipation and diffusion in longer time region, a clear difference would not be observed. Therefore, in order to understand the fast neutron irradiation effects, it is necessary to know the fundamental processes of the reactions induced by radiations. (author)

  9. Depigmented Allergoids Reveal New Epitopes with Capacity to Induce IgG Blocking Antibodies

    OpenAIRE

    L?pez-Matas, M. Angeles; Gallego, Mayte; Iraola, V?ctor; Robinson, Douglas; Carn?s, Jer?nimo

    2013-01-01

    Background. The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT) has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol) allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. Methods. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtain...

  10. Fluorescent, MRI, and colorimetric chemical sensors for the first-row d-block metal ions.

    Science.gov (United States)

    Zhu, Hao; Fan, Jiangli; Wang, Benhua; Peng, Xiaojun

    2015-07-07

    Transition metals (d-blocks) are recognized as playing critical roles in biology, and they most often act as cofactors in diverse enzymes; however, improper regulation of transition metal stores is also connected to serious disorders. Therefore, the monitoring and imaging of transition metals are significant for biological research as well as clinical diagnosis. In this article, efforts have been made to review the chemical sensors that have been developed for the detection of the first-row d-block metals (except Cu and Zn): Cr, Mn, Fe, Co, and Ni. We focus on the development of fluorescent sensors (fall into three classes: "turn-off", "turn-on", and ratiometric), colorimetric sensors, and responsive MRI contrast agents for these transition metals (242 references). Future work will be likely to fill in the blanks: (1) sensors for Sc, Ti, and V; (2) MRI sensors for Cr, Mn, Co, Ni; (3) ratiometric fluorescent sensors for Cr(6+), Mn(2+), and Ni(2+), explore new ways of sensing Fe(3+) or Cr(3+) without the proton interference, as well as extend applications of MRI sensors to living systems.

  11. Advances in metabolic pathway and strain engineering paving the way for sustainable production of chemical building blocks.

    Science.gov (United States)

    Chen, Yun; Nielsen, Jens

    2013-12-01

    Bio-based production of chemical building blocks from renewable resources is an attractive alternative to petroleum-based platform chemicals. Metabolic pathway and strain engineering is the key element in constructing robust microbial chemical factories within the constraints of cost effective production. Here we discuss how the development of computational algorithms, novel modules and methods, omics-based techniques combined with modeling refinement are enabling reduction in development time and thus advance the field of industrial biotechnology. We further discuss how recent technological developments contribute to the development of novel cell factories for the production of the building block chemicals: adipic acid, succinic acid and 3-hydroxypropionic acid. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Depigmented allergoids reveal new epitopes with capacity to induce IgG blocking antibodies.

    Science.gov (United States)

    López-Matas, M Angeles; Gallego, Mayte; Iraola, Víctor; Robinson, Douglas; Carnés, Jerónimo

    2013-01-01

    The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT) has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol) allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtained. Recognition of linear IgG-epitopes of Bet v 1 and Bet v 2 and the capacity of these IgG-antibodies to block binding of human-IgE was determined. Serum from rabbits immunized with native extracts recognised 11 linear epitopes from Bet v 1, while that from Dpg-Pol-immunized animals recognised 8. For Bet v 2, 8 epitopes were recognized by IgG from native immunized animals, and 9 from Dpg-Pol immunized one. Dpg-Pol and native immunized serum did not always recognise the same epitopes, but specific-IgG from both could block human-IgE binding sites for native extract. Depigmented-polymerized birch extract stimulates the synthesis of specific IgG-antibodies which recognize common but also novel epitopes compared with native extracts. IgG-antibodies induced by Dpg-Pol effectively inhibit human-IgE binding to allergens which may be part of the mechanism of action of SIT.

  13. Use of induced chlorophyll deficient mutants to identify 'heterotic blocks' in pearl millet chromosomes

    International Nuclear Information System (INIS)

    Burton, G.W.

    1989-01-01

    Full text: Chlorophyll deficient mutant stocks induced in 'Tift 23' of pearl millet (Pennisetum americanum L. Leeke) were crossed with 'Tift 23' and 5 other normal inbreds to study the effect of these deleterious recessive genes on yield. The difference between near-isogenic S 1 (F 2 ) populations homozygous or heterozygous for the chlorophyll deficiency was not significant. However among 69 S 1 progenies from crosses with other inbreds the heterozygotes were higher yielding than the homozygotes in 53 cases, 15 of which were significant. A mutant like 'M5' identified a high yield 'heterotic block' in 'Inbred 104' and a very low yield 'heterotic block' in 'Inbred 186'. (author)

  14. A progress report for the large block test of the coupled thermal-mechanical-hydrological-chemical processes

    International Nuclear Information System (INIS)

    Lin, W.; Wilder, D.G.; Blink, J.

    1994-10-01

    This is a progress report on the Large Block Test (LBT) project. The purpose of the LBT is to study some of the coupled thermal-mechanical-hydrological-chemical (TMHC) processes in the near field of a nuclear waste repository under controlled boundary conditions. To do so, a large block of Topopah Spring tuff will be heated from within for about 4 to 6 months, then cooled down for about the same duration. Instruments to measure temperature, moisture content, stress, displacement, and chemical changes will be installed in three directions in the block. Meanwhile, laboratory tests will be conducted on small blocks to investigate individual thermal-mechanical, thermal-hydrological, and thermal-chemical processes. The fractures in the large block will be characterized from five exposed surfaces. The minerals on fracture surfaces will be studied before and after the test. The results from the LBT will be useful for testing and building confidence in models that will be used to predict TMHC processes in a repository. The boundary conditions to be controlled on the block include zero moisture flux and zero heat flux on the sides, constant temperature on the top, and constant stress on the outside surfaces of the block. To control these boundary conditions, a load-retaining frame is required. A 3 x 3 x 4.5 m block of Topopah Spring tuff has been isolated on the outcrop at Fran Ridge, Nevada Test Site. Pre-test model calculations indicate that a permeability of at least 10 -15 m 2 is required so that a dryout zone can be created within a practical time frame when the block is heated from within. Neutron logging was conducted in some of the vertical holes to estimate the initial moisture content of the block. It was found that about 60 to 80% of the pore volume of the block is saturated with water. Cores from the vertical holes have been used to map the fractures and to determine the properties of the rock. A current schedule is included in the report

  15. Ultrasound-assisted acid hydrolysis of cellulose to chemical building blocks: Application to furfural synthesis.

    Science.gov (United States)

    Santos, Daniel; Silva, Ubiratan F; Duarte, Fabio A; Bizzi, Cezar A; Flores, Erico M M; Mello, Paola A

    2018-01-01

    In this work, the use of ultrasound energy for the production of furanic platforms from cellulose was investigated and the synthesis of furfural was demonstrated. Several systems were evaluated, as ultrasound bath, cup horn and probe, in order to investigate microcrystalline cellulose conversion using simply a diluted acid solution and ultrasound. Several acid mixtures were evaluated for hydrolysis, as diluted solutions of HNO 3 , H 2 SO 4 , HCl and H 2 C 2 O 4 . The influence of the following parameters in the ultrasound-assisted acid hydrolysis (UAAH) were studied: sonication temperature (30 to 70°C) and ultrasound amplitude (30 to 70% for a cup horn system) for 4 to 8molL -1 HNO 3 solutions. For each evaluated condition, the products were identified by ultra-performance liquid chromatography with high-resolution time-of-flight mass spectrometry (UPLC-ToF-MS), which provide accurate information regarding the products obtained from biomass conversion. The furfural structure was confirmed by nuclear magnetic resonance ( 1 H and 13 C NMR) spectroscopy. In addition, cellulosic residues from hydrolysis reaction were characterized using scanning electron microscopy (SEM), which contributed for a better understanding of physical-chemical effects caused by ultrasound. After process optimization, a 4molL -1 HNO 3 solution, sonicated for 60min at 30°C in a cup horn system at 50% of amplitude, lead to 78% of conversion to furfural. This mild temperature condition combined to the use of a diluted acid solution represents an important contribution for the selective production of chemical building blocks using ultrasound energy. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Reactive Imprint Lithography: Combined Topographical Patterning and Chemical Surface Functionalization of Polystyrene-block-poly(tert-butyl acrylate) Films

    NARCIS (Netherlands)

    Duvigneau, Joost; Cornelissen, Stijn; Bardajı´Valls, Nuria; Schönherr, Holger; Vancso, Gyula J.

    2009-01-01

    Here, reactive imprint lithography (RIL) is introduced as a new, one-step lithographic tool for the fabrication of large-area topographically patterned, chemically activated polymer platforms. Films of polystyrene-block-poly(tert-butyl acrylate) (PS-b-PtBA) are imprinted with PDMS master stamps at

  17. Accelerated detection of brown-rot decay : comparison of soil block test, chemical analysis, mechanical properties, and immunodetection

    Science.gov (United States)

    C. A. Clausen; S. N. Kartal

    2003-01-01

    Early detection of wood decay is critical because decay fungi can cause rapid structural failure. The objective of this study was to compare the sensitivity of different methods purported to detect brown-rot decay in the early stages of development. The immunodiagnostic wood decay (IWD)test, soil block test/cake pan test, mechanical property tests, and chemical...

  18. Effect of gamma irradiation on the chemical compositions of some feed block types

    International Nuclear Information System (INIS)

    Al-Masri, M.R.

    1994-02-01

    The effect of gamma irradiation (100 kilo gray,KGy) on chemical compositions for 3 types of feed blocks was studied. the first type (Type I) contained 28% wheat bran, 31% dried poultry manure, 20% molasses, 10% urea, 6% Co(OH)-2, 5% salt. Type (II) contained 22% wheat bran, 10% dried poultry manure, 30% dried beet pule, 20% molasses, 8% urea, 6% Ca(OH)-2, 4% salt. Type (III) contained 35% olive cake, 30% wheat bran, 10% urea, 15% cement, 10% salt. The results indicate that there were significant differences (P<0.05) between controls and treatments for the crude fibre (CF) and NDF. CF values decreased by 12% for all types. NDF values decreased by 25%, 19% and 16% and hemicellulose (HCL) by 46%, 35%, 44% for types (I), (II) and (III) respectively. Total nitrogen crude fat, crude ash, organic matter, ADF, ADL, cellulose (CL) and CL:ADL ratio did not change as a result of irradiation, CL:CF ratio increased by 14%, 10% and 17%, and CL:NDF ratio increased by 37%, 29% and 25% for types (I), (II) and (III) respectively. HCL:CF ratio decreased by 39%, 27% and 38% and HCL:NDF ratio by 27%, 20% and 33% and HCL:ADL ratio decreased by 45%, 30%, and 40% for types (I), (II), (III) respectively. (author). 27 refs., 4 figs., 3 tabs

  19. Geochemical induced degradation of environmental chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Parlar, H

    1984-09-01

    Attempts to correlate the concentration of organic chemicals in the environment with their production figures have resulted in a large deficit; this includes environmental chemicals such as chlorinated hydrocarbons. It has been assumed that analytical errors accounted for this deficit. Another explanation, however, allows for reactions of compounds under biotic and abiotic conditions. Because of the biostability of many organic chemicals biological transformation mechanisms can bring about slight change only. By contrast, abiotic environmental factors such as the UV-irradiation or decomposition on natural surfaces contribute considerably to the transformation of this substance class. An investigation of such abiotic charges of organic chemicals must therefore pay particular attention to dynamic and catalytic effects primarily attributable to the respective molecular state and interactions with the environment. This paper deals with the photoinduced reactions of organic substances adsorbed on natural surfaces and their significance for the degradability of environmental chemicals.

  20. Advances in metabolic pathway and strain engineering paving the way for sustainable production of chemical building blocks

    DEFF Research Database (Denmark)

    Chen, Yun; Nielsen, Jens

    2013-01-01

    Bio-based production of chemical building blocks from renewable resources is an attractive alternative to petroleum-based platform chemicals. Metabolic pathway and strain engineering is the key element in constructing robust microbial chemical factories within the constraints of cost effective...... production. Here we discuss how the development of computational algorithms, novel modules and methods, omics-based techniques combined with modeling refinement are enabling reduction in development time and thus advance the field of industrial biotechnology. We further discuss how recent technological...

  1. Blocking CHK1 Expression Induces Apoptosis and Abrogates the G2 Checkpoint Mechanism

    Directory of Open Access Journals (Sweden)

    Yan Luo

    2001-01-01

    Full Text Available Checkpoint kinase 1 (Chki is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates the Cdc2 activating phosphatase Cdc25C. This in turn inactivates Cdc2, which leads to G2/M arrest. We report that blocking Chki expression by antisense or ribozymes in mammalian cells induces apoptosis and interferes with the G2/M arrest induced by adriamycin. The Chki inhibitor UCN-01 also blocks the G2 arrest after DNA damage and renders cells more susceptible to adriamycin. These results indicate that Chki is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response.

  2. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study

    DEFF Research Database (Denmark)

    Sorgenfrei, Iben F; Norrild, Kathrine; Larsen, Per Bo

    2006-01-01

    Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.......Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block....

  3. Quantitative NMR Approach to Optimize the Formation of Chemical Building Blocks from Abundant Carbohydrates

    DEFF Research Database (Denmark)

    Elliot, Samuel Gilbert; Tolborg, Søren; Sádaba, Irantzu

    2017-01-01

    -containing catalysts such as Sn-Beta. These compounds are potential building blocks for polyesters with additional olefin and alcohol functionalities. We employ an NMR approach to identify, quantify and optimize the formation these building blocks in the chemocatalytic transformation of abundant carbohydrates by Sn...

  4. Mixed chemical-induced oxidative stress in occupational exposure ...

    African Journals Online (AJOL)

    Mixed chemical-induced oxidative stress in occupational exposure in Nigerians. JI Anetor, SA Yaqub, GO Anetor, AC Nsonwu, FAA Adeniyi, S Fukushima. Abstract. Exposure to single chemicals and associated disorders in occupational environments has received significant attention. Understanding these events holds ...

  5. Depigmented Allergoids Reveal New Epitopes with Capacity to Induce IgG Blocking Antibodies

    Directory of Open Access Journals (Sweden)

    M. Angeles López-Matas

    2013-01-01

    Full Text Available Background. The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. Methods. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtained. Recognition of linear IgG-epitopes of Bet v 1 and Bet v 2 and the capacity of these IgG-antibodies to block binding of human-IgE was determined. Results. Serum from rabbits immunized with native extracts recognised 11 linear epitopes from Bet v 1, while that from Dpg-Pol-immunized animals recognised 8. For Bet v 2, 8 epitopes were recognized by IgG from native immunized animals, and 9 from Dpg-Pol immunized one. Dpg-Pol and native immunized serum did not always recognise the same epitopes, but specific-IgG from both could block human-IgE binding sites for native extract. Conclusions. Depigmented-polymerized birch extract stimulates the synthesis of specific IgG-antibodies which recognize common but also novel epitopes compared with native extracts. IgG-antibodies induced by Dpg-Pol effectively inhibit human-IgE binding to allergens which may be part of the mechanism of action of SIT.

  6. Tuning of Block Copolymer Membrane Morphology through Water Induced Phase Inversion Technique

    KAUST Repository

    Madhavan, Poornima

    2016-06-01

    Isoporous membranes are attractive for the regulation and detection of transport at the molecular level. A well-defined asymmetric membranes from diblock copolymers with an ordered nanoporous membrane morphologies were fabricated by the combination of block copolymer self-assembly and non-solvent-induced phase separation (NIPS) technique. This is a straightforward and fast one step procedure to develop integrally anisotropic (“asymmetric”) membranes having isoporous top selective layer. Membranes prepared via this method exhibit an anisotropic cross section with a thin separation layer supported from underneath a macroporous support. These membrane poses cylindrical pore structure with ordered nanopores across the entire membrane surfaces with pore size in the range from 20 to 40 nm. Tuning the pore morphology of the block copolymer membranes before and after fabrication are of great interest. In this thesis, we first investigated the pore morphology tuning of asymmetric block copolymer membrane by complexing with small organic molecules. We found that the occurrence of hydrogen-bond formation between PS-b-P4VP block copolymer and –OH/ –COOH functionalized organic molecules significantly tunes the pore morphology of asymmetric nanoporous membranes. In addition, we studied the complexation behavior of ionic liquids with PS-b-P4VP block copolymer in solutions and investigated their effect on final membrane morphology during the non-solvent induced phase separation process. We found that non-protic ionic liquids facilitate the formation of hexagonal nanoporous block copolymer structure, while protic ionic liquids led to a lamella-structured membrane. Secondly, we demonstrated the catalytic activity of the gold nanoparticle-enhanced hollow fiber membranes by the reduction of nitrophenol. Also, we systematically investigated the pore morphology of isoporous PS-b-P4VP using 3D imaging technique. Thirdly, we developed well-distributed silver nanoparticles on the

  7. Hydrogen Bond Induces Hierarchical Self-Assembly in Liquid-Crystalline Block Copolymers.

    Science.gov (United States)

    Huang, Shuai; Pang, Linlin; Chen, Yuxuan; Zhou, Liming; Fang, Shaoming; Yu, Haifeng

    2018-03-01

    Microphase-separated structures of block copolymers (BCs) with a size of sub-10 nm are usually obtained by hydrogen-bond-induced self-assembly of BCs through doping with small molecules as functional additives. Here, fabrication of hierarchically self-assembled sub-10 nm structures upon microphase separation of amphiphilic liquid-crystalline BCs (LCBCs) at the existence of hydrogen bonds but without any dopants is reported. The newly introduced urethane groups in the side chain of the hydrophobic block of LCBCs interact with the ether groups of the hydrophilic poly(ethylene oxide) (PEO) block, leading to imperfect crystallization of the PEO blocks. Both crystalline and amorphous domains coexist in the separated PEO phase, enabling a lamellar structure to appear inside the PEO nanocylinders. This provides an elegant method to fabricate controllable sub-10 nm microstructures in well-defined polymer systems without the introduction of any dopants. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Single- and Multilayered Nanostructures via Laser-Induced Block Copolymer Self-Assembly

    Science.gov (United States)

    Majewski, Pawel; Yager, Kevin; Rahman, Atikur; Black, Charles

    We present a novel method of accelerated self-assembly of block copolymer thin films utilizing laser light, called Laser Zone Annealing (LZA). In our approach, steep temperature transients are induced in block copolymer films by rastering narrowly focused laser line over the light-absorbing substrate. Extremely steep temperature gradients accelerate the process of self-assembly by several orders-of-magnitude compared to conventional oven annealing, and, when coupled to photo-thermal shearing, lead to global alignment of block copolymer domains assessed by GISXAS diffraction studies and real-space SEM imaging. We demonstrate monolithic alignment of various block-copolymer thin films including PS-b-PMMA, PS-b-PEO, PS-b-P2VP, PS-b-PI and observe different responsiveness to the shearing rate depending on the characteristic relaxation timescale of the particular material. Subsequently, we use the aligned polymeric films as templates for synthesis of single- and multi-layered arrays of inorganic, metallic or semiconducting nanowires and nanomeshes and investigate their anisotropic electro-optical properties. Research carried out in part at the Center for Functional Nanomaterials, Brookhaven National Laboratory, which is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract No. DE-AC02-98CH10886.

  9. Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats.

    Science.gov (United States)

    Yusoff, Nurul H M; Mansor, Sharif M; Müller, Christian P; Hassan, Zurina

    2018-06-01

    Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABA B receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABA B receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABA B receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABA B receptor. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Metformin and phenformin block the peripheral antinociception induced by diclofenac and indomethacin on the formalin test.

    Science.gov (United States)

    Ortiz, Mario I

    2012-01-02

    Recent evidence has shown that systemic administration of sulfonylureas and biguanides block the diclofenac-induced antinociception, but not the effect produced by indomethacin. However, there are no reports about the peripheral interaction between analgesics and the biguanides metformin and phenformin. Therefore, this work was undertaken to determine whether glibenclamide and glipizide and the biguanides metformin and phenformin have any effect on the peripheral antinociception induced by diclofenac and indomethacin. Diclofenac and indomethacin were administered locally in the formalin-injured rat paw, and the antinociceptive effect was evaluated using the 1% formalin test. To determine whether peripheral antinociception induced by diclofenac or indomethacin was mediated by either the ATP-sensitive K(+) channels or biguanides-induced mechanisms, the effect of pretreatment with the appropriates vehicles or glibenclamide, glipizide, metformin and phenformin on the antinociceptive effect induced by local peripheral diclofenac and indomethacin was assessed. Local peripheral injections of diclofenac (50-200 μg/paw) and indomethacin (200-800 μg/paw) produced a dose-dependent antinociception during the second phase of the test. Local pretreatment with glibenclamide, glipizide, metformin and phenformin blocked the diclofenac-induced antinociception. On the other hand, the pretreatment with glibenclamide and glipizide did not prevent the local antinociception produced by indomethacin. Nonetheless, metformin and phenformin reversed the local antinociception induced by indomethacin. Data suggest that diclofenac could activate the K(+) channels and biguanides-dependent mechanisms to produce its peripheral antinociceptive effects in the formalin test. Likewise, a biguanides-dependent mechanism could be activated by indomethacin consecutively to generate its peripheral antinociceptive effect. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. A survey of chemicals inducing lipid peroxidation in biological systems.

    Science.gov (United States)

    Kappus, H

    1987-01-01

    A great number of drugs and chemicals are reviewed which have been shown to stimulate lipid peroxidation in any biological system. The underlying mechanisms, as far as known, are also dealt with. Lipid peroxidation induced by iron ions, organic hydroperoxides, halogenated hydrocarbons, redox cycling drugs, glutathione depleting chemicals, ethanol, heavy metals, ozone, nitrogen dioxide and a number of miscellaneous compounds, e.g. hydrazines, pesticides, antibiotics, are mentioned. It is shown that lipid peroxidation is stimulated by many of these compounds. However, quantitative estimates cannot be given yet and it is still impossible to judge the biological relevance of chemical-induced lipid peroxidation.

  12. Laser-induced chemical vapor deposition reactions

    International Nuclear Information System (INIS)

    Teslenko, V.V.

    1990-01-01

    The results of investigation of chemical reactions of deposition of different substances from the gas phase when using the energy of pulse quasicontinuous and continuous radiation of lasers in the wave length interval from 0.193 to 10.6 μm are generalized. Main attetion is paid to deposition of inorganic substances including nonmetals (C, Si, Ge and others), metals (Cu, Au, Zn, Cd, Al, Cr, Mo, W, Ni) and some simple compounds. Experimental data on the effect of laser radiation parameters and reagent nature (hydrides, halogenides, carbonyls, alkyl organometallic compounds and others) on the deposition rate and deposit composition are described in detail. Specific features of laser-chemical reactions of deposition and prospects of their application are considered

  13. Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine.

    Directory of Open Access Journals (Sweden)

    Lemmens Hendrikus JM

    2010-09-01

    Full Text Available Abstract Background Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia. Methods Patients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events. Results Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36. Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes compared with neostigmine (66.2 minutes; p Conclusions Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694.

  14. Bi-directional block is superior to non-inducibility in predicting freedom from atrial fibrillation after pulmonary vein isolation

    Directory of Open Access Journals (Sweden)

    Sherif H. Zaky

    2011-03-01

    Conclusion: Achieving BD block improves results and may predict maintenance of sinus rhythm more than NI of AF after PVI. It can be used as an electrophysiological endpoint alternative to or in conjunction with non inducibility in AF ablation procedures.

  15. Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity.

    Science.gov (United States)

    Kimani, Stanley G; Kumar, Sushil; Bansal, Nitu; Singh, Kamalendra; Kholodovych, Vladyslav; Comollo, Thomas; Peng, Youyi; Kotenko, Sergei V; Sarafianos, Stefan G; Bertino, Joseph R; Welsh, William J; Birge, Raymond B

    2017-03-08

    TAM receptors (Tyro-3, Axl, and Mertk) are a family of three homologous type I receptor tyrosine kinases that are implicated in several human malignancies. Overexpression of TAMs and their major ligand Growth arrest-specific factor 6 (Gas6) is associated with more aggressive staging of cancers, poorer predicted patient survival, acquired drug resistance and metastasis. Here we describe small molecule inhibitors (RU-301 and RU-302) that target the extracellular domain of Axl at the interface of the Ig-1 ectodomain of Axl and the Lg-1 of Gas6. These inhibitors effectively block Gas6-inducible Axl receptor activation with low micromolar IC 50s in cell-based reporter assays, inhibit Gas6-inducible motility in Axl-expressing cell lines, and suppress H1299 lung cancer tumor growth in a mouse xenograft NOD-SCIDγ model. Furthermore, using homology models and biochemical verifications, we show that RU301 and 302 also inhibit Gas6 inducible activation of Mertk and Tyro3 suggesting they can act as pan-TAM inhibitors that block the interface between the TAM Ig1 ectodomain and the Gas6 Lg domain. Together, these observations establish that small molecules that bind to the interface between TAM Ig1 domain and Gas6 Lg1 domain can inhibit TAM activation, and support the further development of small molecule Gas6-TAM interaction inhibitors as a novel class of cancer therapeutics.

  16. Micropore extrusion-induced alignment transition from perpendicular to parallel of cylindrical domains in block copolymers.

    Science.gov (United States)

    Qu, Ting; Zhao, Yongbin; Li, Zongbo; Wang, Pingping; Cao, Shubo; Xu, Yawei; Li, Yayuan; Chen, Aihua

    2016-02-14

    The orientation transition from perpendicular to parallel alignment of PEO cylindrical domains of PEO-b-PMA(Az) films has been demonstrated by extruding the block copolymer (BCP) solutions through a micropore of a plastic gastight syringe. The parallelized orientation of PEO domains induced by this micropore extrusion can be recovered to perpendicular alignment via ultrasonication of the extruded BCP solutions and subsequent annealing. A plausible mechanism is proposed in this study. The BCP films can be used as templates to prepare nanowire arrays with controlled layers, which has enormous potential application in the field of integrated circuits.

  17. Biorefineries for the production of top building block chemicals and their derivatives

    DEFF Research Database (Denmark)

    Choi, Sol; Song, Chan Woo; Shin, Jae Ho

    2015-01-01

    commercialized or are close to commercialization. In this paper, we review the current status of biorefinery development for the production of these platform chemicals and their derivatives. In addition, current technological advances on industrial strain development for the production of platform chemicals...... years after its announcement, many studies have been performed for the development of efficient technologies for the bio-based production of these chemicals and derivatives. Now, ten chemicals among these top 12 chemicals, excluding the l-aspartic acid and 3-hydroxybutyrolactone, have already been...

  18. Chemical Detection Based on Adsorption-Induced and Photo-Induced Stresses in MEMS Devices

    Energy Technology Data Exchange (ETDEWEB)

    Datskos, P.G.

    1999-04-05

    Recently there has been an increasing demand to perform real-time in-situ chemical detection of hazardous materials, contraband chemicals, and explosive chemicals. Currently, real-time chemical detection requires rather large analytical instrumentation that are expensive and complicated to use. The advent of inexpensive mass produced MEMS (micro-electromechanical systems) devices opened-up new possibilities for chemical detection. For example, microcantilevers were found to respond to chemical stimuli by undergoing changes in their bending and resonance frequency even when a small number of molecules adsorb on their surface. In our present studies, we extended this concept by studying changes in both the adsorption-induced stress and photo-induced stress as target chemicals adsorb on the surface of microcantilevers. For example, microcantilevers that have adsorbed molecules will undergo photo-induced bending that depends on the number of absorbed molecules on the surface. However, microcantilevers that have undergone photo-induced bending will adsorb molecules on their surfaces in a distinctly different way. Depending on the photon wavelength and microcantilever material, the microcantilever can be made to bend by expanding or contracting the irradiated surface. This is important in cases where the photo-induced stresses can be used to counter any adsorption-induced stresses and increase the dynamic range. Coating the surface of the microstructure with a different material can provide chemical specificity for the target chemicals. However, by selecting appropriate photon wavelengths we can change the chemical selectivity due to the introduction of new surface states in the MEMS device. We will present and discuss our results on the use of adsorption-induced and photo-induced bending of microcantilevers for chemical detection.

  19. Tn5-induced pBS286 plasmid mutations blocking early stages of napthalene oxidation

    International Nuclear Information System (INIS)

    Kosheleva, I.A.; Tsoi, T.V.; Ivashina, T.V.; Selifonov, S.A.; Starovoitov, I.I.; Boronin, A.M.

    1988-01-01

    The authors present data on the further analysis of the structural and functional organization of the nah region of plasmid pBS286 controlling the constitutive oxidation of naphthalene by Pseudomonas putida cells. They have studied Tn5-induced mutations blocking early stages of naphthalene oxidation. They present and discuss data providing evidence that, in contrast to plasmid NAH7, the mechanism of regulation of the nahl operon of plasmid NPL-1, the parent plasmid of plasmid pBS286, with inducible synthesis of naphthalene dioxygenase can include elements of a negative control with participation of the regulatory locus R, located proximal to the structural nah genes and closely linked to or overlapped by the inverted control DNA segment (4.2 kb). They also present data on the possibility of regulation of the activity of the catechol-splitting meta-pathway genes with the participation of products of early stages of naphthalene oxidation

  20. Rare Coumarins Induce Apoptosis, G1 Cell Block and Reduce RNA Content in HL60 Cells

    Directory of Open Access Journals (Sweden)

    Widelski Jarosław

    2017-02-01

    Full Text Available The rare coumarins stenocarpin, stenocarpin isobutyrate, oficinalin, oficinalin isobutyrate, 8-methoxypeucedanin and the known xanthotoxin, isoimperatorin, bergapten, peucedanin and 8–methoxyisoimperatorin were isolated from Peucedanum luxurians Tamamsch. (Apiaceae and identified by means of spectral data (1D and 2D NMR. Their immunomodulating activity was evaluated by flow cytometry and their influence on HL60 cells as well as on PHA-stimulated PBLs was tested. All tested coumarins induce apoptosis (maximal in the 48 h culture and decrease cell proliferation in a time- and dose-dependent manner, especially in HL60 cells. They also induce partial G1 block, but only in HL60 cells (at 100 µM concentrations. Dose-dependent reduction of RNA content was also found in G1 cells treated by the coumarins. All of the tested coumarins also possessed immunomodulatory activities. Bergapten and xanthotoxin were found to be the best candidates for further evaluation as anti-cancer drugs.

  1. Influence of chemical crosslinks on the elastic behavior of segmented block copolymers

    NARCIS (Netherlands)

    van der Schuur, J.M.; Gaymans, R.J.

    2005-01-01

    Polyether(ester–amide)s (PEEA) segmented block copolymers with di- and tri-functional poly(propylene oxide)s and amide segments were synthesized and the elastic properties studied. The difunctional polyether used had a molecular weight of 2300 g/mol end capped with 20 wt% ethylene oxide. The

  2. Block-induced Complex Structures Building the Flare-productive Solar Active Region 12673

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shuhong; Zhang, Jun [CAS Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China); Zhu, Xiaoshuai [Max-Planck Institute for Solar System Research, D-37077 Göttingen (Germany); Song, Qiao, E-mail: shuhongyang@nao.cas.cn [Key Laboratory of Space Weather, National Center for Space Weather, China Meteorological Administration, Beijing 100081 (China)

    2017-11-10

    Solar active region (AR) 12673 produced 4 X-class, 27 M-class, and numerous lower-class flares during its passage across the visible solar disk in 2017 September. Our study is to answer the questions why this AR was so flare-productive and how the X9.3 flare, the largest one of the past decade, took place. We find that there was a sunspot in the initial several days, and then two bipolar regions emerged nearby it successively. Due to the standing of the pre-existing sunspot, the movement of the bipoles was blocked, while the pre-existing sunspot maintained its quasi-circular shaped umbra only with the disappearance of a part of penumbra. Thus, the bipolar patches were significantly distorted, and the opposite polarities formed two semi-circular shaped structures. After that, two sequences of new bipolar regions emerged within the narrow semi-circular zone, and the bipolar patches separated along the curved channel. The new bipoles sheared and interacted with the previous ones, forming a complex topological system, during which numerous flares occurred. At the highly sheared region, a great deal of free energy was accumulated. On September 6, one negative patch near the polarity inversion line began to rapidly rotate and shear with the surrounding positive fields, and consequently the X9.3 flare erupted. Our results reveal that the block-induced complex structures built the flare-productive AR and the X9.3 flare was triggered by an erupting filament due to the kink instability. To better illustrate this process, a block-induced eruption model is proposed for the first time.

  3. Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Araceli Gutiérrez-Rodríguez

    2017-01-01

    Full Text Available Progesterone-induced blocking factor (PIBF is a progesterone (P4 regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P4 and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas. PIBF mRNA expression was upregulated by P4 (10 nM from 12 to 24 h. Glioblastoma cells expressed two PIBF isoforms, 90 and 57 kDa. The content of the shorter isoform was increased by P4 at 24 h, while progesterone receptor antagonist RU486 (10 μM blocked this effect. PIBF (100 ng/mL increased the number of U87 cells on days 4 and 5 of treatment and induced cell proliferation on day 4. Wound-healing assays showed that PIBF increased the migration of U87 (12–48 h and U251 (24 and 48 h cells. Transwell invasion assays showed that PIBF augmented the number of invasive cells in both cell lines at 24 h. These data suggest that PIBF promotes proliferation, migration, and invasion of human glioblastoma cells.

  4. Effects of cardiac output on the onset of rocuronium-induced neuromuscular block in elderly patients.

    Science.gov (United States)

    Shiraishi, Naoki; Aono, Mayu; Kameyama, Yasuhito; Yamamoto, Mai; Kitajima, Osamu; Suzuki, Takahiro

    2018-05-21

    The aim of this study was to elucidate the relationship between the onset of rocuronium-induced neuromuscular block and arterial pressure-based cardiac output (CO) in elderly patients. Forty elderly patients aged 65-83 years were enrolled in this study. After induction of anesthesia, contractions of the adductor pollicis muscle to ulnar nerve train-of-four stimulation were acceleromyographically evaluated and 1 mg/kg rocuronium was administered following CO measurement. The correlation between onset of rocuronium action and CO was analyzed. The mean [SD] CO reduced after induction of anesthesia from 5.1 [1.8] L/min to 3.8 [1.1] L/min. The onset time of rocuronium-induced neuromuscular block was 110.3 [23.9] s (range 60-165). There was a statistically significant inverse correlation between the onset time of rocuronium and CO [onset time (s) = - 13.2·CO + 159.7, R 2  = 0.376]. In the elderly, CO influences the onset of action of rocuronium.

  5. A chemical platform approach on cardanol oil: from the synthesis of building blocks to polymer synthesis

    Directory of Open Access Journals (Sweden)

    Jaillet Fanny

    2016-09-01

    Full Text Available This review proposes a platform approach for the synthesis of various building blocks from cardanol oil in one or two-steps synthesis. Cardanol is a natural phenol issued from Cashew nutshell liquid (CNSL. CNSL is a non-edible renewable resource, co-produced from cashew industry in large commercial volumes. Cardanol is non-toxic and particularly suitable as an aromatic renewable resource for polymers and materials. Various routes were used for the synthesis of di- and poly-functional building blocks used thereafter in polymer syntheses. Phenolation was used to dimerize/oligomerize cardanol to propose increase functionality of cardanol. Thio-ene was used to synthesize new reactive amines. Epoxidation and (methacrylation were also used to insert oxirane or (methacrylate groups in order to synthesize polymers and materials.

  6. Lithium blocks ethanol-induced modulation of protein kinases in the developing brain

    International Nuclear Information System (INIS)

    Chakraborty, Goutam; Saito, Mitsuo; Mao, Rui-Fen; Wang, Ray; Vadasz, Csaba; Saito, Mariko

    2008-01-01

    Lithium has been shown to be neuroprotective against various insults including ethanol exposure. We previously reported that ethanol-induced apoptotic neurodegeneration in the postnatal day 7 (P7) mice is associated with decreases in phosphorylation levels of Akt, glycogen synthase kinase-3β (GSK-3β), and AMP-activated protein kinase (AMPK), and alteration in lipid profiles in the brain. Here, P7 mice were injected with ethanol and lithium, and the effects of lithium on ethanol-induced alterations in phosphorylation levels of protein kinases and lipid profiles in the brain were examined. Immunoblot and immunohistochemical analyses showed that lithium significantly blocked ethanol-induced caspase-3 activation and reduction in phosphorylation levels of Akt, GSK-3β, and AMPK. Further, lithium inhibited accumulation of cholesterol ester (ChE) and N-acylphosphatidylethanolamine (NAPE) triggered by ethanol in the brain. These results suggest that Akt, GSK-3β, and AMPK are involved in ethanol-induced neurodegeneration and the neuroprotective effects of lithium by modulating both apoptotic and survival pathways

  7. Electrically and chemically tunable soft-solid block copolymer structural color (Conference Presentation)

    Science.gov (United States)

    Park, Cheolmin

    2016-09-01

    1D photonic crystals based on the periodic stacking of two different dielectric layers have been widely studied due to their potential use in low-power reflective mode displays, e-books and sensors, but the fabrication of mechanically flexible polymer structural color (SC) films, with electro-active color switching, remains challenging. Here, we demonstrate free-standing electric field tunable ionic liquid swollen block copolymer films. Placement of a polymer/ionic liquid (IL) film-reservoir adjacent to a self-assembled poly(styrene-block-quaternized 2vinyl pyridine) (PS-b-QP2VP) copolymer SC film allowed the development of R, G and B full-color SC block copolymer films by swelling of the QP2VP domains by the ionic liquid associated with water molecules. The IL-polymer/BCP SC film is mechanically flexible with excellent color stability over several days at ambient conditions. The selective swelling of the QP2VP domains could be controlled by both the ratio of the IL to a polymer in the gel-like IL reservoir layer and by an applied voltage in the range of -3V to +6V using a metal/IL reservoir/SC film/IL reservoir/metal capacitor type device.

  8. Evidence against associative blocking as a cause of cue-independent retrieval-induced forgetting.

    Science.gov (United States)

    Hulbert, Justin C; Shivde, Geeta; Anderson, Michael C

    2012-01-01

    Selectively retrieving an item from long-term memory reduces the accessibility of competing traces, a phenomenon known as retrieval-induced forgetting (RIF). RIF exhibits cue independence, or the tendency for forgetting to generalize to novel test cues, suggesting an inhibitory basis for this phenomenon. An alternative view (Camp, Pecher, & Schmidt, 2007; Camp et al., 2009; Perfect et al., 2004) suggests that using novel test cues to measure cue independence actually engenders associative interference when participants covertly supplement retrieval with practiced cues that then associatively block retrieval. Accordingly, the covert-cueing hypothesis assumes that the relative strength of the practiced items at final test – and not the inhibition levied on the unpracticed items during retrieval practice – underlies cue-independent forgetting. As such, this perspective predicts that strengthening practiced items by any means, even if not via retrieval practice, should induce forgetting. Contrary to these predictions, however, we present clear evidence that cue-independent forgetting is induced by retrieval practice and not by repeated study exposures. This dissociation occurred despite significant, comparable levels of strengthening of practiced items in each case, and despite the use of Anderson and Spellman's original (1995) independent probe method criticized by covert-cueing theorists as being especially conducive to associative blocking. These results demonstrate that cue-independent RIF is unrelated to the strengthening of practiced items, and thereby fail to support a key prediction of the covert-cueing hypothesis. The results, instead, favor a role of inhibition in resolving retrieval interference. © 2011 Hogrefe Publishing

  9. UV-blocking spectacle lens protects against UV-induced decline of visual performance.

    Science.gov (United States)

    Liou, Jyh-Cheng; Teng, Mei-Ching; Tsai, Yun-Shan; Lin, En-Chieh; Chen, Bo-Yie

    2015-01-01

    Excessive exposure to sunlight may be a risk factor for ocular diseases and reduced visual performance. This study was designed to examine the ability of an ultraviolet (UV)-blocking spectacle lens to prevent visual acuity decline and ocular surface disorders in a mouse model of UVB-induced photokeratitis. Mice were divided into 4 groups (10 mice per group): (1) a blank control group (no exposure to UV radiation), (2) a UVB/no lens group (mice exposed to UVB rays, but without lens protection), (3) a UVB/UV400 group (mice exposed to UVB rays and protected using the CR-39™ spectacle lens [UV400 coating]), and (4) a UVB/photochromic group (mice exposed to UVB rays and protected using the CR-39™ spectacle lens [photochromic coating]). We investigated UVB-induced changes in visual acuity and in corneal smoothness, opacity, and lissamine green staining. We also evaluated the correlation between visual acuity decline and changes to the corneal surface parameters. Tissue sections were prepared and stained immunohistochemically to evaluate the structural integrity of the cornea and conjunctiva. In blank controls, the cornea remained undamaged, whereas in UVB-exposed mice, the corneal surface was disrupted; this disruption significantly correlated with a concomitant decline in visual acuity. Both the UVB/UV400 and UVB/photochromic groups had sharper visual acuity and a healthier corneal surface than the UVB/no lens group. Eyes in both protected groups also showed better corneal and conjunctival structural integrity than unprotected eyes. Furthermore, there were fewer apoptotic cells and less polymorphonuclear leukocyte infiltration in corneas protected by the spectacle lenses. The model established herein reliably determines the protective effect of UV-blocking ophthalmic biomaterials, because the in vivo protection against UV-induced ocular damage and visual acuity decline was easily defined.

  10. Inorganic Nanoparticle Induced Morphological Transition for Confined Self-Assembly of Block Copolymers within Emulsion Droplets.

    Science.gov (United States)

    Zhang, Yan; He, Yun; Yan, Nan; Zhu, Yutian; Hu, Yuexin

    2017-09-07

    Recently, it has been reported that the incorporation of functional inorganic nanoparticles (NPs) into the three-dimensional (3D) confined self-assembly of block copolymers (BCPs) creates the unique nanostructured hybrid composites, which can not only introduce new functions to BCPs but also induce some interesting morphological transitions of BCPs. In the current study, we systematically investigate the cooperative self-assembly of a series of size-controlled and surface chemistry-tunable gold nanoparticles (AuNPs) and polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) diblock copolymer within the emulsion droplets. The influences of the size, content, and surface chemistry of the AuNPs on the coassembled nanostructures as well as the spatial distribution of AuNPs in the hybrid particles are examined. It is found that the size and content of the AuNPs are related to the entropic interaction, while the surface chemistry of AuNPs is related to the enthalpic interaction, which can be utilized to tailor the self-assembled morphologies of block copolymer confined in the emulsion droplets. As the content of PS-coated AuNPs increases, the morphology of the resulting AuNPs/PS-b-P2VP hybrid particles changes from the pupa-like particles to the bud-like particles and then to the onion-like particles. However, a unique morphological transition from the pupa-like particles to the mushroom-like particles is observed as the content of P4VP-coated AuNPs increases. More interestingly, it is observed that the large AuNPs are expelled to the surface of the BCP particles to reduce the loss in the conformational entropy of the block segment, which can arrange into the strings of necklaces on the surfaces of the hybrid particles.

  11. Technical basis and programmatic requirements for large block testing of coupled thermal-mechanical-hydrological-chemical processes

    International Nuclear Information System (INIS)

    Lin, Wunan.

    1993-09-01

    This document contains the technical basis and programmatic requirements for a scientific investigation plan that governs tests on a large block of tuff for understanding the coupled thermal- mechanical-hydrological-chemical processes. This study is part of the field testing described in Section 8.3.4.2.4.4.1 of the Site Characterization Plan (SCP) for the Yucca Mountain Project. The first, and most important objective is to understand the coupled TMHC processes in order to develop models that will predict the performance of a nuclear waste repository. The block and fracture properties (including hydrology and geochemistry) can be well characterized from at least five exposed surfaces, and the block can be dismantled for post-test examinations. The second objective is to provide preliminary data for development of models that will predict the quality and quantity of water in the near-field environment of a repository over the current 10,000 year regulatory period of radioactive decay. The third objective is to develop and evaluate the various measurement systems and techniques that will later be employed in the Engineered Barrier System Field Tests (EBSFT)

  12. Sugammadex reversal of rocuronium-induced neuromuscular block in a patient with ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Kang, E.; Jung, J.W.

    2015-01-01

    A 17-year-old adolescent with ataxia-telangiectasia was scheduled to have laparoscopic colectomy for a resection of colon cancer. He had symptoms and signs of dyspnea, generalized dystonia, dysmetria, ataxia, and telangiectasia on the orbit. General anesthesia was performed, and rocuronium 30 mg was administered for muscle relaxation. Deep neuromuscular block (post-tetanic count: 0-8) was maintained for 95 minutes without additional rocuronium. On completion of surgery, sugammadex 80 mg was injected and train-of-four ratio was 0.93 at 210 seconds after administration. The tracheal tube was removed 5 min after the end of surgery. He recovered full spontaneous respiration and voluntary movements within 1 minute after extubation. After the surgery, he transferred to the intensive care unit and discharged 14 days after the surgery without any concrete problem. The reversal of rocuronium induced neuromuscular block by sugammadex was fast, complete, and recovered to the initial preoperative level of neuromuscular function in this patient. (author)

  13. Anti-GM2 gangliosides IgM paraprotein induces neuromuscular block without neuromuscular damage.

    Science.gov (United States)

    Santafé, Manel M; Sabaté, M Mar; Garcia, Neus; Ortiz, Nico; Lanuza, M Angel; Tomàs, Josep

    2008-11-15

    We analyzed the effect on the mouse neuromuscular synapses of a human monoclonal IgM, which binds specifically to gangliosides with the common epitope [GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-]. We focused on the role of the complement. Evoked neurotransmission was partially blocked by IgM both acutely (1 h) and chronically (10 days). Transmission electron microscopy shows important nerve terminal growth and retraction remodelling though axonal injury can be ruled out. Synapses did not show mouse C5b-9 immunofluorescence and were only immunolabelled when human complement was added. Therefore, the IgM-induced synaptic changes occur without complement-mediated membrane attack.

  14. Heart block and acute kidney injury due to hyperparathyroidism-induced hypercalcemic crisis.

    Science.gov (United States)

    Brown, Taylor C; Healy, James M; McDonald, Mary J; Hansson, Joni H; Quinn, Courtney E

    2014-12-01

    We describe a patient who presented with multi-system organ failure due to extreme hypercalcemia (serum calcium 19.8 mg/dL), resulting from primary hyperparathyroidism. He was found to have a 4.8 cm solitary atypical parathyroid adenoma. His course was complicated by complete heart block, acute kidney injury, and significant neurocognitive disturbances. Relevant literature was reviewed and discussed. Hyperparathyroidism-induced hypercalcemic crisis (HIHC) is a rare presentation of primary hyperparathyroidism and only a small minority of these patients develop significant cardiac and renal complications. In cases of HIHC, a multidisciplinary effort can facilitate rapid treatment of life-threatening hypercalcemia and definitive treatment by surgical resection. As such, temporary transvenous cardiac pacing and renal replacement therapy can provide a life-saving bridge to definitive parathyroidectomy in cases of HIHC.

  15. P7C3 Neuroprotective Chemicals Block Axonal Degeneration and Preserve Function after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Terry C. Yin

    2014-09-01

    Full Text Available The P7C3 class of neuroprotective aminopropyl carbazoles has been shown to block neuronal cell death in models of neurodegeneration. We now show that P7C3 molecules additionally preserve axonal integrity after injury, before neuronal cell death occurs, in a rodent model of blast-mediated traumatic brain injury (TBI. This protective quality may be linked to the ability of P7C3 molecules to activate nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in nicotinamide adenine dinucleotide salvage. Initiation of daily treatment with our recently reported lead agent, P7C3-S243, 1 day after blast-mediated TBI blocks axonal degeneration and preserves normal synaptic activity, learning and memory, and motor coordination in mice. We additionally report persistent neurologic deficits and acquisition of an anxiety-like phenotype in untreated animals 8 months after blast exposure. Optimized variants of P7C3 thus offer hope for identifying neuroprotective agents for conditions involving axonal damage, neuronal cell death, or both, such as occurs in TBI.

  16. Cooperative unfolding of apolipoprotein A-1 induced by chemical denaturation.

    Science.gov (United States)

    Eckhardt, D; Li-Blatter, X; Schönfeld, H-J; Heerklotz, H; Seelig, J

    2018-05-25

    Apolipoprotein A-1 (Apo A-1) plays an important role in lipid transfer and obesity. Chemical unfolding of α-helical Apo A-1 is induced with guanidineHCl and monitored with differential scanning calorimetry (DSC) and CD spectroscopy. The unfolding enthalpy and the midpoint temperature of unfolding decrease linearly with increasing guanidineHCl concentration, caused by the weak binding of denaturant. At room temperature, binding of 50-60 molecules guanidineHCl leads to a complete Apo A-1 unfolding. The entropy of unfolding decreases to a lesser extent than the unfolding enthalpy. Apo A-1 chemical unfolding is a dynamic multi-state equilibrium that is analysed with the Zimm-Bragg theory modified for chemical unfolding. The chemical Zimm-Bragg theory predicts the denaturant binding constant K D and the protein cooperativity σ. Chemical unfolding of Apo A-1 is two orders of magnitude less cooperative than thermal unfolding. The free energy of thermal unfolding is ~0.2 kcal/mol per amino acid residue and ~1.0 kcal/mol for chemical unfolding at room temperature. The Zimm-Bragg theory calculates conformational probabilities and the chemical Zimm-Bragg theory predicts stretches of α-helical segments in dynamic equilibrium, unfolding and refolding independently and fast. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Studies of Basalt Through Laser Induced Breakdown Spectroscopy (LIBS for the Manufacturing of Lapilli Blocks

    Directory of Open Access Journals (Sweden)

    Ismael De la Viuda-Pérez

    2016-10-01

    Full Text Available Basaltic samples selected from different areas of Tenerife were analyzed by applying laser induced breakdown spectroscopy (LIBS, Raman spectroscopy and X Ray Diffraction (XRD in order to identify the basic chemical composition and mineralogy. The basic composition obtained from the analysis was: O, F, Na, K, Mg, Al Si, Ca, Ti and Fe. Raman spectroscopic and XRD analyses indicated a basaltic mineralogy which is consistent with the basic composition results obtained from LIBS. The results of the analyses carried out using portable instrumentation proved the suitability of the LIBS, specially combined with the Raman spectroscopy for their application in the mineralogical-chemical identification in the areas where basalts and lapilli are extracted for construction works in Tenerife.

  18. Gametocytocidal screen identifies novel chemical classes with Plasmodium falciparum transmission blocking activity.

    Directory of Open Access Journals (Sweden)

    Natalie G Sanders

    Full Text Available Discovery of transmission blocking compounds is an important intervention strategy necessary to eliminate and eradicate malaria. To date only a small number of drugs that inhibit gametocyte development and thereby transmission from the mosquito to the human host exist. This limitation is largely due to a lack of screening assays easily adaptable to high throughput because of multiple incubation steps or the requirement for high gametocytemia. Here we report the discovery of new compounds with gametocytocidal activity using a simple and robust SYBR Green I- based DNA assay. Our assay utilizes the exflagellation step in male gametocytes and a background suppressor, which masks the staining of dead cells to achieve healthy signal to noise ratio by increasing signal of viable parasites and subtracting signal from dead parasites. By determining the contribution of exflagellation to fluorescent signal and using appropriate cutoff values, we were able to screen for gametocytocidal compounds. After assay validation and optimization, we screened an FDA approved drug library of approximately 1500 compounds, as well as the 400 compound MMV malaria box and identified 44 gametocytocidal compounds with sub to low micromolar IC50s. Major classes of compounds with gametocytocidal activity included quaternary ammonium compounds with structural similarity to choline, acridine-like compounds similar to quinacrine and pyronaridine, as well as antidepressant, antineoplastic, and anthelminthic compounds. Top drug candidates showed near complete transmission blocking in membrane feeding assays. This assay is simple, reproducible and demonstrated robust Z-factor values at low gametocytemia levels, making it amenable to HTS for identification of novel and potent gametocytocidal compounds.

  19. Reduction of radiation-induced cell cycle blocks by caffeine does not necessarily lead to increased cell killing

    Energy Technology Data Exchange (ETDEWEB)

    Musk, S.R. (Institute of Cancer Research, Sutton, Surrey (England))

    1991-03-01

    The effect of caffeine upon the radiosensitivities of three human tumor lines was examined and correlated with its action upon the radiation-induced S-phase and G2-phase blocks. Caffeine was found to reduce at least partially the S-phase and G2-phase blocks in all the cell lines examined but potentiated cytotoxicity in only one of the three tumor lines. That reductions have been demonstrated to occur in the absence of increased cell killing provides supporting evidence for the hypothesis that reductions may not be causal in those cases when potentiation of radiation-induced cytotoxicity is observed in the presence of caffeine.

  20. A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.

    Directory of Open Access Journals (Sweden)

    Frédérique Végran

    Full Text Available Alternative splicing of caspase-3 produces a short isoform caspase-3s that antagonizes caspase-3 apoptotic activity. However, the mechanism of apoptosis inhibition by caspase-3s remains unknown. Here we show that exogenous caspase-3 sensitizes MCF-7 and HBL100 breast cancers cells to chemotherapeutic treatments such as etoposide and methotrexate whereas co-transfection with caspase-3s strongly inhibits etoposide and methotrexate-induced apoptosis underlying thus the anti-apoptotic role of caspase-3s. In caspase-3 transfected cells, lamin-A and α-fodrin were cleaved when caspase-3 was activated by etoposide or methotrexate. When caspase-3s was co-transfected, this cleavage was strongly reduced. Depletion of caspase-3 by RNA interference in HBL100 containing endogenous caspase-3s caused reduction in etoposide and methotrexate-induced apoptosis, whereas the depletion of caspase-3s sensitized cells to chemotherapy. In the presence of caspase-3s, a lack of interaction between caspase-3 and caspase-9 was observed. Immunoprecipitation assays showed that caspase-3s binds the pro-forms of caspase-3. This result suggested that the absence of interaction with caspase-9 when both variants of caspase-3 are present contribute to block the apoptosome assembly and inhibit apoptosis. These data support that caspases-3s negatively interferes with caspase-3 activation and apoptosis in breast cancer, and that it can play key roles in the modulation of response to chemotherapeutic treatments.

  1. Naltrexone pretreatment blocks microwave-induced changes in central cholinergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Carino, M.A.; Wen, Y.F.; Horita, A.; Guy, A.W. (Univ. of Washington School of Medicine, Seattle (USA))

    1991-01-01

    Repeated exposure of rats to pulsed, circularly polarized microwaves (2,450-MHz, 2-microseconds pulses at 500 pps, power density 1 mW/cm2, at an averaged, whole-body SAR of 0.6 W/kg) induced biphasic changes in the concentration of muscarinic cholinergic receptors in the central nervous system. An increase in receptor concentration occurred in the hippocampus of rats subjected to ten 45-min sessions of microwave exposure, whereas a decrease in concentration was observed in the frontal cortex and hippocampus of rats exposed to ten 20-min sessions. These findings, which confirm earlier work in the authors' laboratory, were extended to include pretreatment of rats with the narcotic antagonist naltrexone (1 mg/kg, IP) before each session of exposure. The drug treatment blocked the microwave-induced changes in cholinergic receptors in the brain. These data further support the authors' hypothesis that endogenous opioids play a role in the effects of microwaves on central cholinergic systems.

  2. Acute stress blocks the caffeine-induced enhancement of contextual memory retrieval in mice.

    Science.gov (United States)

    Pierard, Chistophe; Krazem, Ali; Henkous, Nadia; Decorte, Laurence; Béracochéa, Daniel

    2015-08-15

    This study investigated in mice the dose-effect of caffeine on memory retrieval in non-stress and stress conditions. C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board which involved either distinct contextual (CSD) or similar contextual (SSD) cues. All mice received an i.p. injection of vehicle or caffeine (8, 16 or 32mg/kg) 30min before the test session. Results showed that in non-stress conditions, the 16mg/kg caffeine dose induced a significant enhancement of D1 performance in CSD but not in SSD. Hence, we studied the effect of an acute stress (electric footshocks) administered 15min before the test session on D1 performance in caffeine-treated mice. Results showed that stress significantly decreased D1 performance in vehicle-treated controls and the memory-enhancing effect induced by the 16mg/kg caffeine dose in non-stress condition is no longer observed. Interestingly, whereas caffeine-treated mice exhibited weaker concentrations of plasma corticosterone as compared to vehicles in non-stress condition, stress significantly increased plasma corticosterone concentrations in caffeine-treated mice which reached similar level to that of controls. Overall, the acute stress blocked both the endocrinological and memory retrieval enhancing effects of caffeine. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. A model for chemically-induced mechanical loading on MEMS

    DEFF Research Database (Denmark)

    Amiot, Fabien

    2007-01-01

    The development of full displacement field measurements as an alternative to the optical lever technique to measure the mechanical response for microelectro-mechanical systems components in their environment calls for a modeling of chemically-induced mechanical fields (stress, strain, and displac......The development of full displacement field measurements as an alternative to the optical lever technique to measure the mechanical response for microelectro-mechanical systems components in their environment calls for a modeling of chemically-induced mechanical fields (stress, strain...... of the system free energy and its dependence on the surface amount. It is solved in the cantilever case thanks to an asymptotic analysis, and an approached closed-form solution is obtained for the interfacial stress field. Finally, some conclusions regarding the transducer efficiency of cantilevers are drawn...

  4. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  5. On the Chemical Mixing Induced by Internal Gravity Waves

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, T. M. [School of Mathematics, Statistics and Physics, Newcastle University, Newcastle upon Tyne (United Kingdom); McElwaine, J. N. [Planetary Science Institute, Tucson, AZ 85721 (United States)

    2017-10-10

    Detailed modeling of stellar evolution requires a better understanding of the (magneto)hydrodynamic processes that mix chemical elements and transport angular momentum. Understanding these processes is crucial if we are to accurately interpret observations of chemical abundance anomalies, surface rotation measurements, and asteroseismic data. Here, we use two-dimensional hydrodynamic simulations of the generation and propagation of internal gravity waves in an intermediate-mass star to measure the chemical mixing induced by these waves. We show that such mixing can generally be treated as a diffusive process. We then show that the local diffusion coefficient does not depend on the local fluid velocity, but rather on the wave amplitude. We then use these findings to provide a simple parameterization for this diffusion, which can be incorporated into stellar evolution codes and tested against observations.

  6. Modulation of radiation-induced apoptosis and G{sub 2}/M block in murine T-lymphoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N. [Harvard Medical School, Boston, MA (United States)

    1995-03-01

    Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to {sup 137}Cs {gamma} irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of {gamma} radiation. We studied the effect of several pharmacological agents on the radiation-induced G{sub 2}/M block and DNA fragmentation. The agents which reduced the radiation-induced G{sub 2}/M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G{sub 2}/M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-induced genetic damage are eliminated by apoptosis subsequent to a G{sub 2}/M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G{sub 2}/M block, and to use this effect in the treatment of patients with malignant disease. 59 refs., 7 figs.

  7. Modulation of radiation-induced apoptosis and G2/M block in murine T-lymphoma cells

    International Nuclear Information System (INIS)

    Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N.

    1995-01-01

    Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to 137 Cs γ irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of γ radiation. We studied the effect of several pharmacological agents on the radiation-induced G 2 /M block and DNA fragmentation. The agents which reduced the radiation-induced G 2 /M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G 2 /M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-induced genetic damage are eliminated by apoptosis subsequent to a G 2 /M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G 2 /M block, and to use this effect in the treatment of patients with malignant disease. 59 refs., 7 figs

  8. A Corpus Luteum Is Not a Prerequisite for the Expression of Progesterone Induced Blocking Factor by T-Lymphocytes a Week After Implantation

    OpenAIRE

    Check, Jerome H.; Szekeres-Bartho, Julia; Nazari, Parvin; Katz, Youval; Check, Matthew L.

    2001-01-01

    Purpose: To determine if production of the immunomodulatory protein, progesterone induced blocking factor (PIBF), requires merely progesterone or whether other factors made by the corpus luteum are required.

  9. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei

    2015-01-01

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release

  10. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei, E-mail: chtw@sina.com

    2015-03-06

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release.

  11. Carbon monoxide induced PPARγ SUMOylation and UCP2 block inflammatory gene expression in macrophages.

    Directory of Open Access Journals (Sweden)

    Arvand Haschemi

    Full Text Available Carbon monoxide (CO dampens pro-inflammatory responses in a peroxisome proliferator-activated receptor-γ (PPARγ and p38 mitogen-activated protein kinase (MAPK dependent manner. Previously, we demonstrated that CO inhibits lipopolysaccharide (LPS-induced expression of the proinflammatory early growth response-1 (Egr-1 transcription factor in macrophages via activation of PPARγ. Here, we further characterize the molecular mechanisms by which CO modulates the activity of PPARγ and Egr-1 repression. We demonstrate that CO enhances SUMOylation of PPARγ which we find was attributed to mitochondrial ROS generation. Ectopic expression of a SUMOylation-defective PPARγ-K365R mutant partially abolished CO-mediated suppression of LPS-induced Egr-1 promoter activity. Expression of a PPARγ-K77R mutant did not impair the effect of CO. In addition to PPARγ SUMOylation, CO-activated p38 MAPK was responsible for Egr-1 repression. Blocking both CO-induced PPARγ SUMOylation and p38 activation, completely reversed the effects of CO on inflammatory gene expression. In primary macrophages isolated form C57/BL6 male mice, we identify mitochondrial ROS formation by CO as the upstream trigger for the observed effects on Egr-1 in part through uncoupling protein 2 (UCP2. Macrophages derived from bone marrow isolated from Ucp2 gene Knock-Out C57/BL6 mice (Ucp2(-/-, produced significantly less ROS with CO exposure versus wild-type macrophages. Moreover, absence of UCP2 resulted in a complete loss of CO mediated Egr-1 repression. Collectively, these results indentify p38 activation, PPARγ-SUMOylation and ROS formation via UCP2 as a cooperative system by which CO impacts the inflammatory response.

  12. New way of dosing sugammadex for termination of vecuronium induced neuromuscular block

    Directory of Open Access Journals (Sweden)

    Blaž Peček

    2015-06-01

    Full Text Available Background and Goal of Study: Sugammadex is a selective binding agent that bindsaminosteroid muscle relaxants. Each molecule of sugammadex binds one molecule of musclerelaxant. To produce the same depth of the neuromuscular block (NMB much less molecules ofvecuronium are needed than molecules of rocuronium. In theory less sugammadex would beneeded to neutralise the neuromuscular block if vecuronium was used to produce the neuromuscular block. Our aim was to compare reversal of vecuronium induced muscle relaxation between a new way of dosing sugammadex, which takes into account TOF value at the end of the surgery and the amount of vecuronium given during the surgery with neostigmine atropine combination. We also wanted to know how much this dosage regime can save compared to standard per kg dosage.Materials and Methods: 20 adult patients requiring a general anesthesia for surgery were analysed. The first group of 11 patients (SUG received sugammadex at the end of the surgery according to the table one for NMB reversal. The second group of 9 patients (NEO received neostigmine and atropine. Train of four (TOF value was recorded at the end of the surgery and then continuously until the TOF value reached more than 0.9 and the patient was extubated. The time required for the TOF value reaching 0.9 was compared between the groups. For economical evaluation we compared the amount of sugammadex used in the SUG group to standard sugammadex per kg dosage.Results and Discussion: Mean time to recovery to a TOF ratio of 0.9 with sugammadex was 5.12min versus 12.6 min with neostigmine atropine (P < 0.05. No sign of postoperative residual curarisation was observed in the SUG group. For patients in our study 530 mg of sugammadex were used to neutralise the NMB. If standard per kg sugammadex dosing had been used we would have used 2420 mg for the NMB reversal.Conclusion(s: New dosing for sugammadex was successful in neutralising the NMB regardlessof the TOF value

  13. Distinct Adsorption Configurations and Self-Assembly Characteristics of Fibrinogen on Chemically Uniform and Alternating Surfaces including Block Copolymer Nanodomains

    Science.gov (United States)

    2015-01-01

    Understanding protein–surface interactions is crucial to solid-state biomedical applications whose functionality is directly correlated with the precise control of the adsorption configuration, surface packing, loading density, and bioactivity of protein molecules. Because of the small dimensions and highly amphiphilic nature of proteins, investigation of protein adsorption performed on nanoscale topology can shed light on subprotein-level interaction preferences. In this study, we examine the adsorption and assembly behavior of a highly elongated protein, fibrinogen, on both chemically uniform (as-is and buffered HF-treated SiO2/Si, and homopolymers of polystyrene and poly(methyl methacrylate)) and varying (polystyrene-block-poly(methyl methacrylate)) surfaces. By focusing on high-resolution imaging of individual protein molecules whose configurations are influenced by protein–surface rather than protein–protein interactions, fibrinogen conformations characteristic to each surface are identified and statistically analyzed for structural similarities/differences in key protein domains. By exploiting block copolymer nanodomains whose repeat distance is commensurate with the length of the individual protein, we determine that fibrinogen exhibits a more neutral tendency for interaction with both polystyrene and poly(methyl methacrylate) blocks relative to the case of common globular proteins. Factors affecting fibrinogen–polymer interactions are discussed in terms of hydrophobic and electrostatic interactions. In addition, assembly and packing attributes of fibrinogen are determined at different loading conditions. Primary orientations of fibrinogen and its rearrangements with respect to the underlying diblock nanodomains associated with different surface coverage are explained by pertinent protein interaction mechanisms. On the basis of two-dimensional stacking behavior, a protein assembly model is proposed for the formation of an extended fibrinogen network

  14. Lunasin-aspirin combination against NIH/3T3 cells transformation induced by chemical carcinogens.

    Science.gov (United States)

    Hsieh, Chia-Chien; Hernández-Ledesma, Blanca; de Lumen, Ben O

    2011-06-01

    Carcinogenesis is a multistage process involving a number of molecular pathways sensitive to intervention. Chemoprevention is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. To achieve greater inhibitory effects on cancer cells, combination of two or more chemopreventive agents is commonly considered as a better preventive and/or therapeutic strategy. Lunasin is a promising cancer preventive peptide identified in soybean and other seeds. Its efficacy has been demonstrated by both in vitro and in vivo models. This peptide has been found to inhibit human breast cancer MDA-MB-231 cells proliferation, suppressing cell cycle progress and inducing cell apoptosis. Moreover, lunasin potentiates the effects on these cells of different synthetic and natural compounds, such as aspirin and anacardic acid. This study explored the role of lunasin, alone and in combination with aspirin and anacardic acid on cell proliferation and foci formation of transformed NIH/3T3 cells induced by chemical carcinogens 7,12-dimethylbenz[a]anthracene or 3-methylcholanthrene. The results revealed that lunasin, acting as a single agent, inhibits cell proliferation and foci formation. When combined with aspirin, these effects were significantly increased, indicating that this combination might be a promising strategy to prevent/treat cancer induced by chemical carcinogens.

  15. Chemical determination of free radical-induced damage to DNA.

    Science.gov (United States)

    Dizdaroglu, M

    1991-01-01

    Free radical-induced damage to DNA in vivo can result in deleterious biological consequences such as the initiation and promotion of cancer. Chemical characterization and quantitation of such DNA damage is essential for an understanding of its biological consequences and cellular repair. Methodologies incorporating the technique of gas chromatography/mass spectrometry (GC/MS) have been developed in recent years for measurement of free radical-induced DNA damage. The use of GC/MS with selected-ion monitoring (SIM) facilitates unequivocal identification and quantitation of a large number of products of all four DNA bases produced in DNA by reactions with hydroxyl radical, hydrated electron, and H atom. Hydroxyl radical-induced DNA-protein cross-links in mammalian chromatin, and products of the sugar moiety in DNA are also unequivocally identified and quantitated. The sensitivity and selectivity of the GC/MS-SIM technique enables the measurement of DNA base products even in isolated mammalian chromatin without the necessity of first isolating DNA, and despite the presence of histones. Recent results reviewed in this article demonstrate the usefulness of the GC/MS technique for chemical determination of free radical-induced DNA damage in DNA as well as in mammalian chromatin under a vast variety of conditions of free radical production.

  16. Chemical memory reactions induced bursting dynamics in gene expression.

    Science.gov (United States)

    Tian, Tianhai

    2013-01-01

    Memory is a ubiquitous phenomenon in biological systems in which the present system state is not entirely determined by the current conditions but also depends on the time evolutionary path of the system. Specifically, many memorial phenomena are characterized by chemical memory reactions that may fire under particular system conditions. These conditional chemical reactions contradict to the extant stochastic approaches for modeling chemical kinetics and have increasingly posed significant challenges to mathematical modeling and computer simulation. To tackle the challenge, I proposed a novel theory consisting of the memory chemical master equations and memory stochastic simulation algorithm. A stochastic model for single-gene expression was proposed to illustrate the key function of memory reactions in inducing bursting dynamics of gene expression that has been observed in experiments recently. The importance of memory reactions has been further validated by the stochastic model of the p53-MDM2 core module. Simulations showed that memory reactions is a major mechanism for realizing both sustained oscillations of p53 protein numbers in single cells and damped oscillations over a population of cells. These successful applications of the memory modeling framework suggested that this innovative theory is an effective and powerful tool to study memory process and conditional chemical reactions in a wide range of complex biological systems.

  17. Lysophosphatidic acid directly induces macrophage-derived foam cell formation by blocking the expression of SRBI.

    Science.gov (United States)

    Chen, Linmu; Zhang, Jun; Deng, Xiao; Liu, Yan; Yang, Xi; Wu, Qiong; Yu, Chao

    2017-09-23

    The leading cause of morbidity and mortality is the result of cardiovascular disease, mainly atherosclerosis. The formation of macrophage foam cells by ingesting ox-LDL and focal retention in the subendothelial space are the hallmarks of the early atherosclerotic lesion. Lysophosphatidic acid (LPA), which is a low-molecular weight lysophospholipid enriched in oxidized LDL, exerts a range of effects on the cardiovascular system. Previous reports show that LPA increases the uptake of ox-LDL to promote the formation of foam cells. However, as the most active component of ox-LDL, there is no report showing whether LPA directly affects foam cell formation. The aim of this study was to investigate the effects of LPA on foam cell formation, as well as to elucidate the underlying mechanism. Oil red O staining and a Cholesterol/cholesteryl ester quantitation assay were used to evaluate foam cell formation in Raw264.7 macrophage cells. We utilized a Western blot and RT-PCR to investigate the relationship between LPA receptors and lipid transport related proteins. We found that LPA promoted foam cell formation, using 200 μM for 24 h. Meanwhile, the expression of the Scavenger receptor BI (SRBI), which promotes the efflux of free cholesterol, was decreased. Furthermore, the LPA 1/3 receptor antagonist Ki16425 significantly abolished the LPA effects, indicating that LPA 1/3 was involved in the foam cell formation and SRBI expression induced by LPA. Additionally, the LPA-induced foam cell formation was blocked with an AKT inhibitor. Our results suggest that LPA-enhanced foam cell formation is mediated by LPA 1/3 -AKT activation and subsequent SRBI expression. Copyright © 2017. Published by Elsevier Inc.

  18. Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts.

    Science.gov (United States)

    Xu, Lu-lu; Lu, Yun-tao; Zhang, Jing; Wu, Lian; Merrilees, Mervyn J; Qu, Jie-ming

    2015-08-15

    COPD lung is characterized by loss of alveolar elastic fibers and an increase in the chondroitin sulfate (CS) matrix proteoglycan versican V1 (V1). V1 is a known inhibitor of elastic fiber deposition and this study investigates the effects of knockdown of V1, and add-back of CS, on CCL-210 lung fibroblasts treated with cigarette smoke extract (CSE) as a model for COPD. CSE inhibited fibroblast proliferation, viability, tropoelastin synthesis, and elastin deposition, and increased V1 synthesis and secretion. V1 siRNA decreased V1 and constituent CS, did not affect tropoelastin production, but blocked the CSE-induced loss in insoluble elastin. Exogenous CS reduced insoluble elastin, even in the presence of V1 siRNA. These findings confirm that V1 and CS impair the assembly of tropoelastin monomers into insoluble fibers, and further demonstrate that specific knockdown of V1 alleviates the impaired assembly of elastin seen in cultures of pulmonary fibroblasts exposed to CSE, indicating a regulatory role for this protein in the pathophysiology of COPD. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Diagnosis of exercise-induced left bundle branch block at rest by scintigraphic phase analysis

    International Nuclear Information System (INIS)

    Schultz, D.A.; Wahl, R.L.; Juni, J.E.; Buda, A.J.; McMeekin, J.D.; Struble, L.R.; Tuscan, M.J.

    1986-01-01

    Accurate diagnosis of disease of the ventricular conducting system is essential for their appropriate therapy. Some conduction abnormalities, such as exercise-induced left bundle branch block (EX-LBBB), are not apparent on resting electrocardiograms. Phase analysis of rest and exercise radionuclide ventriculograms (RVG's) was used to compare four EX-LBBB patients with six normal controls. All patients had normal resting electrocardiograms, ejection fractions, and visually normal wall motion. First harmonic phase images were generated reflecting the timing of ventricular contraction. Dynamic phase displays were reviewed and graded in a blinded fashion by three independent experienced observers. Phase angle histograms of the right and left ventricle were determined for both resting and exercise images. The mean phase angle and standard deviation were also calculated for each ventricle. Visual grading of the resting phase images failed to show a significant difference between normal patients and patients with EX-LBBB. Quantitative analysis, however, revealed a significant difference in mean phase angle differences (LV-RV) in resting studies: 0.8 0 (+-1.9 0 SEM) in normal versus 9.3 0 (+-2.3 0 SEM) in EX-LBBB patients (P 0 in normals vs. 31.2 0 in EX-LBBB patients (P<0.001). Qualitative phase analysis of resting RVG's permits the diagnosis of cardiac conduction disease that is not apparent on the resting EKG and may result in better monitoring and treatment. (orig.)

  20. Inorganic-Macroion-Induced Formation of Bicontinuous Block Copolymer Nanocomposites with Enhanced Conductivity and Modulus.

    Science.gov (United States)

    Zhang, Liying; Cui, Tingting; Cao, Xiao; Zhao, Chengji; Chen, Quan; Wu, Lixin; Li, Haolong

    2017-07-24

    A facile and electrostatically driven approach has been developed to prepare bicontinuous polymer nanocomposites that is based on the polyoxometalate (POM) macroion induced phase transition of PS-b-P2VP from an initial lamellar phase to a stable bicontinuous phase. The multi-charged POMs can electrostatically cross-link P2VP blocks and give rise to bicontinuous phases in which the POM hybrid conductive domains occupy a large volume fraction of more than 50 %. Furthermore, the POMs can give rise to high proton conductivity and serve as nanoenhancers, endowing the bicontinuous nanocomposites with a conductivity of 0.1 mS cm -1 and a Young's modulus of 7.4 GPa at room temperature; these values are greater than those of pristine PS-b-P2VP by two orders of magnitude and a factor of 1.8, respectively. This approach can provide a new concept based on electrostatic control to design functional bicontinuous polymer materials. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Three-dimensional block copolymer nanostructures by the solvent-annealing-induced wetting in anodic aluminum oxide templates.

    Science.gov (United States)

    Chu, Chiang-Jui; Chung, Pei-Yun; Chi, Mu-Huan; Kao, Yi-Huei; Chen, Jiun-Tai

    2014-09-01

    Block copolymers have been extensively studied over the last few decades because they can self-assemble into well-ordered nanoscale structures. The morphologies of block copolymers in confined geometries, however, are still not fully understood. In this work, the fabrication and morphologies of three-dimensional polystyrene-block-polydimethylsiloxane (PS-b-PDMS) nanostructures confined in the nanopores of anodic aluminum oxide (AAO) templates are studied. It is discovered that the block copolymers can wet the nanopores using a novel solvent-annealing-induced nanowetting in templates (SAINT) method. The unique advantage of this method is that the problem of thermal degradation can be avoided. In addition, the morphologies of PS-b-PDMS nanostructures can be controlled by changing the wetting conditions. Different solvents are used as the annealing solvent, including toluene, hexane, and a co-solvent of toluene and hexane. When the block copolymer wets the nanopores in toluene vapors, a perpendicular morphology is observed. When the block copolymer wets the nanopores in co-solvent vapors (toluene/hexane = 3:2), unusual circular and helical morphologies are obtained. These three-dimensional nanostructures can serve as naontemplates for refilling with other functional materials, such as Au, Ag, ZnO, and TiO2 . © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Directed evolution strategies for enantiocomplementary haloalkane dehalogenases: from chemical waste to enantiopure building blocks.

    Science.gov (United States)

    van Leeuwen, Jan G E; Wijma, Hein J; Floor, Robert J; van der Laan, Jan-Metske; Janssen, Dick B

    2012-01-02

    We used directed evolution to obtain enantiocomplementary haloalkane dehalogenase variants that convert the toxic waste compound 1,2,3-trichloropropane (TCP) into highly enantioenriched (R)- or (S)-2,3-dichloropropan-1-ol, which can easily be converted into optically active epichlorohydrins-attractive intermediates for the synthesis of enantiopure fine chemicals. A dehalogenase with improved catalytic activity but very low enantioselectivity was used as the starting point. A strategy that made optimal use of the limited capacity of the screening assay, which was based on chiral gas chromatography, was developed. We used pair-wise site-saturation mutagenesis (SSM) of all 16 noncatalytic active-site residues during the initial two rounds of evolution. The resulting best R- and S-enantioselective variants were further improved in two rounds of site-restricted mutagenesis (SRM), with incorporation of carefully selected sets of amino acids at a larger number of positions, including sites that are more distant from the active site. Finally, the most promising mutations and positions were promoted to a combinatorial library by using a multi-site mutagenesis protocol with restricted codon sets. To guide the design of partly undefined (ambiguous) codon sets for these restricted libraries we employed structural information, the results of multiple sequence alignments, and knowledge from earlier rounds. After five rounds of evolution with screening of only 5500 clones, we obtained two strongly diverged haloalkane dehalogenase variants that give access to (R)-epichlorohydrin with 90 % ee and to (S)-epichlorohydrin with 97 % ee, containing 13 and 17 mutations, respectively, around their active sites. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Anticonvulsant activity of B2, an adenosine analog, on chemical convulsant-induced seizures.

    Directory of Open Access Journals (Sweden)

    Min Li

    Full Text Available Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6-(3-methoxyl-4-hydroxybenzyl adenine riboside (B2 is a N(6-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP, pentylenetetrazol (PTZ, picrotoxin, kainite acid (KA, or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A1 and A2A receptors. Furthermore, DPCPX, a selective A1 receptor antagonist, but not SCH58261, a selective A2A receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A1 receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy.

  4. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    International Nuclear Information System (INIS)

    Zhang, Yan; Choksi, Swati; Liu, Zheng-Gang

    2013-01-01

    Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80 + macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206 + TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer

  5. Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1).

    NARCIS (Netherlands)

    Molina, A.L.; Boer, H.D. de; Klimek, M.; Heeringa, M.; Klein, J.

    2007-01-01

    Sugammadex is the first selective relaxant binding agent and reverses rocuronium-induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and

  6. Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

    Science.gov (United States)

    Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

    2016-06-01

    Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

  7. Kinetics of electrically and chemically induced swelling in polyelectrolyte gels

    Science.gov (United States)

    Grimshaw, P. E.; Nussbaum, J. H.; Grodzinsky, A. J.; Yarmush, M. L.

    1990-09-01

    Controlled swelling and shrinking of polyelectrolyte gels is useful for regulating the transport of solutes into, out of, and through these materials. A macroscopic continuum model is presented to predict the kinetics of swelling in polyelectrolyte gel membranes induced by augmentation of electrostatic swelling forces arising from membrane fixed charge groups. The model accounts for ionic transport within the membrane, electrodiffusion phenomena, dissociation of membrane charge groups, intramembrane fluid flow, and mechanical deformation of the membrane matrix. Model predictions are compared with measurements of chemically and electrically induced swelling and shrinking in crosslinked polymethacrylic acid (PMAA) membranes. Large, reversible changes in PMAA membrane hydration were observed after changing the bath pH or by applying an electric field to modify the intramembrane ionic environment and fixed charge density. A relatively slow swelling process and more rapid shrinking for both chemical and electrical modulation of the intramembrane pH are observed. The model indicates that retardation of membrane swelling is dominated by diffusion-limited reaction of H+ ions with membrane charge groups, and that the more rapid shrinking is limited primarily by mechanical processes.

  8. Gallic acid prevents nonsteroidal anti-inflammatory drug-induced gastropathy in rat by blocking oxidative stress and apoptosis.

    Science.gov (United States)

    Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd Shameel; Maity, Pallab; Adhikari, Susanta S; Bandyopadhyay, Uday

    2010-07-15

    Nonsteroidal anti-inflammatory drug (NSAID)-induced oxidative stress plays a critical role in gastric mucosal cell apoptosis and gastropathy. NSAIDs induce the generation of hydroxyl radical ((*)OH) through the release of free iron, which plays an important role in developing gastropathy. Thus, molecules having both iron-chelating and antiapoptotic properties will be beneficial in preventing NSAID-induced gastropathy. Gallic acid (GA), a polyphenolic natural product, has the capacity to chelate free iron. Here, we report that GA significantly prevents, as well as heals, NSAID-induced gastropathy. In vivo, GA blocks NSAID-mediated mitochondrial oxidative stress by preventing mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. In vitro, GA scavenges free radicals and blocks (*)OH-mediated oxidative damage. GA also attenuates gastric mucosal cell apoptosis in vivo as well as in vitro in cultured gastric mucosal cells as evident from the TUNEL assay. GA prevents NSAID-induced activation of caspase-9, a marker for the mitochondrial pathway of apoptosis, and restores NSAID-mediated collapse of the mitochondrial transmembrane potential and dehydrogenase activity. Thus, the inhibition of mitochondrial oxidative stress by GA is associated with the inhibition of NSAID-induced mitochondrial dysfunction and activation of apoptosis in gastric mucosal cells, which are responsible for gastric injury or gastropathy. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Environment-induced self-assembly in phase separated block copolymer systems: A SANS investigation

    International Nuclear Information System (INIS)

    Dutta, Naba K.; Thompson, Sandra; Roy Choudhury, Namita; Knott, Robert

    2006-01-01

    In this research, we examine the effect of non-selective solvent on the large-scale mesoscopic ordering in asymmetric block copolymers, poly(styrene-block-ethylene/butylene-block-styrene) (SEBS) using small angle neutron scattering technique (SANS). SANS measurements were carried out over a wide range of concentrations and temperatures. Evolution of the self-assembled phase morphology in such polymer with the thermodynamic selectivity of solvent, temperature and concentration has been discussed. Correlation between morphology and thermorheological behavior of the gels has also been established

  10. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  11. Anti-Inflammatory Effects of Fargesin on Chemically Induced Inflammatory Bowel Disease in Mice

    Directory of Open Access Journals (Sweden)

    Bei Yue

    2018-06-01

    Full Text Available Fargesin is a bioactive lignan from Flos Magnoliae, an herb widely used in the treatment of allergic rhinitis, sinusitis, and headache in Asia. We sought to investigate whether fargesin ameliorates experimental inflammatory bowel disease (IBD in mice. Oral administration of fargesin significantly attenuated the symptoms of dextran sulfate sodium (DSS-induced colitis in mice by decreasing the inflammatory infiltration and myeloperoxidase (MPO activity, reducing tumor necrosis factor (TNF-α secretion, and inhibiting nitric oxide (NO production in colitis mice. The degradation of inhibitory κBα (IκBα, phosphorylation of p65, and mRNA expression of nuclear factor κB (NF-κB target genes were inhibited by fargesin treatment in the colon of the colitis mice. In vitro, fargesin blocked the nuclear translocation of p-p65, downregulated the protein levels of inducible NO synthase (iNOS and cyclooxygenase-2 (COX-2, and dose-dependently inhibited the activity of NF-κB-luciferase in lipopolysaccharide (LPS-stimulated RAW264.7 macrophages. Taken together, for the first time, the current study demonstrated the anti-inflammatory effects of fargesin on chemically induced IBD might be associated with NF-κB signaling suppression. The findings may contribute to the development of therapies for human IBD by using fargesin or its derivatives.

  12. Abnormal development of tapetum and microspores induced by chemical hybridization agent SQ-1 in wheat.

    Science.gov (United States)

    Wang, Shuping; Zhang, Gaisheng; Song, Qilu; Zhang, Yingxin; Li, Zheng; Guo, Jialin; Niu, Na; Ma, Shoucai; Wang, Junwei

    2015-01-01

    Chemical hybridization agent (CHA)-induced male sterility is an important tool in crop heterosis. To demonstrate that CHA-SQ-1-induced male sterility is associated with abnormal tapetal and microspore development, the cytology of CHA-SQ-1-treated plant anthers at various developmental stages was studied by light microscopy, scanning and transmission electron microscopy, in situ terminal deoxynucleotidyl transferasemediated dUTP nick end-labelling (TUNEL) assay and DAPI staining. The results indicated that the SQ-1-treated plants underwent premature tapetal programmed cell death (PCD), which was initiated at the early-uninucleate stage of microspore development and continued until the tapetal cells were completely degraded; the process of microspore development was then blocked. Microspores with low-viability (fluorescein diacetate staining) were aborted. The study suggests that premature tapetal PCD is the main cause of pollen abortion. Furthermore, it determines the starting period and a key factor in CHA-SQ-1-induced male sterility at the cell level, and provides cytological evidence to further study the mechanism between PCD and male sterility.

  13. Abnormal development of tapetum and microspores induced by chemical hybridization agent SQ-1 in wheat.

    Directory of Open Access Journals (Sweden)

    Shuping Wang

    Full Text Available Chemical hybridization agent (CHA-induced male sterility is an important tool in crop heterosis. To demonstrate that CHA-SQ-1-induced male sterility is associated with abnormal tapetal and microspore development, the cytology of CHA-SQ-1-treated plant anthers at various developmental stages was studied by light microscopy, scanning and transmission electron microscopy, in situ terminal deoxynucleotidyl transferasemediated dUTP nick end-labelling (TUNEL assay and DAPI staining. The results indicated that the SQ-1-treated plants underwent premature tapetal programmed cell death (PCD, which was initiated at the early-uninucleate stage of microspore development and continued until the tapetal cells were completely degraded; the process of microspore development was then blocked. Microspores with low-viability (fluorescein diacetate staining were aborted. The study suggests that premature tapetal PCD is the main cause of pollen abortion. Furthermore, it determines the starting period and a key factor in CHA-SQ-1-induced male sterility at the cell level, and provides cytological evidence to further study the mechanism between PCD and male sterility.

  14. Chemical-induced disease relation extraction with various linguistic features.

    Science.gov (United States)

    Gu, Jinghang; Qian, Longhua; Zhou, Guodong

    2016-01-01

    Understanding the relations between chemicals and diseases is crucial in various biomedical tasks such as new drug discoveries and new therapy developments. While manually mining these relations from the biomedical literature is costly and time-consuming, such a procedure is often difficult to keep up-to-date. To address these issues, the BioCreative-V community proposed a challenging task of automatic extraction of chemical-induced disease (CID) relations in order to benefit biocuration. This article describes our work on the CID relation extraction task on the BioCreative-V tasks. We built a machine learning based system that utilized simple yet effective linguistic features to extract relations with maximum entropy models. In addition to leveraging various features, the hypernym relations between entity concepts derived from the Medical Subject Headings (MeSH)-controlled vocabulary were also employed during both training and testing stages to obtain more accurate classification models and better extraction performance, respectively. We demoted relation extraction between entities in documents to relation extraction between entity mentions. In our system, pairs of chemical and disease mentions at both intra- and inter-sentence levels were first constructed as relation instances for training and testing, then two classification models at both levels were trained from the training examples and applied to the testing examples. Finally, we merged the classification results from mention level to document level to acquire final relations between chemicals and diseases. Our system achieved promisingF-scores of 60.4% on the development dataset and 58.3% on the test dataset using gold-standard entity annotations, respectively. Database URL:https://github.com/JHnlp/BC5CIDTask. © The Author(s) 2016. Published by Oxford University Press.

  15. Improving the photovoltaic parameters in Quantum dot sensitized solar cells through employment of chemically deposited compact titania blocking layer

    Energy Technology Data Exchange (ETDEWEB)

    Rajendra Prasad, M.B., E-mail: rajendraprasadmb75@gmail.com [Advanced Physics Laboratory, Department of Physics, SavitibaiPhule Pune University, Pune, 411007 (India); National Defence Academy, Khadakwasla, Pune, 411023 (India); Kadam, Vishal [Advanced Physics Laboratory, Department of Physics, SavitibaiPhule Pune University, Pune, 411007 (India); Joo, Oh-Shim [Korea Institute of Science and Technology, PO Box No. 131, Chongryang, Seoul, 130-650 (Korea, Republic of); Pathan, Habib M. [Advanced Physics Laboratory, Department of Physics, SavitibaiPhule Pune University, Pune, 411007 (India)

    2017-06-15

    Incorporation of compact blocking layer at the Transparent Conducting Oxide (TCO)/Electrolyte interface is an effective method to improve the device performance in QDSSC through mitigation of electron recombinations at this interface. This paper reports the most facile and cost effective method of depositing a rutile titania Compact Layer (CL) over Fluorine doped Tin Oxide (FTO) substrate and its application in titania based CdS QD sensitized solar cells. The deposited compact layers are characterized to study their structural, optical, morphological and electrochemical properties using X-Ray Diffractometry, UV–Visible spectroscopy, Scanning electron microscopy, Cyclic Voltammetry and Contact Angle measurements. Sandwich solar cells are fabricated using these CL based electrodes and characterized using Electrochemical Impedance Spectroscopy, Open Circuit Voltage Decay and J-V characteristics. The CL incorporated CdS QDSSC showed more than 100% increase in the photoconversion efficiency (1.68%) as compared to its bare FTO counterpart (0.73%) proving the efficacy of employed strategy. - Highlights: • Deposited titania compact layer by a facile room temperature chemical bath method. • Employed this to mitigate back electron transfer at TCO/Electrolyte interface. • Compact layer incorporation has improved the solar cell performance by 130%.

  16. Chemically induced and light-independent cryptochrome photoreceptor activation.

    Science.gov (United States)

    Rosenfeldt, Gesa; Viana, Rafael Muñoz; Mootz, Henning D; von Arnim, Albrecht G; Batschauer, Alfred

    2008-01-01

    The cryptochrome photoreceptors of higher plants are dimeric proteins. Their N-terminal photosensory domain mediates dimerization, and the unique C-terminal extension (CCT) mediates signaling. We made use of the human FK506-binding protein (FKBP) that binds with high affinity to rapamycin or rapamycin analogs (rapalogs). The FKBP-rapamycin complex is recognized by another protein, FRB, thus allowing rapamycin-induced dimerization of two target proteins. Here we demonstrate by bioluminescence resonance energy transfer (BRET) assays the applicability of this regulated dimerization system to plants. Furthermore, we show that fusion proteins consisting of the C-terminal domain of Arabidopsis cryptochrome 2 fused to FKBP and FRB and coexpressed in Arabidopsis cells specifically induce the expression of cryptochrome-controlled reporter and endogenous genes in darkness upon incubation with the rapalog. These results demonstrate that the activation of cryptochrome signal transduction can be chemically induced in a dose-dependent fashion and uncoupled from the light signal, and provide the groundwork for gain-of-function experiments to study specifically the role of photoreceptors in darkness or in signaling cross-talk even under light conditions that activate members of all photoreceptor families.

  17. Detection block

    International Nuclear Information System (INIS)

    Bezak, A.

    1987-01-01

    A diagram is given of a detection block used for monitoring burnup of nuclear reactor fuel. A shielding block is an important part of the detection block. It stabilizes the fuel assembly in the fixing hole in front of a collimator where a suitable gamma beam is defined for gamma spectrometry determination of fuel burnup. The detector case and a neutron source case are placed on opposite sides of the fixing hole. For neutron measurement for which the water in the tank is used as a moderator, the neutron detector-fuel assembly configuration is selected such that neutrons from spontaneous fission and neutrons induced with the neutron source can both be measured. The patented design of the detection block permits longitudinal travel and rotation of the fuel assembly to any position, and thus more reliable determination of nuclear fuel burnup. (E.S.). 1 fig

  18. Bupivacaine-induced cellular entry of QX-314 and its contribution to differential nerve block

    Science.gov (United States)

    Brenneis, C; Kistner, K; Puopolo, M; Jo, S; Roberson, DP; Sisignano, M; Segal, D; Cobos, EJ; Wainger, BJ; Labocha, S; Ferreirós, N; Hehn, C; Tran, J; Geisslinger, G; Reeh, PW; Bean, BP; Woolf, C J

    2014-01-01

    Background and Purpose: Selective nociceptor fibre block is achieved by introducing the cell membrane impermeant sodium channel blocker lidocaine N-ethyl bromide (QX-314) through transient receptor potential V1 (TRPV1) channels into nociceptors. We screened local anaesthetics for their capacity to activate TRP channels, and characterized the nerve block obtained by combination with QX-314. Experimental Approach: We investigated TRP channel activation in dorsal root ganglion (DRG) neurons by calcium imaging and patch-clamp recordings, and cellular QX-314 uptake by MS. To characterize nerve block, compound action potential (CAP) recordings from isolated nerves and behavioural responses were analysed. Key Results: Of the 12 compounds tested, bupivacaine was the most potent activator of ruthenium red-sensitive calcium entry in DRG neurons and activated heterologously expressed TRPA1 channels. QX-314 permeated through TRPA1 channels and accumulated intracellularly after activation of these channels. Upon sciatic injections, QX-314 markedly prolonged bupivacaine's nociceptive block and also extended (to a lesser degree) its motor block. Bupivacaine's blockade of C-, but not A-fibre, CAPs in sciatic nerves was extended by co-application of QX-314. Surprisingly, however, this action was the same in wild-type, TRPA1-knockout and TRPV1/TRPA1-double knockout mice, suggesting a TRP-channel independent entry pathway. Consistent with this, high doses of bupivacaine promoted a non-selective, cellular uptake of QX-314. Conclusions and Implications: Bupivacaine, combined with QX-314, produced a long-lasting sensory nerve block. This did not require QX-314 permeation through TRPA1, although bupivacaine activated these channels. Regardless of entry pathway, the greatly extended duration of block produced by QX-314 and bupivacaine may be clinically useful. PMID:24117225

  19. Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

    International Nuclear Information System (INIS)

    Sousa, A.M.; Ashmawi, H.A.; Costa, L.S.; Posso, I.P.; Slullitel, A.

    2011-01-01

    Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group) were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg) was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg) increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s) and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN) at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg) blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics

  20. Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

    Directory of Open Access Journals (Sweden)

    A.M. Sousa

    2012-02-01

    Full Text Available Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics.

  1. Chemically induced magnetism in atomically precise gold clusters.

    Science.gov (United States)

    Krishna, Katla Sai; Tarakeshwar, Pilarisetty; Mujica, Vladimiro; Kumar, Challa S S R

    2014-03-12

    Comparative theoretical and experimental investigations are reported into chemically induced magnetism in atomically-precise, ligand-stabilized gold clusters Au25 , Au38 and Au55 . The results indicate that [Au25 (PPh3 )10 (SC12 H25 )5 Cl2 ](2+) and Au38 (SC12 H25 )24 are diamagnetic, Au25 (SC2 H4 Ph)18 is paramagnetic, and Au55 (PPh3 )12 Cl6 , is ferromagnetic at room temperature. Understanding the magnetic properties resulting from quantum size effects in such atomically precise gold clusters could lead to new fundamental discoveries and applications. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Inducing β Phase Crystallinity in Block Copolymers of Vinylidene Fluoride with Methyl Methacrylate or Styrene

    Directory of Open Access Journals (Sweden)

    Nahal Golzari

    2017-07-01

    Full Text Available Block copolymers of poly(vinylidene fluoride (PVDF with either styrene or methyl methacrylate (MMA were synthesized and analyzed with respect to the type of the crystalline phase occurring. PVDF with iodine end groups (PVDF-I was prepared by iodine transfer polymerization either in solution with supercritical CO2 or in emulsion. To activate all iodine end groups Mn2(CO10 is employed. Upon UV irradiation Mn(CO5 radicals are obtained, which abstract iodine from PVDF-I generating PVDF radicals. Subsequent polymerization with styrene or methyl methacrylate (MMA yields block copolymers. Size exclusion chromatography and NMR results prove that the entire PVDF-I is converted. XRD, FT-IR, and differential scanning calorimetry (DSC analyses allow for the identification of crystal phase transformation. It is clearly shown that the original α crystalline phase of PVDF-I is changed to the β crystalline phase in case of the block copolymers. For ratios of the VDF block length to the MMA block length ranging from 1.4 to 5 only β phase material was detected.

  3. Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J; Schneider, Pascal

    2014-02-14

    Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated.

  4. Generation and Characterization of Function-blocking Anti-ectodysplasin A (EDA) Monoclonal Antibodies That Induce Ectodermal Dysplasia*

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J.; Schneider, Pascal

    2014-01-01

    Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

  5. Chemical changes in titanate surfaces induced by Ar+ ion bombardment

    International Nuclear Information System (INIS)

    Gonzalez-Elipe, A.R.; Fernandez, A.; Espinos, J.P.; Munuera, G.; Sanz, J.M.

    1992-01-01

    The reduction effects and compositional changes induced by 3.5 keV Ar + bombardment of several titanates (i.e. SrTiO 3 , Al 2 TiO 5 and NiTiO 3 ) have been quantitatively investigated by XPS. In all the samples studied here the original Ti 4+ species were reduced to lower oxidation states (i.e. Ti 3+ and Ti 2+ ), although to a lesser extent than in pure TiO 2 . On the contrary, whereas Sr 2+ and Al 3+ seem to remain unaffected by Ar + bombardment, in agreement with the behaviour of the respective oxides (i.e. SrO and Al 2 O 3 ), Ni 2+ appears more easily reducible to Ni o in NiTiO 3 than in NiO. In addition, other specific differences were observed between the titanates, which reveal the existence of interesting chemical effects related to the presence of the different counter-ions in the titanates. In the case of Al 2 TiO 5 , its Ar + -induced decomposition to form TiO 2 + Al 2 O 3 could be followed by XPS. (Author)

  6. Chemical reactions induced and probed by positive muons

    International Nuclear Information System (INIS)

    Ito, Yasuo

    1990-01-01

    The application of μ + science, collectively called μSR, but encompassing a variety of methods including muon spin rotation, muon spin relaxation, muon spin repolarization, muon spin resonance and level-crossing resonance, to chemistry is introduced emphasizing the special aspects of processes which are 'induced and probed' by the μ + itself. After giving a general introduction to the nature and methods of muon science and a short history of muon chemistry, selected topics are given. One concerns the usefulness of muonium as hydrogen-like probes of chemical reactions taking polymerization of vinyl monomers and reaction with thiosulphate as examples. Probing solitons in polyacetylene induced and probed by μ + is also an important example which shows the unique nature of muonium. Another important topic is 'lost polarization'. Although this term is particular to muonium. Another important topic is 'lost polarization'. Although this term is particular to muon chemistry, the chemistry underlining the phenomenon of lost polarization has an importance to both radiation and hot atom chemistries. (orig.)

  7. Inhibiting focal adhesion kinase (FAK) blocks IL-4 induced VCAM-1 expression and eosinophil recruitment in vitro and in vivo.

    Science.gov (United States)

    Aulakh, Gurpreet K; Petri, Björn; Wojcik, Katarzyna M; Colarusso, Pina; Lee, James J; Patel, Kamala D

    2018-04-06

    Leukocyte recruitment plays a critical role during both normal inflammation and chronic inflammatory diseases, and ongoing studies endeavor to better understand the complexities of this process. Focal adhesion kinase (FAK) is well known for its role in cancer, yet it also has been shown to regulate aspects of neutrophil and B16 melanoma cell recruitment by rapidly influencing endothelial cell focal adhesion dynamics and junctional opening. Recently, we found that FAK related non-kinase (FRNK), a protein that is often used as a FAK dominant negative, blocked eosinophil transmigration by preventing the transcription of vascular cell adhesion molecule-1 (VCAM-1) and eotaxin-3 (CCL26). Surprisingly, the blocking occurred even in the absence of endogenous FAK. To better understand the role of FAK in leukocyte recruitment, we used a FAK-specific inhibitor (PF-573228) and determined the effect on IL-4 induced eosinophil recruitment in vitro and in vivo. PF-573228 prevented the expression of VCAM-1 and CCL26 expression in IL-4-stimulated human endothelial cells in vitro. As a result, eosinophil adhesion and transmigration were blocked. PF-572338 also prevented IL-4-induced VCAM-1 expression in vivo. Using brightfield intravital microscopy, we found that PF-573228 decreased leukocyte rolling flux, adhesion, and emigration. We specifically examined eosinophil recruitment in vivo by using an eosinophil-GFP reporter mouse and found PF-573228 attenuated eosinophil emigration. This study reveals that a FAK inhibitor influences inflammation through its action on eosinophil recruitment. ©2018 Society for Leukocyte Biology.

  8. Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy

    Science.gov (United States)

    Kim, Ji Eun; Chun, Hea Rim

    2017-01-01

    Abstract Introduction: Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. Clinical features: An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. Conclusion: A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD. PMID:28353578

  9. Local anesthetic-induced myotoxicity as a cause of severe trismus after inferior alveolar nerve block.

    Science.gov (United States)

    Smolka, Wenko; Knoesel, Thomas; Mueller-Lisse, Ullrich

    2018-01-01

    A case of a 60-year-old man with severe trismus after inferior alveolar nerve block is presented. MRI scans as well as histologic examination revealed muscle fibrosis and degeneration of the medial part of the left temporal muscle due to myotoxicity of a local anesthetic agent.

  10. Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases

    International Nuclear Information System (INIS)

    Huang, T.-Y.; Chu, H.-C.; Lin, Y.-L.; Lin, C.-K.; Hsieh, T.-Y.; Chang, W.-K.; Chao, Y.-C.; Liao, C.-L.

    2009-01-01

    In addition to its antimicrobial activity, minocycline exerts anti-inflammatory effects in several disease models. However, whether minocycline affects the pathogenesis of inflammatory bowel disease has not been determined. We investigated the effects of minocycline on experimental colitis and its underlying mechanisms. Acute and chronic colitis were induced in mice by treatment with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), and the effect of minocycline on colonic injury was assessed clinically and histologically. Prophylactic and therapeutic treatment of mice with minocycline significantly diminished mortality rate and attenuated the severity of DSS-induced acute colitis. Mechanistically, minocycline administration suppressed inducible nitric oxide synthase (iNOS) expression and nitrotyrosine production, inhibited proinflammatory cytokine expression, repressed the elevated mRNA expression of matrix metalloproteinases (MMPs) 2, 3, 9, and 13, diminished the apoptotic index in colonic tissues, and inhibited nitric oxide production in the serum of mice with DSS-induced acute colitis. In DSS-induced chronic colitis, minocycline treatment also reduced body weight loss, improved colonic histology, and blocked expression of iNOS, proinflammatory cytokines, and MMPs from colonic tissues. Similarly, minocycline could ameliorate the severity of TNBS-induced acute colitis in mice by decreasing mortality rate and inhibiting proinflammatory cytokine expression in colonic tissues. These results demonstrate that minocycline protects mice against DSS- and TNBS-induced colitis, probably via inhibition of iNOS and MMP expression in intestinal tissues. Therefore, minocycline is a potential remedy for human inflammatory bowel diseases.

  11. Fabrication of an open Au/nanoporous film by water-in-oil emulsion-induced block copolymer micelles.

    Science.gov (United States)

    Koh, Haeng-Deog; Kang, Nam-Goo; Lee, Jae-Suk

    2007-12-18

    Water-in-oil (W/O) emulsion-induced micelles with narrow size distributions of approximately 140 nm were prepared by sonicating the polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) block copolymer in the toluene/water (50:1 vol %). The ordered nanoporous block copolymer films with the hydrophilic P2VP interior and the PS matrix were distinctly fabricated by casting the resultant solution on substrates, followed by evaporating the organic solvent and water. The porous diameter was estimated to be about 70 nm. Here, we successfully prepared the open nanoporous nanocomposites, the P2VP domain decorated by Au (5+/-0.4 nm) nanoparticles based on the methodology mentioned. We anticipate that this novelty enhances the specific function of nanoporous films.

  12. Quantifying seismic anisotropy induced by small-scale chemical heterogeneities

    Science.gov (United States)

    Alder, C.; Bodin, T.; Ricard, Y.; Capdeville, Y.; Debayle, E.; Montagner, J. P.

    2017-12-01

    Observations of seismic anisotropy are usually used as a proxy for lattice-preferred orientation (LPO) of anisotropic minerals in the Earth's mantle. In this way, seismic anisotropy observed in tomographic models provides important constraints on the geometry of mantle deformation associated with thermal convection and plate tectonics. However, in addition to LPO, small-scale heterogeneities that cannot be resolved by long-period seismic waves may also produce anisotropy. The observed (i.e. apparent) anisotropy is then a combination of an intrinsic and an extrinsic component. Assuming the Earth's mantle exhibits petrological inhomogeneities at all scales, tomographic models built from long-period seismic waves may thus display extrinsic anisotropy. In this paper, we investigate the relation between the amplitude of seismic heterogeneities and the level of induced S-wave radial anisotropy as seen by long-period seismic waves. We generate some simple 1-D and 2-D isotropic models that exhibit a power spectrum of heterogeneities as what is expected for the Earth's mantle, that is, varying as 1/k, with k the wavenumber of these heterogeneities. The 1-D toy models correspond to simple layered media. In the 2-D case, our models depict marble-cake patterns in which an anomaly in shear wave velocity has been advected within convective cells. The long-wavelength equivalents of these models are computed using upscaling relations that link properties of a rapidly varying elastic medium to properties of the effective, that is, apparent, medium as seen by long-period waves. The resulting homogenized media exhibit extrinsic anisotropy and represent what would be observed in tomography. In the 1-D case, we analytically show that the level of anisotropy increases with the square of the amplitude of heterogeneities. This relation is numerically verified for both 1-D and 2-D media. In addition, we predict that 10 per cent of chemical heterogeneities in 2-D marble-cake models can

  13. Chrysin inhibits tumor promoter-induced MMP-9 expression by blocking AP-1 via suppression of ERK and JNK pathways in gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Yong Xia

    Full Text Available Cell invasion is a crucial mechanism of cancer metastasis and malignancy. Matrix metalloproteinase-9 (MMP-9 is an important proteolytic enzyme involved in the cancer cell invasion process. High expression levels of MMP-9 in gastric cancer positively correlate with tumor aggressiveness and have a significant negative correlation with patients' survival times. Recently, mechanisms suppressing MMP-9 by phytochemicals have become increasingly investigated. Chrysin, a naturally occurring chemical in plants, has been reported to suppress tumor metastasis. However, the effects of chrysin on MMP-9 expression in gastric cancer have not been well studied. In the present study, we tested the effects of chrysin on MMP-9 expression in gastric cancer cells, and determined its underlying mechanism. We examined the effects of chrysin on MMP-9 expression and activity via RT-PCR, zymography, promoter study, and western blotting in human gastric cancer AGS cells. Chrysin inhibited phorbol-12-myristate 13-acetate (PMA-induced MMP-9 expression in a dose-dependent manner. Using AP-1 decoy oligodeoxynucleotides, we confirmed that AP-1 was the crucial transcriptional factor for MMP-9 expression. Chrysin blocked AP-1 via suppression of the phosphorylation of c-Jun and c-Fos through blocking the JNK1/2 and ERK1/2 pathways. Furthermore, AGS cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by chrysin and MMP-9 antibody. Our results suggest that chrysin may exert at least part of its anticancer effect by controlling MMP-9 expression through suppression of AP-1 activity via a block of the JNK1/2 and ERK1/2 signaling pathways in gastric cancer AGS cells.

  14. Thermally induced structural evolution and performance of mesoporous block copolymer-directed alumina perovskite solar cells.

    KAUST Repository

    Tan, Kwan Wee

    2014-04-11

    Structure control in solution-processed hybrid perovskites is crucial to design and fabricate highly efficient solar cells. Here, we utilize in situ grazing incidence wide-angle X-ray scattering and scanning electron microscopy to investigate the structural evolution and film morphologies of methylammonium lead tri-iodide/chloride (CH3NH3PbI(3-x)Cl(x)) in mesoporous block copolymer derived alumina superstructures during thermal annealing. We show the CH3NH3PbI(3-x)Cl(x) material evolution to be characterized by three distinct structures: a crystalline precursor structure not described previously, a 3D perovskite structure, and a mixture of compounds resulting from degradation. Finally, we demonstrate how understanding the processing parameters provides the foundation needed for optimal perovskite film morphology and coverage, leading to enhanced block copolymer-directed perovskite solar cell performance.

  15. Thermally induced structural evolution and performance of mesoporous block copolymer-directed alumina perovskite solar cells.

    KAUST Repository

    Tan, Kwan Wee; Moore, David T; Saliba, Michael; Sai, Hiroaki; Estroff, Lara A; Hanrath, Tobias; Snaith, Henry J; Wiesner, Ulrich

    2014-01-01

    Structure control in solution-processed hybrid perovskites is crucial to design and fabricate highly efficient solar cells. Here, we utilize in situ grazing incidence wide-angle X-ray scattering and scanning electron microscopy to investigate the structural evolution and film morphologies of methylammonium lead tri-iodide/chloride (CH3NH3PbI(3-x)Cl(x)) in mesoporous block copolymer derived alumina superstructures during thermal annealing. We show the CH3NH3PbI(3-x)Cl(x) material evolution to be characterized by three distinct structures: a crystalline precursor structure not described previously, a 3D perovskite structure, and a mixture of compounds resulting from degradation. Finally, we demonstrate how understanding the processing parameters provides the foundation needed for optimal perovskite film morphology and coverage, leading to enhanced block copolymer-directed perovskite solar cell performance.

  16. Thermally Induced Structural Evolution and Performance of Mesoporous Block Copolymer-Directed Alumina Perovskite Solar Cells

    Science.gov (United States)

    2015-01-01

    Structure control in solution-processed hybrid perovskites is crucial to design and fabricate highly efficient solar cells. Here, we utilize in situ grazing incidence wide-angle X-ray scattering and scanning electron microscopy to investigate the structural evolution and film morphologies of methylammonium lead tri-iodide/chloride (CH3NH3PbI3–xClx) in mesoporous block copolymer derived alumina superstructures during thermal annealing. We show the CH3NH3PbI3–xClx material evolution to be characterized by three distinct structures: a crystalline precursor structure not described previously, a 3D perovskite structure, and a mixture of compounds resulting from degradation. Finally, we demonstrate how understanding the processing parameters provides the foundation needed for optimal perovskite film morphology and coverage, leading to enhanced block copolymer-directed perovskite solar cell performance. PMID:24684494

  17. Mucin2 is Required for Probiotic Agents-Mediated Blocking Effects on Meningitic E. coli-Induced Pathogenicities.

    Science.gov (United States)

    Yu, Jing-Yi; He, Xiao-Long; Puthiyakunnon, Santhosh; Peng, Liang; Li, Yan; Wu, Li-Sha; Peng, Wen-Ling; Zhang, Ya; Gao, Jie; Zhang, Yao-Yuan; Boddu, Swapna; Long, Min; Cao, Hong; Huang, Sheng-He

    2015-10-01

    Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl- L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5- Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.

  18. Temperature-induced phase transition in aqueous solutions of poly(N-isopropylacrylamide)-based block copolymer

    Czech Academy of Sciences Publication Activity Database

    Spěváček, Jiří; Konefal, Rafal; Dybal, Jiří

    2016-01-01

    Roč. 369, č. 1 (2016), s. 92-96 ISSN 1022-1360. [International IUPAC Conference on Polymer-Solvent Complexes and Intercalates /11./ - POLYSOLVAT-11. Kolkata, 27.01.2016-30.01.2016] R&D Projects: GA ČR(CZ) GA15-13853S Institutional support: RVO:61389013 Keywords : aqueous solutions * block copolymers * micelles Subject RIV: CD - Macromolecular Chemistry

  19. Utilizing the virus-induced blocking of apoptosis in an easy baculovirus titration method.

    Science.gov (United States)

    Niarchos, Athanasios; Lagoumintzis, George; Poulas, Konstantinos

    2015-10-22

    Baculovirus-mediated protein expression is a robust experimental technique for producing recombinant higher-eukaryotic proteins because it combines high yields with considerable post-translational modification capabilities. In this expression system, the determination of the titer of recombinant baculovirus stocks is important to achieve the correct multiplicity of infection for effective amplification of the virus and high expression of the target protein. To overcome the drawbacks of existing titration methods (e.g., plaque assay, real-time PCR), we present a simple and reliable assay that uses the ability of baculoviruses to block apoptosis in their host cells to accurately titrate virus samples. Briefly, after incubation with serial dilutions of baculovirus samples, Sf9 cells were UV irradiated and, after apoptosis induction, they were viewed via microscopy; the presence of cluster(s) of infected cells as islets indicated blocked apoptosis. Subsequently, baculovirus titers were calculated through the determination of the 50% endpoint dilution. The method is simple, inexpensive, and does not require unique laboratory equipment, consumables or expertise; moreover, it is versatile enough to be adapted for the titration of every virus species that can block apoptosis in any culturable host cells which undergo apoptosis under specific conditions.

  20. Concepts in causality: chemically induced human urinary bladder cancer

    International Nuclear Information System (INIS)

    Lower, G.M. Jr.

    1982-01-01

    A significant portion of the incidence of human urinary bladder cancer can be attributed to occupational and cultural (tobacco smoking) situations associated with exposures to various arylamines, many of which represent established human carcinogens. A brief historical overview of research in bladder cancer causality indicates that the identification of causal agents and causal mechanism has been approached and rests upon information gathered at the organismal (geographical/historical), cellular, and molecular levels of biologic organization. This viewpoint speaks of a natural evolution within the biomedical sciences; a natural evolution from descriptive approaches to mechanistic approaches; and a natural evolution from more or less independent discipline-oriented approaches to hierarchically organized multidisciplinary approaches. Available information relevant to bladder cancer causality can be readily integrated into general conceptual frameworks to yield a hierarchial view of the natural history of urinary bladder cancer, a view consistent with contemporary natural systems and information theory and perhaps relevant also to other chemically induced epithelial cancers. Such frameworks are useful in appreciating the spatial and temporal boundaries and interrelationships in causality and the conceptual interrelationships within the biomedical sciences. Recent approaches in molecular epidemiology and the assessment of relative individual susceptibility to bladder cancer indicate that such frameworks are useful in forming hypotheses

  1. Radiation induced chemical reaction of carbon monoxide and hydrogen mixture

    International Nuclear Information System (INIS)

    Sugimoto, Shun-ichi; Nishii, Masanobu

    1985-01-01

    Previous studies of radiation induced chemical reactions of CO-H 2 mixture have revealed that the yields of oxygen containing products were larger than those of hydrocarbons. In the present study, methane was added to CO-H 2 mixture in order to increase further the yields of the oxygen containing products. The yields of most products except a few products such as formaldehyde increased with the addition of small amount of methane. Especially, the yields of trioxane and tetraoxane gave the maximum values when CO-H 2 mixture containing 1 mol% methane was irradiated. When large amounts of methane were added to the mixture, the yields of aldehydes and carboxylic acids having more than two carbon atoms increased, whereas those of trioxane and tetraoxane decreased. From the study at reaction temperature over the range of 200 to 473 K, it was found that the yields of aldehydes and carboxylic acids showed maxima at 323 K. The studies on the effects of addition of cationic scavenger (NH 3 ) and radical scavenger (O 2 ) on the products yields were also carried out on the CO-H 2 -CH 4 mixture. (author)

  2. Override of the radiation-induced mitotic block in human tumour cells by methylxanthines and its relationship to the potentiation of cytotoxicity

    International Nuclear Information System (INIS)

    Musk, S.R.R.; Steel, G.G.

    1990-01-01

    Caffeine, theophylline, theobromine and paraxanthine, were tested for ability to override mitotic block induced by ionizing radiation in the human bladder carcinoma cell line RT112. All were found to partially override the block, at a concentration of 1mM in the order caffeine > theophylline > theobromine = paraxanthine. At a concentration of 1 mM only caffeine was found to potentiate cell killing as well as causing block override; at higher concentrations all had a significant effect on survival but little or no further influence on the degree of block override. It is concluded that override of a mitotic block is not in itself sufficient to cause increased killing when irradiated cells are incubated in the presence of caffeine, and that caffeine exerts its potentiating effect by directly inhibiting repair of damage in DNA or by causing override of radiation-induced inhibition of DNA synthesis. (author)

  3. Override of the radiation-induced mitotic block in human tumour cells by methylxanthines and its relationship to the potentiation of cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Musk, S.R.R.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1990-06-01

    Caffeine, theophylline, theobromine and paraxanthine, were tested for ability to override mitotic block induced by ionizing radiation in the human bladder carcinoma cell line RT112. All were found to partially override the block, at a concentration of 1mM in the order caffeine > theophylline > theobromine = paraxanthine. At a concentration of 1 mM only caffeine was found to potentiate cell killing as well as causing block override; at higher concentrations all had a significant effect on survival but little or no further influence on the degree of block override. It is concluded that override of a mitotic block is not in itself sufficient to cause increased killing when irradiated cells are incubated in the presence of caffeine, and that caffeine exerts its potentiating effect by directly inhibiting repair of damage in DNA or by causing override of radiation-induced inhibition of DNA synthesis. (author).

  4. Circulating blocking factors of lymphoid-cell cytotoxicity in x-ray-induced rat small-bowel adenocarcinoma

    International Nuclear Information System (INIS)

    Stevens, R.H.; Brooks, G.P.; Osborne, J.W.

    1979-01-01

    Circulating blocking factors capable of abrogating cell-mediated immune responses measured by in vitro lymphoid-cell cytotoxicity were identified in the sera of Holtzman outbred rats 6 to 9 months after a single exposure of only the temporarily exteriorized, hypoxic ileum and jejunum to 1700 to 2000 R of X radiation. Such factors were found to exist in the serum of every animal exposed to the ionizing radiation regardless of whether a visibly identifiable small-bowel adenocarcinoma existed or subsequently would develop. Protection of cultured x-ray-induced rat small-bowel cancer cells from destruction by tumor-sensitized lymphoid cells as measured by the release of lactoperoxidase-catalyzed radioiodinated membrane proteins from the tumor target cells was conferred by the action of the blocking factors at both effector and target cell levels. The results of this study demonstrate that exposure of only the rat small intestine to ionizing radiation leads to elaboration of circulating factors identifiable several months postirradiation which will block cell-mediated immune responses directed against cancer cells developing in the exposed tissue

  5. Mechanism of Estradiol-Induced Block of Voltage-Gated K+ Currents in Rat Medial Preoptic Neurons

    Science.gov (United States)

    Druzin, Michael; Malinina, Evgenya; Grimsholm, Ola; Johansson, Staffan

    2011-01-01

    The present study was conducted to characterize possible rapid effects of 17-β-estradiol on voltage-gated K+ channels in preoptic neurons and, in particular, to identify the mechanisms by which 17-β-estradiol affects the K+ channels. Whole-cell currents from dissociated rat preoptic neurons were studied by perforated-patch recording. 17-β-estradiol rapidly (within seconds) and reversibly reduced the K+ currents, showing an EC50 value of 9.7 µM. The effect was slightly voltage dependent, but independent of external Ca2+, and not sensitive to an estrogen-receptor blocker. Although 17-α-estradiol also significantly reduced the K+ currents, membrane-impermeant forms of estradiol did not reduce the K+ currents and other estrogens, testosterone and cholesterol were considerably less effective. The reduction induced by estradiol was overlapping with that of the KV-2-channel blocker r-stromatoxin-1. The time course of K+ current in 17-β-estradiol, with a time-dependent inhibition and a slight dependence on external K+, suggested an open-channel block mechanism. The properties of block were predicted from a computational model where 17-β-estradiol binds to open K+ channels. It was concluded that 17-β-estradiol rapidly reduces voltage-gated K+ currents in a way consistent with an open-channel block mechanism. This suggests a new mechanism for steroid action on ion channels. PMID:21625454

  6. Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

    International Nuclear Information System (INIS)

    Hu, Dong; Wu, Jing; Wang, Wan; Mu, Min; Zhao, Runpeng; Xu, Xuewei; Chen, Zhaoquan; Xiao, Jian; Hu, Fengyu; Yang, Yabo; Zhang, Rongbo

    2015-01-01

    The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. - Highlights: • A mechanism for disrupting autophagosome-lysosome fusion induced by SapM. • Rab7 is involved in SapM-inhibited autophagy. • SapM interacts with Rab7 by CT-domain. • CT-domain is indispensable to SapM-inhibited autophagy

  7. Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Dong, E-mail: austhudong@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Wu, Jing, E-mail: wujing8008@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Wang, Wan; Mu, Min; Zhao, Runpeng; Xu, Xuewei; Chen, Zhaoquan [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Xiao, Jian [School of Pharmacy, Wenzhou Medical College, Wenzhou (China); Hu, Fengyu; Yang, Yabo [Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou (China); Zhang, Rongbo, E-mail: lory456@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China)

    2015-05-29

    The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. - Highlights: • A mechanism for disrupting autophagosome-lysosome fusion induced by SapM. • Rab7 is involved in SapM-inhibited autophagy. • SapM interacts with Rab7 by CT-domain. • CT-domain is indispensable to SapM-inhibited autophagy.

  8. Nerve Blocks

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Nerve Blocks A nerve block is an injection to ... the limitations of Nerve Block? What is a Nerve Block? A nerve block is an anesthetic and/ ...

  9. Commentary: critical questions, misconceptions and a road map for improving the use of the lymphocyte cytokinesis-block micronucleus assay for in vivo biomonitoring of human exposure to genotoxic chemicals-a HUMN project perspective.

    Science.gov (United States)

    Kirsch-Volders, Micheline; Bonassi, Stefano; Knasmueller, Siegfried; Holland, Nina; Bolognesi, Claudia; Fenech, Michael F

    2014-01-01

    The lymphocyte cytokinesis-block micronucleus (CBMN) assay has been applied in hundreds of in vivo biomonitoring studies of humans exposed to genotoxic chemicals because it allows the measurement of both structural and numerical chromosome aberrations. The CBMN cytome assay version which, apart from measuring micronuclei (MN) already present in cells in vivo or expressed ex vivo, also includes measurement of nucleoplasmic bridges (NPB), nuclear buds (NBUD), necrosis and apoptosis, is also increasingly being used in such studies. Because of the numerous published studies there is now a need to re-evaluate the use of MN and other biomarkers within the lymphocyte CBMN cytome assay as quantitative indicators of exposure to chemical genotoxins and the genetic hazard this may cause. This review has identified some important misconceptions as well as knowledge gaps that need to be addressed to make further progress in the proper application of this promising technique and enable its full potential to be realised. The HUMN project consortium recommends a three pronged approach to further improve the knowledge base and application of the lymphocyte CBMN cytome assay to measure DNA damage in humans exposed to chemical genotoxins: (i) a series of systematic reviews, one for each class of chemical genotoxins, of studies which have investigated the association of in vivo exposure in humans with MN, NPB and NBUD induction in lymphocytes; (ii) a comprehensive analysis of the literature to obtain new insights on the potential mechanisms by which different classes of chemicals may induce MN, NPB and NBUD in vitro and in vivo and (iii) investigation of the potential advantages of using the lymphocyte CBMN cytome assay in conjunction with other promising complementary DNA damage diagnostics to obtain an even more complete assessment of the DNA damage profile induced by in vivo exposure to chemical genotoxins in humans. Copyright © 2014 The Authors. Published by Elsevier B.V. All

  10. Sensitivity to Rocuronium-Induced Neuromuscular Block and Reversibility with Sugammadex in a Patient with Myotonic Dystrophy

    Directory of Open Access Journals (Sweden)

    Akihiro Kashiwai

    2012-01-01

    Full Text Available We report a patient with myotonic dystrophy who showed prolonged rocuronium-induced neuromuscular blockade, although with a fast recovery with sugammadex. During general anesthesia with propofol and remifentanil, the times to spontaneous recovery of the first twitch (T1 of train of four to 10% of control values after an intubating dose of rocuronium 1 mg/kg and an additional dose of 0.2 mg/kg were 112 min and 62 min, respectively. Despite the high sensitivity to rocuronium, sugammadex 2 mg/kg administered at a T1 of 10% safely and effectively antagonized rocuronium-induced neuromuscular block in 90 s.

  11. Inhibition of polymerases-alpha and -beta completely blocks DNA repair induced by UV irradiation in cultured mouse neuronal cells

    International Nuclear Information System (INIS)

    Licastro, F.; Sarafian, T.; Verity, A.M.; Walford, R.L.

    1985-01-01

    The effects of hydroxyurea, aphidicolin and dideoxythymidine on UV-induced DNA repair of mouse neuronal granular cells were studied. Aphidicolin, which is considered a specific inhibitor of polymerase-alpha, decreased spontaneous DNA synthesis by 93% and totally suppressed DNA repair. Dideoxythymidine, an inhibitor of polymerase-beta, was more potent in decreasing scheduled DNA synthesis than aphidicolin, and also completely blocked the UV-induced DNA repair. Hydroxyurea, a specific inhibitor of ribonucleotide reductase, inhibited scheduled DNA synthesis, but unscheduled DNA synthesis after UV irradiation was always well detectable. Our data suggest that in neuronal cells from 5 to 10 days old mice both polymerases-alpha and -beta are required for both DNA synthesis and repair. These two enzymes may act jointly in filling up the gaps along the DNA molecule and elongating the DNA chain

  12. CF3DODA-Me induces apoptosis, degrades Sp1, and blocks the transformation phase of the blebbishield emergency program.

    Science.gov (United States)

    Taoka, Rikiya; Jinesh, Goodwin G; Xue, Wenrui; Safe, Stephen; Kamat, Ashish M

    2017-05-01

    Cancer stem cells are capable of undergoing cellular transformation after commencement of apoptosis through the blebbishield emergency program in a VEGF-VEGFR2-dependent manner. Development of therapeutics targeting the blebbishield emergency program would thus be important in cancer therapy. Specificity protein 1 (Sp1) orchestrates the transcription of both VEGF and VEGFR2; hence, Sp1 could act as a therapeutic target. Here, we demonstrate that CF 3 DODA-Me induced apoptosis, degraded Sp1, inhibited the expression of multiple drivers of the blebbishield emergency program such as VEGFR2, p70S6K, and N-Myc through activation of caspase-3, inhibited reactive oxygen species; and inhibited K-Ras activation to abolish transformation from blebbishields as well as transformation in soft agar. These findings confirm CF 3 DODA-Me as a potential therapeutic candidate that can induce apoptosis and block transformation from blebbishields.

  13. Exercise-Induced Secretion of FGF21 and Follistatin Are Blocked by Pancreatic Clamp and Impaired in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Hansen, Jakob Schiøler; Pedersen, Bente Klarlund; Xu, Guowang

    2016-01-01

    blocking the increase in the glucagon to insulin ratio. In addition, we evaluated exercise-induced plasma FGF21 and follistatin in patients with T2D compared with healthy controls in response to 1 hour of bicycle exercise followed by a 3-hour recovery period. RESULTS: In healthy individuals, we observed......CONTEXT: Hepatokines have emerged as liver-derived hormone-like factors. Plasma fibroblast growth factor (FGF)-21 and follistatin increase with a high glucagon to insulin ratio and exercise, and resting levels are elevated in patients with type 2 diabetes (T2D). OBJECTIVE: The objective...... of the study was to investigate the regulatory roles of glucagon to insulin ratio and T2D on exercise-induced FGF21 and follistatin secretion. Design /Interventions: Young healthy males performed a 2-hour bicycle exercise bout followed by 5 hours of rest in supine position with and without a pancreatic clamp...

  14. Time-resolved resonance fluorescence spectroscopy for study of chemical reactions in laser-induced plasmas.

    Science.gov (United States)

    Liu, Lei; Deng, Leimin; Fan, Lisha; Huang, Xi; Lu, Yao; Shen, Xiaokang; Jiang, Lan; Silvain, Jean-François; Lu, Yongfeng

    2017-10-30

    Identification of chemical intermediates and study of chemical reaction pathways and mechanisms in laser-induced plasmas are important for laser-ablated applications. Laser-induced breakdown spectroscopy (LIBS), as a promising spectroscopic technique, is efficient for elemental analyses but can only provide limited information about chemical products in laser-induced plasmas. In this work, time-resolved resonance fluorescence spectroscopy was studied as a promising tool for the study of chemical reactions in laser-induced plasmas. Resonance fluorescence excitation of diatomic aluminum monoxide (AlO) and triatomic dialuminum monoxide (Al 2 O) was used to identify these chemical intermediates. Time-resolved fluorescence spectra of AlO and Al 2 O were used to observe the temporal evolution in laser-induced Al plasmas and to study their formation in the Al-O 2 chemistry in air.

  15. Systemic morphine blocks the seizures induced by intracerebroventricular (i.c.v.) injections of opiates and opioid peptides.

    Science.gov (United States)

    Urca, G; Frenk, H

    1982-08-19

    Intracerebroventricular (i.c.v.) injections of the endorphins and of morphine in rats produce highly characteristic, naloxone sensitive, electrographic seizures. In contrast, systemic injections of morphine have been shown to exert a marked anticonvulsant effect. The present study demonstrates that systemic morphine pretreatment can prevent the occurrence of electrographic seizures injected by i.c.v. morphine, Leu-enkephalin and beta-endorphin and that the anti-epileptic effect of morphine can be reversed by naloxone. Male albino rats, previously prepared for chronic i.c.v. injections and EEG recordings, were pretreated with 0--100 mg/kg of intraperitoneal (i.p.) morphine. Thirty five minutes later morphine (520 nmol), Leu-enkephalin (80 nmol) or beta-endorphin (5 nmol) were injected i.c.v. Pretreatment with i.p. morphine blocked the occurrence of seizures induced by morphine and both endogenous opioids. Lower doses of systemic morphine (50 mg/kg) were necessary to block i.c.v. morphine seizures than the dose (100 mg/kg) necessary to block seizures induced by i.c.v. Leu-enkephalin and beta-endorphin. Naloxone (1 mg/kg) administered 25 min following 50 mg/kg of i.p. morphine and preceding the injections of i.c.v. morphine reversed the antiepileptic effect of systemic morphine. These results demonstrate the possible existence of two opiate sensitive systems, one with excitatory-epileptogenic effects and the other possessing inhibitory-antiepileptic properties. The possible relationship between these findings and the known heterogeneity of opiate receptors and opiate actions is discussed.

  16. Study on the identification method of chemical warfare agents with spectroscopy of neutron induced γ rays

    International Nuclear Information System (INIS)

    Liu Boxue; Li Yun; Li Xiangbao

    1996-01-01

    The paper briefly describes some non-destructive verification technologies of chemical warfare agents in-site, and some application of neutron induced gamma ray analysis, such as multi-elements analysis of coal, hidden explosive detection and identification of chemical agents. It also describes some problems in developing the portable isotopic neutron spectroscopy for non-destructive evaluation of chemical warfare agents

  17. Coarse grain model for coupled thermo-mechano-chemical processes and its application to pressure-induced endothermic chemical reactions

    International Nuclear Information System (INIS)

    Antillon, Edwin; Banlusan, Kiettipong; Strachan, Alejandro

    2014-01-01

    We extend a thermally accurate model for coarse grain dynamics (Strachan and Holian 2005 Phys. Rev. Lett. 94 014301) to enable the description of stress-induced chemical reactions in the degrees of freedom internal to the mesoparticles. Similar to the breathing sphere model, we introduce an additional variable that describes the internal state of the particles and whose dynamics is governed both by an internal potential energy function and by interparticle forces. The equations of motion of these new variables are derived from a Hamiltonian and the model exhibits two desired features: total energy conservation and Galilean invariance. We use a simple model material with pairwise interactions between particles and study pressure-induced chemical reactions induced by hydrostatic and uniaxial compression. These examples demonstrate the ability of the model to capture non-trivial processes including the interplay between mechanical, thermal and chemical processes of interest in many applications. (paper)

  18. Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study.

    NARCIS (Netherlands)

    Boer, H.D. de; Driessen, J.J.; Marcus, M.A.; Kerkkamp, H.E.M.; Heeringa, M.; Klimek, M.

    2007-01-01

    BACKGROUND: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular

  19. The cytokinesis-block micronucleus assay: a sensitive technique for measuring radiation-induced chromosome damage

    International Nuclear Information System (INIS)

    Fenech, M.; Morley, A.A.

    1987-01-01

    The sensitivity of the cytokinesis-block micronucleus assay was demonstrated by the detection in human lymphocytes of in vitro exposures of as low as 0.02 Gy of X-rays. To determine the suitability of this new method for measuring in vivo exposure to radiation the authors have performed initial longitudinal studies on (a) cancer patients undergoing partial body fractionated radiotherapy and (b) BALB-C mice following in vivo whole body irradiation with acute single doses of X-rays. The results for radiotherapy patients indicate that the dose fractions have an additive effect on the observed micronucleus frequency which appeared to decline following three months after completion of therapy. Results with irradiated mice showed a sharp increase in micronucleus frequency for splenocytes sampled immediately after treatment and the rate of decline in micronucleus frequency during the first week after treatment was dose-dependent. (author)

  20. Reversal with sugammadex for rocuronium-induced deep neuromuscular block after pretreatment of magnesium sulfate in rabbits.

    Science.gov (United States)

    Kang, Woon Seok; Kim, Kyo Sang; Song, Shin Mi

    2017-04-01

    Magnesium sulfate (MgSO 4 ) has been used in the treatment of pre-eclampsia, hypertension and arrhythmia. Magnesium enhances the neuromuscular block of rocuronium. This study has been conducted to evaluate the reversal efficacy of sugammadex from deep rocuronium-induced neuromuscular block (NMB) during consistent pretreatment of MgSO 4 in rabbits. Twenty-eight rabbits were randomly assigned to four groups, a control group or study groups (50% MgSO 4 150-200 mg/kg and 25 mg/kg/h IV), and received rocuronium 0.6 mg/kg. When post-tetanic count 1-2 appeared, sugammadex 2, 4, and 8 mg/kg was administered in the 2-mg group, control and 4-mg group, and 8-mg group, respectively. The recovery course after reversal of sugammadex administration was evaluated in each group. The mean serum concentration of magnesium was maintained at more than 2 mmol/L in the study groups, and the total dose of MgSO 4 was more than 590 mg. The reversal effect of sugammadex on rocuronium-induced NMB in pretreated MgSO 4 was not different from that in the group without MgSO 4 . The recovery time to train-of-four ratio 0.9 after sugammadex administration in the 2-mg group was longer than in the other groups (P rocuronium-induced NMB during large pretreatment of MgSO 4 was not affected. However, we should consider that the reversal effect of sugammadex varied depending on the dose.

  1. Pioglitazone Attenuates Drug-Eluting Stent-Induced Proinflammatory State in Patients by Blocking Ubiquitination of PPAR

    Directory of Open Access Journals (Sweden)

    Zhongxia Wang

    2016-01-01

    Full Text Available The inflammatory response after polymer-based drug-eluting stent (DES placement has recently emerged as a major concern. The biologic roles of peroxisome proliferator-activated receptor-γ (PPAR-γ activators thiazolidinedione (TZD remain controversial in cardiovascular disease. Herein, we investigated the antiinflammatory effects of pioglitazone (PIO on circulating peripheral blood mononuclear cells (MNCs in patients after coronary DES implantation. Methods and Results. Twenty-eight patients with coronary artery disease and who underwent DES implantations were randomly assigned to pioglitazone (30 mg/d; PIO or placebo (control; Con treatment in addition to optimal standard therapy. After 12 weeks of treatment, plasma concentrations of high-sensitivity C-reactive protein (hs-CRP, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and matrix metalloproteinase-9 (MMP-9 were significantly decreased in PIO group compared to the Con group (P=0.035, 0.011, 0.008, and 0.012, resp.. DES-induced mRNA expressions of IL-6, TNF-α, and MMP-9 in circulating MNC were significantly blocked by PIO (P=0.031, 0.012, and 0.007, resp.. In addition, PIO markedly inhibited DES-enhanced NF-κB function and DES-blocked PPAR-γ activity. Mechanically, DES induced PPAR-γ ubiquitination and degradation in protein level, which can be totally reversed by PIO. Conclusion. PIO treatment attenuated DES-induced PPAR loss, NF-κB activation, and proinflammation, indicating that PIO may have a novel direct protective role in modulating proinflammation in DES era.

  2. Microwave plasma enhanced chemical vapor deposition growth of few-walled carbon nanotubes using catalyst derived from an iron-containing block copolymer precursor

    International Nuclear Information System (INIS)

    Wang Peng; Lu, Jennifer; Zhou, Otto

    2008-01-01

    The microwave plasma enhanced chemical vapor deposition (MPECVD) method is now commonly used for directional and conformal growth of carbon nanotubes (CNTs) on supporting substrates. One of the shortcomings of the current process is the lack of control of the diameter and diameter distribution of the CNTs due to difficulties in synthesizing well-dispersed catalysts. Recently, block copolymer derived catalysts have been developed which offer the potential of fine control of both the size of and the spacing between the metal clusters. In this paper we report the successful growth of CNTs with narrow diameter distribution using polystyrene-block-polyferrocenylethylmethylsilane (PS-b-PFEMS) as the catalyst precursor. The study shows that higher growth pressure leads to better CNT growth. Besides the pressure, the effects on the growth of CNTs of the growth parameters, such as temperature and precursor gas ratio, are also studied

  3. An Antibody Blocking Activin Type II Receptors Induces Strong Skeletal Muscle Hypertrophy and Protects from Atrophy

    Science.gov (United States)

    Minetti, Giulia C.; Sheppard, KellyAnn; Ibebunjo, Chikwendu; Feige, Jerome N.; Hartmann, Steffen; Brachat, Sophie; Rivet, Helene; Koelbing, Claudia; Morvan, Frederic; Hatakeyama, Shinji

    2014-01-01

    The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts and counteracts the inhibition of differentiation induced by myostatin or activin A. BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin mutant mice, further confirming a beneficial effect on muscle growth beyond myostatin inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic force losses. These data highlight the compelling therapeutic potential of BYM338 for the treatment of skeletal muscle atrophy and weakness in multiple settings. PMID:24298022

  4. Increasing Humidity Blocks Continuous Positive Airflow-induced Apnea Responses in Rats

    Directory of Open Access Journals (Sweden)

    Ching-Ting Tan

    2010-07-01

    Conclusion: Laryngeal cold dry air stimulation triggered an apneic response, which could be eliminated by humidification but not by the heating of air. These results suggest that using continuous positive airway pressure (CPAP with humidified air decreases CPAP-induced apnea.

  5. Surface chemical reactions induced by molecules electronically-excited in the gas

    DEFF Research Database (Denmark)

    Petrunin, Victor V.

    2011-01-01

    and alignment are taking place, guiding all the molecules towards the intersections with the ground state PES, where transitions to the ground state PES will occur with minimum energy dissipation. The accumulated kinetic energy may be used to overcome the chemical reaction barrier. While recombination chemical...... be readily produced. Products of chemical adsorption and/or chemical reactions induced within adsorbates are aggregated on the surface and observed by light scattering. We will demonstrate how pressure and spectral dependencies of the chemical outcomes, polarization of the light and interference of two laser...... beams inducing the reaction can be used to distinguish the new process we try to investigate from chemical reactions induced by photoexcitation within adsorbed molecules and/or gas phase photolysis....

  6. Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

    Science.gov (United States)

    Bunnell, Bryan E; Escobar, Jillian F; Bair, Kirsten L; Sutton, Mark D; Crane, John K

    2017-01-01

    Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

  7. Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Bryan E Bunnell

    Full Text Available Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

  8. The iSelect 9 K SNP analysis revealed polyploidization induced revolutionary changes and intense human selection causing strong haplotype blocks in wheat.

    Science.gov (United States)

    Hao, Chenyang; Wang, Yuquan; Chao, Shiaoman; Li, Tian; Liu, Hongxia; Wang, Lanfen; Zhang, Xueyong

    2017-01-30

    A Chinese wheat mini core collection was genotyped using the wheat 9 K iSelect SNP array. Total 2420 and 2396 polymorphic SNPs were detected on the A and the B genome chromosomes, which formed 878 haplotype blocks. There were more blocks in the B genome, but the average block size was significantly (P polyploidization of wheat (both tetraploidization and hexaploidization) induced revolutionary changes in both the A and the B genomes, with a greater increase of gene diversity compared to their diploid ancestors. Modern breeding has dramatically increased diversity in the gene coding regions, though obvious blocks were formed on most of the chromosomes in both tetraploid and hexaploid wheats. Tag-SNP markers identified in this study can be used for marker assisted selection using haplotype blocks as a wheat breeding strategy. This strategy can also be employed to facilitate genome selection in other self-pollinating crop species.

  9. Fluctuation induced critical behavior at nonzero temperature and chemical potential

    International Nuclear Information System (INIS)

    Splittorff, K.; Lenaghan, J.T.; Wirstam, J.

    2003-01-01

    We discuss phase transitions in relativistic systems as a function of both the chemical potential and temperature. The presence of a chemical potential explicitly breaks Lorentz invariance and may additionally break other internal symmetries. This introduces new subtleties in the determination of the critical properties. We discuss separately three characteristic effects of a nonzero chemical potential. First, we consider only the explicit breaking of Lorentz invariance using a scalar field theory with a global U(1) symmetry. Second, we study the explicit breaking of an internal symmetry in addition to Lorentz invariance using two-color QCD at nonzero baryonic chemical potential. Finally, we consider the spontaneous breaking of a symmetry using three-color QCD at nonzero baryonic and isospin chemical potential. For each case, we derive the appropriate three-dimensional effective theory at criticality and study the effect of the chemical potential on the fixed point structure of the β functions. We find that the order of the phase transition is not affected by the explicit breaking of Lorentz invariance but is sensitive to the breaking of additional symmetries by the chemical potential

  10. Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis.

    Science.gov (United States)

    Kleinschnitz, Christoph; Braeuninger, Stefan; Pham, Mirko; Austinat, Madeleine; Nölte, Ingo; Renné, Thomas; Nieswandt, Bernhard; Bendszus, Martin; Stoll, Guido

    2008-04-01

    Models of photochemically-induced thrombosis are widely used in cerebrovascular research. Photothrombotic brain infarctions can be induced by systemic application of photosensitizing dyes followed by focal illumination of the cerebral cortex. Although the ensuing activation of platelets is well established, their contribution for thrombosis and tissue damage has not formally been proved. Infarction to the cerebral cortex was induced in mice by Rose Bengal and a cold light source. To assess the functional role of platelets, animals were platelet-depleted by anti-GPIbalpha antibodies or treated with GPIIb/IIIa-blocking F(ab)(2) fragments. The significance of the plasmatic coagulation cascade was determined by using blood coagulation factor XII (FXII)-deficient mice or heparin. Infarct development and infarct volumes were determined by serial MRI and conventional and electron microscopy. There was no difference in development and final size of photothrombotic infarctions in mice with impaired platelet function. Moreover, deficiency of FXII, which initiates the intrinsic pathway of coagulation and is essential for thrombus formation, or blockade of FXa, the key protease during the waterfall cascade of plasmatic coagulation, by heparin likewise did not affect lesion development. Our data demonstrate that platelet activation, factor XII-driven thrombus formation, and plasmatic coagulation pathways downstream of FX are not a prerequisite for ensuing tissue damage in models of photothrombotic vessel injury indicating that other pathomechanisms are involved. We suggest that this widely used model does not depend on platelet- or plasmatic coagulation-derived thrombosis.

  11. Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Kazuyo [Microscopy and Imaging Core Facility, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD (United States); Adhikari, Rewati [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); Yamada, Kenneth M. [National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Dhawan, Subhash, E-mail: subhash.dhawan@fda.hhs.gov [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

    2015-08-14

    The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection.

  12. Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism

    International Nuclear Information System (INIS)

    Baba, Miyako; Inoue, Masahiro; Itoh, Kazuyuki; Nishizawa, Yasuko

    2008-01-01

    CD147 is a multifunctional transmembrane protein and promotes cancer progression. We found that the anti-human CD147 mouse monoclonal antibody MEM-M6/1 strongly induces necrosis-like cell death in LoVo, HT-29, WiDr, and SW620 colon cancer cells and A2058 melanoma cells, but not in WI-38 and TIG-113 normal fibroblasts. Silencing or overexpression of CD147 in LoVo cells enhanced or decreased the MEM-M6/1 induced cell death, respectively. CD147 is known to form complex with proton-linked monocarboxylate transporters (MCTs), which is critical for lactate transport and intracellular pH (pHi) homeostasis. In LoVo cells, CD147 and MCT-1 co-localized on the cell surface, and MEM-M6/1 inhibited the association of these molecules. MEM-M6/1 inhibited lactate uptake, lactate release, and reduced pHi. Further, the induction of acidification was parallel to the decrease of the glycolytic flux and intracellular ATP levels. These effects were not found in the normal fibroblasts. As cancer cells depend on glycolysis for their energy production, CD147 inhibition might induce cell death specific to cancer cells

  13. Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    Takeda, Kazuyo; Adhikari, Rewati; Yamada, Kenneth M.; Dhawan, Subhash

    2015-01-01

    The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection

  14. Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems.

    Science.gov (United States)

    Li, Xiang; Huang, Mengbing; Yang, Lihua; Guo, Ningning; Yang, Xiaoyan; Zhang, Zhimin; Bai, Ming; Ge, Lu; Zhou, Xiaoshuang; Li, Ye; Bai, Jie

    2018-01-01

    Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1) is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP) in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA) and γ-aminobutyric acid (GABA) systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG) mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in wild-type (WT) mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH) and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABA B R were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABA B R in the VTA and NAc.

  15. Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2018-05-01

    Full Text Available Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1 is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA and γ-aminobutyric acid (GABA systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA and nucleus accumbens (NAc in wild-type (WT mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABABR were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABABR in the VTA and NAc.

  16. Radiation-induced crosslinking of poly(styrene–butadiene–styrene) block copolymers and their sulfonation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun-Young [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Song, Ju-Myung; Sohn, Joon-Yong [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Shul, Yong-Gun [Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Shin, Junhwa, E-mail: shinj@kaeri.re.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of)

    2013-12-01

    Highlights: • The c-SBS films were prepared using a gamma ray or electron beam. • The crosslinking degree of the c-SBS films were increased with the irradiation dose. • The prepared c-SBS films were sulfonated with various concentration of CSA. • The sulfonation of the c-SBS film is largely dependent on the concentration of CSA. • The sulfonation process is progressed from the surface to the inner part of c-SBS film. -- Abstract: Several crosslinked poly(styrene–butadiene–styrene) (c-SBS) block copolymer films were prepared using a gamma ray or electron beam with various irradiation doses and the prepared c-SBS film was then subjected to sulfonation using a chlorosulfonic acid (CSA) solution to introduce a sulfonic acid group. To estimate the degree of crosslinking, the gel fractions and FT-IR spectra of the c-SBS films were used and the results indicate that the degree of crosslinking is increased with an increase in the radiation dose. The surface morphology and mechanical property of the c-SBS films were observed using SEM and UTM instruments, respectively. The sulfonated c-SBS films were investigated by measuring the ion exchange capacity (IEC) and by observing the cross-sectional distribution patterns of sulfonic acid group using an SEM-EDX instrument. The IEC and SEM-EDX studies indicate that the sulfonated c-SBS membranes can be successfully prepared through the radiation crosslinking of the SBS film and the subsequent sulfonation with a diluted CSA solution.

  17. Nek1 silencing slows down DNA repair and blocks DNA damage-induced cell cycle arrest.

    Science.gov (United States)

    Pelegrini, Alessandra Luíza; Moura, Dinara Jaqueline; Brenner, Bethânia Luise; Ledur, Pitia Flores; Maques, Gabriela Porto; Henriques, João Antônio Pegas; Saffi, Jenifer; Lenz, Guido

    2010-09-01

    Never in mitosis A (NIMA)-related kinases (Nek) are evolutionarily conserved proteins structurally related to the Aspergillus nidulans mitotic regulator NIMA. Nek1 is one of the 11 isoforms of the Neks identified in mammals. Different lines of evidence suggest the participation of Nek1 in response to DNA damage, which is also supported by the interaction of this kinase with proteins involved in DNA repair pathways and cell cycle regulation. In this report, we show that cells with Nek1 knockdown (KD) through stable RNA interference present a delay in DNA repair when treated with methyl-methanesulfonate (MMS), hydrogen peroxide (H(2)O(2)) and cisplatin (CPT). In particular, interstrand cross links induced by CPT take much longer to be resolved in Nek1 KD cells when compared to wild-type (WT) cells. In KD cells, phosphorylation of Chk1 in response to CPT was strongly reduced. While WT cells accumulate in G(2)/M after DNA damage with MMS and H(2)O(2), Nek1 KD cells do not arrest, suggesting that G(2)/M arrest induced by the DNA damage requires Nek1. Surprisingly, CPT-treated Nek1 KD cells arrest with a 4N DNA content similar to WT cells. This deregulation in cell cycle control in Nek1 KD cells leads to an increased sensitivity to genotoxic agents when compared to WT cells. These results suggest that Nek1 is involved in the beginning of the cellular response to genotoxic stress and plays an important role in preventing cell death induced by DNA damage.

  18. Cold temperature blocks thyroid hormone-induced changes in lipid and energy metabolism in the liver of Lithobates catesbeianus tadpoles.

    Science.gov (United States)

    Suzuki, Shunsuke; Awai, Koichiro; Ishihara, Akinori; Yamauchi, Kiyoshi

    2016-01-01

    Exposure of the American bullfrog Lithobates catesbeianus tadpoles to low temperature affects many biological processes including lipid metabolism and the thyroid hormone (TH) signaling pathway, resulting in arrest of TH-induced metamorphosis. To clarify what molecular events occur in this phenomenon, we investigated the glycerophospholipid and fatty acid (FA) compositions, the activities of mitochondrial enzymes and the transcript levels of related genes in the liver of control (26 °C) and cold-treated (4 °C) tadpoles with or without 5 nM 3,3',5-triiodothyronine (T3). Exposure to T3 decreased the tail height and polyunsaturation of FAs in the glycerophospholipids, and increased plasma glucose levels and transcript levels of primary TH-response genes including TH receptor, and some energy metabolic (cox4, srebp1 and fas) and FA chain elongase genes (elovl3 and elovl5). However, these T3-induced responses were abolished at 4 °C. Exposure to cold temperature enhanced plasma glucose, triglyceride and free FA levels, monounsaturation of FAs, mitochondrial enzymes activities (cytochrome c oxidase and carnitine palmitoyltransferase; U/g liver), with the upregulation of the genes involved in glycogenolysis (pygl), gluconeogenesis (pck1 and g6pc2), FA β-oxidation (acadl), and cholesterol uptake and synthesis (hmgcr, srebp2 and ldlr1), glycerophospholipids synthesis (pcyt1, pcyt2, pemt, and pparg), and FA monounsaturation (scd1) and chain elongation (elovl1 and elovl2). T3 had little effect on the cold-induced changes. Our study demonstrated that exposures to T3 and cold temperature exert different effects on lipid metabolism, resulting in changes in the FA composition in glycerophospholipids, and suggests that a cold-induced signal may block TH-signaling pathway around primary TH-response genes.

  19. Inhibition of radiation induced migration of human head and neck squamous cell carcinoma cells by blocking of EGF receptor pathways

    International Nuclear Information System (INIS)

    Pickhard, Anja C; Schlegel, Jürgen; Arnold, Wolfgang; Reiter, Rudolf; Margraf, Johanna; Knopf, Andreas; Stark, Thomas; Piontek, Guido; Beck, Carolin; Boulesteix, Anne-Laure; Scherer, Elias Q; Pigorsch, Steffi

    2011-01-01

    Recently it has been shown that radiation induces migration of glioma cells and facilitates a further spread of tumor cells locally and systemically. The aim of this study was to evaluate whether radiotherapy induces migration in head and neck squamous cell carcinoma (HNSCC). A further aim was to investigate the effects of blocking the epidermal growth factor receptor (EGFR) and its downstream pathways (Raf/MEK/ERK, PI3K/Akt) on tumor cell migration in vitro. Migration of tumor cells was assessed via a wound healing assay and proliferation by a MTT colorimeritric assay using 3 HNSCC cell lines (BHY, CAL-27, HN). The cells were treated with increasing doses of irradiation (2 Gy, 5 Gy, 8 Gy) in the presence or absence of EGF, EGFR-antagonist (AG1478) or inhibitors of the downstream pathways PI3K (LY294002), mTOR (rapamycin) and MEK1 (PD98059). Biochemical activation of EGFR and the downstream markers Akt and ERK were examined by Western blot analysis. In absence of stimulation or inhibition, increasing doses of irradiation induced a dose-dependent enhancement of migrating cells (p < 0.05 for the 3 HNSCC cell lines) and a decrease of cell proliferation (p < 0.05 for the 3 HNSCC cell lines). The inhibition of EGFR or the downstream pathways reduced cell migration significantly (almost all p < 0.05 for the 3 HNSCC cell lines). Stimulation of HNSCC cells with EGF caused a significant increase in migration (p < 0.05 for the 3 HNSCC cell lines). After irradiation alone a pronounced activation of EGFR was observed by Western blot analysis. Our results demonstrate that the EGFR is involved in radiation induced migration of HNSCC cells. Therefore EGFR or the downstream pathways might be a target for the treatment of HNSCC to improve the efficacy of radiotherapy

  20. Effects of methylprednisolone on the duration of rocuronium-induced neuromuscular block

    Science.gov (United States)

    Geng, Weilian; Nie, Yuyan; Huang, Shaoqiang

    2017-01-01

    Abstract Background: We aim to investigate whether intraoperative use of methylprednisolone could affect the duration of rocuronium-induced neuromuscular blockade. Methods: A double blind, randomized, placebo-controlled trial was conducted. A total of 136 patients underwent gynecologic laparoscopic surgery were randomly divided into 3 groups: pregroup, receiving intravenous injection of methylprednisolone (40 mg) 30 minutes before induction of anesthesia; postgroup, receiving intravenous injection of methylprednisolone (40 mg) immediately after induction of anesthesia and intubation; and control group, receiving intravenous injection of normal saline. Patients were intravenously administrated with rocuronium 0.6 mg/kg, and changes in adductor policies evoked twitch responses were measured by ulnar nerve stimulator. Results: We found that all patients achieved maximum blockade effects, and there was no difference in onset time among the 2 groups. For time required to achieve train-of-four ratio (TOFR) 90%, pregroup (64.50 ± 10.52 minutes) and postgroup (65.29 ± 11.64 minutes) were significantly shorter than that of the control group (71.04 ± 10.55 minutes, P = .027), whereas clinical duration and total duration were significantly shorter in the 2 groups received methylprednisolone than the control group. However, there was no significant difference between the 2 treatment groups either in clinical duration and total duration of muscle relaxants, or time required to achieve TOFR 90%. No significant difference was found in recovery index among the 3 groups. Conclusion: Our findings suggest that a single intravenous injection of methylprednisolone, no matter preoperatively or intraoperatively, could shorten the duration of rocuronium-induced neuromuscular blockade. PMID:28953616

  1. N-Terminal Prodomain of Pfs230 Synthesized Using a Cell-Free System Is Sufficient To Induce Complement-Dependent Malaria Transmission-Blocking Activity▿

    Science.gov (United States)

    Tachibana, Mayumi; Wu, Yimin; Iriko, Hideyuki; Muratova, Olga; MacDonald, Nicholas J.; Sattabongkot, Jetsumon; Takeo, Satoru; Otsuki, Hitoshi; Torii, Motomi; Tsuboi, Takafumi

    2011-01-01

    The aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluated Escherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein. The rabbit antisera reacted to the surface of cultured gametocytes and gametes of the Plasmodium falciparum NF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by Western blot assay, and reduced the infectivity of NF54 parasites to Anopheles stefensi mosquitoes in the presence of complement in a standard membrane feeding assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is sufficient to induce complement-dependent transmission-blocking activity against P. falciparum. PMID:21715579

  2. N-terminal prodomain of Pfs230 synthesized using a cell-free system is sufficient to induce complement-dependent malaria transmission-blocking activity.

    Science.gov (United States)

    Tachibana, Mayumi; Wu, Yimin; Iriko, Hideyuki; Muratova, Olga; MacDonald, Nicholas J; Sattabongkot, Jetsumon; Takeo, Satoru; Otsuki, Hitoshi; Torii, Motomi; Tsuboi, Takafumi

    2011-08-01

    The aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluated Escherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein. The rabbit antisera reacted to the surface of cultured gametocytes and gametes of the Plasmodium falciparum NF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by Western blot assay, and reduced the infectivity of NF54 parasites to Anopheles stefensi mosquitoes in the presence of complement in a standard membrane feeding assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is sufficient to induce complement-dependent transmission-blocking activity against P. falciparum.

  3. Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6

    Directory of Open Access Journals (Sweden)

    Nina Kerres

    2017-09-01

    Full Text Available The transcription factor BCL6 is a known driver of oncogenesis in lymphoid malignancies, including diffuse large B cell lymphoma (DLBCL. Disruption of its interaction with transcriptional repressors interferes with the oncogenic effects of BCL6. We used a structure-based drug design to develop highly potent compounds that block this interaction. A subset of these inhibitors also causes rapid ubiquitylation and degradation of BCL6 in cells. These compounds display significantly stronger induction of expression of BCL6-repressed genes and anti-proliferative effects than compounds that merely inhibit co-repressor interactions. This work establishes the BTB domain as a highly druggable structure, paving the way for the use of other members of this protein family as drug targets. The magnitude of effects elicited by this class of BCL6-degrading compounds exceeds that of our equipotent non-degrading inhibitors, suggesting opportunities for the development of BCL6-based lymphoma therapeutics.

  4. Rinse-resistant superhydrophobic block copolymer fabrics by electrospinning, electrospraying and thermally-induced self-assembly

    Science.gov (United States)

    Wu, Jie; Li, Xin; Wu, Yang; Liao, Guoxing; Johnston, Priscilla; Topham, Paul D.; Wang, Linge

    2017-11-01

    An inherent problem that restricts the practical application of superhydrophobic materials is that the superhydrophobic property is not sustainable; it can be diminished, or even lost, when the surface is physically damaged. In this work, we present an efficient approach for the fabrication of superhydrophobic fibrous fabrics with great rinse-resistance where a block copolymer has been electrospun into a nanofibrous mesh while micro-sized beads have been subsequently electrosprayed to give a morphologically composite material. The intricate nano- and microstructure of the composite was then fixed by thermally annealing the block copolymer to induce self-assembly and interdigitation of the microphase separated domains. To demonstrate this approach, a polystyrene-b-poly(ethylene-co-butylene)-b-polystyrene (SEBS) nanofibrous scaffold was produced by electrospinning before SEBS beads were electrosprayed into this mesh to form a hierarchical micro/nanostructure of beads and fibers. The effects of type and density of SEBS beads on the surface morphology and wetting properties of composite membranes were studied extensively. Compared with a neat SEBS fibrous mesh, the composite membrane had enhanced hydrophobic properties. The static water contact angle increased from 139° (±3°) to 156° (±1°), while the sliding angle decreased to 8° (±1°) from nearly 90°. In order to increase the rinse-resistance of the composite membrane, a thermal annealing step was applied to physically bind the fibers and beads. Importantly, after 200 h of water flushing, the hierarchical surface structure and superhydrophobicity of the composite membrane were well retained. This work provides a new route for the creation of superhydrophobic fabrics with potential in self-cleaning applications.

  5. Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

    Directory of Open Access Journals (Sweden)

    Gunduz Feyza

    2012-08-01

    Full Text Available Abstract Background Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC patients. The mechanism of response to interferon-alpha (IFN-α therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV replication and IFN-α antiviral response in a cell culture model. Methods Sub-genomic replicon (S3-GFP and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. Results FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. Conclusion These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN

  6. Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective.

    NARCIS (Netherlands)

    Muller, Andre; Jacobsen, Helene; Healy, Edel; McMickan, Sinead; Istace, Fréderique; Blaude, Marie-Noëlle; Howden, Peter; Fleig, Helmut; Schulte, Agnes

    2006-01-01

    Haemolytic anaemia is often induced following prolonged exposure to chemical substances. Currently, under EU Council Directive 67/548/EEC, substances which induce such effects are classified as dangerous and assigned the risk phrase R48 'Danger of serious damage to health by prolonged exposure.'

  7. Chemically Induced Phase Transformation in Austenite by Focused Ion Beam

    Science.gov (United States)

    Basa, Adina; Thaulow, Christian; Barnoush, Afrooz

    2014-03-01

    A highly stable austenite phase in a super duplex stainless steel was subjected to a combination of different gallium ion doses at different acceleration voltages. It was shown that contrary to what is expected, an austenite to ferrite phase transformation occurred within the focused ion beam (FIB) milled regions. Chemical analysis of the FIB milled region proved that the gallium implantation preceded the FIB milling. High resolution electron backscatter diffraction analysis also showed that the phase transformation was not followed by the typical shear and plastic deformation expected from the martensitic transformation. On the basis of these observations, it was concluded that the change in the chemical composition of the austenite and the local increase in gallium, which is a ferrite stabilizer, results in the local selective transformation of austenite to ferrite.

  8. Autolyse the cell in order to save it? Inducing, then blocking, autolysis as a strategy for delaying cell death in the probiotic Lactobacillus reuteri.

    Science.gov (United States)

    Zimmerman, Tahl; Gyawali, Rabin; Ibrahim, Salam

    2017-10-01

    To examine whether choline and its derivatives can be used to preserve viable cells of Lactobacillus reuteri in autolytic models. A phosphate-induced autolytic model in de Man, Rogosa and Sharpe medium (MRS) was used. Viable cell counts were determined by plated on MRS-agar. Choline and hemicholinium-3 (HC-3) significantly blocked autolysis of L. reuteri at 360 mM and 4 mM, respectively. Viable cell counts corroborated these observations. Importantly, autolytically induced cells treated with choline and hemicholinium-3 were significantly more viable then even non-induced cells. Over-production of a known autolytic protein, spirosin, was not attenuated in the presence of choline and hemicholinium-3. Inducing autolysis and then blocking it with choline and its analogs is a promising approach for retaining the viability of L. reuteri cells.

  9. Feeder cells support the culture of induced pluripotent stem cells even after chemical fixation.

    Directory of Open Access Journals (Sweden)

    Xiao-Shan Yue

    Full Text Available Chemically fixed mouse embryonic fibroblasts (MEFs, instead of live feeder cells, were applied to the maintenance of mouse induced pluripotent stem (miPS cells. Formaldehyde and glutaraldehyde were used for chemical fixation. The chemically fixed MEF feeders maintained the pluripotency of miPS cells, as well as their undifferentiated state. Furthermore, the chemically fixed MEF feeders were reused several times without affecting their functions. These results indicate that chemical fixation can be applied to modify biological feeders chemically, without losing their original functions. Chemically fixed MEF feeders will be applicable to other stem cell cultures as a reusable extracellular matrix candidate that can be preserved on a long-term basis.

  10. Chemical products induce resistance to Xanthomonas perforans in tomato

    Directory of Open Access Journals (Sweden)

    Adriana Terumi Itako

    2015-09-01

    Full Text Available The bacterial spot of tomato, caused by Xanthomonas spp., is a very important disease, especially in the hot and humid periods of the year. The chemical control of the disease has not been very effective for a number of reasons. This study aimed to evaluate, under greenhouse conditions, the efficacy of leaf-spraying chemicals (acibenzolar-S-methyl (ASM (0.025 g.L−1, fluazinam (0.25 g.L−1, pyraclostrobin (0.08 g.L−1, pyraclostrobin + methiran (0.02 g.L−1 + 2.2 g.L−1, copper oxychloride (1.50 g.L−1, mancozeb + copper oxychloride (0.88 g.L−1 + 0.60 g.L−1, and oxytetracycline (0.40 g.L−1 on control of bacterial spot. Tomatoes Santa Clara and Gisele cultivars were pulverized 3 days before inoculation with Xanthomonas perforans. The production of enzymes associated with resistance induction (peroxidase, polyphenol oxidase, phenylalanine ammonia-lyase, β-1,3-glucanase, and protease was quantified from leaf samples collected 24 hours before and 24 hours after chemical spraying and at 1, 2, 4, 6, and 8 days after bacterial inoculation. All products tested controlled bacterial spot, but only ASM, pyraclostrobin, and pyraclostrobin + metiram increased the production of peroxidase in the leaves of the two tomato cultivars, and increased the production of polyphenol oxidase and β-1,3-glucanase in the Santa Clara cultivar.

  11. Chemical products induce resistance to Xanthomonas perforans in tomato.

    Science.gov (United States)

    Itako, Adriana Terumi; Tolentino Júnior, João Batista; Silva Júnior, Tadeu Antônio Fernandes da; Soman, José Marcelo; Maringoni, Antonio Carlos

    2015-01-01

    The bacterial spot of tomato, caused by Xanthomonas spp., is a very important disease, especially in the hot and humid periods of the year. The chemical control of the disease has not been very effective for a number of reasons. This study aimed to evaluate, under greenhouse conditions, the efficacy of leaf-spraying chemicals (acibenzolar-S-methyl (ASM) (0.025 g.L(-1)), fluazinam (0.25 g.L(-1)), pyraclostrobin (0.08 g.L(-1)), pyraclostrobin + methiran (0.02 g.L(-1) + 2.2 g.L(-1)), copper oxychloride (1.50 g.L(-1)), mancozeb + copper oxychloride (0.88 g.L(-1) + 0.60 g.L(-1)), and oxytetracycline (0.40 g.L(-1))) on control of bacterial spot. Tomatoes Santa Clara and Gisele cultivars were pulverized 3 days before inoculation with Xanthomonas perforans. The production of enzymes associated with resistance induction (peroxidase, polyphenol oxidase, phenylalanine ammonia-lyase, β-1,3-glucanase, and protease) was quantified from leaf samples collected 24 hours before and 24 hours after chemical spraying and at 1, 2, 4, 6, and 8 days after bacterial inoculation. All products tested controlled bacterial spot, but only ASM, pyraclostrobin, and pyraclostrobin + metiram increased the production of peroxidase in the leaves of the two tomato cultivars, and increased the production of polyphenol oxidase and β-1,3-glucanase in the Santa Clara cultivar.

  12. Characterization of the Environmentally Induced Chemical Transformations of Uranium Tetrafluoride

    Energy Technology Data Exchange (ETDEWEB)

    Wellons, M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2017-09-29

    A key challenge with nuclear safeguards environmental sampling is identification of the materials post release due to subsequent chemical reactions with ambient water and oxygen. Uranium Tetrafluoride (UF4) is of interest as an intermediate in both the upstream and downstream portions of uranium feedstock and metal production processes used in nuclear fuel production; however minimal published research exists relating to UF4 hydrolysis. FY16 efforts were dedicated to in-situ Raman spectroscopy and X-ray diffraction characterization of UF4 during exposure to various relative humidity conditions. This effort mapped several hydrolysis reaction pathways and identified both intermediate, and terminal progeny species.

  13. Effects of Transcranial Direct Current Stimulation Block Remifentanil-Induced Hyperalgesia: A Randomized, Double-Blind Clinical Trial

    Directory of Open Access Journals (Sweden)

    Gilberto Braulio

    2018-02-01

    Full Text Available Background: Remifentanil-induced hyperalgesia (r-IH involves an imbalance in the inhibitory and excitatory systems. As the transcranial Direct Current Stimulation (tDCS modulates the thalamocortical synapses in a top-down manner, we hypothesized that the active (a-t-DCS would be more effective than sham(s-tDCS to prevent r-IH. We used an experimental paradigm to induce temporal summation of pain utilizing a repetitive cold test (rCOLDT assessed by the Numerical Pain Score (NPS 0-10 and we evaluated the function of the descending pain modulatory system (DPMS by the change on the NPS (0–10 during the conditioned pain modulation (CPM-task (primary outcomes. We tested whether a-tDCS would be more effective than s-tDCS to improve pain perception assessed by the heat pain threshold (HPT and the reaction time during the ice-water pain test (IPT (secondary outcomes.Methods: This double-blinded, factorial randomized trial included 48 healthy males, ages ranging 19–40 years. They were randomized into four equal groups: a-tDCS/saline, s-tDCS/saline, a-tDCS/remifentanil and s-tDCS/remifentanil. tDCS was applied over the primary motor cortex, during 20 min at 2 mA, which was introduced 10 min after starting remifentanil infusion at 0.06 μg⋅kg-1⋅min-1 or saline.Results: An ANCOVA mixed model revealed that during the rCOLDT, there was a significant main effect on the NPS scores (F = 3.81; P = 0.01. The s-tDCS/remifentanil group presented larger pain scores during rCOLDT, [mean (SD 5.49 (1.04] and a-tDCS/remifentanil group had relative lower pain scores [4.15 (1.62]; showing its blocking effect on r-IH. a-tDCS/saline and s-tDCS/saline groups showed lowest pain scores during rCOLDT, [3.11 (1.2] and [3.15 (1.62], respectively. The effect of sedation induced by remifentanil during the rCOLDT was not significant (F = 0.76; P = 0.38. Remifentanil groups showed positive scores in the NPS (0–10 during the CPM-task, that is, it produced a disengagement of

  14. Atmospheric Pressure Plasma Induced Sterilization and Chemical Neutralization

    Science.gov (United States)

    Garate, Eusebio; Evans, Kirk; Gornostaeva, Olga; Alexeff, Igor; Lock Kang, Weng; Wood, Thomas K.

    1998-11-01

    We are studying chemical neutralization and surface decontamination using atmospheric pressure plasma discharges. The plasma is produced by corona discharge from an array of pins and a ground plane. The array is constructed so that various gases, like argon or helium, can be flowed past the pins where the discharge is initiated. The pin array can be biased using either DC, AC or pulsed discharges. Results indicate that the atmospheric plasma is effective in sterilizing surfaces with biological contaminants like E-coli and bacillus subtilus cells. Exposure times of less than four minutes in an air plasma result in a decrease in live colony counts by six orders of magnitude. Greater exposure times result in a decrease of live colony counts of up to ten orders of magnitude. The atmospheric pressure discharge is also effective in decomposing organic phosphate compounds that are simulants for chemical warfare agents. Details of the decomposition chemistry, by-product formation, and electrical energy consumption of the system will be discussed.

  15. Involvement of MAPK proteins in bystander effects induced by chemicals and ionizing radiation

    International Nuclear Information System (INIS)

    Asur, Rajalakshmi; Balasubramaniam, Mamtha; Marples, Brian; Thomas, Robert A.; Tucker, James D.

    2010-01-01

    Many studies have examined bystander effects induced by ionizing radiation, however few have evaluated the ability of chemicals to induce similar effects. We previously reported the ability of two chemicals, mitomycin C (MMC) and phleomycin (PHL) to induce bystander effects in normal human lymphoblastoid cell lines. The focus of the current study was to determine the involvement of the MAPK proteins in bystander effects induced by physical and chemical DNA damaging agents and to evaluate the effects of MAPK inhibition on bystander-induced caspase 3/7 activation. The phosphorylation levels of the MAPK proteins ERK1/2, JNK, and p38, were measured from 1 to 24 h following direct or bystander exposure to MMC, PHL or radiation. We observed transient phosphorylation, at early time points, of all 3 proteins in bystander cells. We also evaluated the effect of MAPK inhibition on bystander-induced caspase 3/7 activity to determine the role of MAPK proteins in bystander-induced apoptosis. We observed bystander-induced activation of caspase 3/7 in bystander cells. Inhibition of MAPK proteins resulted in a decrease in caspase 3/7 activity at the early time points, and the caspase activity increased (in the case of ERK inhibition) or returned to basal levels (in the case of JNK or p38 inhibition) between 12 and 24 h. PHL is considered to be a radiomimetic agent, however in the present study PHL behaved more like a chemical and not like radiation in terms of MAPK phosphorylation. These results point to the involvement of MAPK proteins in the bystander effect induced by radiation and chemicals and provide additional evidence that this response is not limited to radiation but is a generalized stress response in cells.

  16. Inducible nitric oxide inhibitors block NMDA antagonist-stimulated motoric behaviors and medial prefrontal cortical glutamate efflux

    Directory of Open Access Journals (Sweden)

    Hadley C Bergstrom

    2015-12-01

    Full Text Available Nitric oxide (NO plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS for studying the neurobehavioral effects of noncompetitive NMDA-antagonist stimulants such as dizocilpine (MK-801 and phencyclidine (PCP. This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS aminoguanidine (AG and (--epigallocatechin-3-gallate (EGCG in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux. Adult male rats were administered a dose range of AG, EGCG or vehicle prior to receiving NMDA antagonists MK-801, PCP or a conventional psychostimulant (cocaine and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated medial prefrontal cortical glutamate efflux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate efflux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in green tea and chocolate may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia.

  17. Improving the chemical compatibility of sealing glass for solid oxide fuel cells: Blocking the reactive species by controlled crystallization

    Science.gov (United States)

    Zhang, Teng; Zou, Qi; Zeng, Fanrong; Wang, Shaorong; Tang, Dian; Yang, Hiswen

    2012-10-01

    The chemical compatibility of sealing glass is of great importance for Solid oxide fuel cell (SOFC). In this work, the interfacial reaction between sealing glass and Cr-containing interconnect alloy is characterized by reacting Cr2O3 powders with a representative SrO-containing glass crystallized by different heat-treatment schedules. The crystalline structure and crystalline content of sealing glass are determined by X-ray diffraction. The results show that the fraction of Cr6+ decreases from 39.8 ± 1.9% for quenched glass to 8.2 ± 0.4% for glass crystallized at 900 °C for 2 h. In addition, the interfacial reaction can be further reduced with increasing crystallization temperature and time as well as the addition of nucleation agent (TiO2). The formation of some Sr-containing crystalline phases, Sr2SiO4 and Sr(TiO3), contributes to the improvement of chemical compatibility of sealing glass, in agreement with the results of thermodynamic calculations.

  18. Chemical consequences of laser-induced breakdown in molecular gases

    Czech Academy of Sciences Publication Activity Database

    Babánková, Dagmar; Civiš, Svatopluk; Juha, Libor

    2006-01-01

    Roč. 30, č. 2-3 (2006), s. 75-88 ISSN 0079-6727 R&D Projects: GA ČR GA203/06/1278; GA MŠk LC510; GA MŠk LC528; GA MŠk 1P04LA235 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z10100523 Keywords : laser spark * laser-induced dielectric breakdown * laser-plasma chemistry Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.500, year: 2006

  19. Chemical and radiation induced late dominant lethal effects in mice

    International Nuclear Information System (INIS)

    Favor, J.; Crenshaw, J.W. Jr.; Soares, E.R.

    1978-01-01

    Although theoretically expected, experimental data to date have not shown dominant lethal expression to occur throughout the developmental period. Specifically, late post-implantation effects have not been demonstrated. The authors routinely use an experimental technique in which parental females mated to mutagenically treated males are allowed to give birth and wean their litter, and their uterine horns are then inspected for uterine scars indicative of live and dead embryos. In a number of experiments in which males were mutagenically treated with either chemicals or X-irradiation, a discrepancy was observed between the number of live embryos as determined by the scar technique and the number of live observed at birth, suggesting the possibility of embryonic losses at a late stage in development. Initial analyses showed that mutagenic treatment increased the percentage of these late losses. These differences were statistically significant in 2 of 3 analyses. Factors affecting statistical significance and an understanding of dominant lethal mutations are discussed. (Auth.)

  20. Quantitative Three-Dimensional Characterization of Block Copolymer Directed Self-Assembly on Combined Chemical and Topographical Prepatterned Templates.

    Science.gov (United States)

    Segal-Peretz, Tamar; Ren, Jiaxing; Xiong, Shisheng; Khaira, Gurdaman; Bowen, Alec; Ocola, Leonidas E; Divan, Ralu; Doxastakis, Manolis; Ferrier, Nicola J; de Pablo, Juan; Nealey, Paul F

    2017-02-28

    Characterization of the three-dimensional (3D) structure in directed self-assembly (DSA) of block copolymers is crucial for understanding the complex relationships between the guiding template and the resulting polymer structure so DSA could be successfully implemented for advanced lithography applications. Here, we combined scanning transmission electron microscopy (STEM) tomography and coarse-grain simulations to probe the 3D structure of P2VP-b-PS-b-P2VP assembled on prepatterned templates using solvent vapor annealing. The templates consisted of nonpreferential background and raised guiding stripes that had PS-preferential top surfaces and P2VP-preferential sidewalls. The full 3D characterization allowed us to quantify the shape of the polymer domains and the interface between domains as a function of depth in the film and template geometry and offered important insights that were not accessible with 2D metrology. Sidewall guiding was advantageous in promoting the alignment and lowering the roughness of the P2VP domains over the sidewalls, but incommensurate confinement from the increased topography could cause roughness and intermittent dislocations in domains over the background region at the bottom of the film. The 3D characterization of bridge structures between domains over the background and breaks within domains on guiding lines sheds light on possible origins of common DSA defects. The positional fluctuations of the PS/P2VP interface between domains showed a depth-dependent behavior, with high levels of fluctuations near both the free surface of the film and the substrate and lower fluctuation levels in the middle of the film. This research demonstrates how 3D characterization offers a better understanding of DSA processes, leading to better design and fabrication of directing templates.

  1. Characterization of Chemically-Induced Bacterial Ghosts (BGs Using Sodium Hydroxide-Induced Vibrio parahaemolyticus Ghosts (VPGs

    Directory of Open Access Journals (Sweden)

    Hyun Jung Park

    2016-11-01

    Full Text Available Acellular bacterial ghosts (BGs are empty non-living bacterial cell envelopes, commonly generated by controlled expression of the cloned lysis gene E of bacteriophage PhiX174. In this study, Vibrio parahaemolyticus ghosts (VPGs were generated by chemically-induced lysis and the method is based on minimum inhibitory concentration (MIC of sodium hydroxide (NaOH, acetic acid, boric acid, citric acid, maleic acid, hydrochloric acid, and sulfuric acid. The MIC values of the respective chemicals were 3.125, 6.25, <50.0, 25.0, 6.25, 1.56, and 0.781 mg/mL. Except for boric acid, the lysis efficiency reached more than 99.99% at 5 min after treatment of all chemicals. Among those chemicals, NaOH-induced VPGs appeared completely DNA-free, which was confirmed by quantitative real-time PCR. Besides, lipopolysaccharides (LPS extracted from the NaOH-induced VPGs showed no distinctive band on SDS-PAGE gel after silver staining. On the other hand, LPS extracted from wild-type bacterial cells, as well as the organic acids-induced VPGs showed triple major bands and LPS extracted from the inorganic acids-induced VPGs showed double bands. It suggests that some surface structures in LPS of the NaOH-induced VPGs may be lost, weakened, or modified by the MIC of NaOH. Nevertheless, Limulus amoebocyte lysate assay revealed that there is no significant difference in endotoxic activity between the NaOH-induced VPGs and wild-type bacterial cells. Macrophages exposed to the NaOH-induced VPGs at 0.5 × 106 CFU/mL showed cell viability of 97.9%, however, the MIC of NaOH did not reduce the cytotoxic effect of wild-type bacterial cells. Like Escherichia coli LPS, the NaOH-induced VPGs are an excellent activator of pro-inflammatory cytokines (IL-1β and iNOS, anti-inflammatory cytokine (IL-10, and dual activities (IL-6 in the stimulated macrophage cells. On the other hand, the induction of TNF-α mRNA was remarkable in the macrophages exposed with wild-type cells. Scanning

  2. Andrographolide Restores Steroid Sensitivity To Block Lipopolysaccharide/IFN-γ-Induced IL-27 and Airway Hyperresponsiveness in Mice.

    Science.gov (United States)

    Liao, Wupeng; Tan, W S Daniel; Wong, W S Fred

    2016-06-01

    LPS and IFN-γ alone or in combination have been implicated in the development of steroid resistance. Combined LPS/IFN-γ strongly upregulates IL-27 production, which has been linked to steroid-resistant airway hyperresponsiveness (AHR). Andrographolide, a bioactive molecule isolated from the plant Andrographis paniculata, has demonstrated anti-inflammatory and antioxidant properties. The present study investigated whether andrographolide could restore steroid sensitivity to block LPS/IFN-γ-induced IL-27 production and AHR via its antioxidative property. The mouse macrophage cell line Raw 264.7, mouse primary lung monocytes/macrophages, and BALB/c mice were treated with LPS/IFN-γ, in the presence and absence of dexamethasone and/or andrographolide. Levels of IL-27 in vitro and in vivo were examined and mouse AHR was assessed. Dexamethasone alone failed to inhibit LPS/IFN-γ-induced IL-27 production and AHR in mice. Andrographolide significantly restored the suppressive effect of dexamethasone on LPS/IFN-γ-induced IL-27 mRNA and protein levels in the macrophage cell line and primary lung monocytes/macrophages, mouse bronchoalveolar lavage fluid and lung tissues, and AHR in mice. LPS/IFN-γ markedly reduced the nuclear level of histone deacetylase (HDAC)2, an essential epigenetic enzyme that mediates steroid anti-inflammatory action. LPS/IFN-γ also decreased total HDAC activity but increased the total histone acetyltransferase/HDAC activity ratio in mouse lungs. Andrographolide significantly restored nuclear HDAC2 protein levels and total HDAC activity, and it diminished the total histone acetyltransferase/HDAC activity ratio in mouse lungs exposed to LPS/IFN-γ, possibly via suppression of PI3K/Akt/HDAC2 phosphorylation, and upregulation of the antioxidant transcription factor NF erythroid-2-related factor 2 level and DNA binding activity. Our data suggest that andrographolide may have therapeutic value in resensitizing steroid action in respiratory disorders

  3. In situ and real-time small-angle neutron scattering studies of living anionic polymerization process and polymerization-induced self-assembly of block copolymers

    International Nuclear Information System (INIS)

    Tanaka, H.; Yamauchi, K.; Hasegawa, H.; Miyamoto, N.; Koizumi, S.; Hashimoto, T.

    2006-01-01

    We have studied a simultaneous living anionic polymerization process of isoprene and deuterated styrene in deuterated benzene with sec-buthyl lithium as an initiator into polyisoprene-block-poly(styrene-d 8 ) and the polymerization-induced self-assembling process. This polymerization-induced self-assembling process was directly observed by an in situ and real-time small-angle neutron scattering (SANS) experiment. The time-resolved SANS studies enabled us to explore a time evolution of hierarchical structures induced by a time evolution of the primary structure (linear sequential connection of two monomers)

  4. Anisotropic chemical strain in cubic ceria due to oxygen-vacancy-induced elastic dipoles.

    Science.gov (United States)

    Das, Tridip; Nicholas, Jason D; Sheldon, Brian W; Qi, Yue

    2018-06-06

    Accurate characterization of chemical strain is required to study a broad range of chemical-mechanical coupling phenomena. One of the most studied mechano-chemically active oxides, nonstoichiometric ceria (CeO2-δ), has only been described by a scalar chemical strain assuming isotropic deformation. However, combined density functional theory (DFT) calculations and elastic dipole tensor theory reveal that both the short-range bond distortions surrounding an oxygen-vacancy and the long-range chemical strain are anisotropic in cubic CeO2-δ. The origin of this anisotropy is the charge disproportionation between the four cerium atoms around each oxygen-vacancy (two become Ce3+ and two become Ce4+) when a neutral oxygen-vacancy is formed. Around the oxygen-vacancy, six of the Ce3+-O bonds elongate, one of the Ce3+-O bond shorten, and all seven of the Ce4+-O bonds shorten. Further, the average and maximum chemical strain values obtained through tensor analysis successfully bound the various experimental data. Lastly, the anisotropic, oxygen-vacancy-elastic-dipole induced chemical strain is polarizable, which provides a physical model for the giant electrostriction recently discovered in doped and non-doped CeO2-δ. Together, this work highlights the need to consider anisotropic tensors when calculating the chemical strain induced by dilute point defects in all materials, regardless of their symmetry.

  5. Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

    Science.gov (United States)

    Chen, Louise; Sloey, Christopher; Zhang, Zhongqi; Bondarenko, Pavel V; Kim, Hyojin; Ren, Da; Kanapuram, Sekhar

    2015-02-01

    Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. Coal structure and reactivity changes induced by chemical demineralisation

    Energy Technology Data Exchange (ETDEWEB)

    Rubiera, F.; Arenillas, A.; Pevida, C.; Garcia, R.; Pis, J.J. [Department of Energy and Environment, Instituto Nacional del Carbon, CSIC, Apartado 73, 33080 Oviedo (Spain); Steel, K.M.; Patrick, J.W. [Fuel Technology Group, School of Chemical, Environmental and Mining Engineering, Nottingham University, University Park, NG7 2RD Nottingham (United Kingdom)

    2002-12-01

    The aim of this work was to determine the influence that an advanced demineralisation procedure has on the combustion characteristics of coal. A high-volatile bituminous coal with 6.2% ash content was treated in a mixture of hydrofluoric and fluorosilicic acids (HF/H{sub 2}SiF{sub 6}). Nitric acid was used either as a pretreatment, or as a washing stage after HF/H{sub 2}SiF{sub 6} demineralisation, with an ash content as low as 0.3% being attained in the latter case. The structural changes produced by the chemical treatment were evaluated by comparison of the FTIR spectra of the raw and treated coal samples. The devolatilisation and combustibility behaviour of the samples was studied by using a thermobalance coupled to a mass spectrometer (TGA-MS) for evolved gas analysis. The combustibility characteristics of the cleaned samples were clearly improved, there being a decrease in SO{sub 2} emissions.

  7. Plume-induced dynamic instabilities near cratonic blocks: Implications for P-T-t paths and metallogeny

    NARCIS (Netherlands)

    Guillou-Frottier, L.; Burov, E.; Cloetingh, S.; Le Goff, E.; Deschamps, Y.; Huet, B.; Bouchot, V.

    2012-01-01

    Plume head - lithosphere interactions around cratonic blocks result in thermo-mechanical disturbances that lead to heating and burial phases of crustal rocks. We present results from numerical models of plume head - cratonic blocks interactions where a free upper surface condition and realistic

  8. Methyl chloride via oxyhydrochlorination of methane: A building block for chemicals and fuels from natural gas. Environmental assessment

    International Nuclear Information System (INIS)

    1996-09-01

    DOE's natural gas mission, in partnership with its stakeholders, is to undertake and promote activities to maximize the Nation's ability to supply, transport, and use natural gas to encourage economic growth, enhance energy interests security, and improve the environment. In implementing this mission, DOE has been involved in promoting domestic natural gas as a clean, abundant, and reliable source of energy. In particular, DOE is interested in technologies capable of converting natural gas to other valuable resources, such as transportation fuels, hydrogen, and premium chemicals. The purpose of the proposed action is to further examine the potential of one such technology for natural gas conversion. Over the past five years, DOE's Pittsburgh Energy Technology Center has supported a research program to determine the feasibility of producing methyl chloride (CH 3 Cl), a key ingredient used in the silicone industry, directly from methane (the primary component of natural gas) via an oxyhydrochlorination (OHC) process. As a result of this research program the OHC process is now ready for further development. The proposed action would advance the OHC natural gas conversion technology to an integrated engineering-scale process at the Dow Corning plant in Carrollton, Kentucky

  9. Suppressive effects of coffee on the SOS responses induced by UV and chemical mutagens

    International Nuclear Information System (INIS)

    Obana, Hirotaka; Nakamura, Sei-ichi; Tanaka, Ryou-ichi

    1986-01-01

    SOS-inducing activity of UV or chemical mutagens was strongly suppressed by instant coffee in Salmonella typhimurium TA1535/pSK1002. As decaffeinated instant coffee showed a similarly strong suppressive effect, it would seem that caffeine, a known inhibitor of SOS responses, is not responsible for the effect observed. The suppression was also shown by freshly brewed coffee extracts. However, the suppression was absent in green coffee-bean extracts. These results suggest that coffee contains some substance(s) which, apart from caffeine, suppresses SOS-inducing activity of UV or chemical mutagens and that the suppressive substance(s) are produced by roasting coffee beans. (Auth.)

  10. Block copolymer membranes for aqueous solution applications

    KAUST Repository

    Nunes, Suzana Pereira

    2016-03-22

    Block copolymers are known for their intricate morphology. We review the state of the art of block copolymer membranes and discuss perspectives in this field. The main focus is on pore morphology tuning with a short introduction on non-porous membranes. The two main strategies for pore formation in block copolymer membranes are (i) film casting and selective block sacrifice and (ii) self-assembly and non-solvent induced phase separation (SNIPS). Different fundamental aspects involved in the manufacture of block copolymer membranes are considered, including factors affecting the equilibrium morphology in solid films, self-assembly of copolymer in solutions and macrophase separation by solvent-non-solvent exchange. Different mechanisms are proposed for different depths of the SNIPS membrane. Block copolymer membranes can be prepared with much narrower pore size distribution than homopolymer membranes. Open questions and indications of what we consider the next development steps are finally discussed. They include the synthesis and application of new copolymers and specific functionalization, adding characteristics to respond to stimuli and chemical environment, polymerization-induced phase separation, and the manufacture of organic-inorganic hybrids.

  11. Block copolymer membranes for aqueous solution applications

    KAUST Repository

    Nunes, Suzana Pereira

    2016-01-01

    Block copolymers are known for their intricate morphology. We review the state of the art of block copolymer membranes and discuss perspectives in this field. The main focus is on pore morphology tuning with a short introduction on non-porous membranes. The two main strategies for pore formation in block copolymer membranes are (i) film casting and selective block sacrifice and (ii) self-assembly and non-solvent induced phase separation (SNIPS). Different fundamental aspects involved in the manufacture of block copolymer membranes are considered, including factors affecting the equilibrium morphology in solid films, self-assembly of copolymer in solutions and macrophase separation by solvent-non-solvent exchange. Different mechanisms are proposed for different depths of the SNIPS membrane. Block copolymer membranes can be prepared with much narrower pore size distribution than homopolymer membranes. Open questions and indications of what we consider the next development steps are finally discussed. They include the synthesis and application of new copolymers and specific functionalization, adding characteristics to respond to stimuli and chemical environment, polymerization-induced phase separation, and the manufacture of organic-inorganic hybrids.

  12. Radiation chemically induced telomerization of ethylene with selected telogens

    International Nuclear Information System (INIS)

    Wachtendunk, H.J. von.

    1975-01-01

    The suitability of different compounds for the use as telogenes in the telomerization of ethylene has been studied. In all cases the reactions are initiated by the γ-radiation of a 60 Co-source. Temperature programed gas chromatography has proved to be an adequate method of analysis. In the teleomerization process with ethylene also methane tri carboxylic acid tri-ethylene ester (MTE), ortho-formic acid tri-ethylene ester (o-ASE), formic acid, bromium cyane, chlorine cyane and dicyane have been used. The telomerization of MTE and ethylene has been performed successfully with a high yield. The dependence of the reaction on temperature, pressure, radiation dose has been studied as well as the influence of a solvent (acetonitrile). In the attempt to telomerize ortho-formic acid tri-ethylene ester only high molecular weight solid product could be isolated. No interpretable results could be obtained for the telomerization of formic acid with ethylene. In the case of the radiation induced telomerization of chlorine cyane or di-cyane with ethylene in the gas phase, no reaction products could be found. No telomerization between di-cyane and ethylene has been observed even when palladium (II)-cyanide is used as a catalyst of after cocatalys is with triphenyl-phosphile in acetonitrile. (orig./HK) [de

  13. Radiation-induced oxidative chemical changes in dehydrated egg products

    International Nuclear Information System (INIS)

    Katusin-Rasem, B.; Mihaljevic, B.; Razem, D.

    1992-01-01

    Radiation-induced buildup of lipid hydroperoxides (LOOH) and destruction of carotenoids were followed in whole egg powder and egg yolk powder as functions of dose, dose rate, and the presence of oxygen. In the absence of air the formation of LOOH was limited by the available oxygen, while destruction of carotenoids progressed linearly with dose; neither process depended on the dose rate. In the presence of air, the accumulation of LOOH and the destruction of carotenoids were strongly coupled and inversely proportional to the dose rate. The induction dose of 2.5 kGy was observed in air in both whole egg powder and egg yolk powder, independent of the dose rate. The practical consequence is that radiation decontamination can be carried out in the presence of air at the highest available dose rate by a dose not exceeding 2.5 kGy to avoid extensive degradation. This dose is adequate for a 10(3) reduction factor of Salmonella and well within the threshold dose of 3 kGy for organoleptic changes

  14. Transcriptome Sequencing of Chemically Induced Aquilaria sinensis to Identify Genes Related to Agarwood Formation.

    Science.gov (United States)

    Ye, Wei; Wu, Hongqing; He, Xin; Wang, Lei; Zhang, Weimin; Li, Haohua; Fan, Yunfei; Tan, Guohui; Liu, Taomei; Gao, Xiaoxia

    2016-01-01

    Agarwood is a traditional Chinese medicine used as a clinical sedative, carminative, and antiemetic drug. Agarwood is formed in Aquilaria sinensis when A. sinensis trees are threatened by external physical, chemical injury or endophytic fungal irritation. However, the mechanism of agarwood formation via chemical induction remains unclear. In this study, we characterized the transcriptome of different parts of a chemically induced A. sinensis trunk sample with agarwood. The Illumina sequencing platform was used to identify the genes involved in agarwood formation. A five-year-old Aquilaria sinensis treated by formic acid was selected. The white wood part (B1 sample), the transition part between agarwood and white wood (W2 sample), the agarwood part (J3 sample), and the rotten wood part (F5 sample) were collected for transcriptome sequencing. Accordingly, 54,685,634 clean reads, which were assembled into 83,467 unigenes, were obtained with a Q20 value of 97.5%. A total of 50,565 unigenes were annotated using the Nr, Nt, SWISS-PROT, KEGG, COG, and GO databases. In particular, 171,331,352 unigenes were annotated by various pathways, including the sesquiterpenoid (ko00909) and plant-pathogen interaction (ko03040) pathways. These pathways were related to sesquiterpenoid biosynthesis and defensive responses to chemical stimulation. The transcriptome data of the different parts of the chemically induced A. sinensis trunk provide a rich source of materials for discovering and identifying the genes involved in sesquiterpenoid production and in defensive responses to chemical stimulation. This study is the first to use de novo sequencing and transcriptome assembly for different parts of chemically induced A. sinensis. Results demonstrate that the sesquiterpenoid biosynthesis pathway and WRKY transcription factor play important roles in agarwood formation via chemical induction. The comparative analysis of the transcriptome data of agarwood and A. sinensis lays the foundation

  15. Effect of genes controlling radiation sensitivity on chemically induced mutations in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Prakash, L.

    1976-01-01

    The effect of 16 different genes (rad) conferring radiation sensitivity on chemically induced reversion in the yeast Saccharomyces cerevisiae was determined. The site of reversion used was a well-defined chain initiation mutant mapping in the structural gene coding for iso-1-cytochrome c. High doses of EMS and HNO 2 resulted in decreased reversion of cyc1-131 in rad6, rad9 and rad15 strains compared to the normal RAD + strains. In addition, rad52 greatly decreased EMS reversion of cyc1-131 but had no effect on HNO 2 -induced reversion; rad18, on the other hand, increased HNO 2 -induced reversion but did not alter EMS-induced reversion. When NQO was used as the mutagen, every rad gene tested, except for rad18, had an effect on reversion; rad6, rad9, rad15, rad17, rad18, rad22, rev1, rev2, and rev3 lowered NQO reversion while rad1, rad2, rad3, rad4, rad10, rad12, and rad16 increased it compared to the RAD + strain. The effect of rad genes on chemical mutagenesis is discussed in terms of their effect on uv mutagenesis. It is concluded that although the nature of the repair pathways may differ for uv- and chemically-induced mutations in yeast, a functional repair system is required for the induction of mutation by the chemical agents NQO, EMS, and HNO 2

  16. Supradural inflammatory soup in awake and freely moving rats induces facial allodynia that is blocked by putative immune modulators.

    Science.gov (United States)

    Wieseler, Julie; Ellis, Amanda; McFadden, Andrew; Stone, Kendra; Brown, Kimberley; Cady, Sara; Bastos, Leandro F; Sprunger, David; Rezvani, Niloofar; Johnson, Kirk; Rice, Kenner C; Maier, Steven F; Watkins, Linda R

    2017-06-01

    Facial allodynia is a migraine symptom that is generally considered to represent a pivotal point in migraine progression. Treatment before development of facial allodynia tends to be more successful than treatment afterwards. As such, understanding the underlying mechanisms of facial allodynia may lead to a better understanding of the mechanisms underlying migraine. Migraine facial allodynia is modeled by applying inflammatory soup (histamine, bradykinin, serotonin, prostaglandin E2) over the dura. Whether glial and/or immune activation contributes to such pain is unknown. Here we tested if trigeminal nucleus caudalis (Sp5C) glial and/or immune cells are activated following supradural inflammatory soup, and if putative glial/immune inhibitors suppress the consequent facial allodynia. Inflammatory soup was administered via bilateral indwelling supradural catheters in freely moving rats, inducing robust and reliable facial allodynia. Gene expression for microglial/macrophage activation markers, interleukin-1β, and tumor necrosis factor-α increased following inflammatory soup along with robust expression of facial allodynia. This provided the basis for pursuing studies of the behavioral effects of 3 diverse immunomodulatory drugs on facial allodynia. Pretreatment with either of two compounds broadly used as putative glial/immune inhibitors (minocycline, ibudilast) prevented the development of facial allodynia, as did treatment after supradural inflammatory soup but prior to the expression of facial allodynia. Lastly, the toll-like receptor 4 (TLR4) antagonist (+)-naltrexone likewise blocked development of facial allodynia after supradural inflammatory soup. Taken together, these exploratory data support that activated glia and/or immune cells may drive the development of facial allodynia in response to supradural inflammatory soup in unanesthetized male rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

    Directory of Open Access Journals (Sweden)

    Yoshiki Shionoya

    Full Text Available This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB in a canine model. This study involved two experiments-in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow.

  18. Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

    Science.gov (United States)

    Sunada, Katsuhisa; Shigeno, Keiji; Nakada, Akira; Honda, Michitaka; Nakamura, Tatsuo

    2017-01-01

    This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow. PMID:29220373

  19. Antibiotic-induced immediate type hypersensitivity is a risk factor for positive allergy skin tests for neuromuscular blocking agents.

    Science.gov (United States)

    Hagau, Natalia; Gherman, Nadia; Cocis, Mihaela; Petrisor, Cristina

    2016-01-01

    Skin tests for neuromuscular blocking agents (NMBAs) are not currently recommended for the general population undergoing general anaesthesia. In a previous study we have reported a high incidence of positive allergy tests for NMBAs in patients with a positive history of non-anaesthetic drug allergy, a larger prospective study being needed to confirm those preliminary results. The objective of this study was to compare the skin tests results for patients with a positive history of antibiotic-induced immediate type hypersensitivity reactions to those of controls without drug allergies. Ninety eight patients with previous antibiotic hypersensitivity and 72 controls were prospectively included. Skin tests were performed for atracurium, pancuronium, rocuronium, and suxamethonium. We found 65 positive skin tests from the 392 tests performed in patients with a positive history of antibiotic hypersensitivity (1 6.58%) and 23 positive skin tests from the 288 performed in controls (7.98%), the two incidences showing significant statistical difference (p = 0.0011). The relative risk for having a positive skin test for NMBAs for patients versus controls was 1.77 (1.15-2.76). For atracurium, skin tests were more often positive in patients with a positive history of antibiotic hypersensitivity versus controls (p = 0.02). For pancuronium, rocuronium and suxamethonium the statistical difference was not attained (p-values 0.08 for pancuronium, 0.23 for rocuronium, and 0.26 for suxamethonium). Patients with a positive history of antibiotic hypersensitivity seem to have a higher incidence of positive skin tests for NMBAs. They might represent a group at higher risk for developing intraoperative anaphylaxis compared to the general population. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  20. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsuneyama, Koichi [Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Sugitani, Toyama 930‐0194 (Japan); Endo, Shinya [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsukui, Tohru [Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka 350‐1241 (Japan); Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Yokoi, Tsuyoshi, E-mail: tyokoi@p.kanazawa-u.ac.jp [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan)

    2012-10-01

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  1. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    International Nuclear Information System (INIS)

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori; Tsuneyama, Koichi; Endo, Shinya; Tsukui, Tohru; Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2012-01-01

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  2. Force-induced chemical reactions on the metal centre in a single metalloprotein molecule

    Science.gov (United States)

    Zheng, Peng; Arantes, Guilherme M.; Field, Martin J.; Li, Hongbin

    2015-01-01

    Metalloproteins play indispensable roles in biology owing to the versatile chemical reactivity of metal centres. However, studying their reactivity in many metalloproteins is challenging, as protein three-dimensional structure encloses labile metal centres, thus limiting their access to reactants and impeding direct measurements. Here we demonstrate the use of single-molecule atomic force microscopy to induce partial unfolding to expose metal centres in metalloproteins to aqueous solution, thus allowing for studying their chemical reactivity in aqueous solution for the first time. As a proof-of-principle, we demonstrate two chemical reactions for the FeS4 centre in rubredoxin: electrophilic protonation and nucleophilic ligand substitution. Our results show that protonation and ligand substitution result in mechanical destabilization of the FeS4 centre. Quantum chemical calculations corroborated experimental results and revealed detailed reaction mechanisms. We anticipate that this novel approach will provide insights into chemical reactivity of metal centres in metalloproteins under biologically more relevant conditions. PMID:26108369

  3. Chemical inducible promotor used to obtain transgenic plants with a silent marker

    Science.gov (United States)

    Chua, Nam-Hai; Aoyama, Takashi

    2000-01-01

    A chemically inducible promoter is described which may be used to transform plants with genes which are easily regulatable by adding plants or plant cells to a medium containing an inducer of the promoter or by removing the plants or plant cells from such medium. The promoter described is one which is inducible by a glucocorticoid which is not endogenous to plants. Such promoters may be used with a variety of genes such as ipt or knotted1 to induce shoot formation in the presence of a glucocorticoid. The promoter may also be used with antibiotic or herbicide resistance genes which are then regulatable by the presence or absence of inducer rather than being constitutive. Other examples of genes which may be placed under the control of the inducible promoter are also presented.

  4. Chemical inducible promoter used to obtain transgenic plants with a silent marker

    Science.gov (United States)

    Aoyama, Takashi; Zuo, Jianru; Chua, Nam-Hai

    2004-08-31

    A chemically inducible promoter is described that may be used to transform plants, including tobacco and lettuce, with genes which are easily regulatable by adding the plants or plant cells to a medium containing an inducer of the promoter or by removing the plants or plant cells from such medium. The promoter described is one that is inducible by a glucocorticoid which is not endogenous to plants. Such promoters may be used with a variety of genes such as ipt or knotted1 to induce shoot formation in the presence of a glucocorticoid. The promoter may also be used with antibiotic or herbicide resistance genes which are then regulatable by the presence or absence of inducer rather than being constitutive. Other examples of genes which may be placed under the control of the inducible promoter are also presented.

  5. Direct Reprogramming of Fibroblasts via a Chemically Induced XEN-like State.

    Science.gov (United States)

    Li, Xiang; Liu, Defang; Ma, Yantao; Du, Xiaomin; Jing, Junzhan; Wang, Lipeng; Xie, Bingqing; Sun, Da; Sun, Shaoqiang; Jin, Xueqin; Zhang, Xu; Zhao, Ting; Guan, Jingyang; Yi, Zexuan; Lai, Weifeng; Zheng, Ping; Huang, Zhuo; Chang, Yanzhong; Chai, Zhen; Xu, Jun; Deng, Hongkui

    2017-08-03

    Direct lineage reprogramming, including with small molecules, has emerged as a promising approach for generating desired cell types. We recently found that during chemical induction of induced pluripotent stem cells (iPSCs) from mouse fibroblasts, cells pass through an extra-embryonic endoderm (XEN)-like state. Here, we show that these chemically induced XEN-like cells can also be induced to directly reprogram into functional neurons, bypassing the pluripotent state. The induced neurons possess neuron-specific expression profiles, form functional synapses in culture, and further mature after transplantation into the adult mouse brain. Using similar principles, we were also able to induce hepatocyte-like cells from the XEN-like cells. Cells in the induced XEN-like state were readily expandable over at least 20 passages and retained genome stability and lineage specification potential. Our study therefore establishes a multifunctional route for chemical lineage reprogramming and may provide a platform for generating a diverse range of cell types via application of this expandable XEN-like state. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Disparate roles of zinc in chemical hypoxia-induced neuronal death

    Directory of Open Access Journals (Sweden)

    Sujeong eKim

    2015-01-01

    Full Text Available Accumulating evidence has provided a causative role of zinc (Zn2+ in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2, deferoxamine (3 mM DFX, and sodium azide (2 mM NaN3, we evaluated whether Zn2+ is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn2+ release/accumulation in viable neurons. The immediate addition of the Zn2+ chelator, CaEDTA or N,N,N’N’-tetrakis-(2-pyridylmethyl ethylenediamine (TPEN, prevented the intracellular Zn2+ load and CoCl2-induced neuronal death, but neither 3-hour-later Zn2+ chelation nor a non-Zn2+ chelator ZnEDTA (1 mM demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn2+ rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn2+ release/accumulation is common during chemical hypoxia, Zn2+ might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

  7. Disparate roles of zinc in chemical hypoxia-induced neuronal death.

    Science.gov (United States)

    Kim, Sujeong; Seo, Jung-Woo; Oh, Shin Bi; Kim, So Hee; Kim, Inki; Suh, Nayoung; Lee, Joo-Yong

    2015-01-01

    Accumulating evidence has provided a causative role of zinc (Zn(2+)) in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2), deferoxamine (3 mM DFX), and sodium azide (2 mM NaN3), we evaluated whether Zn(2+) is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn(2+) release/accumulation in viable neurons. The immediate addition of the Zn(2+) chelator, CaEDTA or N,N,N'N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), prevented the intracellular Zn(2+) load and CoCl2-induced neuronal death, but neither 3 hour later Zn(2+) chelation nor a non-Zn(2+) chelator ZnEDTA (1 mM) demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn(2+) rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn(2+) release/accumulation is common during chemical hypoxia, Zn(2+) might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

  8. Nutrient Induced Type 2 and Chemical Induced Type 1 Experimental Diabetes Differently Modulate Gastric GLP-1 Receptor Expression

    Directory of Open Access Journals (Sweden)

    Olga Bloch

    2015-01-01

    Full Text Available T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced in Psammomys obesus (PO by high-energy (HE diet and by streptozotocin (STZ in Sprague Dawly (SD rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis.

  9. Systematic trends in photonic reagent induced reactions in a homologous chemical family.

    Science.gov (United States)

    Tibbetts, Katharine Moore; Xing, Xi; Rabitz, Herschel

    2013-08-29

    The growing use of ultrafast laser pulses to induce chemical reactions prompts consideration of these pulses as "photonic reagents" in analogy to chemical reagents. This work explores the prospect that photonic reagents may affect systematic trends in dissociative ionization reactions of a homologous family of halomethanes, much as systematic outcomes are often observed for reactions between homologous families of chemical reagents and chemical substrates. The experiments in this work with photonic reagents of varying pulse energy and linear spectral chirp reveal systematic correlations between observable ion yields and the following set of natural variables describing the substrate molecules: the ionization energy of the parent molecule, the appearance energy of each fragment ion, and the relative strength of carbon-halogen bonds in molecules containing two different halogens. The results suggest that reactions induced by photonic reagents exhibit systematic behavior analogous to that observed in reactions driven by chemical reagents, which provides a basis to consider empirical "rules" for predicting the outcomes of photonic reagent induced reactions.

  10. Reversal of rocuronium-induced neuromuscular block by sugammadex is independent of renal perfusion in anesthetized cats

    NARCIS (Netherlands)

    Staals, L.M.; Boer, H.D. de; Egmond, J. van; Hope, F.; Pol, F.M. van de; Bom, A.H.; Driessen, J.J.; Booij, L.H.D.J.

    2011-01-01

    PURPOSE: Sugammadex is a selective relaxant binding agent designed to encapsulate the aminosteroidal neuromuscular blocking agent rocuronium, thereby reversing its effect. Both sugammadex and the sugammadex-rocuronium complex are eliminated by the kidneys. This study investigated the effect of

  11. Biomarkers of DNA and cytogenetic damages induced by environmental chemicals or radiation

    International Nuclear Information System (INIS)

    1999-01-01

    This paper presents and discusses results from the studies on various biomarkers of the DNA and cytogenetic damages induced by environmental chemicals or radiation. Results of the biomonitoring studies have shown that particularly in the condition of Poland, health hazard from radiation exposure is overestimated in contradistinction to the environmental hazard

  12. A proposal for study of ion-beam induced chemical reactions using JAERI tandem accelerator

    International Nuclear Information System (INIS)

    1985-11-01

    Problems in ion-beam induced chemical reactions using JAERI Tandem Accelerator were discussed. Research philosophy, some proposed experiments which are based on measurements during ion-beam bombardment, and main features of the experimental apparatus are briefly described in this report. (author)

  13. Epidural block

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000484.htm Epidural block - pregnancy To use the sharing features on this page, please enable JavaScript. An epidural block is a numbing medicine given by injection (shot) ...

  14. Optimization of microwave-induced chemical etching for rapid development of neutron-induced recoil tracks in CR-39 detectors

    International Nuclear Information System (INIS)

    Sahoo, G.S.; Tripathy, S.P.; Bandyopadhyay, T.

    2014-01-01

    A systematic investigation is carried out to optimize the recently established microwave-induced chemical etching (MICE) parameters for rapid development of neutron-induced recoil tracks in CR-39 detectors. Several combinations of all available microwave powers with different etching durations were analysed to determine the most suitable etching condition. The etching duration was found to reduce with increasing microwave power and the tracks were observed at about 18, 15, 12, and 6 min for 300, 450, 600 and 900 W of microwave powers respectively compared to a few hours in chemical etching (CE) method. However, for complete development of tracks the etching duration of 30, 40, 50 and 60 min were found to be suitable for the microwave powers of 900, 600, 450 and 300 W, respectively. Temperature profiles of the etchant for all the available microwave powers at different etching durations were generated to regulate the etching process in a controlled manner. The bulk etch rates at different microwave powers were determined by 2 methods, viz., gravimetric and removed thickness methods. A logarithmic expression was used to fit the variation of bulk etch rate with microwave power. Neutron detection efficiencies were obtained for all the cases and the results on track parameters obtained with MICE technique were compared with those obtained from another detector processed with chemical etching. - Highlights: • Microwave-induced chemical etching method is optimized for rapid development of recoil tracks due to neutrons in CR-39 detector. • Several combinations of microwave powers and etching durations are investigated to standardize the suitable etching condition. • Bulk-etch rates are determined for all microwave powers by two different methods, viz. gravimetric and removed thickness method. • The method is found to be simple, effective and much faster compared to conventional chemical etching

  15. Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolimod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation

    International Nuclear Information System (INIS)

    Yagi, Yukihiro; Nakamura, Yuji; Kitahara, Ken; Harada, Takuma; Kato, Kazuhiko; Ninomiya, Tomohisa; Cao, Xin; Ohara, Hiroshi; Izumi-Nakaseko, Hiroko; Suzuki, Kokichi; Ando, Kentaro

    2014-01-01

    Fingolimod, a sphingosine 1-phosphate (S1P) receptor subtype 1, 3, 4 and 5 modulator, has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular conduction block and/or QT-interval prolongation have been reported in some patients after the first dose. In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events. Fingolimod (0.01 and 0.1 mg/kg) or siponimod (0.001 and 0.01 mg/kg) was intravenously infused over 10 min to the halothane-anaesthetized guinea pigs (n = 4), whereas the effects of fingolimod (1 μmol/L) and siponimod (1 μmol/L) on hERG current were examined (n = 3). The high doses of fingolimod and siponimod induced atrioventricular conduction block, whereas the low dose of siponimod prolonged PR interval, which was not observed by that of fingolimod. The high dose of fingolimod prolonged QT interval, which was not observed by either dose of siponimod. Meanwhile, fingolimod significantly inhibited hERG current, which was not observed by siponimod. These results suggest that S1P receptor subtype 1 in the heart could be one of the candidates for fingolimod- and siponimod-induced atrioventricular conduction block since S1P receptor subtype 5 is localized at the brain, and that direct I Kr inhibition may play a key role in fingolimod-induced QT-interval prolongation. - Highlights: • Fingolimod and siponimod are S1P 1,3,4,5 and S1P 1,5 receptor modulators, respectively. • Fingolimod and siponimod induced AV block in the halothane-anesthetized guinea pigs. • S1P 1 in the hearts may be the target of fingolimod- and siponimod-induced AV block. • Fingolimod directly inhibited hERG current, which was not observed by

  16. Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolimod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation

    Energy Technology Data Exchange (ETDEWEB)

    Yagi, Yukihiro [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Nakamura, Yuji [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Kitahara, Ken [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Division of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143–8541 (Japan); Harada, Takuma [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Kato, Kazuhiko; Ninomiya, Tomohisa [Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Cao, Xin [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Ohara, Hiroshi [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Division of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143–8541 (Japan); Izumi-Nakaseko, Hiroko [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Suzuki, Kokichi [Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Ando, Kentaro [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); and others

    2014-11-15

    Fingolimod, a sphingosine 1-phosphate (S1P) receptor subtype 1, 3, 4 and 5 modulator, has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular conduction block and/or QT-interval prolongation have been reported in some patients after the first dose. In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events. Fingolimod (0.01 and 0.1 mg/kg) or siponimod (0.001 and 0.01 mg/kg) was intravenously infused over 10 min to the halothane-anaesthetized guinea pigs (n = 4), whereas the effects of fingolimod (1 μmol/L) and siponimod (1 μmol/L) on hERG current were examined (n = 3). The high doses of fingolimod and siponimod induced atrioventricular conduction block, whereas the low dose of siponimod prolonged PR interval, which was not observed by that of fingolimod. The high dose of fingolimod prolonged QT interval, which was not observed by either dose of siponimod. Meanwhile, fingolimod significantly inhibited hERG current, which was not observed by siponimod. These results suggest that S1P receptor subtype 1 in the heart could be one of the candidates for fingolimod- and siponimod-induced atrioventricular conduction block since S1P receptor subtype 5 is localized at the brain, and that direct I{sub Kr} inhibition may play a key role in fingolimod-induced QT-interval prolongation. - Highlights: • Fingolimod and siponimod are S1P{sub 1,3,4,5} and S1P{sub 1,5} receptor modulators, respectively. • Fingolimod and siponimod induced AV block in the halothane-anesthetized guinea pigs. • S1P{sub 1} in the hearts may be the target of fingolimod- and siponimod-induced AV block. • Fingolimod directly inhibited hERG current, which was not

  17. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  18. Chemically induced transition phenomena in polyurethanes as seen from generalized mode Grueneisen parameters

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, U; Philipp, M; Bactavatchalou, R; Sanctuary, R; Baller, J; Zielinski, B; Krueger, J K [Laboratoire de Physique des Materiaux, Universite du Luxembourg, 162A, Avenue de la Faiencerie, L-1115 (Luxembourg); Possart, W; Alnot, P [Laboratoire Europeen de Recherche, Universitaire Saarland-Lorraine (Luxembourg)], E-mail: ulrich.mueller@uni.lu

    2008-05-21

    Many phenomenological properties of reactive polymers like polyurethanes increase or decrease continuously in the course of the curing process before saturating at the end of the chemical reaction. This holds true for instance for the mass density, the refractive index, the chemical turnover and the hypersonic properties. The reason for this monotone behaviour is that the chemical reaction behaves like a continuous succession of irreversible phase transitions. These transitions are superposed by the sol-gel transition and possibly by the chemically induced glass transition, with the drawback that the latter two highlighted transitions are often hidden by the underlying curing process. In this work we propose generalized mode Grueneisen parameters as an alternative probe for elucidating the polymerization process itself and the closely related transition phenomena. As a model system we use polyurethane composed of a diisocyanate and varying ratios of difunctional and trifunctional alcohols.

  19. Inhibition of Neoplastic Transformation and Chemically-Induced Skin Hyperplasia in Mice by Traditional Chinese Medicinal Formula Si-Wu-Tang

    Directory of Open Access Journals (Sweden)

    Mandy M. Liu

    2017-03-01

    Full Text Available Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT, comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women’s diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT’s activity of cancer prevention. In the Ames test, SWT demonstrated an antimutagenic activity against mutagenicity induced by the chemical carcinogen 7,12-dimethylbenz(aanthracene (DMBA. In JB6 P+ cells, a non-cancerous murine epidermal model for studying tumor promotion, SWT inhibited epidermal growth factor (EGF-induced neoplastic transformation. The luciferase reporter gene assays demonstrated that SWT suppressed EGF-induced AP-1 and TNF-α-induced NF-κB activation, which are essential factors involved in skin carcinogenesis. In a DMBA-induced skin hyperplasia assay in ‘Sensitivity to Carcinogenesis’ (SENCAR mice, both topical and oral SWT inhibited DMBA-induced epidermal hyperplasia, expression of the proliferation marker Proliferating cell nuclear antigen (PCNA, and H-ras mutations. These findings demonstrate, for the first time, that SWT prevents tumor promoter and chemical-induced carcinogenesis in vitro and in vivo, partly by inhibiting DNA damage and blocking the activation of AP-1 and NF-κB.

  20. The chemical cue tetrabromopyrrole from a biofilm bacterium induces settlement of multiple Caribbean corals.

    Science.gov (United States)

    Sneed, Jennifer M; Sharp, Koty H; Ritchie, Kimberly B; Paul, Valerie J

    2014-07-07

    Microbial biofilms induce larval settlement for some invertebrates, including corals; however, the chemical cues involved have rarely been identified. Here, we demonstrate the role of microbial biofilms in inducing larval settlement with the Caribbean coral Porites astreoides and report the first instance of a chemical cue isolated from a marine biofilm bacterium that induces complete settlement (attachment and metamorphosis) of Caribbean coral larvae. Larvae settled in response to natural biofilms, and the response was eliminated when biofilms were treated with antibiotics. A similar settlement response was elicited by monospecific biofilms of a single bacterial strain, Pseudoalteromonas sp. PS5, isolated from the surface biofilm of a crustose coralline alga. The activity of Pseudoalteromonas sp. PS5 was attributed to the production of a single compound, tetrabromopyrrole (TBP), which has been shown previously to induce metamorphosis without attachment in Pacific acroporid corals. In addition to inducing settlement of brooded larvae (P. astreoides), TBP also induced larval settlement for two broadcast-spawning species, Orbicella (formerly Montastraea) franksi and Acropora palmata, indicating that this compound may have widespread importance among Caribbean coral species. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  1. Redox Active Transition Metal ions Make Melanin Susceptible to Chemical Degradation Induced by Organic Peroxide.

    Science.gov (United States)

    Zadlo, Andrzej; Pilat, Anna; Sarna, Michal; Pawlak, Anna; Sarna, Tadeusz

    2017-12-01

    With aging, retinal pigment epithelium melanosomes, by fusion with the age pigment lipofuscin, form complex granules called melanolipofuscin. Lipofuscin granules may contain oxidized proteins and lipid hydroperoxides, which in melanolipofuscin could chemically modify melanin polymer, while transition metal ions present in melanin can accelerate such oxidative modifications. The aim of this research was to examine the effect of selected transition metal ions on melanin susceptibility to chemical modification induced by the water-soluble tert-butyl hydroperoxide used as an oxidizing agent. Synthetic melanin obtained by DOPA autooxidation and melanosomes isolated from bovine retinal pigment epithelium were analyzed. To monitor tert-butyl hydroperoxide-induced oxidative changes of DMa and BMs, electron paramagnetic resonance spectroscopy, UV-vis absorption spectroscopy, dynamic light scattering, atomic force microscopy and electron paramagnetic resonance oximetry were employed. These measurements revealed that both copper and iron ions accelerated chemical degradation induced by tert-butyl hydroperoxide, while zinc ions had no effect. Strong prooxidant action was detected only in the case of melanosomes and melanin degraded in the presence of iron. It can be postulated that similar chemical processes, if they occur in situ in melanolipofuscin granules of the human retinal pigment epithelium, would modify antioxidant properties of melanin and its reactivity.

  2. Strain-induced structural changes and chemical reactions. 1: Thermomechanical and kinetic models

    International Nuclear Information System (INIS)

    Levitas, V.I.; Nesterenko, V.F.; Meyers, M.A.

    1998-01-01

    Strain-induced chemical reactions were observed recently (Nesterenko et al) in experiments in the shear band in both Ti-Si and Nb-Si mixtures. Reactions can start in the solid state or after melting of at least one component. One of the aims is to find theoretically whether there are possible macroscopic mechanisms of mechanical intensification of the above and other chemical reactions due to plastic shear in the solid state. Continuum thermodynamical theory of structural changes with an athermal kinetics, which includes martensitic phase transformations, plastic strain-induced chemical reactions and polymorphic transformations, is developed at finite strains. The theory includes kinematics, criterion of structural change and extremum principle for determination of all unknown variable parameters for the case with neglected elastic strains. Thermodynamically consistent kinetic theory of thermally activated structural changes is suggested. The concept of the effective temperature is introduced which takes into account that temperature can vary significantly (on 1,000 K) during the chemical reactions under consideration. The theory will be applied in Part 2 of the paper for the description of chemical reactions in the shear band

  3. Overexpression of pig selenoprotein S blocks OTA-induced promotion of PCV2 replication by inhibiting oxidative stress and p38 phosphorylation in PK15 cells

    Science.gov (United States)

    Gan, Fang; Hu, Zhihua; Huang, Yu; Xue, Hongxia; Huang, Da; Qian, Gang; Hu, Junfa; Chen, Xingxiang; Wang, Tian; Huang, Kehe

    2016-01-01

    Porcine circovirus type 2 (PCV2) is the primary cause of porcine circovirus disease, and ochratoxin A (OTA)-induced oxidative stress promotes PCV2 replication. In humans, selenoprotein S (SelS) has antioxidant ability, but it is unclear whether SelS affects viral infection. Here, we stably transfected PK15 cells with pig pCDNA3.1-SelS to overexpress SelS. Selenium (Se) at 2 or 4 μM and SelS overexpression blocked the OTA-induced increases of PCV2 DNA copy number and infected cell numbers. SelS overexpression also increased glutathione (GSH), NF-E2-related factor 2 (Nrf2) mRNA, and γ-glutamyl-cysteine synthetase mRNA levels; decreased reactive oxygen species (ROS) levels; and inhibited p38 phosphorylation in PCV2-infected PK15 cells, regardless of OTA treatment. Buthionine sulfoximine reversed all of the above SelS-induced changes. siRNA-mediated SelS knockdown decreased Nrf2 mRNA and GSH levels, increased ROS levels, and promoted PCV2 replication in OTA-treated PK15 cells. These data indicate that pig SelS blocks OTA-induced promotion of PCV2 replication by inhibiting the oxidative stress and p38 phosphorylation in PK15 cells. PMID:26943035

  4. Systemic treatment with D-fenfluramine, but not sibutramine, blocks cue-induced reinstatement of food-seeking behavior in the rat.

    Science.gov (United States)

    Pratt, Wayne E; Ford, Ryan T

    2013-11-27

    Individuals struggling with obesity often have difficulty maintaining dietary regimens. One source of dietary relapse is the reinstatement of previous feeding behaviors following the presentation of cues indicating the availability of palatable but highly caloric food reward. The drugs fenfluramine and sibutramine have previously been prescribed because they enhance satiety mechanisms and decrease meal size. However, it is unclear whether these anorectic agents are also effective in blocking the cue-induced reinstatement of food-seeking behaviors. In these three experiments, we compared the effects of systemic treatment of d-fenfluramine (3mg/kg; N=10) and sibutramine (3mg/kg; N=11) with that of the D1 antagonist SCH 23390 (6μg/kg; N=11) at a dose that has previously been shown to attenuate cue-induced reinstatement. d-Fenfluramine treatment blocked the cue's ability to reinstate lever pressing as compared to the saline injection day. In contrast, sibutramine had no effect on cue-induced reinstatement; all animals reinstated their lever pressing during the first reinstatement test, and this was unaffected by sibutramine treatment. SCH 23390 treatment did not significantly reduce cue-induced reinstatement in this set of experiments. The results suggest that the motivational effects of d-fenfluramine is not limited to the promotion of satiety once a meal has been initiated, and demonstrate that some anorectic treatments may inhibit the effectiveness of conditioned cues to elicit relapse of food-seeking behavior. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Electrochemically induced chemical sensor properties in graphite screen-printed electrodes: The case of a chemical sensor for uranium

    International Nuclear Information System (INIS)

    Kostaki, Vasiliki T.; Florou, Ageliki B.; Prodromidis, Mamas I.

    2011-01-01

    Highlights: → Electrochemical treatment endows analytical characteristics to SPEs. → A sensitive chemical sensor for uranium is described. → Performance is due to a synergy between electrochemical treatment and ink's solvents. → The amount of the solvent controls the achievable sensitivity. - Abstract: We report for the first time on the possibility to develop chemical sensors based on electrochemically treated, non-modified, graphite screen-printed electrodes (SPEs). The applied galvanostatic treatment (5 μA for 6 min in 0.1 M H 2 SO 4 ) is demonstrated to be effective for the development of chemical sensors for the determination of uranium in aqueous solutions. A detailed study of the effect of various parameters related to the fabrication of SPEs on the performance of the resulting sensors along with some diagnostic experiments on conventional graphite electrodes showed that the inducible analytical characteristics are due to a synergy between electrochemical treatment and ink's solvents. Indeed, the amount of the latter onto the printed working layer controls the achievable sensitivity. The preconcentration of the analyte was performed in an electroless mode in an aqueous solutions of U(VI), pH 4.6, and then, the accumulated species was reduced by means of a differential pulse voltammetry scan in 0.1 M H 3 BO 3 , pH 3. Under selected experimental conditions, a linear calibration curve over the range 5 x 10 -9 to 10 -7 M U(VI) was constructed. The 3σ limit of detection at a preconcentration time of 30 min, and the relative standard deviation of the method were 4.5 x 10 -9 M U(VI) and >12% (n = 5, 5 x 10 -8 M U(VI)), respectively. The effect of potential interferences was also examined.

  6. Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Szepesi

    Full Text Available Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs, a family of extracellularly acting and Zn(2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.

  7. Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer

    Directory of Open Access Journals (Sweden)

    Kristine von Maltzan

    2016-02-01

    Full Text Available The Slug transcription factor plays an important role in ultraviolet radiation (UVR-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[α]anthracene application followed by 12-O-tetradecanoylphorbol-13-acetate (TPA treatment. TPA-induced transient elevation of Slug and Snail proteins in normal mouse epidermis and studies in Slug transgenic mice indicated that Slug modulates TPA-induced epidermal hyperplasia and cutaneous inflammation. Although Snail family factors have been linked to inflammation via interactions with the cyclooxygenase-2 (COX-2 pathway, a pathway that also plays an important role in skin carcinogenesis, transient TPA induction of Slug and Snail appeared unrelated to COX-2 expression. In cultured human keratinocytes, TPA induced Snail mRNA expression while suppressing Slug expression, and this differential regulation was due specifically to activation of the TPA receptor. These studies show that Slug and Snail exhibit similar patterns of expression during both UVR and chemical skin carcinogenesis, that Slug and Snail can be differentially regulated under some conditions and that in vitro findings may not recapitulate in vivo results.

  8. A key agonist-induced conformational change in the cannabinoid receptor CB1 is blocked by the allosteric ligand Org 27569.

    Science.gov (United States)

    Fay, Jonathan F; Farrens, David L

    2012-09-28

    Allosteric ligands that modulate how G protein-coupled receptors respond to traditional orthosteric drugs are an exciting and rapidly expanding field of pharmacology. An allosteric ligand for the cannabinoid receptor CB1, Org 27569, exhibits an intriguing effect; it increases agonist binding, yet blocks agonist-induced CB1 signaling. Here we explored the mechanism behind this behavior, using a site-directed fluorescence labeling approach. Our results show that Org 27569 blocks conformational changes in CB1 that accompany G protein binding and/or activation, and thus inhibit formation of a fully active CB1 structure. The underlying mechanism behind this behavior is that simultaneous binding of Org 27569 produces a unique agonist-bound conformation, one that may resemble an intermediate structure formed on the pathway to full receptor activation.

  9. Chemical leucoderma induced by ear-ring stoppers made of polyvinyl chloride

    Directory of Open Access Journals (Sweden)

    Reena Sharma

    2012-01-01

    Full Text Available We report a case of chemical leucoderma (CL in a 15-year-old girl, who developed patterned depigmentation at the back of both ear lobules after contact with plastic ear-ring stoppers made of polyvinyl chloride (PVC after continuous use for 6-7 months. Patch test with Indian standard series and cosmetic series was negative after 48 h, but she refused patch testing for extended duration as the possibility of induced depigmentation at the test site was unacceptable to her. To the best of our knowledge, this is the first report of plastic ear-ring stopper induced CL.

  10. Atomic Force Microscopy Based Thermal Lithography of Poly(tert-butyl acrylate) Block Copolymer Films for Bioconjugation

    NARCIS (Netherlands)

    Duvigneau, Joost; Schönherr, Holger; Vancso, Gyula J.

    2008-01-01

    In this paper, we report on the local thermal activation of thin polymer films for area-selective surface chemical modification on micrometer and nanometer length scales. The thermally induced activation of tert-butyl ester moieties in polystyrene-block-poly(tert-butyl acrylate) (PS-b-PtBA) block

  11. Pre-emptive administration of intravenous acetaminophen with transversus abdominis plane block (tap-blocke in the prevention of fentanil-induced hyperalgesia in pediatric oncological patient undergoing abdominal surgery

    Directory of Open Access Journals (Sweden)

    Dmytro Dmytriiev

    2015-10-01

      Abstract Background: Acetaminophen is a selective COX-2 agonist that has been shown to decrease the intensity of opioid-induced hyperalgesia (OIH in children. We aimed to investigate the effects of preemptive administration of intravenous acitomenofen  in the prevention of high-dose fentanil-induced hyperalgesia in pediatric patients. Methods: 45 patients of  American Society of Anesthesiologists physical status 1-3 undergoing abdominal surgery were randomly assigned to one of the following three groups. each of which received either IV acetaminophen  (an initial dose of 1.5 ml/kg for 40 min before before the induction of anesthesia or placebo saline 40 min before the induction of anesthesia and intraoperative fentanil infusion: group LFH received a placebo and 0.05 μg/kg/min fentanil; group FH received a placebo and 0.3 μg/kg/min fentanil; and group AFH received IV preemptive administration acetaminophen  and TAP-blocke bupivacaine 0,3 mg/kg.             Results: The mechanical hyperalgesia threshold 12 hr after surgery was significantly lower in group FH than in the other two groups. Postoperative pain intensity using visual analog scale (VAS and cumulative volume of a patient controlled analgesia (PCA containing morphine over 12 hr were significantly greater in group FH than in group AFH. The time to the first postoperative analgesic requirement was significantly shorter in group RH than in the other two groups. The sevoflurane requirement was significantly greater in group LFH than in the other groups. The frequency of hypotension and bradycardia was significantly higher, but shivering and postoperative nausea and vomiting were significantly lower in group AFH than in the other two groups. Conclusions: High-doses of fentanil induced hyperalgesia, which presented a decreased mechanical hyperalgesia threshold, enhanced pain intensity, a shorter time to first postoperative analgesic requirement, and greater morphine consumption, but IV

  12. Anti mutagenesis of chemical modulators against damage induced by reactor thermal neutrons

    International Nuclear Information System (INIS)

    Zambrano A, F.; Guzman R, J.; Garcia B, A.; Paredes G, L.; Delfin L, A.

    1999-01-01

    The mutations are changes in the genetic information whether for spontaneous form or induced by the exposure of the genetic material to certain agents, called mutagens: chemical or physical (diverse types of radiations). As well as exist a great variety of mutagens and pro mutagens (these last are agents which transform themselves in mutagens after the metabolic activation). Also several chemical compounds exist which are called antimutagens because they reduce the mutagens effect. The C vitamin or ascorbic acid (A A) presents antimutagenic and anti carcinogenic properties. On the other hand a sodium/copper salt derived from chlorophyll belonging to the porphyrin group (C L) contains a chelated metal ion in the center of molecule. It is also an antioxidant, antimutagenic and anti carcinogenic compound, it is called chlorophyllin. The objective of this work is to establish if the A A or the C L will reduce the damages induced by thermal and fast reactor neutrons. (Author)

  13. Chemical changes induced on a TiO2 surface by electron bombardment

    International Nuclear Information System (INIS)

    Vergara, L.I.; Passeggi, M.C.G.; Ferron, J.

    2007-01-01

    We study the TiO 2 (Ti 4+ ) chemical reduction induced by electron bombardment using Auger electron spectroscopy and factor analysis. We show that the electron irradiation of a TiO 2 sample is characterized by the appearance of a lower Ti oxidation state, Ti 2 O 3 (Ti 3+ ), followed by a further deposition of carbon, which is present inevitably in the environment even under ultra-high vacuum conditions. The appearance of C over the surface is found to be a complex mechanism which affects the reduction process through passivation of the electron-induced oxygen desorption and formation of titanium carbide. For very high irradiation doses, we also found that the chemical changes on the surface are stopped due to the deposition of carbon in a graphitic form

  14. Dexamethasone as Adjuvant to Bupivacaine Prolongs the Duration of Thermal Antinociception and Prevents Bupivacaine-Induced Rebound Hyperalgesia via Regional Mechanism in a Mouse Sciatic Nerve Block Model

    Science.gov (United States)

    An, Ke; Elkassabany, Nabil M.; Liu, Jiabin

    2015-01-01

    Background Dexamethasone has been studied as an effective adjuvant to prolong the analgesia duration of local anesthetics in peripheral nerve block. However, the route of action for dexamethasone and its potential neurotoxicity are still unclear. Methods A mouse sciatic nerve block model was used. The sciatic nerve was injected with 60ul of combinations of various medications, including dexamethasone and/or bupivacaine. Neurobehavioral changes were observed for 2 days prior to injection, and then continuously for up to 7 days after injection. In addition, the sciatic nerves were harvested at either 2 days or 7 days after injection. Toluidine blue dyeing and immunohistochemistry test were performed to study the short-term and long-term histopathological changes of the sciatic nerves. There were six study groups: normal saline control, bupivacaine (10mg/kg) only, dexamethasone (0.5mg/kg) only, bupivacaine (10mg/kg) combined with low-dose (0.14mg/kg) dexamethasone, bupivacaine (10mg/kg) combined with high-dose (0.5mg/kg) dexamethasone, and bupivacaine (10mg/kg) combined with intramuscular dexamethasone (0.5mg/kg). Results High-dose perineural dexamethasone, but not systemic dexamethasone, combined with bupivacaine prolonged the duration of both sensory and motor block of mouse sciatic nerve. There was no significant difference on the onset time of the sciatic nerve block. There was “rebound hyperalgesia” to thermal stimulus after the resolution of plain bupivacaine sciatic nerve block. Interestingly, both low and high dose perineural dexamethasone prevented bupivacaine-induced hyperalgesia. There was an early phase of axon degeneration and Schwann cell response as represented by S-100 expression as well as the percentage of demyelinated axon and nucleus in the plain bupivacaine group compared with the bupivacaine plus dexamethasone groups on post-injection day 2, which resolved on post-injection day 7. Furthermore, we demonstrated that perineural dexamethasone

  15. Comparative experimental study of cancer induced by ionizing radiations or by chemical carcinogens

    International Nuclear Information System (INIS)

    Lafuma, J.

    1983-01-01

    Animal experiments have contributed to specify a number of parameters used in setting human safety limits for ionizing radiation. In the same way, comparisons have been made between cancers induced in man and in animals in well-defined conditions. In order to use the same experimental data for chemical carcinogens, the mechanisms of carcinogenesis should be the same, i.e. additivity of responses instead of synergy of effects, which requires the development of a new experimental method [fr

  16. Decay Accelerating Factor (CD55) Protects Neuronal Cells from Chemical Hypoxia-Induced Injury

    Science.gov (United States)

    2010-04-09

    Pavlakovic G, Isom GE: Dopaminergic neurotoxicity of cyanide: neurochemical, histological and behavioral characterization. Toxicol Appl Pharmacol...provided the original work is properly cited. ResearchDecay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury...deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured

  17. Assessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS).

    Science.gov (United States)

    Lauenstein, L; Switalla, S; Prenzler, F; Seehase, S; Pfennig, O; Förster, C; Fieguth, H; Braun, A; Sewald, K

    2014-06-01

    Occupational asthma can be induced by a number of chemicals at the workplace. Risk assessment of potential sensitizers is mostly performed in animal experiments. With increasing public demand for alternative methods, human precision-cut lung slices (PCLS) have been developed as an ex vivo model. Human PCLS were exposed to increasing concentrations of 20 industrial chemicals including 4 respiratory allergens, 11 contact allergens, and 5 non-sensitizing irritants. Local respiratory irritation was characterized and expressed as 75% (EC25) and 50% (EC50) cell viability with respect to controls. Dose-response curves of all chemicals except for phenol were generated. Local respiratory inflammation was quantified by measuring the production of cytokines and chemokines. TNF-α and IL-1α were increased significantly in human PCLS after exposure to the respiratory sensitizers trimellitic anhydride (TMA) and ammonium hexachloroplatinate (HClPt) at subtoxic concentrations, while contact sensitizers and non-sensitizing irritants failed to induce the release of these cytokines to the same extent. Interestingly, significant increases in T(H)1/T(H)2 cytokines could be detected only after exposure to HClPt at a subtoxic concentration. In conclusion, allergen-induced cytokines were observed but not considered as biomarkers for the differentiation between respiratory and contact sensitizers. Our preliminary results show an ex vivo model which might be used for prediction of chemical-induced toxicity, but is due to its complex three-dimensional structure not applicable for a simple screening of functional and behavior changes of certain cell populations such as dendritic cells and T-cells in response to allergens. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Evaluation of mechano-chemical degradation induced stresses of polyolefin pipes

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Byoung Ho [Korea Univ., Seoul (Korea, Republic of); Chudnovsky, Alexander [The University of Illinois, Chicago (United States)

    2008-07-01

    The fracture phenomena in engineering thermoplastics resulting from chemical degradation is usually observed in the form of a microcrack network within a surface layer of degraded polymer exposed to a combined action of mechanical stresses and chemically aggressive environment. Degradation of polymers is usually manifested in a reduction of molecular weight, increase of crystallinity in semi crystalline polymers, increase of material density, a subtle increase in yield strength, and a dramatic reduction in toughness. The critical level of degradation for fracture initiation depends on the rates of toughness deterioration and build-up of the degradation related stresses as well as on the manufacturing and service stresses. In this paper, the evaluation of mechano-chemical degradation induced stress is attempted, and the application of the evaluated stress to the fracture initiation of polymer pipes is presented.

  19. Evaluation of mechano-chemical degradation induced stresses of polyolefin pipes

    International Nuclear Information System (INIS)

    Choi, Byoung Ho; Chudnovsky, Alexander

    2008-01-01

    The fracture phenomena in engineering thermoplastics resulting from chemical degradation is usually observed in the form of a microcrack network within a surface layer of degraded polymer exposed to a combined action of mechanical stresses and chemically aggressive environment. Degradation of polymers is usually manifested in a reduction of molecular weight, increase of crystallinity in semi crystalline polymers, increase of material density, a subtle increase in yield strength, and a dramatic reduction in toughness. The critical level of degradation for fracture initiation depends on the rates of toughness deterioration and build-up of the degradation related stresses as well as on the manufacturing and service stresses. In this paper, the evaluation of mechano-chemical degradation induced stress is attempted, and the application of the evaluated stress to the fracture initiation of polymer pipes is presented

  20. Radiation-induced mammary carcinogenesis in rodent models. What's different from chemical carcinogenesis?

    International Nuclear Information System (INIS)

    Imaoka, Tatsuhiko; Nishimura, Mayumi; Iizuka, Daisuke; Daino, Kazuhiro; Takabatake, Takashi; Okamoto, Mieko; Kakinuma, Shizuko; Shimada, Yoshiya

    2009-01-01

    Ionizing radiation is one of a few well-characterized etiologic factors of human breast cancer. Laboratory rodents serve as useful experimental models for investigating dose responses and mechanisms of cancer development. Using these models, a lot of information has been accumulated about mammary gland cancer, which can be induced by both chemical carcinogens and radiation. In this review, we first list some experimental rodent models of breast cancer induction. We then focus on several topics that are important in understanding the mechanisms and risk modification of breast cancer development, and compare radiation and chemical carcinogenesis models. We will focus on the pathology and natural history of cancer development in these models, genetic changes observed in induced cancers, indirect effects of carcinogens, and finally risk modification by reproductive factors and age at exposure to the carcinogens. In addition, we summarize the knowledge available on mammary stem/progenitor cells as a potential target of carcinogens. Comparison of chemical and radiation carcinogenesis models on these topics indicates certain similarities, but it also indicates clear differences in several important aspects, such as genetic alterations of induced cancers and modification of susceptibility by age and reproductive factors. Identification of the target cell type and relevant translational research for human risk management may be among the important issues that are addressed by radiation carcinogenesis models. (author)

  1. Lack of chemically induced mutation in repair-deficient mutants of yeast

    International Nuclear Information System (INIS)

    Prakash, L.

    1974-01-01

    Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), β-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents. (auth)

  2. Lack of chemically induced mutation in repair-deficient mutants of yeast.

    Science.gov (United States)

    Prakash, L

    1974-12-01

    Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), beta-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents.

  3. Bioanalytical evidence that chemicals in tattoo ink can induce adaptive stress responses.

    Science.gov (United States)

    Neale, Peta A; Stalter, Daniel; Tang, Janet Y M; Escher, Beate I

    2015-10-15

    Tattooing is becoming increasingly popular, particularly amongst young people. However, tattoo inks contain a complex mixture of chemical impurities that may pose a long-term risk for human health. As a first step towards the risk assessment of these complex mixtures we propose to assess the toxicological hazard potential of tattoo ink chemicals with cell-based bioassays. Targeted modes of toxic action and cellular endpoints included cytotoxicity, genotoxicity and adaptive stress response pathways. The studied tattoo inks, which were extracted with hexane as a proxy for the bioavailable fraction, caused effects in all bioassays, with the red and yellow tattoo inks having the greatest response, particularly inducing genotoxicity and oxidative stress response endpoints. Chemical analysis revealed the presence of polycyclic aromatic hydrocarbons in the tested black tattoo ink at concentrations twice the recommended level. The detected polycyclic aromatic hydrocarbons only explained 0.06% of the oxidative stress response of the black tattoo ink, thus the majority of the effect was caused by unidentified components. The study indicates that currently available tattoo inks contain components that induce adaptive stress response pathways, but to evaluate the risk to human health further work is required to understand the toxicokinetics of tattoo ink chemicals in the body. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Soft X-ray induced chemical modification of polysaccharides in vascular plant cell walls

    International Nuclear Information System (INIS)

    Cody, George D.; Brandes, Jay; Jacobsen, Chris; Wirick, Susan

    2009-01-01

    Scanning transmission X-ray microscopy and micro carbon X-ray Absorption Near Edge Spectroscopy (C-XANES) can provide quantitative information regarding the distribution of the biopolymers cellulose, hemicellulose, and lignin in vascular plant cell walls. In the case of angiosperms, flowering plants, C-XANES may also be able to distinguish variations in lignin monomer distributions throughout the cell wall. Polysaccharides are susceptible to soft X-ray irradiation induced chemical transformations that may complicate spectral analysis. The stability of a model polysaccharide, cellulose acetate, to variable doses of soft X-rays under conditions optimized for high quality C-XANES spectroscopy was investigated. The primary chemical effect of soft X-ray irradiation on cellulose acetate involves mass loss coincident with de-acetylation. A lesser amount of vinyl ketone formation also occurs. Reduction in irradiation dose via defocusing does enable high quality pristine spectra to be obtained. Radiation induced chemical modification studies of oak cell wall reveals that cellulose and hemicellulose are less labile to chemical modification than cellulose acetate. Strategies for obtaining pristine C-XANES spectra of polysaccharides are presented.

  5. A crowdsourcing workflow for extracting chemical-induced disease relations from free text

    Science.gov (United States)

    Li, Tong Shu; Bravo, Àlex; Furlong, Laura I.; Good, Benjamin M.; Su, Andrew I.

    2016-01-01

    Relations between chemicals and diseases are one of the most queried biomedical interactions. Although expert manual curation is the standard method for extracting these relations from the literature, it is expensive and impractical to apply to large numbers of documents, and therefore alternative methods are required. We describe here a crowdsourcing workflow for extracting chemical-induced disease relations from free text as part of the BioCreative V Chemical Disease Relation challenge. Five non-expert workers on the CrowdFlower platform were shown each potential chemical-induced disease relation highlighted in the original source text and asked to make binary judgments about whether the text supported the relation. Worker responses were aggregated through voting, and relations receiving four or more votes were predicted as true. On the official evaluation dataset of 500 PubMed abstracts, the crowd attained a 0.505 F-score (0.475 precision, 0.540 recall), with a maximum theoretical recall of 0.751 due to errors with named entity recognition. The total crowdsourcing cost was $1290.67 ($2.58 per abstract) and took a total of 7 h. A qualitative error analysis revealed that 46.66% of sampled errors were due to task limitations and gold standard errors, indicating that performance can still be improved. All code and results are publicly available at https://github.com/SuLab/crowd_cid_relex Database URL: https://github.com/SuLab/crowd_cid_relex PMID:27087308

  6. Bactericidal peptidoglycan recognition protein induces oxidative stress in Escherichia coli through a block in respiratory chain and increase in central carbon catabolism.

    Science.gov (United States)

    Kashyap, Des R; Kuzma, Marcin; Kowalczyk, Dominik A; Gupta, Dipika; Dziarski, Roman

    2017-09-01

    Mammalian Peptidoglycan Recognition Proteins (PGRPs) kill both Gram-positive and Gram-negative bacteria through simultaneous induction of oxidative, thiol and metal stress responses in bacteria. However, metabolic pathways through which PGRPs induce these bactericidal stress responses are unknown. We screened Keio collection of Escherichia coli deletion mutants and revealed that deleting genes for respiratory chain flavoproteins or for tricarboxylic acid (TCA) cycle resulted in increased resistance of E. coli to PGRP killing. PGRP-induced killing depended on the production of hydrogen peroxide, which required increased supply of NADH for respiratory chain oxidoreductases from central carbon catabolism (glycolysis and TCA cycle), and was controlled by cAMP-Crp. Bactericidal PGRP induced a rapid decrease in respiration, which suggested that the main source of increased production of hydrogen peroxide was a block in respiratory chain and diversion of electrons from NADH oxidoreductases to oxygen. CpxRA two-component system was a negative regulator of PGRP-induced oxidative stress. By contrast, PGRP-induced thiol stress (depletion of thiols) and metal stress (increase in intracellular free Zn 2+ through influx of extracellular Zn 2+ ) were mostly independent of oxidative stress. Thus, manipulating pathways that induce oxidative, thiol and metal stress in bacteria could be a useful strategy to design new approaches to antibacterial therapy. © 2017 John Wiley & Sons Ltd.

  7. CHEMICALS

    CERN Multimedia

    Medical Service

    2002-01-01

    It is reminded that all persons who use chemicals must inform CERN's Chemistry Service (TIS-GS-GC) and the CERN Medical Service (TIS-ME). Information concerning their toxicity or other hazards as well as the necessary individual and collective protection measures will be provided by these two services. Users must be in possession of a material safety data sheet (MSDS) for each chemical used. These can be obtained by one of several means : the manufacturer of the chemical (legally obliged to supply an MSDS for each chemical delivered) ; CERN's Chemistry Service of the General Safety Group of TIS ; for chemicals and gases available in the CERN Stores the MSDS has been made available via EDH either in pdf format or else via a link to the supplier's web site. Training courses in chemical safety are available for registration via HR-TD. CERN Medical Service : TIS-ME :73186 or service.medical@cern.ch Chemistry Service : TIS-GS-GC : 78546

  8. Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective

    DEFF Research Database (Denmark)

    Muller, A.; Jacobsen, Helene; Healy, E.

    2006-01-01

    Haemolytic anaemia is often induced following prolonged exposure to chemical substances. Currently, under EU Council Directive 67/548/EEC, substances which induce such effects are classified as dangerous and assigned the risk phrase R48 'Danger of serious damage to health by prolonged exposure......! Whilst the general classification criteria for this endpoint are outlined in Annex VI of this Directive, they do not provide specific information to assess haemolytic anaemia. This review produced by the EU Working Group on Haemolytic Anaemia provides a toxicological assessment of haemolytic anaemia...... and proposes criteria that can be used in the assessment for classification of substances which induce such effects. An overview of the primary and secondary effects of haemolytic anaemia which can occur in rodent repeated dose toxicity studies is given. A detailed analysis of the toxicological significance...

  9. The understanding of the R7T7 glass blocks long term behavior: chemical and transport coupling in fractured media; Comprehension de l'alteration a long terme des colis de verre R7T7: etude du couplage chimie transport dans un milieu fissure

    Energy Technology Data Exchange (ETDEWEB)

    Chomat, L

    2008-04-15

    The long term behavior of nuclear waste glass blocks depends highly on chemical reactions which occur at the surface in contact with water. Studies carried out on inactive fractured glass blocks show that fracture networks play a significant part in reactive surface area. Nevertheless, the complexity of results interpretation, due to a weak knowledge of fracture networks and local lixiviation conditions, does not allow us to comprehend the physical and chemical mechanisms involved. Model cracks are a key step to study chemical and transport coupling in fractured media. Crack lixiviation in aggressive conditions (pH{>=}11) show that the crack's position (horizontal or vertical) determines the dominant transport mechanism (respectively diffusion or convection induced by gravity). This gravity driven flow seems to be negligible in lower pH conditions. The convective velocity is estimated by a 1D model of reactive transport. Two other parameters are studied: the influence of thermal gradient and the influence of interconnected cracks on alteration. A strong retroactive effect of convection, due to thermal gradient, on the alteration kinetic is observed inside the crack. These works lead to a complete alteration experiment of a 163 crack network subject to a thermal gradient. The use of the geochemical software, HYTEC, within the framework of this study shows the potential of the software which is however limited by the kinetics law used. (author)

  10. The understanding of the R7T7 glass blocks long term behavior: chemical and transport coupling in fractured media; Comprehension de l'alteration a long terme des colis de verre R7T7: etude du couplage chimie transport dans un milieu fissure

    Energy Technology Data Exchange (ETDEWEB)

    Chomat, L

    2008-04-15

    The long term behavior of nuclear waste glass blocks depends highly on chemical reactions which occur at the surface in contact with water. Studies carried out on inactive fractured glass blocks show that fracture networks play a significant part in reactive surface area. Nevertheless, the complexity of results interpretation, due to a weak knowledge of fracture networks and local lixiviation conditions, does not allow us to comprehend the physical and chemical mechanisms involved. Model cracks are a key step to study chemical and transport coupling in fractured media. Crack lixiviation in aggressive conditions (pH{>=}11) show that the crack's position (horizontal or vertical) determines the dominant transport mechanism (respectively diffusion or convection induced by gravity). This gravity driven flow seems to be negligible in lower pH conditions. The convective velocity is estimated by a 1D model of reactive transport. Two other parameters are studied: the influence of thermal gradient and the influence of interconnected cracks on alteration. A strong retroactive effect of convection, due to thermal gradient, on the alteration kinetic is observed inside the crack. These works lead to a complete alteration experiment of a 163 crack network subject to a thermal gradient. The use of the geochemical software, HYTEC, within the framework of this study shows the potential of the software which is however limited by the kinetics law used. (author)

  11. Moisture-induced solid state instabilities in α-chymotrypsin and their reduction through chemical glycosylation

    Directory of Open Access Journals (Sweden)

    Solá Ricardo J

    2010-08-01

    Full Text Available Abstract Background Protein instability remains the main factor limiting the development of protein therapeutics. The fragile nature (structurally and chemically of proteins makes them susceptible to detrimental events during processing, storage, and delivery. To overcome this, proteins are often formulated in the solid-state which combines superior stability properties with reduced operational costs. Nevertheless, solid protein pharmaceuticals can also suffer from instability problems due to moisture sorption. Chemical protein glycosylation has evolved into an important tool to overcome several instability issues associated with proteins. Herein, we employed chemical glycosylation to stabilize a solid-state protein formulation against moisture-induced deterioration in the lyophilized state. Results First, we investigated the consequences of moisture sorption on the stability and structural conformation of the model enzyme α-chymotrypsin (α-CT under controlled humidity conditions. Results showed that α-CT aggregates and inactivates as a function of increased relative humidity (RH. Furthermore, α-CT loses its native secondary and tertiary structure rapidly at increasing RH. In addition, H/D exchange studies revealed that α-CT structural dynamics increased at increasing RH. The magnitude of the structural changes in tendency parallels the solid-state instability data (i.e., formation of buffer-insoluble aggregates, inactivation, and loss of native conformation upon reconstitution. To determine if these moisture-induced instability issues could be ameliorated by chemical glycosylation we proceeded to modify our model protein with chemically activated glycans of differing lengths (lactose and dextran (10 kDa. The various glycoconjugates showed a marked decrease in aggregation and an increase in residual activity after incubation. These stabilization effects were found to be independent of the glycan size. Conclusion Water sorption leads to

  12. Three-dimensional laser-induced fluorescence measurements of turbulent chemical plumes

    Science.gov (United States)

    True, Aaron; Crimaldi, John

    2017-11-01

    In order to find prey, mates, and suitable habitat, many organisms must navigate through complex chemical plume structures in turbulent flow environments. In this context, we investigate the spatial and temporal structure of chemical plumes released isokinetically into fractal-grid-generated turbulence in an open channel flow. We first utilized particle image velocimetry (PIV) to characterize flow conditions (mean free stream velocities, turbulence intensities, turbulent kinetic energy dissipation rates, Taylor Reynolds numbers). We then implemented a newly developed high-resolution, high-speed, volumetric scanning laser-induced fluorescence (LIF) system for near time-resolved measurements of three-dimensional chemical plume structures. We investigated cases with and without a cylinder wake, and compare statistical (mean, variance, intermittency, probability density functions) and spectral (power spectrum of concentration fluctuations) characteristics of the chemical plume structure. Stretching and folding of complex three-dimensional filament structures during chaotic turbulent mixing is greatly enhanced in the cylinder wake case. In future experiments, we will implement simultaneous PIV and LIF, enabling computation of the covariance of the velocity and chemical concentration fluctuations and thus estimation of turbulent eddy diffusivities. NSF PHY 1555862.

  13. A plant-based chemical genomics screen for the identification of flowering inducers.

    Science.gov (United States)

    Fiers, Martijn; Hoogenboom, Jorin; Brunazzi, Alice; Wennekes, Tom; Angenent, Gerco C; Immink, Richard G H

    2017-01-01

    Floral timing is a carefully regulated process, in which the plant determines the optimal moment to switch from the vegetative to reproductive phase. While there are numerous genes known that control flowering time, little information is available on chemical compounds that are able to influence this process. We aimed to discover novel compounds that are able to induce flowering in the model plant Arabidopsis. For this purpose we developed a plant-based screening platform that can be used in a chemical genomics study. Here we describe the set-up of the screening platform and various issues and pitfalls that need to be addressed in order to perform a chemical genomics screening on Arabidopsis plantlets. We describe the choice for a molecular marker, in combination with a sensitive reporter that's active in plants and is sufficiently sensitive for detection. In this particular screen, the firefly Luciferase marker was used, fused to the regulatory sequences of the floral meristem identity gene APETALA1 (AP1) , which is an early marker for flowering. Using this screening platform almost 9000 compounds were screened, in triplicate, in 96-well plates at a concentration of 25 µM. One of the identified potential flowering inducing compounds was studied in more detail and named Flowering1 (F1). F1 turned out to be an analogue of the plant hormone Salicylic acid (SA) and appeared to be more potent than SA in the induction of flowering. The effect could be confirmed by watering Arabidopsis plants with SA or F1, in which F1 gave a significant reduction in time to flowering in comparison to SA treatment or the control. In this study a chemical genomics screening platform was developed to discover compounds that can induce flowering in Arabidopsis. This platform was used successfully, to identify a compound that can speed-up flowering in Arabidopsis.

  14. Estradiol-induced increase in the magnitude of long-term potentiation is prevented by blocking NR2B-containing receptors.

    Science.gov (United States)

    Smith, Caroline C; McMahon, Lori L

    2006-08-16

    Estradiol, through activation of genomic estrogen receptors, induces changes in synaptic morphology and function in hippocampus, a brain region important for memory acquisition. Specifically, this hormone increases CA1 pyramidal cell dendritic spine density, NMDA receptor (NMDAR)-mediated transmission, and the magnitude of long-term potentiation (LTP) at CA3-CA1 synapses. We recently reported that the estradiol-induced increase in LTP magnitude occurs only when there is a simultaneous increase in the fractional contribution of NMDAR-mediated transmission relative to AMPA receptor transmission, suggesting a direct role for the increase in NMDAR transmission to the heightened LTP magnitude. Estradiol has been shown to increase expression of the NMDAR subunit NR2B, but whether this translates into an increase in function of NR2B-containing receptors remains to be determined. Here we show that not only is the estradiol-induced increase in NMDAR transmission mediated by NR2B-containing receptors, but blocking these receptors using RO25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol] (0.5 microM), an NR2B selective antagonist, prevents the estradiol-induced increase in LTP magnitude. Thus, our data show a causal link between the estradiol-induced increase in transmission mediated by NR2B-containing NMDARs and the increase in LTP magnitude.

  15. A viral vectored prime-boost immunization regime targeting the malaria Pfs25 antigen induces transmission-blocking activity.

    Directory of Open Access Journals (Sweden)

    Anna L Goodman

    Full Text Available The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63, human adenovirus serotype 5 (AdHu5 and modified vaccinia virus Ankara (MVA viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25 resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera. In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit

  16. Dynamin inhibitors induce caspase-mediated apoptosis following cytokinesis failure in human cancer cells and this is blocked by Bcl-2 overexpression

    Directory of Open Access Journals (Sweden)

    Braithwaite Antony W

    2011-06-01

    Full Text Available Abstract Background The aim of both classical (e.g. taxol and targeted anti-mitotic agents (e.g. Aurora kinase inhibitors is to disrupt the mitotic spindle. Such compounds are currently used in the clinic and/or are being tested in clinical trials for cancer treatment. We recently reported a new class of targeted anti-mitotic compounds that do not disrupt the mitotic spindle, but exclusively block completion of cytokinesis. This new class includes MiTMAB and OcTMAB (MiTMABs, which are potent inhibitors of the endocytic protein, dynamin. Like other anti-mitotics, MiTMABs are highly cytotoxic and possess anti-proliferative properties, which appear to be selective for cancer cells. The cellular response following cytokinesis failure and the mechanistic pathway involved is unknown. Results We show that MiTMABs induce cell death specifically following cytokinesis failure via the intrinsic apoptotic pathway. This involves cleavage of caspase-8, -9, -3 and PARP, DNA fragmentation and membrane blebbing. Apoptosis was blocked by the pan-caspase inhibitor, ZVAD, and in HeLa cells stably expressing the anti-apoptotic protein, Bcl-2. This resulted in an accumulation of polyploid cells. Caspases were not cleaved in MiTMAB-treated cells that did not enter mitosis. This is consistent with the model that apoptosis induced by MiTMABs occurs exclusively following cytokinesis failure. Cytokinesis failure induced by cytochalasin B also resulted in apoptosis, suggesting that disruption of this process is generally toxic to cells. Conclusion Collectively, these data indicate that MiTMAB-induced apoptosis is dependent on both polyploidization and specific intracellular signalling components. This suggests that dynamin and potentially other cytokinesis factors are novel targets for development of cancer therapeutics.

  17. Evaluation of Chemical Changes in Some Soybean Mutants Induced by Gamma Irradiation

    International Nuclear Information System (INIS)

    Abd-Elkalik, K.; Mekkawy, S.H.; El-Demerdash, H.M.

    2010-01-01

    The Egyptian soybean cultivar Giza-22 was used to induce genetic variability by using gamma rays at dose levels of 100, 150 and 200 Gy. Sixteen mutants (including parental cultivar) were evaluated in M3 generation for their agronomic traits and chemical analysis was done in seeds of M3 generation. Four mutants A21 (150 Gy), A22, A23 and A24 (200 Gy) showed superiority in their agronomic traits compared with parental cultivar. The results of chemical analysis of seeds of M3 generation showed that, oil and energy contents were unaffected by irradiation treatments while protein contents were significantly increased at doses 150 and 200 Gy. Phenolic and tannin contents in seeds of M3 generation showed no significant changes in their percentages due to irradiation treatments. Gamma irradiation significantly increased in linoleic acid content in most of the mutants compared with the control (Giza-22), whereas, there were decreases in linolenic acid content. Investigation of amino acid composition of mutants of M3 generation revealed significant increases in the essential amino acids in most mutants induced by gamma irradiation at 150 and 200 Gy. It could be suggested that the use of gamma irradiation can induce an improvement of the oil and protein composition in soybean

  18. Multi-block analysis coupled to laser-induced breakdown spectroscopy for sorting geological materials from caves.

    Science.gov (United States)

    Ammari, Faten; Bassel, Léna; Ferrier, Catherine; Lacanette, Delphine; Chapoulie, Rémy; Bousquet, Bruno

    2016-10-01

    In this study, multi-block analysis was applied for the first time to LIBS spectra provided by a portable LIBS system (IVEA Solution, France) equipped with three compact Czerny-Turner spectrometers covering the spectral ranges 200-397nm, 398-571nm and 572-1000nm. 41 geological samples taken from a laboratory-cave situated in the "Vézère valley", an area rich with prehistoric sites and decorated caves listed as a UNESCO world heritage in the south west of France, were analyzed. They were composed of limestone and clay considered as underlying supports and of two types of alterations referred as moonmilk and coralloid. Common Components and Specific Weights Analysis (CCSWA) allowed sorting moonmilk and coralloid samples. The loadings revealed higher amounts of magnesium, silicon, aluminum and strontium in coralloids and the saliences emphasized that among the three spectrometers installed in the LIBS instrument used in this work; that covering the range 572-1000nm was less contributive. This new approach for processing LIBS data not only provides good results for sorting geological materials but also clearly reveals which spectral range contains most of the information. This specific advantage of multi-block analysis could lead for some applications to simplify the design and to reduce the size of LIBS instruments. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays

    OpenAIRE

    Yamashita, Haruhiro; Hoenerhoff, Mark J.; Peddada, Shyamal D.; Sills, Robert C.; Pandiri, Arun R.

    2016-01-01

    Retinal degeneration due to chronic ambient light exposure is a common spontaneous age-related finding in albino rats, but it can also be related to exposures associated with environmental chemicals and drugs. Typically, light induced retinal degeneration has a central/hemispherical localization where as chemical induced retinal degeneration has a diffuse localization. This study was conducted to identify National Toxicology Program (NTP) rodent bioassays with treatment-related retinal degene...

  20. Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells.

    Science.gov (United States)

    Biswas, Dhruba; Jiang, Peng

    2016-02-06

    The ability to generate transplantable neural cells in a large quantity in the laboratory is a critical step in the field of developing stem cell regenerative medicine for neural repair. During the last few years, groundbreaking studies have shown that cell fate of adult somatic cells can be reprogrammed through lineage specific expression of transcription factors (TFs)-and defined culture conditions. This key concept has been used to identify a number of potent small molecules that could enhance the efficiency of reprogramming with TFs. Recently, a growing number of studies have shown that small molecules targeting specific epigenetic and signaling pathways can replace all of the reprogramming TFs. Here, we provide a detailed review of the studies reporting the generation of chemically induced pluripotent stem cells (ciPSCs), neural stem cells (ciNSCs), and neurons (ciN). We also discuss the main mechanisms of actions and the pathways that the small molecules regulate during chemical reprogramming.

  1. Time evolution studies of laser induced chemical changes in InAs nanowire using Raman spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Pal, Suparna; Aggarwal, R.; Kumari Gupta, Vandna; Ingale, Alka [Laser Physics Application Section, Raja Ramanna Centre for Advanced Technology, Indore 452013, MP (India)

    2014-07-07

    We report the study of time evolution of chemical changes on the surface of an InAs nanowire (NW) on laser irradiation in different power density regime, using Raman spectroscopy for a time span of 8–16 min. Mixture of metastable oxides like InAsO{sub 4,} As{sub 2}O{sub 3} are formed upon oxidation, which are reflected as sharp Raman peaks at ∼240–254 and 180–200 cm{sup −1}. Evidence of removal of arsenic layer by layer is also observed at higher power density. Position controlled laser induced chemical modification on a nanometer scale, without changing the core of the NW, can be useful for NW based device fabrication.

  2. Suppression of SOS-inducing activity of chemical mutagens by metabolites from microbial transformation of (-)-isolongifolene.

    Science.gov (United States)

    Sakata, Kazuki; Oda, Yoshimitsu; Miyazawa, Mitsuo

    2010-02-24

    In this study, biotransformation of (-)-isolongifolene (1) by Glomerella cingulata and suppressive effect on umuC gene expression by chemical mutagens 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) and aflatoxin B(1) (AFB(1)) of the SOS response in Salmonella typhimurium TA1535/pSK1002 were investigated. Initially, 1 was carried out the microbial transformation by G. cingulata. The result found that 1 was converted into (-)-isolongifolen-9-one (2), (-)-(2S)-13-hydroxy-isolongifolen-9-one (3), and (-)-(4R)-4-hydroxy-isolongifolen-9-one (4) by G. cingulata, and their conversion rates were 60, 25, and 15%, respectively. The metabolites suppressed the SOS-inducing activity of furylfuramid and AFB(1) in the umu test. Comound 2 showed gene expression by chemical mutagens furylfuramide and AFB(1) was suppressed 54 and 50% at <0.5 mM, respectively. Compound 2 is the most effective compound in this experiment.

  3. A crowdsourcing workflow for extracting chemical-induced disease relations from free text.

    Science.gov (United States)

    Li, Tong Shu; Bravo, Àlex; Furlong, Laura I; Good, Benjamin M; Su, Andrew I

    2016-01-01

    Relations between chemicals and diseases are one of the most queried biomedical interactions. Although expert manual curation is the standard method for extracting these relations from the literature, it is expensive and impractical to apply to large numbers of documents, and therefore alternative methods are required. We describe here a crowdsourcing workflow for extracting chemical-induced disease relations from free text as part of the BioCreative V Chemical Disease Relation challenge. Five non-expert workers on the CrowdFlower platform were shown each potential chemical-induced disease relation highlighted in the original source text and asked to make binary judgments about whether the text supported the relation. Worker responses were aggregated through voting, and relations receiving four or more votes were predicted as true. On the official evaluation dataset of 500 PubMed abstracts, the crowd attained a 0.505F-score (0.475 precision, 0.540 recall), with a maximum theoretical recall of 0.751 due to errors with named entity recognition. The total crowdsourcing cost was $1290.67 ($2.58 per abstract) and took a total of 7 h. A qualitative error analysis revealed that 46.66% of sampled errors were due to task limitations and gold standard errors, indicating that performance can still be improved. All code and results are publicly available athttps://github.com/SuLab/crowd_cid_relexDatabase URL:https://github.com/SuLab/crowd_cid_relex. © The Author(s) 2016. Published by Oxford University Press.

  4. Nuclear magnetic resonance in pulse radiolysis. Chemically induced dynamic nuclear polarization

    International Nuclear Information System (INIS)

    Trifunac, A.D.; Johnson, K.W.; Lowers, R.H.

    1976-01-01

    Nuclear magnetic resonance and chemically induced dynamic nuclear polarization (CIDNP) were applied to the study of pulse radiolysis. Samples were irradiated with a 3-MeV electron beam from the Argonne Van de Graaff accelerator in an EPR magnet (approximately 4000 G) which had axial holes for beam access. A fast flow system transferred the irradiated solution to the rotating 5-mm NMR sample tube. The NMR spectra of mixtures of sodium acetate and methanol were presented to demonstrate the features of the CIDNP in pulse radiolysis

  5. Hydrocortisone Increases the Vinblastine-Induced Chromosomal Damages in L929 Cells Investigated by the Micronucleus Assay on Cytokinesis-Blocked Binucleated Cells

    Directory of Open Access Journals (Sweden)

    Tahere Ebrahimipour

    2017-03-01

    Full Text Available Background: Stress may cause damages to DNA or/and change the ability of the cells to overcome these damages. It may also cause irregularities in the cell cycle and induce abnormal cell divisions through glucocorticoid-dependent functions. The abnormal cell divisions, in turn, lead to chromosomal mal-segregation and aneuploidy. In this study, the effects of the stress hormone, hydrocortisone (HYD, were investigated on the induced chromosomal abnormalities by vinblastine (VIN during cell cycle in L929 cells. Methods: This work was performed in winter 2013 at Department of Biology, University of Ferdowsi, Mashhad, Iran. Cultured cells were divided into different groups including control, VIN-treated, HYD treated and VIN+HYD co-treated cells. The induced chromosomal damages were investigated by micronucleus assay in cytokinesis-blocked binucleated cells. Results: Although HYD by itself did not increase the micronuclei (Mn frequency, co-treatment of cells with VIN and HYD led to significant increase (P<0.05 in the frequency of Mn in comparison to control and VIN treated groups. Conclusion: Cells treated with stress hormone are more sensitive to damages induced by VIN. Therefore, stress may not directly result in genetic instability, it can increase the harmful effects associated with other genotoxic agents.

  6. A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model.

    Science.gov (United States)

    Basu, Hirak S; Thompson, Todd A; Church, Dawn R; Clower, Cynthia C; Mehraein-Ghomi, Farideh; Amlong, Corey A; Martin, Christopher T; Woster, Patrick M; Lindstrom, Mary J; Wilding, George

    2009-10-01

    High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression.

  7. A Small Molecule Polyamine Oxidase Inhibitor Blocks Androgen-Induced Oxidative Stress and Delays Prostate Cancer Progression in the TRAMP Mouse Model

    Science.gov (United States)

    Basu, Hirak S.; Thompson, Todd A.; Church, Dawn R.; Clower, Cynthia C.; Mehraein-Ghomi, Farideh; Amlong, Corey A.; Martin, Christopher T.; Woster, Patrick M.; Lindstrom, Mary J.; Wilding, George

    2009-01-01

    High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiological factor in prostate cancer (CaP) occurrence, recurrence and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data demonstrate that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays prostate cancer progression. PMID:19773450

  8. Shock-induced hotspot formation and chemical reaction initiation in PETN containing a spherical void

    International Nuclear Information System (INIS)

    Shan, Tzu-Ray; Thompson, Aidan P

    2014-01-01

    We present results of reactive molecular dynamics simulations of hotspot formation and chemical reaction initiation in shock-induced compression of pentaerythritol tetranitrate (PETN) with the ReaxFF reactive force field. A supported shockwave is driven through a PETN crystal containing a 20 nm spherical void at a sub-threshold impact velocity of 2 km/s. Formation of a hotspot due to shock-induced void collapse is observed. During void collapse, NO 2 is the dominant species ejected from the upstream void surface. Once the ejecta collide with the downstream void surface and the hotspot develops, formation of final products such as N 2 and H 2 O is observed. The simulation provides a detailed picture of how void collapse and hotspot formation leads to initiation at sub-threshold impact velocities.

  9. Effect of Lepidium meyenii (maca) on testicular function of mice with chemically and physically induced subfertility.

    Science.gov (United States)

    Valdivia Cuya, M; Yarasca De La Vega, K; Lévano Sánchez, G; Vásquez Cavero, J; Temoche García, H; Torres Torres, L; Cruz Ornetta, V

    2016-10-01

    The aim of this study was to evaluate the effect of Lepidium meyenii (maca) in chemically and physically subfertile mice. After 35 days, the following groups of mice were evaluated: control, sham, chemical subfertility, chemical subfertility-maca-supplemented, physical subfertility, physical subfertility-maca-supplemented and maca-supplemented only. Motility (32.36% ± 5.34%) and sperm count (44.4 ± 5.37 × 10(6) /ml) in the chemically and physically subfertile mice (11.81% ± 4.06%, 17.34 ± 13.07 × 10(6) /ml) decreased compared to the control (75.53% ± 2.97% and 57.4 ± 19.6 10(6) /ml) and sham (53.5% ± 7.86% and 58.4 ± 14.10 10(6) /ml). Maca was able to reverse the deleterious effect of motility (76.36 ± 1.97) as well as sperm count (53.5 ± 9.18 × 10(6) /ml) on chemical subfertility. In contrast, maca did not reverse the effects of induced physical subfertility nor motility (18.78% ± 14.41%) or sperm count (20.17 ± 11.20 × 10(6) /ml). The percentage of sperm DNA fragmentation in the physically subfertile mice increased (11.1% ± 19.29%) compared to the control (0.84% ± 0.85%). However, in the physically subfertile group, maca decreased sperm DNA fragmentation (2.29% ± 2.30%) closer to the sham (1.04% ± 0.62%) and the control (0.84% ± 0.85%). The group supplemented only with maca showed 0.54% ± 0.50% of spermatozoa with DNA fragmentation. Yet, the differences observed were statistically not significant. In conclusion, it appears that maca activates the cytochrome P450 system after chemically induced subfertility. However, it does not reverse the low mitochondrial membrane potential in spermatozoa compromised in the physical subfertility group. © 2016 Blackwell Verlag GmbH.

  10. Chemical Inhibition of Histone Deacetylases 1 and 2 Induces Fetal Hemoglobin through Activation of GATA2.

    Directory of Open Access Journals (Sweden)

    Jeffrey R Shearstone

    Full Text Available Therapeutic intervention aimed at reactivation of fetal hemoglobin protein (HbF is a promising approach for ameliorating sickle cell disease (SCD and β-thalassemia. Previous studies showed genetic knockdown of histone deacetylase (HDAC 1 or 2 is sufficient to induce HbF. Here we show that ACY-957, a selective chemical inhibitor of HDAC1 and 2 (HDAC1/2, elicits a dose and time dependent induction of γ-globin mRNA (HBG and HbF in cultured primary cells derived from healthy individuals and sickle cell patients. Gene expression profiling of erythroid progenitors treated with ACY-957 identified global changes in gene expression that were significantly enriched in genes previously shown to be affected by HDAC1 or 2 knockdown. These genes included GATA2, which was induced greater than 3-fold. Lentiviral overexpression of GATA2 in primary erythroid progenitors increased HBG, and reduced adult β-globin mRNA (HBB. Furthermore, knockdown of GATA2 attenuated HBG induction by ACY-957. Chromatin immunoprecipitation and sequencing (ChIP-Seq of primary erythroid progenitors demonstrated that HDAC1 and 2 occupancy was highly correlated throughout the GATA2 locus and that HDAC1/2 inhibition led to elevated histone acetylation at well-known GATA2 autoregulatory regions. The GATA2 protein itself also showed increased binding at these regions in response to ACY-957 treatment. These data show that chemical inhibition of HDAC1/2 induces HBG and suggest that this effect is mediated, at least in part, by histone acetylation-induced activation of the GATA2 gene.

  11. Chemical modifications of polymer films induced by high energy heavy ions

    International Nuclear Information System (INIS)

    Zhu Zhiyong; Sun Youmei; Liu Changlong; Liu Jie; Jin Yunfan

    2002-01-01

    Polymer films including polyethylene terephthalate (PET), polystyrene (PS) and polycarbonate (PC) were irradiated at room temperature with ions of 35 MeV/u 40 Ar, 25 MeV/u 84 Kr, 15.1 MeV/u 136 Xe and 11.4 MeV/u 238 U to fluences ranging from 9x10 9 to 5.5x10 12 ions/cm 2 . The radiation-induced chemical changes of the materials were investigated by Fourier-transform infrared (FTIR) and ultraviolet/visible spectroscopies. It is found that the absorbance in the ultraviolet and visible range induced by all irradiations follows a linear relationship with fluence. The radiation-induced absorbance normalized to one particle increases slowly with increasing of electronic energy loss below about 8 keV/nm followed by a sharp increase up to about 15 keV/nm above which saturation is reached. FTIR measurements reveal that the materials suffer serious degradation through bond breaking. The absorbance of the typical infrared bands decays exponentially with increase of ion fluence and the bond-disruption cross-section shows a sigmoid variation with electronic energy loss. In PET loss of crystallinity is attributed to the configuration transformation of the ethylene glycol residue from trans into the gauche. Alkyne end groups are induced in all the materials above certain electronic energy loss threshold, which is found to be about 0.8 keV/nm for PS and 0.4 keV/nm for PC. The production cross-section of alkyne end group increases with increasing of electronic energy loss and shows saturation at high electronic energy loss values. It is concluded that not only the physical processes but also the chemical processes of the energy deposition determine the modification of polymer

  12. A comparison of G2 phase radiation-induced chromatid break kinetics using calyculin-PCC with those obtained using colcemid block.

    Science.gov (United States)

    Bryant, Peter E; Mozdarani, Hossein

    2007-09-01

    To study the possible influence of cell-cycle delay on cells reaching mitosis during conventional radiation-induced chromatid break experiments using colcemid as a blocking agent, we have compared the chromatid break kinetics following a single dose of gamma rays (0.75 Gy) in metaphase CHO cells using calyculin-induced premature chromosome condensation (PCC), with those using colcemid block. Calyculin-induced PCC causes very rapid condensation of G2 cell chromosomes without the need for a cell to progress to mitosis, hence eliminating any effect of cell-cycle checkpoint on chromatid break frequency. We found that the kinetics of the exponential first-order decrease in chromatid breaks with time after irradiation was similar (not significantly different) between the two methods of chromosome condensation. However, use of the calyculin-PCC technique resulted in a slightly increased rate of disappearance of chromatid breaks and thus higher frequencies of breaks at 1.5 and 2.5 h following irradiation. We also report on the effect of the nucleoside analogue ara A on chromatid break kinetics using the two chromosome condensation techniques. Ara A treatment of cells abrogated the decrease in chromatid breaks with time, both using the calyculin-PCC and colcemid methods. We conclude that cell-cycle delay may be a factor determining the absolute frequency of chromatid breaks at various times following irradiation of cells in G2 phase but that the first-order disappearance of chromatid breaks with time and its abrogation by ara A are not significantly influenced by the G2 checkpoint.

  13. physical, chemical, technological and biological properties of some mutant oil seeds induced by gamma radiation

    International Nuclear Information System (INIS)

    Ali, H.G.M.

    2003-01-01

    The present study has been undertaken to evaluated sesame, sunflower and safflower seeds induced by gamma rays, as plant breeding unit, plant research department, radioisotope application division, nuclear research center, atomic energy authority Inshas. the obtained results indicate the following : chemical composition of mutant seeds: the radiation mutation caused a significant increase in both oil and ash content total carbohydrates showed a significant decreased in sesame seeds. radiation mutation induced significant increase in oil and protein content of sunflower and safflower seeds. while the total carbohydrate showed a significant decrease. physiochemical properties of oils extracted mutant seeds: the radiation mutation had no real effect on the refractive index and A.V of oils extracted from control and mutant sesame, sunflower and safflower seeds. while it caused a slight increase in red color and P.V. of sesame oil, the thiobarbituric acid (TBA) value of mutant sesame oil was not alter upon radiation mutation, but it induced a slight decrease in TBA of mutant sunflower and safflower oils. the unsaponifiable matter percentage of oils extracted from mutant sesame, sunflower and safflower seeds were slightly increased by radiation mutation .radiation mutation of seeds had no real effect on the total SFA and USFA of sesame oil. however, radiation mutation induced a remarkable changes in fatty acid profiles of sunflower and safflower oil as total SFA decreased, while USFA increased. Uric acid was only detected in oil extracted from mutant sunflower seeds

  14. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R., E-mail: mundy.william@epa.gov

    2011-11-15

    cultures were more sensitive to neurite outgrowth inhibitors, they also had a lower dynamic range for detecting chemical-induced neurite outgrowth inhibition and greater variability from culture-to-culture as compared to rat primary cortical cultures.

  15. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    International Nuclear Information System (INIS)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

    2011-01-01

    cultures were more sensitive to neurite outgrowth inhibitors, they also had a lower dynamic range for detecting chemical-induced neurite outgrowth inhibition and greater variability from culture-to-culture as compared to rat primary cortical cultures.

  16. Depletion of STAT5 blocks TEL–SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice

    International Nuclear Information System (INIS)

    Sprissler, C; Belenki, D; Maurer, H; Aumann, K; Pfeifer, D; Klein, C; Müller, T A; Kissel, S; Hülsdünker, J; Alexandrovski, J; Brummer, T; Jumaa, H; Duyster, J; Dierks, C

    2014-01-01

    The spleen tyrosine kinase (SYK) was identified as an oncogenic driver in a broad spectrum of hematologic malignancies. The in vivo comparison of three SYK containing oncogenes, SYK wt , TEL–SYK and IL-2-inducible T-cell kinase (ITK)-SYK revealed a general myeloexpansion and the establishment of three different hematologic (pre)diseases. SYK wt enhanced the myeloid and T-cell compartment, without leukemia/lymphoma development. ITK–SYK caused lethal T-cell lymphomas and the cytoplasmic TEL–SYK fusion induced an acute panmyelosis with myelofibrosis-type acute myeloid leukemia (AML) with up to 50% immature megakaryoblasts infiltrating bone marrow, spleen and liver, additional MPN features (myelofibrosis and granulocyte expansion) and MDS stigmata with megakaryocytic and erythroid dysplasia. LKS cells were reduced and all subsets (LT/ST/MPP) showed reduced proliferation rates. SYK inhibitor treatment (R788) of diseased TEL–SYK mice reduced leukocytosis, spleen and liver infiltration, enhanced the hematocrit and prolonged survival time, but could not significantly reduce myelofibrosis. Stat5 was identified as a major downstream mediator of TEL–SYK in vitro as well as in vivo. Consequently, targeted deletion of Stat5 in vivo completely abrogated TEL–SYK-induced AML and myelofibrosis development, proving Stat5 as a major driver of SYK-induced transformation. Our experiments highlight the important role of SYK in AML and myelofibrosis and prove SYK and STAT5 inhibitors as potent treatment options for those diseases

  17. Several domains from VAR2CSA can induce Plasmodium falciparum adhesion-blocking antibodies

    DEFF Research Database (Denmark)

    Salanti, Ali; Resende, Mafalda; Ditlev, Sisse B

    2010-01-01

    . In this study, it is demonstrated that other domains of VAR2CSA also can induce antibodies with inhibitory activity. METHODS: All VAR2CSA domains from the 3D7 and HB3 parasites were produced in Baculovirus-transfected insect cells. Groups of three rats per protein were immunized and anti-sera were tested...

  18. [Protein kinase A inhibitor H-89 blocks polyploidization of SP600125-induced CMK cells by regulating phosphorylation of ribosomal protein S6 kinase 1].

    Science.gov (United States)

    Zhao, Song; Yang, Jingang; Li, Changling; Xing, Sining; Yu, Ying; Liu, Shuo; Pu, Feifei; Ma, Dongchu

    2016-10-01

    Objective To investigate the regulatory effect of post-translation modification of ribosomal protein S6 kinase 1 (S6K1) on the polyploidization of megakaryocytes. Methods SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, and H-89, a cAMP-dependent protein kinase (PKA) inhibitor, were used to treat CMK cells separately or in combination. With propidium iodide (PI) to dye DNA in the treated cells, the relative DNA content was detected by flow cytometry, and then the DNA polyploidy was analyzed. The change of expression and phosphorylation of ribosomal protein S6 kinase 1 (S6K1), an important mammalian target of rapamycin (mTOR) downstream target molecule, was analyzed by Western blotting. Molecular docking study and kinase activity assay were performed to analyze the combination of H-89 with S6K1 and the effect of H-89 on the activity of S6K1 kinase. Results SP600125 induced CMK cell polyploidization in a time-dependent and dose-dependent manner. At the same time, it increased the phosphorylation of S6K1 at Thr421/Ser424 and decreased the phosphorylation of S6K1 at Thr389. H-89 not only blocked polyploidization, but also decreased the phosphorylation of S6K1 at Thr421/Ser424 and increased the phosphorylation of S6K1 at Thr389. Molecular docking and kinase activity assay showed that H-89 occupied the ATP binding sites of S6K1 and inhibited its activity. Noticeably, both H-89 and SP600125 inhibited the activity of PKA. Moreover, the two drugs further inhibited the activity of PKA when used together. Therefore, these data indicated that H-89 blocked the SP600125-induced polyploidization of CMK cells mainly by changing S6K1 phosphorylation state, rather than its inhibitory effect on PKA. Conclusion H-89 can block the polyploidization of SP600125-induced CMK cells by regulating S6K1 phosphorylation state.

  19. Glutamate Induced Thermal Equilibrium Intermediate and Counteracting Effect on Chemical Denaturation of Proteins.

    Science.gov (United States)

    Anumalla, Bramhini; Prabhu, N Prakash

    2018-01-25

    When organisms are subjected to stress conditions, one of their adaptive responses is accumulation of small organic molecules called osmolytes. These osmolytes affect the structure and stability of the biological macromolecules including proteins. The present study examines the effect of a negatively charged amino acid osmolyte, glutamate (Glu), on two model proteins, ribonuclease A (RNase A) and α-lactalbumin (α-LA), which have positive and negative surface charges at pH 7, respectively. These proteins follow two-state unfolding transitions during both heat and chemical induced denaturation processes. The addition of Glu stabilizes the proteins against temperature and induces an early equilibrium intermediate during unfolding. The stability is found to be enthalpy-driven, and the free energy of stabilization is more for α-LA compared to RNase A. The decrease in the partial molar volume and compressibility of both of the proteins in the presence of Glu suggests that the proteins attain a more compact state through surface hydration which could provide a more stable conformation. This is also supported by molecule dynamic simulation studies which demonstrate that the water density around the proteins is increased upon the addition of Glu. Further, the intermediates could be completely destabilized by lower concentrations (∼0.5 M) of guanidinium chloride and salt. However, urea subverts the Glu-induced intermediate formed by α-LA, whereas it only slightly destabilizes in the case of RNase A which has a positive surface charge and could possess charge-charge interactions with Glu. This suggests that, apart from hydration, columbic interactions might also contribute to the stability of the intermediate. Gdm-induced denaturation of RNase A and α-LA in the absence and the presence of Glu at different temperatures was carried out. These results also show the Glu-induced stabilization of both of the proteins; however, all of the unfolding transitions followed two

  20. Chemically induced aneuploidy in mammalian cells: mechanisms and biological significance in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oshimura, M.; Barrett, J.C.

    1986-01-01

    A literature review with over 200 references examines the growing body of evidence from human and animal cancer cytogenetics that aneuploidy is an important chromosome change in carcinogenesis. Evidence from in vitro cell transformation studies supports the idea that aneuploidy has a direct effect on the conversion of a normal cell to a preneoplastic or malignant cell. Induction of an aneuploid state in a preneoplastic or neoplastic cell could have any of the following four biological effects: a change in gene dosage, a change in gene balance, expression of a recessive mutation, or a change in genetic instability (which could secondarily lead to neoplasia). There are a number of possible mechanisms by which chemicals might induce aneuploidy, including effects on microtubules, damage to essential elements for chromosome function reduction in chromosome condensation or pairing, induction of chromosome interchanges, unresolved recombination structures, increased chromosome stickiness, damage to centrioles, impairment of chromosome alignment ionic alterations during mitosis, damage to the nuclear membrane, and a physical disruption of chromosome segregation. Therefore, a number of different targets exist for chemically induced aneuploidy.

  1. Radiated flow of chemically reacting nanoliquid with an induced magnetic field across a permeable vertical plate

    Directory of Open Access Journals (Sweden)

    B. Mahanthesh

    Full Text Available Impact of induced magnetic field over a flat porous plate by utilizing incompressible water-copper nanoliquid is examined analytically. Flow is supposed to be laminar, steady and two-dimensional. The plate is subjected to a regular free stream velocity as well as suction velocity. Flow formulation is developed by considering Maxwell–Garnetts (MG and Brinkman models of nanoliquid. Impacts of thermal radiation, viscous dissipation, temperature dependent heat source/sink and first order chemical reaction are also retained. The subjected non-linear problems are non-dimensionalized and analytic solutions are presented via series expansion method. The graphs are plotted to analyze the influence of pertinent parameters on flow, magnetism, heat and mass transfer fields as well as friction factor, current density, Nusselt and Sherwood numbers. It is found that friction factor at the plate is more for larger magnetic Prandtl number. Also the rate of heat transfer decayed with increasing nanoparticles volume fraction and the strength of magnetism. Keywords: Induced magnetic field, Nanoliquids, Heat source/sink, Series expansion method, Chemical reaction, Thermal radiation

  2. Effects of ion-neutral chemical reactions on dynamics of lightning-induced electric field

    International Nuclear Information System (INIS)

    Hiraki, Yasutaka

    2009-01-01

    Secondary lightning phenomena in the upper atmosphere called sprites attract interest from the viewpoint of atomic-molecular and plasma physics. Lightning-induced electric field accelerates the ionospheric electrons up to tens of electron-volts, inducing electrical breakdown as well as strong optical emissions, through electron impact ionization of molecules. A large-scale structure of sprites is constructed by collective dynamics of filamentary streamer discharges in a rarified gas, which in turn is controlled by the distribution of the background electric field. In this paper, we firstly reanalyze the relationship between quasi-static field formation and local ion chemistry with first-order perturbation techniques. Secondly, we investigate with a full ion chemical model the effects of electron attachment to oxygen molecules on its density in moderate cases of undervoltage lightning electric fields rather than the cases of intense ionization in streamers. We estimate the minimum values that are provided by the chemical balance with electron detachment from negative ions. We also investigate the recovery timescale of the electron density and find that the scale (≥1 s) is occasionally much larger than the interval of each lightning stroke (∼10 ms). We suggest that the subsequent sprite event as well as the field formation could be well affected by the ghost of the primary event. We discuss further the negative ion chemistry triggered by electron attachment in the nighttime mesosphere.

  3. Chemically-induced solid-state dewetting of thin Au films

    International Nuclear Information System (INIS)

    Gazit, Nimrod; Klinger, Leonid; Rabkin, Eugen

    2017-01-01

    We employed the solid state dewetting technique to produce nanoparticles of silver-gold alloy on a sapphire substrate. We deposited a thin gold layer on the substrate with alloy nanoparticles, and studied its thermal stability at low homological temperatures. We demonstrated that a large number of densely spaced holes form at the initial stages of dewetting of the gold layer with nanoparticles. A similar homogeneous gold film deposited on a bare sapphire substrate remained stable under identical annealing conditions, exhibiting the onset of dewetting at higher temperatures, and with a lower number of holes. We attributed the decreased thermal stability of the gold film deposited on the substrate with the silver-gold nanoparticles to accelerated grooving at the grain boundaries and triple junctions in the film. The grooving process is accelerated by the diffusion fluxes of Au atoms driven from the film towards the nanoparticles by the gradient of chemical potential. We developed a quantitative model of this chemically-induced dewetting process, and discussed its applicability for the design of better catalytic systems. Our work demonstrates that the chemical driving forces have to be reckoned with in the analysis of thermal stability of multicomponent thin films.

  4. Evaluation of Maltose-Induced Chemical Degradation at the Interface of Bilayer Tablets.

    Science.gov (United States)

    Matsuzaki, Naoya; Yamamoto, Yousuke; Murayama, Daisuke; Katakawa, Yoshifumi; Mimura, Hisashi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2017-01-01

    Fixed dose combination tablets consisting of mirabegron (MB) and solifenacin succinate (SS) were developed and formulated into bilayer tablets in the current study. The results of a chemical stability study showed that the original formulation for the tablets led to a significant increase of unknown degradants in the SS layer. Two compatibility studies were conducted to simulate the interface between the MB and SS layers, and the results revealed that the degradants only formed in the presence of both active pharmaceutical ingredients (APIs), and that the presence of maltose in the SS layer was critical to inducing degradation. High resolution mass spectroscopy coupled with high performance liquid chromatography was used to determine the chemical structures of the degradants, which were identified to MB derivatives bearing one or two sugar units. These findings therefore suggested that the degradation of the API could be attributed to the addition of sugar units from maltose to MB under the acidic conditions caused by SS. With this in mind, we developed a new formulation by replacing maltose with hydroxypropyl cellulose as a polymer-type binder. The results showed that this formulation suppressed the formation of the degradants. The results of this study have shown that chemical degradation can occur at the interface of bilayer tablets and that an alternative strategy is available to formulate more stable MB/SS bilayer tablets.

  5. Artificially induced polyploidization in Humulus lupulus L. and its effect on morphological and chemical traits.

    Science.gov (United States)

    Trojak-Goluch, Anna; Skomra, Urszula

    2013-12-01

    Chemically induced polyploids were obtained by the colchicine treatment of shoot tips of Humulus lupulus L. 'Sybilla'. Flow cytometry revealed that most of the treatments resulted in the production of tetraploids. The highest number of tetraploids was obtained when explants were immersed in 0.05% colchicine for 48 h. A field experiment was conducted to compare diploid and tetraploid plants and assess the effect of genome polyploidization on the morphological and chemical characteristics. Tetraploids showed significant differences in relation to diploids. They had thinner and shorter shoots. The influence of chromosome doubling was also reflected in the length, width and area of leaves. The length of female flowers in the tetraploids was significantly shorter than that observed in diploids. Tetraploids produced a diverse number of lupuline glands that were almost twice as large as those observed in diploids. The most distinct effect of genome polyploidization was a significant increase in the weight of cones and spindles. Contents of major chemical constituents of hop cones was little affected by ploidy level. Total essential oils were significantly lower than those in diploids. However there was a significant increase in the proportion of humulene, caryophyllene and farnesene, oils desired by the brewing industry.

  6. Phytohemagglutinin-induced change in the distribution of acidic sugars in surface membrane of lymphoid cells and blocking of the radiation effect

    International Nuclear Information System (INIS)

    Sato, C.; Kojima, K.

    1976-01-01

    Cell electrophoretic mobilities (EPM) of cultured lymphoblastoid cells were measured after removal of acidic sugars to investigate whether the localization of these acidic sugars was altered by the action of phytohaemagglutinin (PHA). After treatment with neuraminidase or hyaluronidase, the EPM of control cells decreased 50.1 and 0.3 percent, while that of PHA-treated cells decreased 25.2 and 39.0 percent, respectively. These results suggest that hyaluronic acid appeared at the periphery of the cell surface in place of some sialic acid after incubation with PHA. The change became evident after 10 min incubation with PHA and reached its maximum after 20 min at 37 0 C, but no change was observed at 4 0 C. The EPM decreased with time after x-irradiation, and reached a minimum value after 4 h. The addition of PHA to culture before irradiation completely blocked the x-ray mediated reduction in EPM. PHA administration after irradiation stopped further EPM reduction. These results seem to suggest a rapid rearrangement of membrane molecules linking with the receptors and acidic sugars induced by PHA, and blocking of further conformation change by x-irradiation

  7. Dasatinib blocks cetuximab- and radiation-induced nuclear translocation of the epidermal growth factor receptor in head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Li Chunrong; Iida, Mari; Dunn, Emily F.; Wheeler, Deric L.

    2010-01-01

    Background and purpose: The aberrant expression of epidermal growth factor receptor (EGFR) has been linked to the etiology of head and neck squamous cell carcinoma (HNSCC). The first major phase III trial combining cetuximab with radiation confirmed a strong survival advantage. However, both cetuximab and radiation can promote EGFR translocation to the nucleus where it enhances resistance to both of these modalities. In this report we sought to determine how to block cetuximab- and radiation-induced translocation of EGFR to the nucleus in HNSCC cell lines. Material and methods: We utilized three established HNSCC cell lines, SCC1, SCC6 and SCC1483 and measured nuclear translocation of EGFR after treatment with cetuximab or radiation. We then utilized dasatinib (BMS-354825), a potent, orally bioavailable inhibitor of several tyrosine kinases, including the Src family kinases, to determine if SFKs blockade could abrogate cetuximab- and radiation-induced nuclear EGFR translocation. Results: Cetuximab and radiation treatment of all three HNSCC lines lead to translocation of the EGFR to the nucleus. Blockade of SFKs abrogated cetuximab- and radiation-induced EGFR translocation to the nucleus. Conclusions: The data presented in this report suggest that both cetuximab and radiation can promote EGFR translocation to the nucleus and dasatinib can inhibit this process. Collectively these findings may suggest that dasatinib can limit EGFR translocation to the nucleus and may enhance radiotherapy plus cetuximab in HNSCC.

  8. Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy.

    Science.gov (United States)

    Freidl, Raphaela; Gstoettner, Antonia; Baranyi, Ulrike; Swoboda, Ines; Stolz, Frank; Focke-Tejkl, Margarete; Wekerle, Thomas; van Ree, Ronald; Valenta, Rudolf; Linhart, Birgit

    2017-06-01

    Fish is a frequent elicitor of severe IgE-mediated allergic reactions. Beside avoidance, there is currently no allergen-specific therapy available. Hypoallergenic variants of the major fish allergen, parvalbumin, for specific immunotherapy based on mutation of the 2 calcium-binding sites have been developed. This study sought to establish a mouse model of fish allergy resembling human disease and to investigate whether mouse and rabbit IgG antibodies induced by immunization with a hypoallergenic mutant of the major carp allergen protect against allergic symptoms in sensitized mice. C3H/HeJ mice were sensitized with recombinant wildtype Cyp c 1 or carp extract by intragastric gavage. Antibody, cellular immune responses, and epitope specificity in sensitized mice were investigated by ELISA, rat basophil leukemia assay, T-cell proliferation experiments using recombinant wildtype Cyp c 1, and overlapping peptides spanning the Cyp c 1 sequence. Anti-hypoallergenic Cyp c 1 mutant mouse and rabbit sera were tested for their ability to inhibit IgE recognition of Cyp c 1, Cyp c 1-specific basophil degranulation, and Cyp c 1-induced allergic symptoms in the mouse model. A mouse model of fish allergy mimicking human disease regarding IgE epitope recognition and symptoms as close as possible was established. Administration of antisera generated in mice and rabbits by immunization with a hypoallergenic Cyp c 1 mutant inhibited IgE binding to Cyp c 1, Cyp c 1-induced basophil degranulation, and allergic symptoms caused by allergen challenge in sensitized mice. Antibodies induced by immunization with a hypoallergenic Cyp c 1 mutant protect against allergic reactions in a murine model of fish allergy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy

    OpenAIRE

    Freidl, Raphaela; Gstoettner, Antonia; Baranyi, Ulrike; Swoboda, Ines; Stolz, Frank; Focke-Tejkl, Margarete; Wekerle, Thomas; van Ree, Ronald; Valenta, Rudolf; Linhart, Birgit

    2016-01-01

    Background Fish is a frequent elicitor of severe IgE-mediated allergic reactions. Beside avoidance, there is currently no allergen-specific therapy available. Hypoallergenic variants of the major fish allergen, parvalbumin, for specific immunotherapy based on mutation of the 2 calcium-binding sites have been developed. Objectives This study sought to establish a mouse model of fish allergy resembling human disease and to investigate whether mouse and rabbit IgG antibodies induced by immunizat...

  10. Polysaccharides from astragali radix restore chemical-induced blood vessel loss in zebrafish

    Science.gov (United States)

    2012-01-01

    Background Astragali Radix has been used widely for the treatment of cardiovascular and cerebrovascular diseases, and to enhance endurance and stamina in traditional Chinese medicine (TCM) for over 2000 years. The polysaccharide constituents of Astragali Radix (ARP) are considered as one of the major constituents contributing to the multiple pharmacological effects of this medicinal plant. The purpose of the study is to evaluate the vascular regenerative activities of ARPs in a chemically-induced blood vessel loss model in zebrafish. Methods Blood vessel loss was induced in both Tg(fli-1a:EGFP)y1 and Tg(fli-1a:nEGFP)y7 embryos by administration of 300 nM VEGFR tyrosine kinase inhibitor II (VRI) for 3 h at 24 hpf (hour post-fertilization). Then, the blood vessel damaged zebrafish were treated with ARPs for 21 h and 45 h after VRI withdrawal. Morphological changes in intersegmental vessels (ISVs) of zebrafish larvae were observed under the fluorescence microscope and measured quantitatively. The rescue effect of ARPs in the zebrafish models was validated by measuring the relative mRNA expressions of Kdrl, Kdr and Flt-1 using real-time PCR. Results Two polysaccharide fractions, P4 (50000 D 0.1 μm), isolated from Astragali Radix by ultrafiltration, produced a significant and dose-dependent recovery in VRI-induced blood vessel loss in zebrafish. Furthermore, the down-regulation of Flk-1 and Flt-1 mRNA expression induced by VRI was reversed by treatment with P4. Conclusion The present study demonstrates that P4 isolated from Astragali Radix reduces VRI-induced blood vessel loss in zebrafish. These findings support the hypothesis that polysaccharides are one of the active constituents in Astragali Radix, contributing to its beneficial effect on treatment of diseases associated with a deficiency in angiogenesis. PMID:22357377

  11. Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer

    Science.gov (United States)

    Pabla, Navjotsingh; Dong, Guie; Jiang, Man; Huang, Shuang; Kumar, M. Vijay; Messing, Robert O.; Dong, Zheng

    2011-01-01

    Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy. PMID:21633170

  12. Selenium and vitamin E inhibit radiogenic and chemically induced transformation in vitro via different mechanisms

    International Nuclear Information System (INIS)

    Borek, C.; Ong, A.; Mason, H.; Donahue, L.; Biaglow, J.E.

    1986-01-01

    Results from in vivo and in vitro studies showing that antioxidants may act as anticarcinogens support the role of active oxygen in carcinogenesis and provide impetus for exploring the functions of dietary antioxidants in cancer prevention by using in vitro models. The authors examined the single and combined effects of selenium, a component of glutathione peroxidase, and vitamin E, a known antioxidant, on cell transformation induced in C3H/10T-1/2 cells by x-rays, benzo[a]pyrene, or tryptophan pyrolysate and on the levels of cellular scavenging systems peroxide destruction. Incubation of C3H/10T-1/2 cells with 2.5 μM Na 2 SeO 3 (selenium) or with 7 μM α-tocopherol succinate (vitamin E) 24 hr prior to exposure to x-rays or the chemical carcinogens resulted in an inhibition of transformation by each of the antioxidants with an additive-inhibitory action when the two nutrients were combined. Cellular pretreatment with selenium resulted in increased levels of cellular glutathione peroxidase, catalase, and nonprotein thiols (glutathione) and in an enhanced destruction of peroxide. The results support our earlier studies showing that free radical-mediated events play a role in radiation and chemically induced transformation. They indicate that selenium and vitamin E act alone and in additive fashion as radioprotecting and chemopreventing agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown while vitamin E appears to confer its protection by and alternate complementary mechanism

  13. 3'-Hydroxy-3,4'-dimethoxyflavone blocks tubulin polymerization and is a potent apoptotic inducer in human SK-MEL-1 melanoma cells.

    Science.gov (United States)

    Estévez-Sarmiento, Francisco; Said, Mercedes; Brouard, Ignacio; León, Francisco; García, Celina; Quintana, José; Estévez, Francisco

    2017-11-01

    Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. A series of flavonols and their 3-methyl ether derivatives were synthesized and assessed for cytotoxicity. It was found that 3'-hydroxy-3,4'-dimethoxyflavone (flavonoid 7a) displayed strong cytotoxicity against human SK-MEL-1 melanoma cells and blocked tubulin polymerization, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. Our analyses showed that flavonoid 7a induces G 2 -M cell cycle arrest and apoptosis in melanoma cells which is associated with cytochrome c release and activation of both extrinsic and intrinsic apoptotic pathways of cell death. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Characterization of chemically induced liver injuries using gene co-expression modules.

    Directory of Open Access Journals (Sweden)

    Gregory J Tawa

    Full Text Available Liver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non-invasive diagnostic tests. Mapping chemical injuries to organ-specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests. Here, we have used DrugMatrix, a toxicogenomics database containing organ-specific gene expression data matched to dose-dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats, to identify groups of co-expressed genes (modules specific to injury endpoints in the liver. We identified 78 such gene co-expression modules associated with 25 diverse injury endpoints categorized from clinical pathology, organ weight changes, and histopathology. Using gene expression data associated with an injury condition, we showed that these modules exhibited different patterns of activation characteristic of each injury. We further showed that specific module genes mapped to 1 known biochemical pathways associated with liver injuries and 2 clinically used diagnostic tests for liver fibrosis. As such, the gene modules have characteristics of both generalized and specific toxic response pathways. Using these results, we proposed three gene signature sets characteristic of liver fibrosis, steatosis, and general liver injury based on genes from the co-expression modules. Out of all 92 identified genes, 18 (20% genes have well-documented relationships with liver disease, whereas the rest are novel and have not previously been associated with liver disease. In conclusion, identifying gene co-expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects.

  15. Exposure to Gulf War Illness chemicals induces functional muscarinic receptor maladaptations in muscle nociceptors.

    Science.gov (United States)

    Cooper, B Y; Johnson, R D; Nutter, T J

    2016-05-01

    Chronic pain is a component of the multisymptom disease known as Gulf War Illness (GWI). There is evidence that pain symptoms could have been a consequence of prolonged and/or excessive exposure to anticholinesterases and other GW chemicals. We previously reported that rats exposed, for 8 weeks, to a mixture of anticholinesterases (pyridostigmine bromide, chlorpyrifos) and a Nav (voltage activated Na(+) channel) deactivation-inhibiting pyrethroid, permethrin, exhibited a behavior pattern that was consistent with a delayed myalgia. This myalgia-like behavior was accompanied by persistent changes to Kv (voltage activated K(+)) channel physiology in muscle nociceptors (Kv7, KDR). In the present study, we examined how exposure to the above agents altered the reactivity of Kv channels to a muscarinic receptor (mAChR) agonist (oxotremorine-M). Comparisons between muscle nociceptors harvested from vehicle and GW chemical-exposed rats revealed that mAChR suppression of Kv7 activity was enhanced in exposed rats. Yet in these same muscle nociceptors, a Stromatoxin-insensitive component of the KDR (voltage activated delayed rectifier K(+) channel) exhibited decreased sensitivity to activation of mAChR. We have previously shown that a unique mAChR-induced depolarization and burst discharge (MDBD) was exaggerated in muscle nociceptors of rats exposed to GW chemicals. We now provide evidence that both muscle and vascular nociceptors of naïve rats exhibit MDBD. Examination of the molecular basis of the MDBD in naïve animals revealed that while the mAChR depolarization was independent of Kv7, the action potential burst was modulated by Kv7 status. mAChR depolarizations were shown to be dependent, in part, on TRPA1. We argue that dysfunction of the MDBD could be a functional convergence point for maladapted ion channels and receptors consequent to exposure to GW chemicals. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Effects of chemical-induced DNA damage on male germ cells

    Energy Technology Data Exchange (ETDEWEB)

    Holme, J.A.; Bjoerge, C.; Trbojevic, M.; Olsen, A.K.; Brunborg, G.; Soederlund, E.J. [National Inst. of Public Health, Oslo (Norway). Dept. of Environmental Medicine; Bjoeras, M.; Seeberg, E. [National Hospital, Oslo (Norway). Dept. of Microbiology; Scholz, T.; Dybing, E.; Wiger, R. [National Hospital, Oslo (Norway). Inst. for Surgical Research and Surgical Dept. B

    1998-12-31

    Several recent studies indicate declines in sperm production, as well as increases in the incidence of genitourinary abnormalities such as testicular cancer, cryptorchidism and hypospadias. It is not known if these effects are due to exposure to chemical pollutants or if other ethiological factors are involved. Animal studies indicate that chemicals will induce such effects by various genetic, epigenetic or non-genetic mechanisms. Recently, much attention has been focused on embryonic/fetal exposure to oestrogen-mimicking chemicals (Toppari et al., 1996). However, the possibility that chemicals may cause reproductive toxicity by other mechanisms such as interactions with DNA, should not be ignored. DNA damage in germ cells may lead to the production of mutated spermatozoa, which in turn may result in spontaneous abortions, malformations and/or genetic defects in the offspring. Regarding the consequences of DNA alterations for carcinogenesis it is possible that genetic damage may occur germ cells, but the consequences are not expressed until certain genetic events occur in postnatal life. Transmission of genetic risk is best demonstrated by cancer-prone disorders such as hereditary retinoblastoma and the Li-Fraumeni syndrome. A number of experiments indicate that germ cells and proliferating cells may be particularly sensitive to DNA damaging agents compared to other cells. Furthermore, several lines of evidence have indicated that one of the best documented male reproductive toxicants, 1,2-dibrome-3-chloropropane (DBCP), causes testicular toxicity through DNA damage. It is possible that testicular cells at certain maturational stages are more subject to DNA damage, have less efficient DNA repair, or have different thresholds for initiating apoptosis following DNA damage than other cell types. (orig.)

  17. Intercellular distribution of mutations induced in oopcytes of Drosophila melanogaster by chemical and physical mutagens

    International Nuclear Information System (INIS)

    Traut, H.

    1979-01-01

    When females of Drosophila melanogaster are treated with chemical or physical mutagens, not only in one but also in both of the two homologous X chromosomes of a given oocyte, a recessive sex-linked lethal mutation may be induced. A method is described that discriminates between such single and double mutations. A theory is developed to show how a comparison betweeen the expected and the observer frequency of double mutations yields an indication of the intercellular distribution (random or nonrandom) of recessive lethal mutations induced by mutagenic agents in oocytes and, consequently, of the distribution (homogenous or nonhomogeneous) of those agents. Three agents were tested: FUdR (12.5, 50.0 and 81.0 μg/ml), mitomycin C (130.0 μg/ml) and x rays (2000 R, 150 kV). After FUdR feeding, no increase in the mutation frequency usually observed in D. melanogaster without mutagenic treatment was obtained (u = 0.13%, namely three single mutations among 2332 chromosomes tested). After mitomycin C feeding 104 single and three double mutations were obtained. All of the 50 mutations observed after x irradiation were single mutations. The results obtained in the mitomycin C and radiation experiments favor the assumption of a random intercellular distribution of recessive lethal mutations induced by these two agents in oocytes of D. melanogaster. Reasons are discussed why for other types of mutagenic agents nonrandom distributions may be observed with our technique

  18. High protein mutants of winter fodder barley induced by radiation and chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Yankulov, M.; Genchev, K.; Nikolov, Kh.

    1982-01-01

    Several induced mutants of winter fodder barley with higher rpotein content are described. These mutants were produced by treating seeds of cvs. Vogelsaenger Gold, Ager and 468 with gamma-rays, sodium azide and ethyl methanesulfonate (alone and in combinations) and with ethylene and formamide. The gamma-ray induced mutants of winter fodder barley have 1-4% higher protein content. The mutant line 109 has, besides high protein content (17,37%), 5.96 lysine per 100 g protein, but its endosperm is wrinkeled. Mutants produced by chemical mutagens have 6-7% higher protein content than the initial cultivars. All induced mutants have 85-95 cm high stems, i.e. they are by 10-20 cm shorter than the initial cultivars. Some of these mutants are now resistant to the diseases Helminthosporium gramineum and Ustilago nuda. The recommended mutants could be successfully used in breeding programs for producing of higher protein content and quality in winter fodder barley.

  19. High protein mutants of winter fodder barley induced by radiation and chemical mutagens

    International Nuclear Information System (INIS)

    Yankulov, M.; Genchev, K.; Nikolov, Kh.

    1982-01-01

    Several induced mutants of winter fodder barley with higher rpotein content are described. These mutants were produced by treating seeds of cvs. Vogelsaenger Gold, Ager and 468 with gamma-rays, sodium azide and ethyl methanesulfonate (alone and in combinations) and with ethylene and formamide. The gamma-ray induced mutants of winter fodder barley have 1-4% higher protein content. The mutant line 109 has, besides high protein content (17,37%), 5.96 lysine per 100 g protein, but its endosperm is wrinkeled. Mutants produced by chemical mutagens have 6-7% higher protein content than the initial cultivars. All induced mutants have 85-95 cm high stems, i.e. they are by 10-20 cm shorter than the initial cultivars. Some of these mutants are now resistant to the diseases Helminthosporium gramineum and Ustilago nuda. The recommended mutants could be successfully used in breeding programs for producing of higher protein content and quality in winter fodder barley

  20. Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Jeong, Jae-Hoon [Division of Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Kang, Seongman [Division of Life Sciences, Korea University, Seoul 136-701 (Korea, Republic of); Lim, Young-Bin, E-mail: yblim@kirams.re.kr [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2014-07-25

    Highlights: • UPR activation precedes caspase activation in irradiated IEC-6 cells. • Chemical ER stress inducers radiosensitize IEC-6 cells. • siRNAs that targeted ER stress responses ameliorate IR-induced cell death. • Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

  1. Arsenic contamination of groundwater and its induced health effects in Shahpur block, Bhojpur district, Bihar state, India: risk evaluation.

    Science.gov (United States)

    Chakraborti, Dipankar; Rahman, Mohammad Mahmudur; Ahamed, Sad; Dutta, Rathindra Nath; Pati, Shyamapada; Mukherjee, Subhash Chandra

    2016-05-01

    The objective of this study was to determine the magnitude of groundwater arsenic contamination in Shahpur block of Bhojpur district, Bihar state, India and its health effects such as dermal, neurological, obstetric effects, and cancer risk. The School of Environmental Studies (SOES) collected 4704 tube-well water samples from all 88 villages of Shahpur, which were analyzed for arsenic. We found 40.3 and 21.1 % of the tube-wells had arsenic above 10 and 50 μg/l, respectively, with maximum concentration of 1805 μg/l. The study shows that 75,000, 39,000, and 10,000 people could be exposed to arsenic-contaminated water greater than 10, 50, and 300 μg/l, respectively. Our medical team examined 1422 villagers from Shahpur and registered 161 (prevalence rate, 11.3 %) with arsenical skin lesions. Arsenical skin lesions were also observed in 29 children of 525 screened. We analyzed 579 biological samples (hair, nail, and urine) from Shahpur and found that 82, 89, and 91 % of hair, nail, and urine, respectively, had arsenic above the normal levels, indicating many people in the study area are sub-clinically affected. Arsenical neuropathy was observed in 48 % of 102 arsenicosis patients. The study also found that arsenic exposed women with severe skin lesions had adversely affected their pregnancies. The carcinogenic and non-carcinogenic risks were also estimated based on the generated data. Safe drinking water supply is urgently required to combat arsenic situation in affected villages of Shahpur.

  2. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    International Nuclear Information System (INIS)

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-01-01

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

  3. Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1.

    Science.gov (United States)

    Gong, Haibin; Wang, Xiuli; Wang, Lei; Liu, Ying; Wang, Jie; Lv, Qian; Pang, Hui; Zhang, Qinglin; Wang, Zhenquan

    2017-07-01

    Bone marrow mesenchymal stem cells (BMSCs) have the potential to transdifferentiate into cardiomyocyte‑like cells (CLCs) if an appropriate cardiac environment is provided. Insulin‑like growth factor‑1 (IGF‑1) plays an important role in the cell migration, survival and differentiation of BMSCs. However, the effect of IGF‑1 on the cellular differentiation remains unclear. In the present study, BMSCs were isolated from rat femurs and tibias and the cells were purified at passage 6 (P6). IGF‑1 and IGF‑1 receptor (IGF‑1R) kinase inhibitor I‑OMe AG538 were added to detect if IGF‑1 could induce BMSCs to transdifferentiate into CLCs and if I‑OMe AG538 could inhibit IGF‑1‑mediated receptor activation and downstream signaling. Immunostaining demonstrated that all P6 BMSCs express CD29 and CD44 but not CD45. BMSCs induced by 15 ng/ml IGF‑1 revealed positivity for cardiac troponin‑T and cardiac troponin‑I. The optimal induction time was 14 days but the expression of these proteins were incompletely inhibited by 300 nmol/l I‑OMe AG538 and completely inhibited by 10 µmol/l I‑OMe AG538. Western blotting showed that the level of IGF‑1R autophosphorylation and the expression of cTnT and cTnI were higher when BMSCs were induced for 14 days. I‑OMe AG538 selectively inhibited IGF‑1‑mediated growth and signal transduction and the inhibitory effect of I‑OMe AG538 were not reverted in the presence of exogenous IGF‑1. In addition, when a time course analysis of the effects of I‑OMe AG538 on mitogen‑activated protein kinase kinase and phosphatidylinositol 3‑kinase signaling were done, we observed a transient inhibitory effect on Erk1/2 and Akt phosphorylation, in keeping with the inhibitory effects on cell growth. Taken together, these data indicate that I‑OMe AG538 could inhibit IGF-1-induced CLCs in BMSCs and this effect is time- and concentration-dependent.

  4. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-02-15

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

  5. Uniaxial backfill block compaction

    International Nuclear Information System (INIS)

    Koskinen, V.

    2012-05-01

    The main parts of the project were: to make a literature survey of the previous uniaxial compaction experiments; do uniaxial compaction tests in laboratory scale; and do industrial scale production tests. Object of the project was to sort out the different factors affecting the quality assurance chain of the backfill block uniaxial production and solve a material sticking to mould problem which appeared during manufacturing the blocks of bentonite and cruched rock mixture. The effect of mineralogical and chemical composition on the long term functionality of the backfill was excluded from the project. However, the used smectite-rich clays have been tested for mineralogical consistency. These tests were done in B and Tech OY according their SOPs. The objective of the Laboratory scale tests was to find right material- and compaction parameters for the industrial scale tests. Direct comparison between the laboratory scale tests and industrial scale tests is not possible because the mould geometry and compaction speed has a big influence for the compaction process. For this reason the selected material parameters were also affected by the previous compaction experiments. The industrial scale tests were done in summer of 2010 in southern Sweden. Blocks were done with uniaxial compaction. A 40 tons of the mixture of bentonite and crushed rock blocks and almost 50 tons of Friedland-clay blocks were compacted. (orig.)

  6. Self-grooming induced by sexual chemical signals in male root voles (Microtus oeconomus Pallas).

    Science.gov (United States)

    Yu, Honghao; Yue, Pengpeng; Sun, Ping; Zhao, Xinquan

    2010-03-01

    Sniffing is one-way animals collect chemical signals, and many males self-groom when they encounter the odor of opposite-sex conspecifics. We tested the hypothesis that sexual chemical signals from females can induce self-grooming behavior in male root voles (Microtus oeconomus Pallas). Specifically, we investigated the sniffing pattern of male root voles in response to odors from the head, trunk, and tail areas of lactating and non-lactating females. The self-grooming behavior of males in response to female individual odorant stimuli was documented, and the relationship between self-grooming and sniffing of odors from the head, trunk, and tails areas were analyzed. Sniffing pattern results showed that males are most interested in odors from the head area, and more interested in odors from the tail as compared to the trunk area. Males displayed different sniffing and self-grooming behaviors when they were exposed to odors from lactating females as compared to non-lactating females. Males also spent more time sniffing and engaged in more sniffing behaviors in response to odors from the lactating females' tail area as compared to the same odors from non-lactating females. Similarly, males spent more time self-grooming and engaged in more self-grooming behaviors in the presence of individual odors from lactating females as compared to individual odors from non-lactating females. Partial correlation analyses revealed that the frequency of self-grooming was significantly correlated with the frequency of tail area sniffs. Results from this experiment suggest that sexual attractiveness of lactating females is stronger than that of non-lactating females. Furthermore, the partial correlation analysis demonstrated that self-grooming in males is induced by odors from the tail area of females. Collectively, these results support the hypothesis that sexual chemical signals from females can induce self-grooming behavior in male root voles. Self-grooming may also reflect the

  7. Stevia Prevents Acute and Chronic Liver Injury Induced by Carbon Tetrachloride by Blocking Oxidative Stress through Nrf2 Upregulation

    Science.gov (United States)

    Ramos-Tovar, Erika; Hernández-Aquino, Erika; Casas-Grajales, Sael; Buendia-Montaño, Laura D.; Tsutsumi, Víctor

    2018-01-01

    The effect of stevia on liver cirrhosis has not been previously investigated. In the present study, the antioxidant and anti-inflammatory properties of stevia leaves were studied in male Wistar rats with carbon tetrachloride- (CCl4-) induced acute and chronic liver damage. Acute and chronic liver damage induced oxidative stress, necrosis, and cholestasis, which were significantly ameliorated by stevia. Chronic CCl4 treatment resulted in liver cirrhosis, as evidenced by nodules of hepatocytes surrounded by thick bands of collagen and distortion of the hepatic architecture, and stevia significantly prevented these alterations. Subsequently, the underlying mechanism of action of the plant was analyzed. Our study for the first time shows that stevia upregulated Nrf2, thereby counteracting oxidative stress, and prevented necrosis and cholestasis through modulation of the main proinflammatory cytokines via NF-κB inhibition. These multitarget mechanisms led to the prevention of experimental cirrhosis. Given the reasonable safety profile of stevia, our results indicated that it may be useful for the clinical treatment of acute and chronic liver diseases. PMID:29849889

  8. Critical role of surface chemical modifications induced by length shortening on multi-walled carbon nanotubes-induced toxicity

    Directory of Open Access Journals (Sweden)

    Bussy Cyrill

    2012-11-01

    Full Text Available Abstract Given the increasing use of carbon nanotubes (CNT in composite materials and their possible expansion to new areas such as nanomedicine which will both lead to higher human exposure, a better understanding of their potential to cause adverse effects on human health is needed. Like other nanomaterials, the biological reactivity and toxicity of CNT were shown to depend on various physicochemical characteristics, and length has been suggested to play a critical role. We therefore designed a comprehensive study that aimed at comparing the effects on murine macrophages of two samples of multi-walled CNT (MWCNT specifically synthesized following a similar production process (aerosol-assisted CVD, and used a soft ultrasonic treatment in water to modify the length of one of them. We showed that modification of the length of MWCNT leads, unavoidably, to accompanying structural (i.e. defects and chemical (i.e. oxidation modifications that affect both surface and residual catalyst iron nanoparticle content of CNT. The biological response of murine macrophages to the two different MWCNT samples was evaluated in terms of cell viability, pro-inflammatory cytokines secretion and oxidative stress. We showed that structural defects and oxidation both induced by the length reduction process are at least as responsible as the length reduction itself for the enhanced pro-inflammatory and pro-oxidative response observed with short (oxidized compared to long (pristine MWCNT. In conclusion, our results stress that surface properties should be considered, alongside the length, as essential parameters in CNT-induced inflammation, especially when dealing with a safe design of CNT, for application in nanomedicine for example.

  9. Rain-Induced Wash-Off of Chemical Warfare Agent (VX) from Foliar Surfaces of Living Plants Maintained in a Surety Hood

    Science.gov (United States)

    2016-09-01

    RAIN-INDUCED WASH-OFF OF CHEMICAL WARFARE AGENT (VX) FROM FOLIAR SURFACES OF LIVING PLANTS MAINTAINED IN A...Final 3. DATES COVERED (From - To) May 2014 – Sep 2015 4. TITLE AND SUBTITLE Rain-Induced Wash-Off of Chemical Warfare Agent (VX) from Foliar...galli Foliage Chemical warfare agent (CWA) O-ethyl-S-(2

  10. Successful tumour necrosis factor (TNF) blocking therapy suppresses oxidative stress and hypoxia-induced mitochondrial mutagenesis in inflammatory arthritis

    LENUS (Irish Health Repository)

    Biniecka, Monika

    2011-07-25

    Abstract Introduction To examine the effects of tumour necrosis factor (TNF) blocking therapy on the levels of early mitochondrial genome alterations and oxidative stress. Methods Eighteen inflammatory arthritis patients underwent synovial tissue oxygen (tpO2) measurements and clinical assessment of disease activity (DAS28-CRP) at baseline (T0) and three months (T3) after starting biologic therapy. Synovial tissue lipid peroxidation (4-HNE), T and B cell specific markers and synovial vascular endothelial growth factor (VEGF) were quantified by immunohistochemistry. Synovial levels of random mitochondrial DNA (mtDNA) mutations were assessed using Random Mutation Capture (RMC) assay. Results 4-HNE levels pre\\/post anti TNF-α therapy were inversely correlated with in vivo tpO2 (P < 0.008; r = -0.60). Biologic therapy responders showed a significantly reduced 4-HNE expression (P < 0.05). High 4-HNE expression correlated with high DAS28-CRP (P = 0.02; r = 0.53), tender joint count for 28 joints (TJC-28) (P = 0.03; r = 0.49), swollen joint count for 28 joints (SJC-28) (P = 0.03; r = 0.50) and visual analogue scale (VAS) (P = 0.04; r = 0.48). Strong positive association was found between the number of 4-HNE positive cells and CD4+ cells (P = 0.04; r = 0.60), CD8+ cells (P = 0.001; r = 0.70), CD20+ cells (P = 0.04; r = 0.68), CD68+ cells (P = 0.04; r = 0.47) and synovial VEGF expression (P = 0.01; r = 063). In patients whose in vivo tpO2 levels improved post treatment, significant reduction in mtDNA mutations and DAS28-CRP was observed (P < 0.05). In contrast in those patients whose tpO2 levels remained the same or reduced at T3, no significant changes for mtDNA mutations and DAS28-CRP were found. Conclusions High levels of synovial oxidative stress and mitochondrial mutation burden are strongly associated with low in vivo oxygen tension and synovial inflammation. Furthermore these significant mitochondrial genome alterations are rescued following successful anti TNF

  11. The ecotoxicogenomic assessment of soil toxicity associated with the production chain of 2,5-furandicarboxylic acid (FDCA), a candidate bio-based green chemical building block

    NARCIS (Netherlands)

    Chen, G.; van Straalen, N.M.; Roelofs, D.

    2016-01-01

    2,5-Furan dicarboxylic acid (FDCA) is one of the top-12 value-added chemicals derived from biomass that may serve as a 'green' substitute for terephthalic acid (TPA) in polyesters. FDCA can be synthesized chemically from 5-(hydroxymethyl)furfural (HMF), which is produced from fructose or glucose. To

  12. Single-wall carbon nanohorns inhibited activation of microglia induced by lipopolysaccharide through blocking of Sirt3

    Science.gov (United States)

    Li, Lihong; Zhang, Jinqian; Yang, Yang; Wang, Qiang; Gao, Li; Yang, Yanlong; Chang, Tao; Zhang, Xingye; Xiang, Guoan; Cao, Yongmei; Shi, Zujin; Zhao, Ming; Gao, Guodong

    2013-02-01

    Single-wall carbon nanohorns (SWNHs) have been demonstrated to accumulate in cytotoxic levels within organs of various animal models and cell types, which emerge as a wide range of promising biomedical imaging. Septic encephalopathy (SE) is an early sign of sepsis and associated with an increased rate of morbidity and mortality. Microglia activation plays an important role in neuroinflammation, which contributes to neuronal damage. Inhibition of microglia activation may have therapeutic benefits, which can alleviate the progression of neurodegeneration. Therefore, we investigated the functional changes of mice microglia cell lines pre-treated with or without lipopolysaccharide (LPS) induced by SWNHs. To address this question, the research about direct role of SWNHs on the growth, proliferation, and apoptosis of microglia cell lines in mice (N9 and BV2) pre-treated with or without LPS had been performed. Our results indicate that the particle diameter of SWNHs in water is between 342 to 712 nm. The images in scanning electron microscope showed that SWNHs on polystyrene surface are individual particles. LPS induced activation of mice microglia, promoted its growth and proliferation, and inhibited its apoptosis. SWNHs inhibited proliferation, delayed mitotic entry, and promoted apoptosis of mice microglia cells. The effects followed gradually increasing cultured time and concentrations of SWNHs, especially in cells pre-treated with LPS. SWNHs induced a significantly increase in G1 phase and inhibition of S phase of mice microglia cells in a dose-manner dependent of SWNHs, especially in cells pre-treated with LPS. The transmission electron microscope images showed that individual spherical SWNH particles smaller than 100 nm in diameters were localized inside lysosomes of mice microglia cells. SWNHs inhibited mitotic entry, growth and proliferation of mice microglia cells, and promoted its apoptosis, especially in cells pre-treated with LPS. SWNHs inhibited expression

  13. Transporter Protein-Coupled DPCPX Nanoconjugates Induce Diaphragmatic Recovery after SCI by Blocking Adenosine A1 Receptors.

    Science.gov (United States)

    Minic, Zeljka; Zhang, Yanhua; Mao, Guangzhao; Goshgarian, Harry G

    2016-03-23

    Respiratory complications in patients with spinal cord injury (SCI) are common and have a negative impact on the quality of patients' lives. Systemic administration of drugs that improve respiratory function often cause deleterious side effects. The present study examines the applicability of a novel nanotechnology-based drug delivery system, which induces recovery of diaphragm function after SCI in the adult rat model. We developed a protein-coupled nanoconjugate to selectively deliver by transsynaptic transport small therapeutic amounts of an A1 adenosine receptor antagonist to the respiratory centers. A single administration of the nanoconjugate restored 75% of the respiratory drive at 0.1% of the systemic therapeutic drug dose. The reduction of the systemic dose may obviate the side effects. The recovery lasted for 4 weeks (the longest period studied). These findings have translational implications for patients with respiratory dysfunction after SCI. The leading causes of death in humans following SCI are respiratory complications secondary to paralysis of respiratory muscles. Systemic administration of methylxantines improves respiratory function but also leads to the development of deleterious side effects due to actions of the drug on nonrespiratory sites. The importance of the present study lies in the novel drug delivery approach that uses nanotechnology to selectively deliver recovery-inducing drugs to the respiratory centers exclusively. This strategy allows for a reduction in the therapeutic drug dose, which may reduce harmful side effects and markedly improve the quality of life for SCI patients. Copyright © 2016 the authors 0270-6474/16/363441-12$15.00/0.

  14. High-intensity Aerobic Exercise Blocks the Facilitation of iTBS-induced Plasticity in the Human Motor Cortex.

    Science.gov (United States)

    Smith, Ashleigh E; Goldsworthy, Mitchell R; Wood, Fiona M; Olds, Timothy S; Garside, Tessa; Ridding, Michael C

    2018-03-01

    Acute exercise studies using transcranial magnetic stimulation (TMS) can provide important insights into the mechanisms underpinning the positive relationship between regular engagement in physical activity and cortical neuroplasticity. Emerging evidence indicates that a single session of aerobic exercise can promote the response to an experimentally induced suppressive neuroplasticity paradigm; however, little is known about the neuroplasticity response to facilitatory paradigms, including intermittent theta burst stimulation (iTBS). To more fully characterize the effects of exercise on brain plasticity we investigated if a single 30 min bout of high-intensity cycling (80% predicted heart rate reserve) modulated the response to an iTBS paradigm compared to rest. In 18 participants (9 females; 25.5 ± 5.0 years, range: 18-35 years) iTBS was applied using standard repetitive transcranial magnetic stimulation techniques immediately following exercise or 30 min of rest. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle at baseline, after the exercise/rest period but before iTBS, and at 5 time points following iTBS (0, 5, 10, 20 and 30 min). Contrary to our hypothesis, MEPs were suppressed following iTBS after a single 30 min bout of lower limb aerobic exercise compared to rest. These results indicate that acute aerobic exercise may not always enhance the response to an experimentally induced neuroplasticity paradigm. Further investigation of the factors that influence the relationship between exercise and neuroplasticity is warranted. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Molecular Dynamics Study of Thermally Augmented Nanodroplet Motion on Chemical Energy Induced Wettability Gradient Surfaces.

    Science.gov (United States)

    Chakraborty, Monojit; Chowdhury, Anamika; Bhusan, Richa; DasGupta, Sunando

    2015-10-20

    Droplet motion on a surface with chemical energy induced wettability gradient has been simulated using molecular dynamics (MD) simulation to highlight the underlying physics of molecular movement near the solid-liquid interface including the contact line friction. The simulations mimic experiments in a comprehensive manner wherein microsized droplets are propelled by the surface wettability gradient against forces opposed to motion. The liquid-wall Lennard-Jones interaction parameter and the substrate temperature are varied to explore their effects on the three-phase contact line friction coefficient. The contact line friction is observed to be a strong function of temperature at atomistic scales, confirming their experimentally observed inverse functionality. Additionally, the MD simulation results are successfully compared with those from an analytical model for self-propelled droplet motion on gradient surfaces.

  16. Chemically induced dynamic electron polarization. Pulse radiolysis of aqueous solutions of alcohols

    International Nuclear Information System (INIS)

    Trifunac, A.D.; Thurnauer, M.C.

    1975-01-01

    The radical pair model of chemically induced dynamic electron polarization (CIDEP) is experimentally verified. Aqueous solutions of alcohols were irradiated with 3 MeV electrons and observed with time resolved electron paramagnetic resonance (EPR) spectroscopy. Relative line intensities of the polarized EPR spectra of radicals from methanol and especially ethylene glycol, alone and in the presence of radicals from compounds containing halogens, illustrates the polarization dependence on the g-factor differences between the radical pair components. The observation of the relative polarization enhancement in the various lines of the multiline EPR spectra illustrates the polarization dependence on the hyperfine terms. Intrinsic enhancements are calculated and are shown to be proportional to the observed enhancement, showing that the radical pair model of CIDEP is qualitatively correct

  17. Chemical composition of waterfall-induced air ions: Spectrometry vs. simulations

    Energy Technology Data Exchange (ETDEWEB)

    Parts, T.-E.; Luts, A. [Tartu Univ. (Estonia). Dept. of Environmental Physics; Laakso, L.; Hirsikko, A.; Groenholm, T.; Kulmala, M. [Helsinki Univ. (Finland). Dept. of Physical Sciences

    2007-07-01

    Our measurements of ion size distributions near a waterfall provided new evidence for a waterfall-induced modification of air ion sizes. The ion size spectrum near a waterfall permanently differs from that in ordinary tropospheric air. In this paper we investigated the near-waterfall air ions chemical nature in detail. We carried out a simulation series of air small negative ion evolution, proposing that falling water, as a new environmental component, increases the concentration of OH{sup -} cluster ions. The produced OH{sup -} ions were employed as an extra input for our ion evolution model. The presence of additional OH{sup -} ions resulted in a decrease of typically model-provided NO{sub 3}{sup -} and/or HSO{sub 4}{sup -} cluster ion concentrations and an increase of the abundance of HCO{sub 3}{sup -} cluster ions. Near the waterfall the latter ions became dominant in our simulations. (orig.)

  18. Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

    Science.gov (United States)

    Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

    2013-01-01

    Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

  19. Radiation-Induced Chemical Dynamics in Ar Clusters Exposed to Strong X-Ray Pulses

    Science.gov (United States)

    Kumagai, Yoshiaki; Jurek, Zoltan; Xu, Weiqing; Fukuzawa, Hironobu; Motomura, Koji; Iablonskyi, Denys; Nagaya, Kiyonobu; Wada, Shin-ichi; Mondal, Subhendu; Tachibana, Tetsuya; Ito, Yuta; Sakai, Tsukasa; Matsunami, Kenji; Nishiyama, Toshiyuki; Umemoto, Takayuki; Nicolas, Christophe; Miron, Catalin; Togashi, Tadashi; Ogawa, Kanade; Owada, Shigeki; Tono, Kensuke; Yabashi, Makina; Son, Sang-Kil; Ziaja, Beata; Santra, Robin; Ueda, Kiyoshi

    2018-06-01

    We show that electron and ion spectroscopy reveals the details of the oligomer formation in Ar clusters exposed to an x-ray free electron laser (XFEL) pulse, i.e., chemical dynamics triggered by x rays. With guidance from a dedicated molecular dynamics simulation tool, we find that van der Waals bonding, the oligomer formation mechanism, and charge transfer among the cluster constituents significantly affect ionization dynamics induced by an XFEL pulse of moderate fluence. Our results clearly demonstrate that XFEL pulses can be used not only to "damage and destroy" molecular assemblies but also to modify and transform their molecular structure. The accuracy of the predictions obtained makes it possible to apply the cluster spectroscopy, in connection with the respective simulations, for estimation of the XFEL pulse fluence in the fluence regime below single-atom multiple-photon absorption, which is hardly accessible with other diagnostic tools.

  20. Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces Apoptosis

    Directory of Open Access Journals (Sweden)

    J. Bolnick

    2011-01-01

    Full Text Available We identified a major peptide signaling target of EGF/EGFR pathway and explored the consequences of blocking or activating this pathway in the first trimester extravillous trophoblast cells, HTR-8/SVneo. A global analysis of protein phosphorylation was undertaken using novel technology (Kinexus Kinetworks that utilizes SDS-polyacrylamide minigel electrophoresis and multi-lane immunoblotting to permit specific and semiquantitative detection of multiple phosphoproteins. Forty-seven protein phosphorylation sites were queried, and the results reported based on relative phosphorylation at each site. EGF- and Iressa-(gefitinib, ZD1839, an inhibitor of EGFR treated HTR-8/SVneo cells were subjected to immunoblotting and flow cytometry to confirm the phosphoprotein screen and to assess the effects of EGF versus Iressa on cell cycle and apoptosis. EGFR mediates the phosphorylation of important signaling proteins, including PKBα/AKT. This pathway is likely to be central to EGFR-mediated trophoblast survival. Furthermore, EGF treatment induces proliferation and inhibits apoptosis, while Iressa induces apoptosis.

  1. AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF and Endonuclease G (EndoG While Promoting Caspase Activation during Cardiac Ischemia

    Directory of Open Access Journals (Sweden)

    Shuai Yang

    2017-03-01

    Full Text Available The AKT (protein kinase B, PKB family has been shown to participate in diverse cellular processes, including apoptosis. Previous studies demonstrated that protein kinase B2 (AKT2−/− mice heart was sensitized to apoptosis in response to ischemic injury. However, little is known about the mechanism and apoptotic signaling pathway. Here, we show that AKT2 inhibition does not affect the development of cardiomyocytes but increases cell death during cardiomyocyte ischemia. Caspase-dependent apoptosis of both the extrinsic and intrinsic pathway was inactivated in cardiomyocytes with AKT2 inhibition during ischemia, while significant mitochondrial disruption was observed as well as intracytosolic translocation of cytochrome C (Cyto C together with apoptosis-inducing factor (AIF and endonuclease G (EndoG, both of which are proven to conduct DNA degradation in a range of cell death stimuli. Therefore, mitochondria-dependent cell death was investigated and the results suggested that AIF and EndoG nucleus translocation causes cardiomyocyte DNA degradation during ischemia when AKT2 is blocked. These data are the first to show a previous unrecognized function and mechanism of AKT2 in regulating cardiomyocyte survival during ischemia by inducing a unique mitochondrial-dependent DNA degradation pathway when it is inhibited.

  2. Transport stress induces heart damage in newly hatched chicks via blocking the cytoprotective heat shock response and augmenting nitric oxide production.

    Science.gov (United States)

    Sun, F; Zuo, Y-Z; Ge, J; Xia, J; Li, X-N; Lin, J; Zhang, C; Xu, H-L; Li, J-L

    2018-04-20

    Transport stress affects the animal's metabolism and psychological state. As a pro-survival pathway, the heat shock response (HSR) protects healthy cells from stressors. However, it is unclear whether the HSR plays a role in transport stress-induced heart damage. To evaluate the effects of transport stress on heart damage and HSR protection, newly hatched chicks were treated with transport stress for 2 h, 4 h and 8 h. Transport stress caused decreases in body weight and increases in serum creatine kinase (CK) activity, nitric oxide (NO) content in heart tissue, cardiac nitric oxide syntheses (NOS) activity and NOS isoforms transcription. The mRNA expression of heat shock factors (HSFs, including HSF1-3) and heat shock proteins (HSPs, including HSP25, HSP40, HSP47, HSP60, HSP70, HSP90 and HSP110) in the heart of 2 h transport-treated chicks was upregulated. After 8 h of transport stress in chicks, the transcription levels of the same HSPs and HSF2 were reduced in the heart. It was also found that the changes in the HSP60, HSP70 and HSP90 protein levels had similar tendencies. These results suggested that transport stress augmented NO generation through enhancing the activity of NOS and the transcription of NOS isoforms. Therefore, this study provides new evidence that transport stress induces heart damage in the newly hatched chicks by blocking the cytoprotective HSR and augmenting NO production.

  3. Pollution-Induced Community Tolerance To Diagnose Hazardous Chemicals in Multiple Contaminated Aquatic Systems.

    Science.gov (United States)

    Rotter, Stefanie; Gunold, Roman; Mothes, Sibylle; Paschke, Albrecht; Brack, Werner; Altenburger, Rolf; Schmitt-Jansen, Mechthild

    2015-08-18

    Aquatic ecosystems are often contaminated with large numbers of chemicals, which cannot be sufficiently addressed by chemical target analyses. Effect-directed analysis (EDA) enables the identification of toxicants in complex contaminated environmental samples. This study suggests pollution-induced community tolerance (PICT) as a confirmation tool for EDA to identify contaminants which actually impact on local communities. The effects of three phytotoxic compounds local periphyton communities, cultivated at a reference (R-site) and a polluted site (P-site), were assessed to confirm the findings of a former EDA study on sediments. The sensitivities of R- and P-communities to prometryn, tributyltin (TBT) and N-phenyl-2-naphthylamine (PNA) were quantified in short-term toxicity tests and exposure concentrations were determined. Prometryn and PNA concentrations were significantly higher at the P-site, whereas TBT concentrations were in the same range at both sites. Periphyton communities differed in biomass, but algal class composition and diatom diversity were similar. Community tolerance of P-communities was significantly enhanced for prometryn, but not for PNA and TBT, confirming site-specific effects on local periphyton for prometryn only. Thus, PICT enables in situ effect confirmation of phytotoxic compounds at the community level and seems to be suitable to support confirmation and enhance ecological realism of EDA.

  4. Aggregation-induced chemical reactions: acid dissociation in growing water clusters.

    Science.gov (United States)

    Forbert, Harald; Masia, Marco; Kaczmarek-Kedziera, Anna; Nair, Nisanth N; Marx, Dominik

    2011-03-23

    Understanding chemical reactivity at ultracold conditions, thus enabling molecular syntheses via interstellar and atmospheric processes, is a key issue in cryochemistry. In particular, acid dissociation and proton transfer reactions are ubiquitous in aqueous microsolvation environments. Here, the full dissociation of a HCl molecule upon stepwise solvation by a small number of water molecules at low temperatures, as relevant to helium nanodroplet isolation (HENDI) spectroscopy, is analyzed in mechanistic detail. It is found that upon successive aggregation of HCl with H(2)O molecules, a series of cyclic heteromolecular structures, up to and including HCl(H(2)O)(3), are initially obtained before a precursor state for dissociation, HCl(H(2)O)(3)···H(2)O, is observed upon addition of a fourth water molecule. The latter partially aggregated structure can be viewed as an "activated species", which readily leads to dissociation of HCl and to the formation of a solvent-shared ion pair, H(3)O(+)(H(2)O)(3)Cl(-). Overall, the process is mostly downhill in potential energy, and, in addition, small remaining barriers are overcome by using kinetic energy released as a result of forming hydrogen bonds due to aggregation. The associated barrier is not ruled by thermal equilibrium but is generated by athermal non-equilibrium dynamics. These "aggregation-induced chemical reactions" are expected to be of broad relevance to chemistry at ultralow temperature much beyond HENDI spectroscopy.

  5. Cadmium-induced disruption of environmental exploration and chemical communication in matrinxa, Brycon amazonicus

    International Nuclear Information System (INIS)

    Honda, R.T.; Fernandes-de-Castilho, M.; Val, A.L.

    2008-01-01

    The effects of cadmium exposure on both environment exploration and behavioral responses induced by alarm substance in matrinxa (Brycon amazonicus), a fish species endemic to the Amazon basin, were investigated. Fish exposed to 9.04 ± 0.07 μg/L waterborne cadmium for 96 h followed by 24 h depuration period in clean water, were video-recorded for 15 min, followed by immediate introduction of conspecific skin extract to the tank and a new 30 min period of fish video-recording. Cd-exposed matrinxa showed a significantly lowered locomotor activity (t-test t 12 = 2.7; p = 0.025) and spatial distribution (t-test t 12 = 2.4; p = 0.03) relative to the unexposed control fish prior to the alarm substance introduction, and did not present any significant reaction when the skin extract was introduced. The control fish, in opposite, showed a higher level of activity and spatial distribution prior the skin extract contact and significantly decreased their response after the chemical stimulus (locomotion-repeated-measure ANOVA F 1,11 = 5.6; p = 0.04; spatial distribution F 1,11 = 19.4; p = 0.001). In conclusion, exposure to a low level of cadmium affects both the environment exploration performance and the conspecific chemical communication in matrinxa. If the reduced environmental exploration performance of Cd-exposed fish is an adjustment to the compromised chemical communication or an independent effect of cadmium is the next step to be investigated

  6. Cadmium-induced disruption of environmental exploration and chemical communication in matrinxa, Brycon amazonicus

    Energy Technology Data Exchange (ETDEWEB)

    Honda, R.T. [Centro Universitario Nilton Lins - CUNL, Laboratory of Toxicology, Av. Prof. Nilton Lins 3259, Parque das Laranjeiras, Zip 69058-040 Manaus, AM (Brazil)], E-mail: rhonda@niltonlins.br; Fernandes-de-Castilho, M. [Universidade Federal do Parana - UFPR, Research Center on Animal Welfare (RECAW), Laboratory of Studies on Animal Stress, Department of Physiology, Sector of Biological Science, Jardim das Americas, Zip 81531-970 Curitiba, PR (Brazil); Val, A.L. [Instituto Nacional de Pesquisas da Amazonia - INPA, Laboratory of Ecophysiology and Molecular Evolution, Av. Andre Araujo 2936, Aleixo, Zip 69083-000 Manaus, AM (Brazil)

    2008-09-17

    The effects of cadmium exposure on both environment exploration and behavioral responses induced by alarm substance in matrinxa (Brycon amazonicus), a fish species endemic to the Amazon basin, were investigated. Fish exposed to 9.04 {+-} 0.07 {mu}g/L waterborne cadmium for 96 h followed by 24 h depuration period in clean water, were video-recorded for 15 min, followed by immediate introduction of conspecific skin extract to the tank and a new 30 min period of fish video-recording. Cd-exposed matrinxa showed a significantly lowered locomotor activity (t-test t{sub 12} = 2.7; p = 0.025) and spatial distribution (t-test t{sub 12} = 2.4; p = 0.03) relative to the unexposed control fish prior to the alarm substance introduction, and did not present any significant reaction when the skin extract was introduced. The control fish, in opposite, showed a higher level of activity and spatial distribution prior the skin extract contact and significantly decreased their response after the chemical stimulus (locomotion-repeated-measure ANOVA F{sub 1,11} = 5.6; p = 0.04; spatial distribution F{sub 1,11} = 19.4; p = 0.001). In conclusion, exposure to a low level of cadmium affects both the environment exploration performance and the conspecific chemical communication in matrinxa. If the reduced environmental exploration performance of Cd-exposed fish is an adjustment to the compromised chemical communication or an independent effect of cadmium is the next step to be investigated.

  7. Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1.

    Science.gov (United States)

    Ghadge, Ghanashyam D; Pavlovic, John D; Koduvayur, Sujatha P; Kay, Brian K; Roos, Raymond P

    2013-08-01

    Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and ~25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons (MNs) because of a gain-of-function toxicity, most likely related to aggregation of mtSOD1. A number of recent reports have suggested that antibodies can be used to treat mtSOD1-induced FALS. To follow up on the use of antibodies as potential therapeutics, we generated single chain fragments of variable region antibodies (scFvs) against SOD1, and then expressed them as 'intrabodies' within a motor neuron cell line. In the present study, we describe isolation of human scFvs that interfere with mtSOD1 in vitro aggregation and toxicity. These scFvs may have therapeutic potential in sporadic ALS, as well as FALS, given that sporadic ALS may also involve abnormalities in the SOD1 protein or activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Potential for supernova-induced chemical enrichment of protoglobular cluster clouds

    International Nuclear Information System (INIS)

    Dopita, M.A.; Smith, G.H.; Dominion Astrophysical Observatory, Victoria, Canada)

    1986-01-01

    This paper seeks to explain the large internal abundance variations that are seen in the globular cluster Omega Cen in terms of supernova-induced chemical enrichment that occurred when the cluster was still largely in a gaseous phase and star formation was continuing. Using a simple power-law density model of this protoglobular gas cloud, the conditions under which this can occur have been established analytically. Clouds less massive than about 100,000 solar masses are completely disrupted by supernova explosions in their adiabatic phase. In clouds of greater mass, supernova explosions occurring near the tidal radius tend to lose their hot gas and metals to the intercloud medium. For explosions occurring closer to the mass center the ejecta must be slowed below the escape velocity, and this can only occur in clouds more massive than about 3 x 10 to the 6th solar masses. If this condition is met, then the slow isothermal momentum-conserving shocks generated by the supernova explosions may eventually induce secondary star formation. For such shocks converging on the mass center, it is found that a cloud mass of at least 10 to the 7th solar masses is required for this process to be efficient. From the observed properties of Omega Cen, a primordial mass of order 10 to the 8th solar masses is estimated, which emphasizes the unusual character of this object. 39 references

  9. Conditionally controlling nuclear trafficking in yeast by chemical-induced protein dimerization.

    Science.gov (United States)

    Xu, Tao; Johnson, Cole A; Gestwicki, Jason E; Kumar, Anuj

    2010-11-01

    We present here a protocol to conditionally control the nuclear trafficking of target proteins in yeast. In this system, rapamycin is used to heterodimerize two chimeric proteins. One chimera consists of a FK506-binding protein (FKBP12) fused to a cellular 'address' (nuclear localization signal or nuclear export sequence). The second chimera consists of a target protein fused to a fluorescent protein and the FKBP12-rapamycin-binding (FRB) domain from FKBP-12-rapamycin associated protein 1 (FRAP1, also known as mTor). Rapamycin induces dimerization of the FKBP12- and FRB-containing chimeras; these interactions selectively place the target protein under control of the cell address, thereby directing the protein into or out of the nucleus. By chemical-induced dimerization, protein mislocalization is reversible and enables the identification of conditional loss-of-function and gain-of-function phenotypes, in contrast to other systems that require permanent modification of the targeted protein. Yeast strains for this analysis can be constructed in 1 week, and the technique allows protein mislocalization within 15 min after drug treatment.

  10. Chemical and biological insights into uranium-induced apoptosis of rat hepatic cell line

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Fang; You, Yong [University of South China, College of Hunan Province, Key Laboratory of Tumor Cellular and Molecular Pathology, Hengyang (China); Du, Ke-Jie [University of South China, School of Chemistry and Chemical Engineering, Hengyang (China); Fang, Zhen [Anhui Normal University, College of Chemistry and Materials Science, Wuhu (China); Wen, Ge-Bo [University of South China, College of Hunan Province, Key Laboratory of Tumor Cellular and Molecular Pathology, Hengyang (China); University of South China, Laboratory of Protein Structure and Function, Hengyang (China); Lin, Ying-Wu [University of South China, School of Chemistry and Chemical Engineering, Hengyang (China); University of South China, Laboratory of Protein Structure and Function, Hengyang (China)

    2015-05-15

    Uranium release into the environment is a threat to human health, and the mechanisms of cytotoxicity caused by uranium are not well-understood. To improve our understanding in this respect, we herein evaluated the effects of uranium exposure on normal rat hepatic BRL cells. As revealed by scanning electron microscopy and transmission electron microscope analysis, uranyl nitrate was found to be transformed into uranyl phosphate particles in the medium and taken up by BRL cells in an endocytotic uptake manner, which presumably initiates apoptosis of the cell, although soluble uranyl ion may also be toxic. The apoptosis of BRL cells upon uranium exposure was also confirmed by both the acridine orange and ethidium bromide double staining assay and the Annexin V/propidium iodide double staining assay. Further studies revealed that uranium induced the loss of mitochondrial membrane potential in a dose-dependent manner. Moreover, the uranium-induced apoptosis was found to be associated with the activation of caspase-3, caspase-8 and caspase-9, indicating both a mitochondria-dependent signaling pathway and a death receptor pathway by a crosstalk. This study provides new chemical and biological insights into the mechanism of uranium toxicity toward hepatic cells, which will help seek approaches for biological remediation of uranium. (orig.)

  11. Near-field photochemical and radiation-induced chemical fabrication of nanopatterns of a self-assembled silane monolayer

    Directory of Open Access Journals (Sweden)

    Ulrich C. Fischer

    2014-09-01

    Full Text Available A general concept for parallel near-field photochemical and radiation-induced chemical processes for the fabrication of nanopatterns of a self-assembled monolayer (SAM of (3-aminopropyltriethoxysilane (APTES is explored with three different processes: 1 a near-field photochemical process by photochemical bleaching of a monomolecular layer of dye molecules chemically bound to an APTES SAM, 2 a chemical process induced by oxygen plasma etching as well as 3 a combined near-field UV-photochemical and ozone-induced chemical process, which is applied directly to an APTES SAM. All approaches employ a sandwich configuration of the surface-supported SAM, and a lithographic mask in form of gold nanostructures fabricated through colloidal sphere lithography (CL, which is either exposed to visible light, oxygen plasma or an UV–ozone atmosphere. The gold mask has the function to inhibit the photochemical reactions by highly localized near-field interactions between metal mask and SAM and to inhibit the radiation-induced chemical reactions by casting a highly localized shadow. The removal of the gold mask reveals the SAM nanopattern.

  12. Prefrontal cortex or basolateral amygdala lesions blocked the stress-induced inversion of serial memory retrieval pattern in mice.

    Science.gov (United States)

    Chauveau, F; Piérard, C; Coutan, M; Drouet, I; Liscia, P; Béracochéa, D

    2008-09-01

    Previous data from our team have shown that pre-test stress in mice reversed the pattern of memory retrieval in a contextual serial spatial task (CSD; Celerier, A., Pierard, C., Rachbauer, D., Sarrieau, A., & Beracochea, D. (2004). Contextual and serial discriminations: A new learning paradigm to assess simultaneously the effects of acute stress on retrieval of flexible or stable information in mice. Learning and Memory, 11, 196-204). The present study is aimed at determining brain areas which might be critically involved in mediating the stress effect on memory retrieval in the CSD task. For that purpose, we studied hereby the effects of ibotenic acid lesions of either the prefrontal cortex (PFC) or the basolateral amygdala (BLA) in Stressed or Non-Stressed Balb/c mice on memory retrieval in the CSD task. In that task, mice learned two successive spatial discriminations (D1 and D2) within two different internal contexts in a four-hole board. The stressor (electric footshocks) was delivered 5 min before test, occurring 24 h after acquisition. During test, mice were relocated either on the floor of the first or of the second discrimination. Results showed that (i) spatial memory was substantial and remained unaffected both by lesions and stress; (ii) Non-Stressed controls as well as Non-Stressed or Stressed PFC and BLA-lesioned mice remembered accurately D1 but not D2; and (iii) in contrast, Stressed controls accurately remembered D2 but not D1. In parallel to behavioral experiments, we also showed that PFC and BLA lesions did not affect the stress-induced increase of plasma corticosterone levels. All together, PFC and BLA integrity are not necessary for retrieval processes per se; in contrast, the PFC and BLA are critically involved in the mediation of the deleterious stress effects on serial order memory retrieval.

  13. Lead (Pb+2) impairs long-term memory and blocks learning-induced increases in hippocampal protein kinase C activity

    International Nuclear Information System (INIS)

    Vazquez, Adrinel; Pena de Ortiz, Sandra

    2004-01-01

    The long-term storage of information in the brain known as long-term memory (LTM) depends on a variety of intracellular signaling cascades utilizing calcium (Ca 2+ ) and cyclic adenosine monophosphate as second messengers. In particular, Ca +2 /phospholipid-dependent protein kinase C (PKC) activity has been proposed to be necessary for the transition from short-term memory to LTM. Because the neurobehavioral toxicity of lead (Pb +2 ) has been associated to its interference with normal Ca +2 signaling in neurons, we studied its effects on spatial learning and memory using a hippocampal-dependent discrimination task. Adult rats received microinfusions of either Na + or Pb +2 acetate in the CA1 hippocampal subregion before each one of four training sessions. A retention test was given 7 days later to examine LTM. Results suggest that intrahippocampal Pb +2 did not affect learning of the task, but significantly impaired retention. The effects of Pb +2 selectively impaired reference memory measured in the retention test, but had no effect on the general performance because it did not affect the latency to complete the task during the test. Finally, we examined the effects of Pb +2 on the induction of hippocampal Ca +2 /phospholipid-dependent PKC activity during acquisition training. The results showed that Pb +2 interfered with the learning-induced activation of Ca +2 /phospholipid-dependent PKC on day 3 of acquisition. Overall, our results indicate that Pb +2 causes cognitive impairments in adult rats and that such effects might be subserved by interference with Ca +2 -related signaling mechanisms required for normal LTM

  14. Post-sensitization treatment with rimonabant blocks the expression of cocaine-induced behavioral sensitization and c-Fos protein in mice.

    Science.gov (United States)

    Marinho, Eduardo A V; Oliveira-Lima, Alexandre J; Yokoyama, Thais S; Santos-Baldaia, Renan; Ribeiro, Luciana T C; Baldaia, Marilia A; da Silva, Raphael Wuo; Hollais, Andre Willian; Talhati, Fernanda; Longo, Beatriz Monteiro; Berro, Lais Fernanda; Frussa-Filho, Roberto

    2017-05-01

    CB1 receptor antagonists have been shown to prevent acute and long-term behavioral effects of cocaine. Here we evaluate the effectiveness of the CB1 receptor antagonist rimonabant to modify sensitized responses to cocaine. Mice were treated with saline or cocaine injections in a 15-day intermittent sensitization treatment and subsequently treated with either vehicle, 1 or 10mg/kg rimonabant in the drug-associated environment for 8 consecutive days. Animals were then challenged with saline and cocaine in the open-field apparatus on subsequent days to evaluate the expression of conditioned and sensitized effects to cocaine. c-Fos protein expression was evaluated in the nucleus accumbens (NAcc), ventral tegmental area (VTA), basolateral amygdala (BLA), medial prefrontal cortex (mPFC) and caudate-putamen (CPu) after the last (cocaine) challenge. Previous treatment with 10mg/kg rimonabant blocked the expression of conditioned hyperlocomotion and behavioral sensitization to cocaine, but not acute cocaine-induced hyperlocomotion. These behavioral effects were accompanied by significant changes in c-Fos expression in the brain reward system. Chronic cocaine sensitization blunted a subsequent acute cocaine-induced increase in c-Fos protein in the NAcc, effect that was reversed by previous treatment with rimonabant. Treatment with 10mg/kg rimonabant also attenuated the significant increase in c-Fos expression in the CPu, mPFC and BLA induced by previous chronic sensitization with cocaine. Our findings add to the evidence that drugs targeting CB1 receptors are good candidates for the treatment of cocaine abuse and provide further insights into the mechanisms underlying endocannabinoid signaling within the brain reward system in the context of cocaine abuse. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yi; Chen, Na; Liu, Xiaojing; Lin, Shumei [Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China); Luo, Wenjuan, E-mail: wenjuanluoxa@163.com [School of Pharmacy, Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China); Liu, Min, E-mail: minliusx@163.com [Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China)

    2016-07-01

    With the increased burden induced by HCV, there is an urgent need to develop better-tolerated agents with good safety. In this study, we evaluated the anti-HCV capability of kushenin, as well as the possible mechanism to Huh7.5-HCV cells. The results demonstrated that kushenin significantly inhibited the HCV-RNA level. Similarly, the expression of HCV-specific protein NS5A was also decreased. Molecular docking results displayed that kushenin bonded well to the active pockets of HCV NS5A, further confirming the effects of kushenin on HCV replication. Coimmunoprecipitation assay determined that kushenin suppressed the interaction between PI3K and NS5A in HCV-replicon cells. Furthermore, kushenin exerted an obviously induced function on HCV-replicon cells apoptosis by inhibiting PI3K-Akt-mTOR pathway, which could be ameliorated by the specific activator IGF-1 addition. Taken together, kushenin possesses the ability to inhibit HCV replication, and contributes to the increased apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A. Our results provide important evidence for a better understanding of the pathogenesis of HCV infection, and suggest that kushenin has the potential to treat HCV disease. - Highlights: • Kushenin inhibits HCV replication. • Kushenin bonds directly to NS5A protein. • Kushenin induces the apoptosis of HCV-infected cells. • kushenin suppresses the interaction between PI3K and NS5A. • Kushenin inhibits PI3K-Akt-mTOR pathway.

  16. Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter.

    Science.gov (United States)

    Kim, Joo Ae; Lee, Somyoung; Kim, Da-Eun; Kim, Moonil; Kwon, Byoung-Mog; Han, Dong Cho

    2015-06-01

    Heat shock factor 1 (HSF1) is a transcription factor for heat shock proteins (HSPs) expression that enhances the survival of cancer cells exposed to various stresses. HSF1 knockout suppresses carcinogen-induced cancer induction in mice. Therefore, HSF1 is a promising therapeutic and chemopreventive target. We performed cell-based screening with a natural compound collection and identified fisetin, a dietary flavonoid, as a HSF1 inhibitor. Fisetin abolished heat shock-induced luciferase activity with an IC50 of 14 μM in HCT-116 cancer cells. The treatment of HCT-116 with fisetin inhibited proliferation with a GI50 of 23 μM. When the cells were exposed to heat shock in the presence of fisetin, the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 (Bcl-2-associated athanogene domain 3), were inhibited. HSP70/BAG3 complexes protect cancer cells from apoptosis by stabilizing anti-apoptotic Bcl-2 family proteins. The downregulation of HSP70/BAG3 by fisetin significantly reduced the amounts of Bcl-2, Bcl-xL and Mcl-1 proteins, subsequently inducing apoptotic cell death. Chromatin immunoprecipitation assays showed that fisetin inhibited HSF1 activity by blocking the binding of HSF1 to the hsp70 promoter. Intraperitoneal treatment of nude mice with fisetin at 30mg/kg resulted in a 35.7% (P < 0.001) inhibition of tumor growth. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A

    International Nuclear Information System (INIS)

    Zhou, Yi; Chen, Na; Liu, Xiaojing; Lin, Shumei; Luo, Wenjuan; Liu, Min

    2016-01-01

    With the increased burden induced by HCV, there is an urgent need to develop better-tolerated agents with good safety. In this study, we evaluated the anti-HCV capability of kushenin, as well as the possible mechanism to Huh7.5-HCV cells. The results demonstrated that kushenin significantly inhibited the HCV-RNA level. Similarly, the expression of HCV-specific protein NS5A was also decreased. Molecular docking results displayed that kushenin bonded well to the active pockets of HCV NS5A, further confirming the effects of kushenin on HCV replication. Coimmunoprecipitation assay determined that kushenin suppressed the interaction between PI3K and NS5A in HCV-replicon cells. Furthermore, kushenin exerted an obviously induced function on HCV-replicon cells apoptosis by inhibiting PI3K-Akt-mTOR pathway, which could be ameliorated by the specific activator IGF-1 addition. Taken together, kushenin possesses the ability to inhibit HCV replication, and contributes to the increased apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A. Our results provide important evidence for a better understanding of the pathogenesis of HCV infection, and suggest that kushenin has the potential to treat HCV disease. - Highlights: • Kushenin inhibits HCV replication. • Kushenin bonds directly to NS5A protein. • Kushenin induces the apoptosis of HCV-infected cells. • kushenin suppresses the interaction between PI3K and NS5A. • Kushenin inhibits PI3K-Akt-mTOR pathway.

  18. The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells

    International Nuclear Information System (INIS)

    Cherukuri, Durga Prasad; Chen, Xiao B.O.; Goulet, Anne-Christine; Young, Robert N.; Han, Yongxin; Heimark, Ronald L.; Regan, John W.; Meuillet, Emmanuelle; Nelson, Mark A.

    2007-01-01

    Accumulating evidence indicates that elevated levels of prostaglandin E 2 (PGE 2 ) can increase intestinal epithelial cell proliferation, and thus play a role in colorectal tumorigenesis. PGE 2 exerts its effects through four G-protein-coupled PGE receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE 2 to stimulate cell proliferation of human colon cancer cells. However, the EP receptor(s) that are involved in this process remain unknown. We provide evidence that L-161,982, a selective EP4 receptor antagonist, completely blocks PGE 2 -induced ERK phosphorylation and cell proliferation of HCA-7 cells. In order to identify downstream target genes of ERK1/2 signaling, we found that PGE 2 induces expression of early growth response gene-1 (EGR-1) downstream of ERK1/2 and regulates its expression at the level of transcription. PGE 2 treatment induces phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 residue and CRE-mediated luciferase activity in HCA-7 cells. Studies with dominant-negative CREB mutant (ACREB) provide clear evidence for the involvement of CREB in PGE 2 driven egr-1 transcription in HCA-7 cells. In conclusion, this study reveals that egr-1 is a target gene of PGE 2 in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. Finally our results support the notion that antagonizing EP4 receptors may provide a novel therapeutic approach to the treatment of colon cancer

  19. H-2 restriction of the T cell response to chemically induced tumors: evidence from F1 → parent chimeras

    International Nuclear Information System (INIS)

    Lannin, D.R.; Yu, S.; McKhann, C.F.

    1982-01-01

    It has been well established that T cells that react to tumor antigen on virus-induced tumors must share H-2D or H-2K specificities with the tumor. It has been impossible to perform similar studies with chemically induced tumors because each chemically induced tumor expresses a unique tumor antigen that cannot be studied in association with other H-2 types. This study provies evidence that H-2 recognition is also necessary for recognition of chemically induced tumors. We have found that F 1 → parent chimeras preferentially recognize chemically induced tumors of parental H-2 type. C3H/HeJ and C57BL/6 mice were lethally irradiated and restored with (C3H x C57BL/6) F 1 hybrid bone marrow. The F 1 → C3H chimera but not the F 1 → C57BL/6 chimera was able to respond to a C3H fibrosarcoma in mixed lymphocyte-tumor cell culture and also to neutralize the tumor in an in vivo tumor neutralization assay. On the other hand, the F 1 → C57BL/6 chimera but not the F 1 → C3H chimera was able to kill the C57BL/6 lymphoma EL4 in an in vitro cytotoxicity assay. Both chimeras were tolerant to C3H and C57BL/6 alloantigens but could respond normally to Con A and to BALB/c spleen cells in mixed lymphocyte cultures and cytotoxicity assay

  20. Chemical-based risk assessment and in vitro models of human health effects induced by organic pollutants in soils from the Olona valley

    Energy Technology Data Exchange (ETDEWEB)

    Baderna, Diego, E-mail: diego.baderna@marionegri.it; Colombo, Andrea; Amodei, Giorgia; Cantù, Stefano; Teoldi, Federico; Cambria, Felice; Rotella, Giuseppe; Natolino, Fabrizio; Lodi, Marco; Benfenati, Emilio

    2013-10-01

    Risk assessment of soils is usually based on chemical measurements and assuming accidental soil ingestion and evaluating induced toxic and carcinogenic effects. Recently biological tools have been coupled to chemical-based risk assessment since they integrate the biological effects of all xenobiotics in soils. We employed integrated monitoring of soils based on chemical analyses, risk assessment and in vitro models in the highly urbanized semirural area of the Olona Valley in northern Italy. Chemical characterization of the soils indicated low levels of toxic and carcinogenic pollutants such as PAHs, PCDD/Fs, PCBs and HCB and human risk assessment did not give any significant alerts. HepG2 and BALB/c 3T3 cells were used as a model for the human liver and as a tool for the evaluation of carcinogenic potential. Cells were treated with soil extractable organic matters (EOMs) and the MTS assay, LDH release and morphological transformation were selected as endpoints for toxicity and carcinogenicity. Soil EOMs induced dose-dependent inhibition of cell growth at low doses and cytotoxicity after exposure to higher doses. This might be the result of block of cell cycle progression to repair DNA damage caused by oxidative stress; if this DNA damage cannot be repaired, cells die. No significant inductions of foci were recorded after exposure to EOMs. These results indicate that, although the extracts contain compounds with proven carcinogenic potential, the levels of these pollutants in the analyzed soils were too low to induce carcinogenesis in our experimental conditions. In this proposed case study, HepG2 cells were found an appropriate tool to assess the potential harm caused by the ingestion of contaminated soil as they were able to detect differences in the toxicity of soil EOMs. Moreover, the cell transformation assay strengthened the combined approach giving useful information on carcinogenic potential of mixtures. Highlights: • A combined approach for risk

  1. Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies.

    Directory of Open Access Journals (Sweden)

    Atul Asati

    Full Text Available Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013-2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA

  2. Epicutaneous immunotherapy (EPIT blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice.

    Directory of Open Access Journals (Sweden)

    Lucie Mondoulet

    Full Text Available Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT on these processes.Mice were sensitized by gavages with whole peanut protein extract (PPE given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure.Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm(2 and reduced villus/crypt ratios (1.6±0.15. In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines as well as esophageal eosinophilia (50 eosinophils/mm(2, p<0.05, mRNA expression of Th2 cytokines in tissue--eotaxin (p<0.05, IL-5 (p<0.05, and IL-13 (p<0.05--GATA-3 (p<0.05, and intestinal villus sub-atrophia (2.3±0.15. EPIT also increased specific IgG2a (p<0.05 and mRNA expression of Foxp3 (p<0.05 in the esophageal mucosa.Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.

  3. Magnesium isoglycyrrhizinate blocks fructose-induced hepatic NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder.

    Science.gov (United States)

    Zhao, Xiao-Juan; Yang, Yan-Zi; Zheng, Yan-Jing; Wang, Shan-Chun; Gu, Hong-Mei; Pan, Ying; Wang, Shui-Juan; Xu, Hong-Jiang; Kong, Ling-Dong

    2017-08-15

    Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels. Furthermore, magnesium isoglycyrrhizinate modulated lipid metabolism-related genes characterized by up-regulating peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyl transferase-1 (CPT-1), and down-regulating sensor for fatty acids to control-1 (SREBP-1) and stearoyl-CoA desaturase 1 (SCD-1) in the liver of fructose-fed rats, resulting in the reduction of triglyceride and total cholesterol levels. These effective actions were further confirmed in fructose-exposed BRL-3A and HepG2 cells. The molecular mechanisms underpinning these observations suggest that magnesium isoglycyrrhizinate may inhibit NF-κB/NLRP3 inflammasome activation to reduce immunological-inflammatory response, which in turn may prevent liver lipid metabolic disorder and accumulation under high fructose condition. Thus, blockade of NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder by magnesium isoglycyrrhizinate may be the potential therapeutic approach for improving fructose-induced liver injury with

  4. Isolation, chemical and functional characterization of several new K(+)-channel blocking peptides from the venom of the scorpion Centruroides tecomanus.

    Science.gov (United States)

    Olamendi-Portugal, Timoteo; Bartok, Adam; Zamudio-Zuñiga, Fernando; Balajthy, Andras; Becerril, Baltazar; Panyi, Gyorgy; Possani, Lourival D

    2016-06-01

    Six new peptides were isolated from the venom of the Mexican scorpion Centruroides tecomanus; their primary structures were determined and the effects on ion channels were verified by patch-clamp experiments. Four are K(+)-channel blockers of the α-KTx family, containing 32 to 39 amino acid residues, cross-linked by three disulfide bonds. They all block Kv1.2 in nanomolar concentrations and show various degree of selectivity over Kv1.1, Kv1.3, Shaker and KCa3.1 channels. One peptide has 42 amino acids cross-linked by four disulfides; it blocks ERG-channels and belongs to the γ-KTx family. The sixth peptide has only 32 amino acid residues, three disulfide bonds and has no effect on the ion-channels assayed. It also does not have antimicrobial activity. Systematic numbers were assigned (time of elution on HPLC): α-KTx 10.4 (time 24.1); α-KTx 2.15 (time 26.2); α-KTx 2.16 (time 23.8); α-KTx 2.17 (time 26.7) and γ-KTx 1.9 (elution time 29.6). A partial proteomic analysis of the short chain basic peptides of this venom, which elutes on carboxy-methyl-cellulose column fractionation, is included. The pharmacological properties of the peptides described in this study may provide valuable tools for understanding the structure-function relationship of K(+) channel blocking scorpion toxins. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Temperature dependence on plasma-induced damage and chemical reactions in GaN etching processes using chlorine plasma

    Science.gov (United States)

    Liu, Zecheng; Ishikawa, Kenji; Imamura, Masato; Tsutsumi, Takayoshi; Kondo, Hiroki; Oda, Osamu; Sekine, Makoto; Hori, Masaru

    2018-06-01

    Plasma-induced damage (PID) on GaN was optimally reduced by high-temperature chlorine plasma etching. Energetic ion bombardments primarily induced PID involving stoichiometry, surface roughness, and photoluminescence (PL) degradation. Chemical reactions under ultraviolet (UV) irradiation and chlorine radical exposure at temperatures higher than 400 °C can be controlled by taking into account the synergism of simultaneous photon and radical irradiations to effectively reduce PID.

  6. Lesions of the lateral habenula increase voluntary ethanol consumption and operant self-administration, block yohimbine-induced reinstatement of ethanol seeking, and attenuate ethanol-induced conditioned taste aversion.

    Directory of Open Access Journals (Sweden)

    Andrew K Haack

    Full Text Available The lateral habenula (LHb plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.

  7. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P.; Guyton, Kathryn Z.; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as “carcinogenic to humans” (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

  8. Radiation-induced chemical evolution of glycine to (Gly)2, (Gly)3, and (Gly)4

    International Nuclear Information System (INIS)

    Matsui, T.; Izumi, Y.; Kamohara, M.; Nakagawa, K.; Yokoya, A.

    2006-01-01

    Recently amino acids were detected from some meteorites. Since these amino acids were found after hydrolysis, some oligopeptides were possibly formed in space. A simulation experiment of chemical evolution from Glycine (Gly) to Glycylglycine ((Gly)2) was reported by Kaneko et al. In this work, we irradiated (Gly)2 with 8 eV vacuum ultraviolet photons or with 530 eV soft X-ray photons and examined absolute values of quantum yield of radiation-induced chemical evolution from Gly2 to Glycylglycylglycine ((Gly)3) and Glycylglycylglycylglycine ((Gly)4). Thin films of (Gly)2 were prepared on quartz plate or CuBe plate with a vacuum evaporation technique. These samples were irradiated by 8 eV photons from a Xe 2 * excimer lamp or by 530 eV soft X-ray photons at SPring-8 Synchrotron Radiation Facility. Irradiated samples were analyzed with a high performance liquid chromatography HPLC. Decomposition of (Gly)2 and production of Gly, (Gly)3 and (Gly)4 were observed. Quantum yield Y was defined to be N = Y N 0 , where N is the number of produced or decomposed molecule, and N 0 is the number of (Gly)2 molecules excited by photons. Obtained results by 8 eV irradiation were summarized in Table 1. The similar magnitude of decomposition of (Gly)2 may show that yield of the primary breaking reaction upon photo-excitation is of similar magnitude. It should be noted that (Gly)3 and (Gly)4 was produced by irradiation with the yield of 10 -4 without any catalysis. For soft X-ray irradiation, yield of Gly was tentatively determined to be about 40. This largervalue than that for 8 eV irradiation may originate from large energy of incident soft X-ray photons just like a result reported by Simakov et al. We will discuss in detail at the conference. (authors)

  9. Chemical stress induced by heliotrope (Heliotropium europaeum L.) allelochemicals and increased activity of antioxidant enzymes.

    Science.gov (United States)

    Abdulghader, Kalantar; Nojavan, Majid; Naghshbandi, Nabat

    2008-03-15

    The aims of this study were to evaluate the allelopathic potential of heliotrope on some biochemical processes of dodder. The preliminary experiments revealed that the effect of aqueous extract of leaves of heliotrope is higher than its seeds and roots. So, the aqueous extract of leaves was used in remaining experiments. Leaf extracts of 5 g powder per 100 mL H2O inhibited the germination of dodder seeds up to 95% and that of radish up to 100%. While, the aqueous extract of vine leaves which is a non-allelopathic plant did not have any inhibitory effect on these seeds. Vine leaf was used as a control to show that the inhibitory effect of heliotrope is due to an inhibitory compound but not due to the concentration. The leaf extract of heliotrope at 0.0, 0.1, 1.0, 2, 3, 4 and 5 g powder per 100 mL H2O reduced the radish seedling growth from 14 cm to about 0.5 cm and that of dodder from 7.5 cm to about 0.25 cm. The effects of heliotrope allelochemicals on some physiological and biochemical processes of radish was also Investigated. The activity of auxin oxidase increased in leaves and roots of radish. Suggesting that the reduced radish growth is due to the decreased active auxin levels in its leaves and roots. The activity of alpha-amylase was reduced, so reduction of starch degradation and lack of respiratory energy is the prime reason of germination inhibition in dodder and radish seeds. The level of soluble sugars increased. This is an indication of reduction of the activity of some respiratory enzymes and reduced consumption of these sugars. Proline levels were also increased, indicating that, the chemical stress is induced by leaf extract. Finally, the activities of GPX and CAT which are antioxidant enzymes were increased, along with increased extract concentration. These finding shows that the chemical stress induced by leaf extract produces super oxide (O2*) and H2O2, which is neutralized to H2O and O2 by these enzymes.

  10. In situ analysis of chemical components induced by steaming between fresh ginseng, steamed ginseng, and red ginseng

    Directory of Open Access Journals (Sweden)

    Gyo In

    2017-07-01

    Conclusion: This study elucidates the dynamic changes in the chemical components of P. ginseng when the steaming process was induced. These results are thought to be helpful for quality control and standardization of herbal drugs using P. ginseng and they also provide a scientific basis for pharmacological research of processed ginseng (Red ginseng.

  11. Evaluation of Yield and Chemical Characteristics of some Peanut Mutants Induced by Gamma Irradiation

    International Nuclear Information System (INIS)

    Abd El-daem, G.A.; Anwar, M.M.

    2013-01-01

    This study was conducted to evaluate some promising mutants in peanut for yielding ability over three generation (M5, M6 and M7) and to evaluate yield attributes as will as chemical characteristics of these mutants in M7 generation induced by 100 Gy gamma radiation. The obtained results showed that the increase of yield / plot over three generation as a percentage of control was 5% for mutant 7, 10.2 % for mutant 10; 22% for mutant 9 and 22.9% for mutant 8. This increase in yield may be due to increase of one or more of yield attributes for most mutant lines. The significant increase for. No .of pods and seeds/ plant, weight of pods and seeds/ plant and 100- seed weight in M7 as compared to the control. For saturated fatty acid composition, results revealed that total saturated fatty acids ranged from 17.79% for mutant 8 to 21.75 for mutant 2 compared to 24.21% for control. Reduction of total saturated fatty acid was noticed for different mutants compared to that of the original variety. However, for total unsaturated fatty acids, results indicated that total unsaturated fatty acid composition ranged from 77.95% for mutant 9 to 82.09% for mutant 8 compared to 75.49% for control. Higher total unsaturated fatty acids for all mutant lines were obtained than that of the control, however, total saturated (TS)/ total unsaturated (TU) ratio was decreased for all mutants compared to control. The physical and chemical contents of Peanut oils showed that the refractive indices were ranged from 1.4620 to 1.4718 specific gravity were in range of 0.9146 to 0.9177. Acid value was range from 0.54 to 0.89% lodine value was ranged from 94.56 to 101.85. Saponification value was ranged from 185.2 to 190.7 and unsaponifiable matter was ranged from 0.98 to 1.33. The peroxide values ranged from 1.15 to 2.33 meq/kg oil. Also, fortified yoghurt made with replaced mutant peanut oil by 50% as milk fat substitute. Data showed that chemical composition and organolyptic properties had the

  12. Evaluation of the chemical model of vestibular lesions induced by arsanilate in rats

    International Nuclear Information System (INIS)

    Vignaux, G.; Chabbert, C.; Gaboyard-Niay, S.; Travo, C.; Machado, M.L.; Denise, P.; Comoz, F.; Hitier, M.; Landemore, G.; Philoxène, B.; Besnard, S.

    2012-01-01

    Several animal models of vestibular deficits that mimic the human pathology phenotype have previously been developed to correlate the degree of vestibular injury to cognate vestibular deficits in a time-dependent manner. Sodium arsanilate is one of the most commonly used substances for chemical vestibular lesioning, but it is not well described in the literature. In the present study, we used histological and functional approaches to conduct a detailed exploration of the model of vestibular lesions induced by transtympanic injection of sodium arsanilate in rats. The arsanilate-induced damage was restricted to the vestibular sensory organs without affecting the external ear, the oropharynx, or Scarpa's ganglion. This finding strongly supports the absence of diffusion of arsanilate into the external ear or Eustachian tubes, or through the eighth cranial nerve sheath leading to the brainstem. One of the striking observations of the present study is the complete restructuring of the sensory epithelia into a non sensory epithelial monolayer observed at 3 months after arsanilate application. This atrophy resembles the monolayer epithelia observed postmortem in the vestibular epithelia of patients with a history of lesioned vestibular deficits such as labyrinthectomy, antibiotic treatment, vestibular neuritis, or Ménière's disease. In cases of Ménière's disease, aminoglycosides, and platinum-based chemotherapy, vestibular hair cells are destroyed, regardless of the physiopathological process, as reproduced with the arsanilate model of vestibular lesion. These observations, together with those presented in this study of arsanilate vestibular toxicity, suggest that this atrophy process relies on a common mechanism of degeneration of the sensory epithelia.

  13. Evaluation of the chemical model of vestibular lesions induced by arsanilate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vignaux, G. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); Chabbert, C.; Gaboyard-Niay, S.; Travo, C. [INSERM U1051, Institut des Neurosciences de Montpellier, Montpellier, F-34090,France (France); Machado, M.L. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); Denise, P. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); CHRU Caen, Explorations Fonctionnelles, Caen, F-14000 (France); Comoz, F. [CHRU Caen, Laboratoire d' anatomopathologie, Caen, F-14000 (France); Hitier, M. [CHRU Caen, Service d' Otorhinolaryngologie, Caen, F-14000,France (France); Landemore, G. [CHRU Caen, Laboratoire d' anatomopathologie, Caen, F-14000 (France); Philoxène, B. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); CHRU Caen, Explorations Fonctionnelles, Caen, F-14000 (France); Besnard, S., E-mail: besnard-s@phycog.org [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); CHRU Caen, Explorations Fonctionnelles, Caen, F-14000 (France)

    2012-01-01

    Several animal models of vestibular deficits that mimic the human pathology phenotype have previously been developed to correlate the degree of vestibular injury to cognate vestibular deficits in a time-dependent manner. Sodium arsanilate is one of the most commonly used substances for chemical vestibular lesioning, but it is not well described in the literature. In the present study, we used histological and functional approaches to conduct a detailed exploration of the model of vestibular lesions induced by transtympanic injection of sodium arsanilate in rats. The arsanilate-induced damage was restricted to the vestibular sensory organs without affecting the external ear, the oropharynx, or Scarpa's ganglion. This finding strongly supports the absence of diffusion of arsanilate into the external ear or Eustachian tubes, or through the eighth cranial nerve sheath leading to the brainstem. One of the striking observations of the present study is the complete restructuring of the sensory epithelia into a non sensory epithelial monolayer observed at 3 months after arsanilate application. This atrophy resembles the monolayer epithelia observed postmortem in the vestibular epithelia of patients with a history of lesioned vestibular deficits such as labyrinthectomy, antibiotic treatment, vestibular neuritis, or Ménière's disease. In cases of Ménière's disease, aminoglycosides, and platinum-based chemotherapy, vestibular hair cells are destroyed, regardless of the physiopathological process, as reproduced with the arsanilate model of vestibular lesion. These observations, together with those presented in this study of arsanilate vestibular toxicity, suggest that this atrophy process relies on a common mechanism of degeneration of the sensory epithelia.

  14. Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

    International Nuclear Information System (INIS)

    Okazaki, Shogo; Nakatani, Fumi; Masuko, Kazue; Tsuchihashi, Kenji; Ueda, Shiho; Masuko, Takashi; Saya, Hideyuki; Nagano, Osamu

    2016-01-01

    The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. - Highlights: • We newly generated four clones of human ErbB4 specific mAb. • ErbB4 mAb clone P6-1 blocks ErbB4 phosphorylation induced by NRG-1. • ErbB4 mAb clone P6-1 suppresses NRG-1-promoted breast cancer cells proliferation on three dimensional culture condition.

  15. Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Okazaki, Shogo [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Nakatani, Fumi [Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kinki University, Higashiosaka, Osaka 577-8502 Japan (Japan); Masuko, Kazue; Tsuchihashi, Kenji [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Ueda, Shiho; Masuko, Takashi [Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kinki University, Higashiosaka, Osaka 577-8502 Japan (Japan); Saya, Hideyuki [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Nagano, Osamu, E-mail: osmna@sb3.so-net.ne.jp [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

    2016-01-29

    The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. - Highlights: • We newly generated four clones of human ErbB4 specific mAb. • ErbB4 mAb clone P6-1 blocks ErbB4 phosphorylation induced by NRG-1. • ErbB4 mAb clone P6-1 suppresses NRG-1-promoted breast cancer cells proliferation on three dimensional culture condition.

  16. Sensitivity of neuroprogenitor cells to chemical-induced apoptosis using a multiplexed assay suitable for high-throughput screening

    International Nuclear Information System (INIS)

    Druwe, Ingrid; Freudenrich, Theresa M.; Wallace, Kathleen; Shafer, Timothy J.; Mundy, William R.

    2015-01-01

    High-throughput methods are useful for rapidly screening large numbers of chemicals for biological activity, including the perturbation of pathways that may lead to adverse cellular effects. In vitro assays for the key events of neurodevelopment, including apoptosis, may be used in a battery of tests for detecting chemicals that could result in developmental neurotoxicity. Apoptosis contributes to nervous system development by regulating the size of the neuroprogenitor cell pool, and the balance between cellular proliferation and apoptosis during neuroprogenitor cell proliferation helps to determine the size and shape of the nervous system. Therefore, chemicals that affect apoptosis during neuronal development can have deleterious effects on the developing brain. The present study examined the utility of a high-throughput assay to detect chemical-induced apoptosis in mouse or human neuroprogenitor cells, as well as differentiated human neurons derived from induced pluripotent stem cells. Apoptosis was assessed using an assay that measures enzymatic activity of caspase-3/7 in a rapid and cost efficient manner. The results show that all three commercially available models generated a robust source of proliferating neuroprogenitor cells, and that the assay was sensitive and reproducible when used in a multi-well plate format. There were differences in the response of rodent and human neuroprogenitor cells to a set of chemicals previously shown to induce apoptosis in vitro. Neuroprogenitor cells were more sensitive to chemical-induced apoptosis than differentiated neurons, suggesting that neuroprogenitor cells are one of the cell models that should be considered for use in a developmental neurotoxicity screening battery

  17. Overexpression and amplification of the c-myc gene in mouse tumors induced by chemical and radiations

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Ohtsura; Enoki, Yoshitaka; Yokoro, Kenjiro

    1989-03-01

    We examined expression of the c-myc gene by the dot blot hybridization of total cellular RNA from mouse primary tumors induced by chemicals and radiations. Expression of the c-myc gene was found to be elevated in 69 cases among 177 independently induced tumors of 12 different types. DNA from tumors overexpressing the myc gene was analyzed by Southern blotting. No case of rearrangement was detected. However, amplification of the c-myc gene was found in 7 cases of primary sarcomas. These included 4 cases out of 24 methylcholanthrene-induced sarcomas and 3 cases out of 7 /alpha/-tocopherol-induced sacromas. We also analyzed 8 cases of sarcomas induced by radiations, but could not find changes in the gene structure of the c-myc gene. Thus, our data indicate tumor type specificity and agent specificity of c-myc gene amplification. (author).

  18. Stress-induced chemical detection using flexible metal-organic frameworks.

    Science.gov (United States)

    Allendorf, Mark D; Houk, Ronald J T; Andruszkiewicz, Leanne; Talin, A Alec; Pikarsky, Joel; Choudhury, Arnab; Gall, Kenneth A; Hesketh, Peter J

    2008-11-05

    In this work we demonstrate the concept of stress-induced chemical detection using metal-organic frameworks (MOFs) by integrating a thin film of the MOF HKUST-1 with a microcantilever surface. The results show that the energy of molecular adsorption, which causes slight distortions in the MOF crystal structure, can be converted to mechanical energy to create a highly responsive, reversible, and selective sensor. This sensor responds to water, methanol, and ethanol vapors, but yields no response to either N2 or O2. The magnitude of the signal, which is measured by a built-in piezoresistor, is correlated with the concentration and can be fitted to a Langmuir isotherm. Furthermore, we show that the hydration state of the MOF layer can be used to impart selectivity to CO2. Finally, we report the first use of surface-enhanced Raman spectroscopy to characterize the structure of a MOF film. We conclude that the synthetic versatility of these nanoporous materials holds great promise for creating recognition chemistries to enable selective detection of a wide range of analytes.

  19. Modification of tolerance of oats to crown rust induced by chemical mutagens

    International Nuclear Information System (INIS)

    Simons, M.D.; Browning, J.A.; Frey, K.J.

    1983-01-01

    Seeds of crown rust (Puccinia coronata) susceptible cultivated oats (Avena sativa) were treated with the mutagenic chemical ethyl methanesulphonate (EMS), and pure lines derived from these treated seeds were tested in later generations for the relative amount of reduction in yield and seed weight caused by crown rust infection. In the absence of crown rust, the yield of most of the treated lines was greatly reduced. The overall means of the treated lines for both yield and seed weight response to infection were significantly lower than the control, but 10 lines significantly exceeded the control for yield response and 15 exceeded it for seed weight response. Recurrent EMS treatment of once-treated lines rated as tolerant resulted in groups of lines that were more tolerant, on the average, than groups of lines from recurrently treated lines rated as susceptible. A few of the recurrently treated individual lines derived from tolerant parents had a higher degree of tolerance than their parental lines. EMS treatment of diploid (A. strigosa) and tetraploid (A. abyssinica) oats resulted in groups of lines showing significant genetic variance for response to crown rust, indicating that treatment had induced real genetic change. A few diploid lines were a little more tolerant than their control, but none of the tetraploid lines showed any consistent improvement. (author)

  20. Studies on chemical and physical mutagens' induced polygenic variability in mungbean (Vigna radiata (L.) Wilczek)

    International Nuclear Information System (INIS)

    Sangwan, H.P.S.; Singh, M.P.

    1990-01-01

    Full text: Pulses used to be and still are cultivated on marginal lands under poor management conditions which result in low production. Genotypes which could respond to better management have been eliminated by past selection. It is, therefore, difficult and challenging to breed high yielding varieties in pulse crops with the limited genetic variability available. Induced mutations could supplement this variability. Extensive studies on genotype-mutagen interaction were undertaken with six varieties of mungbean having contrasting seed characteristics, morphological traits and genetic backgrounds. Each variety was treated with 300 Gy and 600 Gy of gamma rays, 0.1 and 0.5% of EMS, and 0.1 and 0.05 of SA. Dry seeds, water soaked and phosphate buffer soaked seeds served as controls. The following observations were made: differential response of varieties to mutagen treatments - irrespective of the variety or the characters; gamma-rays proved to be more effective than chemical mutagens; mutagenic treatments resulted in development of early maturing mutants that can fit well in multiple cropping systems particularly in raising a mung crop after the wheat harvest. The fact that some mutants were detected in M 4 with significant increase in yield and marginal improvement in protein content generation suggests the possibility of improving both characters provided a large population is screened. (author)

  1. Ab Initio Studies of Shock-Induced Chemical Reactions of Inter-Metallics

    Science.gov (United States)

    Zaharieva, Roussislava; Hanagud, Sathya

    2009-06-01

    Shock-induced and shock assisted chemical reactions of intermetallic mixtures are studied by many researchers, using both experimental and theoretical techniques. The theoretical studies are primarily at continuum scales. The model frameworks include mixture theories and meso-scale models of grains of porous mixtures. The reaction models vary from equilibrium thermodynamic model to several non-equilibrium thermodynamic models. The shock-effects are primarily studied using appropriate conservation equations and numerical techniques to integrate the equations. All these models require material constants from experiments and estimates of transition states. Thus, the objective of this paper is to present studies based on ab initio techniques. The ab inito studies, to date, use ab inito molecular dynamics. This paper presents a study that uses shock pressures, and associated temperatures as starting variables. Then intermetallic mixtures are modeled as slabs. The required shock stresses are created by straining the lattice. Then, ab initio binding energy calculations are used to examine the stability of the reactions. Binding energies are obtained for different strain components super imposed on uniform compression and finite temperatures. Then, vibrational frequencies and nudge elastic band techniques are used to study reactivity and transition states. Examples include Ni and Al.

  2. Serum-induced G0/G1 transition in chemically transformed 3T3 cells

    International Nuclear Information System (INIS)

    Gray, H.E.; Buchou, T.; Mester, J.

    1987-01-01

    Quiescent, chemically transformed (benzo-a-pyrene) BALB/c 3T3 cells (BP A31) enter the cell division cycle when exposed to complete medium containing 10% fetal calf serum (FCS); the number of cells recruited is a function of the duration of serum exposure. The recruitment of cells by short (<4 h) serum pulses is not inhibited by simultaneous exposure to cycloheximide (CH), and therefore the initial commitment does not require protein synthesis. The cells enter S phase with a constant delay following the removal of CH, even if CH exposure has been continued for as long as 20 h after the end of the serum pulse. The cell recruitment by serum pulses was inhibited by 5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole (DRB), an inhibitor of cytoplasmic mRNA accumulation. These data suggest that serum exposure produces a stable memory that is necessary and sufficient for the eventual progression through G1 to S phase that occurs when protein synthesis is resumed after the removal of CH; this memory probably consists of mRNA species that are induced by serum and that are stable in the absence of protein synthesis. Unexpectedly, pretreatment of quiescent BP A31 cells with CH (8-24 h) dramatically increased the fraction of the total cell population that is recruited by a serum pulse of fixed duration

  3. Acidification-induced chemical changes in coniferous forest soils in southern Sweden 1988-1999

    Energy Technology Data Exchange (ETDEWEB)

    Joensson, U.; Rosengren, U.; Thelin, G.; Nihlgaard, B

    2003-05-01

    Acidification of south-Swedish coniferous forest soils continues and soil nutrient status is no longer sustainable in a long-term perspective. - Thirty-two Norway spruce [Picea abies (L.) Karst.] and Scots pine (Pinus sylvestris L.) stands in southern Sweden were studied for a period of 12 years to evaluate acidification-induced chemical changes in the soil. Soil, at 20-30 cm depth in the mineral layer, was sampled three times during this period (1988, 1993 and 1999). The results show that pH(BaCl{sub 2}) in mineral soil decreased by, on average, 0.17 units between 1988 and 1999, accompanied by an increase in aluminium (Al) concentration and a decrease in base saturation in the soil. In 1999, the base saturation was below 5% in 58% of the 32 sites compared with 16% in 1988 and 7% in 1993. Concentrations of calcium (Ca), potassium (K) and magnesium (Mg) are low and decreasing. Based on C/N ratios in humus, 45% of the sites may be subjected to leaching of considerable amounts of nitrate. The results show that the acidification of coniferous forest soils in southern Sweden is continuing, and that the negative effects on the nutrient status in soil are extensive. The results are compared with reference values for productive, long-term sustainably managed boreal coniferous or mixed forest soils and implications for long-term sustainability are discussed.

  4. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat.

    Science.gov (United States)

    Fujita, M; Hong, K; Ito, Y; Fujii, R; Kariya, K; Nishimuro, S

    1995-10-01

    Nattokinase is a new fibrinolytic enzyme which cleaves directly cross-linked fibrin in vitro. In this study, we investigated the thrombolytic effect of nattokinase on a thrombus in the common carotid artery of rat in which the endothelial cells of the vessel wall were injured by acetic acid. When a section of occluded vessel was stained for CD61 antigen by immunofluorescence utilizing a monoclonal antibody, the antigen was localized around the surface of the occluded blood vessels. This result suggests that the occlusive thrombosis was caused by platelet aggregation. In addition, thrombolysis with urokinase (UK; 50000 IU/kg, i.v.) or tissue plasminogen activator (tPA; 13300 IU/kg, i.v.) in our model was observed to restore the blood flow over a 60 min monitoring period. The results indicate that our chemically induced model is useful for screening and evaluating a thrombolytic agent. We evaluated the thrombolytic activity of nattokinase using this model and compared it with fibrino(geno)lytic enzyme, plasmin or elastase. On a molar basis, the recovery of the arterial blood flow with nattokinase, plasmin and elastase were 62.0 +/- 5.3%, 15.8 +/- 0.7% and 0%, respectively. The results indicate that the thrombolytic activity of nattokinase is stronger than that of plasmin or elastase in vivo.

  5. A new route to nanoscale tomographic chemical analysis: Focused ion beam-induced auger electron spectrosocpy

    Science.gov (United States)

    Parvaneh, Hamed

    This research project is aimed to study the application of ion-induced Auger electron spectroscopy (IAES) in combination with the characteristics of focused ion beam (FIB) microscopy for performing chemical spectroscopy and further evaluate its potential for 3-dimensional chemical tomography applications. The mechanism for generation of Auger electrons by bombarding ions is very different from its electron induced counterpart. In the conventional electron-induced Auger electron spectroscopy (EAES), an electron beam with energy typically in the range 1-10kV is used to excite inner-shell (core) electrons of the solid. An electron from a higher electron energy state then de-excites to fill the hole and the extra energy is then transferred to either another electron, i.e. the Auger electron, or generation of an X-ray (photon). In both cases the emitting particles have charac-teristic energies and could be used to identify the excited target atoms. In IAES, however, large excitation cross sections can occur by promotion of in-ner shell electrons through crossing of molecular orbitals. Originally such phenomenological excitation processes were first proposed [3] for bi-particle gas phase collision systems to explain the generation of inner shell vacancies in violent collisions. In addition to excitation of incident or target atoms, due to a much heavier mass of ions compared to electrons, there would also be a substantial momentum transfer from the incident to the target atoms. This may cause the excited target atom to recoil from the lattice site or alternatively sputter off the surface with the possibility of de-excitation while the atom is either in motion in the matrix or traveling in vacuum. As a result, one could expect differences between the spectra induced by incident electrons and ions and interpretation of the IAE spectra requires separate consideration of both excitation and decay processes. In the first stage of the project, a state-of-the-art mass

  6. Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-κB signaling and depleting Bcr-Abl

    Science.gov (United States)

    2010-01-01

    Background Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. Bcr-Abl-T315I is the notorious point mutation that causes resistance to imatinib and the second generation tyrosine kinase inhibitors, leading to poor prognosis. CML blasts have constitutive p65 (RelA NF-κB) transcriptional activity, and NF-κB may be a potential target for molecular therapies in CML that may also be effective against CML cells with Bcr-Abl-T315I. Results In this report, we discovered that pristimerin, a quinonemethide triterpenoid isolated from Celastraceae and Hippocrateaceae, inhibited growth and induced apoptosis in CML cells, including the cells harboring Bcr-Abl-T315I mutation. Additionally, pristimerin inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Pristimerin blocked the TNFα-induced IκBα phosphorylation, translocation of p65, and expression of NF-κB-regulated genes. Pristimerin inhibited two steps in NF-κB signaling: TAK1→IKK and IKK→IκBα. Pristimerin potently inhibited two pairs of CML cell lines (KBM5 versus KBM5-T315I, 32D-Bcr-Abl versus 32D-Bcr-Abl-T315I) and primary cells from a CML patient with acquired resistance to imatinib. The mRNA and protein levels of Bcr-Abl in imatinib-sensitive (KBM5) or imatinib-resistant (KBM5-T315I) CML cells were reduced after pristimerin treatment. Further, inactivation of Bcr-Abl by imatinib pretreatment did not abrogate the TNFα-induced NF-κB activation while silencing p65 by siRNA did not affect the levels of Bcr-Abl, both results together indicating that NF-κB inactivation and Bcr-Abl inhibition may be parallel independent pathways. Conclusion To our knowledge, this is the first report to show that pristimerin is effective in vitro and in vivo against CML cells, including those with the T315I mutation. The mechanisms may involve inhibition of NF-κB and Bcr-Abl. We concluded that pristimerin could be a lead compound for further drug development to

  7. Heat shock protein 70 negatively regulates the heat-shock-induced suppression of the IκB/NF-κB cascade by facilitating IκB kinase renaturation and blocking its further denaturation

    International Nuclear Information System (INIS)

    Lee, Kyoung-Hee; Lee, Choon-Taek; Kim, Young Whan; Han, Sung Koo; Shim, Young-Soo; Yoo, Chul-Gyu

    2005-01-01

    Heat shock (HS) treatment has been previously shown to suppress the IκB/nuclear factor-κB (NF-κB) cascade by denaturing, and thus inactivating IκB kinase (IKK). HS is characterized by the induction of a group of heat shock proteins (HSPs). However, their role in the HS-induced suppression of the IκB/NF-κB cascade is unclear. Adenovirus-mediated HSP70 overexpression was found not to suppress the TNF-α-induced activation of the IκB/NF-κB pathway, thus suggesting that HSP70 is unlikely to suppress this pathway. When TNF-α-induced activation of the IκB/NF-κB pathway was regained 24 h after HS, HSP70 was found to be highly up-regulated. Moreover, blocking HSP70 induction delayed TNF-α-induced IκBα degradation and the resolubilization of IKK. In addition, HSP70 associated physically with IKK, suggesting that HSP70 is involved in the recovery process via molecular chaperone effect. Adenovirus-mediated HSP70 overexpression prior to HS blocked the IκBα stabilizing effect of HS by suppressing IKK insolubilization. Moreover, the up-regulation of endogenous HSP70 by preheating, suppressed this subsequent HS-induced IKK insolubilization, and this effect was abrogated by blocking HSP70 induction. These findings indicate that HSP70 accumulates during HS and negatively regulates the HS-induced suppression of the IκB/NF-κB cascade by facilitating the renaturation of IKK and blocking its further denaturation

  8. An efficient, block-by-block algorithm for inverting a block tridiagonal, nearly block Toeplitz matrix

    International Nuclear Information System (INIS)

    Reuter, Matthew G; Hill, Judith C

    2012-01-01

    We present an algorithm for computing any block of the inverse of a block tridiagonal, nearly block Toeplitz matrix (defined as a block tridiagonal matrix with a small number of deviations from the purely block Toeplitz structure). By exploiting both the block tridiagonal and the nearly block Toeplitz structures, this method scales independently of the total number of blocks in the matrix and linearly with the number of deviations. Numerical studies demonstrate this scaling and the advantages of our method over alternatives.

  9. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    International Nuclear Information System (INIS)

    Camats, Nuria; Garcia, Francisca; Parrilla, Juan Jose; Calaf, Joaquim; Martin, Miguel; Caldes, Montserrat Garcia

    2008-01-01

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p ≤ 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p ≤ 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal cells

  10. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, Joaquim [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin, Miguel [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, Montserrat Garcia [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)], E-mail: Montserrat.Garcia.Caldes@uab.es

    2008-04-02

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p {<=} 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p {<=} 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal

  11. Al-induced root cell wall chemical components differences of wheat ...

    African Journals Online (AJOL)

    Root growth is different in plants with different levels of Al-tolerance under Al stress. Cell wall chemical components of root tip cell are related to root growth. The aim of this study was to explore the relationship between root growth difference and cell wall chemical components. For this purpose, the cell wall chemical ...

  12. Analysis of Block OMP using Block RIP

    OpenAIRE

    Wang, Jun; Li, Gang; Zhang, Hao; Wang, Xiqin

    2011-01-01

    Orthogonal matching pursuit (OMP) is a canonical greedy algorithm for sparse signal reconstruction. When the signal of interest is block sparse, i.e., it has nonzero coefficients occurring in clusters, the block version of OMP algorithm (i.e., Block OMP) outperforms the conventional OMP. In this paper, we demonstrate that a new notion of block restricted isometry property (Block RIP), which is less stringent than standard restricted isometry property (RIP), can be used for a very straightforw...

  13. Cytogenetic damages induced in vivo in human lymphocytes by environmental chemicals or radiation

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.

    1999-01-01

    The importance of various environmental exposures has been evident in variation in cancer incidence and mortality. Benzene is considered to be a human carcinogen, is clastogenic to rodents and humans, and it affects the immune response. Workers in various industrial plants, are exposed to benzene and benzene related compounds as a result of various activities in which benzene is processed, generated or used. Major sources of environmental exposure to benzene related compounds, continue to be active and passive smoking, auto exhaust, and driving or riding in automobiles. Benzene is of a particular interest, not only because of its known toxicity, but also because this was to be the parent compound and a model for extensive programs of metabolism of a variety of aromatic chemicals. Ionizing radiation is an unavoidable physical agent that is presented in environment, and public opinion is well aware against radiation risk and strongly against it. The aim of the presentation was comparison between cytogenetic damages induced in vivo by environmental chemicals with those of radiation. Results from biomonitoring survey on genotoxicity in human blood cells of benzene and benzene related compounds were compared to damages detected in lymphocytes of persons who had been accidentally exposed to gamma radiation. In the groups, that had been occupationally or environmentally exposed to benzene related compound, total aberration frequencies, or percent of aberrant cells ranged between 0 - 0.16 aberrations/cell or 16% of aberrant cells respectively. A multivariate regression analysis confirmed: (i) a significant association between cytogenetic damage and exposure to benzene related compound, (ii) a possible association between cytogenetic damage and cancer, (iii) a significant influence of smoking habit. In 1996 few persons were suspected of accidental exposure to gamma radiation. To estimate the absorbed doses, lymphocytes from their blood have been analyzed for the presence of

  14. Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: Implications for chemical-induced peripheral sensory neuropathies

    Directory of Open Access Journals (Sweden)

    Melemedjian Ohannes K

    2008-03-01

    Full Text Available Abstract Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG, which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

  15. Effect of dexmedetomidine as adjuvant in ropivacaine-induced supraclavicular brachial plexus block: A prospective, double-blinded and randomized controlled study

    Directory of Open Access Journals (Sweden)

    Anjan Das

    2014-01-01

    Full Text Available Background and Aims: Different additives have been used to prolong brachial plexus block. We evaluated the effect of adding dexmedetomidine to ropivacaine for supraclavicular brachial plexus blockade. The primary endpoints were the onset and duration of sensory and motor block and duration of analgesia. Materials and Methods: A total of 84 patients (20-50 years posted for elective forearm and hand surgery under supraclavicular brachial plexus block were divided into two equal groups (Group R and RD in a randomized, double-blind fashion. In group RD (n = 42 30 ml 0.5% ropivacaine +1 ml (100 μg of dexmedetomidine and group R (n = 42 30 ml 0.5% ropivacaine +1 ml normal saline were administered in supraclavicular block. Sensory and motor block onset times and block durations, time to first analgesic use, total analgesic need, postoperative visual analog scale (VAS, hemodynamics and side-effects were recorded for each patient. Results: Though with similar demographic profile in both groups, sensory and motor block in group RD (P < 0.05 was earlier than group R. Sensory and motor block duration and time to first analgesic use were significantly longer and the total need for rescue analgesics was lower in group RD (P < 0.05 than group R. Post-operative VAS value at 12 h were significantly lower in group RD (P < 0.05. Intra-operative hemodynamics were significantly lower in group RD (P < 0.05 without any appreciable side-effects. Conclusion: It can be concluded that adding dexmedetomidine to supraclavicular brachial plexus block increases the sensory and motor block duration and time to first analgesic use, and decreases total analgesic use with no side-effects.

  16. Combination of high-performance refractometry and infrared spectroscopy as a probe for chemically induced gelation and vitrification of epoxies

    International Nuclear Information System (INIS)

    Mueller, U; Philipp, M; Gervais, P-C; Sanctuary, R; Krueger, J K; Possart, W; Wehlack, C; Kieffer, J

    2010-01-01

    A combination of infrared spectroscopy and high-performance refractometry was used to investigate the chemically induced sol-gel and glass transition during the polymerization of epoxies. Representations of the refractive index versus chemical conversion reveal an interesting insight into the optical properties accompanying gelation and vitrification. Whereas the electronic polarizability of the liquid state of small average molecular mass and the glassy state is dominated by the mass density, an unexpected excess polarizability observed during the gelation is attributed to cooperative dipole-dipole interactions.

  17. Combination of high-performance refractometry and infrared spectroscopy as a probe for chemically induced gelation and vitrification of epoxies

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, U; Philipp, M; Gervais, P-C; Sanctuary, R; Krueger, J K [Laboratoire de Physique des Materiaux, Universite du Luxembourg, 162A avenue de la faiencerie, L-1511 Luxembourg (Luxembourg); Possart, W; Wehlack, C [Fachbereich Werkstoffwissenschaften, Universitaet des Saarlandes, D-66123 Saarbruecken (Germany); Kieffer, J, E-mail: ulrich.mueller@uni.l [Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI (United States)

    2010-08-15

    A combination of infrared spectroscopy and high-performance refractometry was used to investigate the chemically induced sol-gel and glass transition during the polymerization of epoxies. Representations of the refractive index versus chemical conversion reveal an interesting insight into the optical properties accompanying gelation and vitrification. Whereas the electronic polarizability of the liquid state of small average molecular mass and the glassy state is dominated by the mass density, an unexpected excess polarizability observed during the gelation is attributed to cooperative dipole-dipole interactions.

  18. Uncoupling of the hnRNP Npl3p from mRNAs during the stress-induced block in mRNA export.

    Science.gov (United States)

    Krebber, H; Taura, T; Lee, M S; Silver, P A

    1999-08-01

    Npl3p, the major mRNA-binding protein of the yeast Saccharomyces cerevisiae shuttles between the nucleus and the cytoplasm. A single amino acid change in the carboxyl terminus of Npl3p (E409 --> K) renders the mutant protein largely cytoplasmic because of a delay in its import into the nucleus. This import defect can be reversed by increasing the intracellular concentration of Mtr10p, the nuclear import receptor for Npl3p. Conversely, using this mutant, we show that Npl3p and mRNA export out of the nucleus is significantly slowed in cells bearing mutations in XPO1/CRM1, which encodes the export receptor for NES-containing proteins and in RAT7, which encodes an essential nucleoporin. Interestingly, following induction of stress by heat shock, high salt, or ethanol, conditions under which most mRNA export is blocked, Npl3p is still exported from the nucleus. The stress-induced export of Npl3p is independent of both the activity of Xpo1p and the continued selective export of heat-shock mRNAs that occurs following stress. UV-cross-linking experiments show that Npl3p is bound to mRNA under normal conditions, but is no longer RNA associated in stressed cells. Taken together, we suggest that the uncoupling of Npl3p and possibly other mRNA-binding proteins from mRNAs in the nucleus provides a general switch that regulates mRNA export. By this model, under normal conditions Npl3p is a major component of an export-competent RNP complex. However, under conditions of stress, Npl3p no longer associates with the export complex, rendering it export incompetent and thus nuclear.

  19. Delineating pathological pathways in a chemically induced mouse model of Gaucher disease.

    Science.gov (United States)

    Vardi, Ayelet; Zigdon, Hila; Meshcheriakova, Anna; Klein, Andrés D; Yaacobi, Chen; Eilam, Raya; Kenwood, Brandon M; Rahim, Ahad A; Massaro, Giulia; Merrill, Alfred H; Vitner, Einat B; Futerman, Anthony H

    2016-08-01

    Great interest has been shown in understanding the pathology of Gaucher disease (GD) due to the recently discovered genetic relationship with Parkinson's disease. For such studies, suitable animal models of GD are required. Chemical induction of GD by inhibition of acid β-glucosidase (GCase) using the irreversible inhibitor conduritol B-epoxide (CBE) is particularly attractive, although few systematic studies examining the effect of CBE on the development of symptoms associated with neurological forms of GD have been performed. We now demonstrate a correlation between the amount of CBE injected into mice and levels of accumulation of the GD substrates, glucosylceramide and glucosylsphingosine, and show that disease pathology, indicated by altered levels of pathological markers, depends on both the levels of accumulated lipids and the time at which their accumulation begins. Gene array analysis shows a remarkable similarity in the gene expression profiles of CBE-treated mice and a genetic GD mouse model, the Gba(flox/flox) ;nestin-Cre mouse, with 120 of the 144 genes up-regulated in CBE-treated mice also up-regulated in Gba(flox/flox) ;nestin-Cre mice. We also demonstrate that various aspects of neuropathology and some behavioural abnormalities can be arrested upon cessation of CBE treatment during a specific time window. Together, our data demonstrate that injection of mice with CBE provides a rapid and relatively easy way to induce symptoms typical of neuronal forms of GD. This is particularly useful when examining the role of specific biochemical pathways in GD pathology, since CBE can be injected into mice defective in components of putative pathological pathways, alleviating the need for time-consuming crossing of mice. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. Thermal, chemical and pH induced unfolding of turmeric root lectin: modes of denaturation.

    Directory of Open Access Journals (Sweden)

    Himadri Biswas

    Full Text Available Curcuma longa rhizome lectin, of non-seed origin having antifungal, antibacterial and α-glucosidase inhibitory activities, forms a homodimer with high thermal stability as well as acid tolerance. Size exclusion chromatography and dynamic light scattering show it to be a dimer at pH 7, but it converts to a monomer near pH 2. Circular dichroism spectra and fluorescence emission maxima are virtually indistinguishable from pH 7 to 2, indicating secondary and tertiary structures remain the same in dimer and monomer within experimental error. The tryptophan environment as probed by acrylamide quenching data yielded very similar data at pH 2 and pH 7, implying very similar folding for monomer and dimer. Differential scanning calorimetry shows a transition at 350.3 K for dimer and at 327.0 K for monomer. Thermal unfolding and chemical unfolding induced by guanidinium chloride for dimer are both reversible and can be described by two-state models. The temperatures and the denaturant concentrations at which one-half of the protein molecules are unfolded, are protein concentration-dependent for dimer but protein concentration-independent for monomer. The free energy of unfolding at 298 K was found to be 5.23 Kcal mol-1 and 14.90 Kcal mol-1 for the monomer and dimer respectively. The value of change in excess heat capacity upon protein denaturation (ΔCp is 3.42 Kcal mol-1 K-1 for dimer. The small ΔCp for unfolding of CLA reflects a buried hydrophobic core in the folded dimeric protein. These unfolding experiments, temperature dependent circular dichroism and dynamic light scattering for the dimer at pH 7 indicate its higher stability than for the monomer at pH 2. This difference in stability of dimeric and monomeric forms highlights the contribution of inter-subunit interactions in the former.

  1. Combining machine learning, crowdsourcing and expert knowledge to detect chemical-induced diseases in text.

    Science.gov (United States)

    Bravo, Àlex; Li, Tong Shu; Su, Andrew I; Good, Benjamin M; Furlong, Laura I

    2016-01-01

    Drug toxicity is a major concern for both regulatory agencies and the pharmaceutical industry. In this context, text-mining methods for the identification of drug side effects from free text are key for the development of up-to-date knowledge sources on drug adverse reactions. We present a new system for identification of drug side effects from the literature that combines three approaches: machine learning, rule- and knowledge-based approaches. This system has been developed to address the Task 3.B of Biocreative V challenge (BC5) dealing with Chemical-induced Disease (CID) relations. The first two approaches focus on identifying relations at the sentence-level, while the knowledge-based approach is applied both at sentence and abstract levels. The machine learning method is based on the BeFree system using two corpora as training data: the annotated data provided by the CID task organizers and a new CID corpus developed by crowdsourcing. Different combinations of results from the three strategies were selected for each run of the challenge. In the final evaluation setting, the system achieved the highest Recall of the challenge (63%). By performing an error analysis, we identified the main causes of misclassifications and areas for improving of our system, and highlighted the need of consistent gold standard data sets for advancing the state of the art in text mining of drug side effects.Database URL: https://zenodo.org/record/29887?ln¼en#.VsL3yDLWR_V. © The Author(s) 2016. Published by Oxford University Press.

  2. Radiation induced chemical changes in foodstuffs model reaction systems and strawberries

    International Nuclear Information System (INIS)

    Breitfellner, F.

    1999-10-01

    In the first part of this work 4-hydroxybenzoic acid (4-HBA) and 4-hydroxybenzoic acid ethyl ester (4-HBAEE) were investigated in order to elucidate the reaction mechanisms leading to final products after reaction with OH-radicals (N 2 O-saturated and aerated aqueous solutions) at various pH. Irradiation of 5*10 -4 mol l -1 solutions of 4-HBA at pH 6.0 leads to formation of 3,4-dihydroxybenzoic acid and hydroquinone. In case of the ester neither hydroxylation nor decarboxylation products are observable. By means of pulse radiolysis it could be shown that water splitting from the ester OH-adducts is 17 times faster than from that of the acid. Therefore the main transients are phenoxyl radicals in case of the ester. At pH 10, where base catalyzed water elimination takes place, no hydroxylation products are observable either. In aerated solutions dihydroxy-compounds are formed with both substrates. In the case of 4-HBA 68 % of the OH-radicals result in 3,4-dihydroxyderivate, for 4-HBAEE these are only 25 %. Comparison of the initial degradation yields demonstrates 4-HBAEE to be 1.6-times more stable towards radiation. The second part of this work deals with radiation induced chemical changes in strawberries. Dose/concentration relationships could be obtained for 7 components, i.e. gallic acid, 4-hydroxybenzoic acid, cinnamic acid, 4-hydroxycinnamic acid, 3,4-dihydroxy-cinnamic acid, (-)-epicatechin and (+)-catechin. Linear dose relationships have been found for 4-HBA (formation) and (+)-catechin (degradation). In addition a specific radiolytically formed compound which can be used as marker for irradiation treatment of strawberries could be detected. There are strong indications that it is a radiolytic product of kaempferol, however, it could not yet be identified exactly. (author)

  3. 1H chemically induced dynamic nuclear polarization in the photodecomposition of uranyl carboxylates

    International Nuclear Information System (INIS)

    Rykov, S.V.; Khudyakov, I.V.; Skakovsky, E.D.; Burrows, H.D.; Formosinho, S.J.; Miguel, M. da G.M.

    1991-01-01

    Chemically induced dynamic nuclear polarization ( 1 H CIDNP) has been observed during photolysis of uranyl salts of pivalic, propionic, and acetic acids in D 2 O solution, [ 2 H 6 ]acetone, [ 2 H 4 ]methanol, or in some other solvent. The multiplet polarization of isobutene and isobutane protons has been found under photolysis of deoxygenated pivalate solution. The polarized compounds are formed in the triplet pairs of tert-butyl free radicals. 1 H Emission of the tert-butylperoxyl group and emission of 1 H from isobutene have been recorded under photolysis of air-saturated pivalate solutions. The CIDNP of butane protons stays as a multiplet. Such changes in the presence of air/oxygen have arisen apparently because of the formation of tert-butylperoxyl free radical and its reaction with tert-butyl radical products, i.e. hydroperoxide (peroxide) and isobutene. Isobutene probably forms a complex with molecular oxygen which has a very short proton relaxation time. During the photolysis of uranyl pivalate in the presence of p-benzoquinone (5 x 10 -2 -0.1 mol dm -3 ) we have not observed any CIDNP, whereas under p-benzoquinone concentrations of 10 -3 -10 -2 mol dm -3 the CIDNP from both hydroquinone and p-benzoquinone has been followed. Photolysis of uranyl propionate has led to CIDNP from butane protons. An emission from methyl group protons of a compound with an ethylperoxyl fragment in the presence of air/oxygen has been observed. The same polarization picture has arisen under interaction of photoexcited uranyl with propionic acid. During the photolysis of uranyl acetate at relatively low concentrations (10 -2 mol dm -3 ) a CIDNP very similar to that registered for uranyl propionate was recorded. The ethyl fragment is probably obtained in reactions for two methyl radicals formed from acetate with the parent uranyl acetate, namely hydrogen-atom abstraction and addition reactions. (author)

  4. Stress-induced chemical detection using flexible metal-organic frameworks.

    Energy Technology Data Exchange (ETDEWEB)

    Allendorf, Mark D.; Hesketh, Peter J. (Georgia Institute of Technology, Atlanta, GA); Gall, Kenneth A. (Georgia Institute of Technology, Atlanta, GA); Choudhury, A. (Georgia Institute of Technology, Atlanta, GA); Pikarsky, J. (Georgia Institute of Technology, Atlanta, GA); Andruszkiewicz, Leanne (Georgia Institute of Technology, Atlanta, GA); Houk, Ronald J. T.; Talin, Albert Alec (National Institute of Standards & Technology, Gaithersburg, MD)

    2009-09-01

    In this work we demonstrate the concept of stress-induced chemical detection using metal-organic frameworks (MOFs) by integrating a thin film of the MOF HKUST-1 with a microcantilever surface. The results show that the energy of molecular adsorption, which causes slight distortions in the MOF crystal structure, can be efficiently converted to mechanical energy to create a highly responsive, reversible, and selective sensor. This sensor responds to water, methanol, and ethanol vapors, but yields no response to either N{sub 2} or O{sub 2}. The magnitude of the signal, which is measured by a built-in piezoresistor, is correlated with the concentration and can be fitted to a Langmuir isotherm. Furthermore, we show that the hydration state of the MOF layer can be used to impart selectivity to CO{sub 2}. We also report the first use of surface-enhanced Raman spectroscopy to characterize the structure of a MOF film. We conclude that the synthetic versatility of these nanoporous materials holds great promise for creating recognition chemistries to enable selective detection of a wide range of analytes. A force field model is described that successfully predicts changes in MOF properties and the uptake of gases. This model is used to predict adsorption isotherms for a number of representative compounds, including explosives, nerve agents, volatile organic compounds, and polyaromatic hydrocarbons. The results show that, as a result of relatively large heats of adsorption (> 20 kcal mol{sup -1}) in most cases, we expect an onset of adsorption by MOF as low as 10{sup -6} kPa, suggesting the potential to detect compounds such as RDX at levels as low as 10 ppb at atmospheric pressure.

  5. Sister chromatid exchanges in the bone marrow cells of in vivo rats induced by gamma radiation and chemical mutagens

    International Nuclear Information System (INIS)

    Rodriguez R, R.G.

    1981-01-01

    Sister chromatid exchanges (SCE) in the bone marrow of in vivo rats induced by gamma radiation doses and by the chemical mutagens, mitomycin C (MMC), cyclophosphamide (CP), and sulphonate-methylmethane (SMM), were studied. The purpose was to evaluate the sensitivity and reproducibility of a simplified SCE in vivo detecting system developed in our laboratory and to compare the results obtained with those reported elsewhere. Simplification consisted in administering the amounts of 5-bromo-2'-deoxyuridine (BrdU) necessary to observe the SCE, after first adsorbing the BrdU in activated carbon and then injecting it interperitoneally, into the rats. The results were a longer time in vivo ADN incorporation without convulsions in the rats, and a reduction in the time course as compared to other methods. We observed a basal rate of 3.6+-0.37 SCE/cell and that: 0.44 Gy of gamma radiation induced 7.7+-0.73 SCE/cell; 1.6 μg/g of MMC induced 8.1+-1.20 SCE/cell; 5 μg/g of CP induced 8.25+-1.5 SCE/cell, 40 μg/g of SMM induced 22.0+-5 SCE/cell and 380 μg/g of sulphonate-ethylmethane induced 8.6+-1.2 SCE/cell. This showed that all the agents were capable of inducing SCE in the bone marrow cells of rats in vivo under our conditions. We noted a greater induced efficiency for gamma radiation than the obtained by other investigators and a relatively similar efficiency in the case of chemical mutagens as reported in other studies. (author)

  6. Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: Implication in manganese-induced pulmonary inflammation

    International Nuclear Information System (INIS)

    Han, Jeongoh; Lee, Jong-Suk; Choi, Daekyu; Lee, Youna; Hong, Sungchae; Choi, Jungyun; Han, Songyi; Ko, Yujin; Kim, Jung-Ae; Mi Kim, Young; Jung, Yunjin

    2009-01-01

    Manganese (II), a transition metal, causes pulmonary inflammation upon environmental or occupational inhalation in excess. We investigated a potential molecular mechanism underlying manganese-induced pulmonary inflammation. Manganese (II) delayed HIF-1α protein disappearance, which occurred by inhibiting HIF-prolyl hydroxylase (HPH), the key enzyme for HIF-1α hydroxylation and subsequent von Hippel-Lindau(VHL)-dependent HIF-1α degradation. HPH inhibition by manganese (II) was neutralized significantly by elevated dose of iron. Consistent with this, the induction of cellular HIF-1α protein by manganese (II) was abolished by pretreatment with iron. Manganese (II) induced the HIF-1 target gene involved in pulmonary inflammation, vascular endothelial growth factor (VEGF), in lung carcinoma cell lines. The induction of VEGF was dependent on HIF-1. Manganese-induced VEGF promoted tube formation of HUVEC. Taken together, these data suggest that HIF-1 may be a potential mediator of manganese-induced pulmonary inflammation

  7. Ingested plastic transfers hazardous chemicals to fish and induces hepatic stress

    Science.gov (United States)

    Rochman, Chelsea M.; Hoh, Eunha; Kurobe, Tomofumi; Teh, Swee J.

    2013-01-01

    Plastic debris litters aquatic habitats globally, the majority of which is microscopic (plastic and accumulated pollutants are largely unknown. Here, we show that fish, exposed to a mixture of polyethylene with chemical pollutants sorbed from the marine environment, bioaccumulate these chemical pollutants and suffer liver toxicity and pathology. Fish fed virgin polyethylene fragments also show signs of stress, although less severe than fish fed marine polyethylene fragments. We provide baseline information regarding the bioaccumulation of chemicals and associated health effects from plastic ingestion in fish and demonstrate that future assessments should consider the complex mixture of the plastic material and their associated chemical pollutants. PMID:24263561

  8. Comparison of two chemically-induced colitis-models in adult zebrafish, using optical projection tomography and novel transcriptional markers

    DEFF Research Database (Denmark)

    Haarder, Simon; Kania, Per Walter; Holm, Thomas

    2016-01-01

    , induced by the haptenizing agents oxazolone and TNBS. In addition, goblet cell dynamics in the scales and intestine and 5-HT (serotonin) in intestinal tissues were investigated through optical projection tomography. Gene expression studies revealed a distinct and significant upregulation...... of proinflammatory cytokines, acute-phase reactants and metalloprotease 9 in both chemical models, primarily after 72 hours. In comparison, transcription factors and cytokines associated with Th1 and Th17 (Crohn’s) and Th2 (ulcerative colitis) were mainly not affected in this acute setting. However, elevated...... transcript levels were detected in Foxp3, IL-10 and T-bet, which are linked with tolerance and Tregs in mammals. Goblet cells in scales were depleted in both chemical models and in the intestine of oxazolone-treated fish. A marked 5-HT signal was noted in intestinal tissue of some chemically treated...

  9. Physical and chemical changes induced by 70 MeV carbon ions in polyvinylidene difluoride (PVDF) polymer

    International Nuclear Information System (INIS)

    Virk, H.S.; Chandi, P.S.; Srivastava, A.K.

    2001-01-01

    Physical and chemical changes induced by 70 MeV carbon ions ( 12 C 5+ ) have been investigated in bulk polyvinylidene fluoride (PVDF) polymer. The induced changes have been studied with respect to their optical, chemical and structural response using UV-visible, FTIR and XRD techniques. The ion fluences ranging from 2.5x10 11 to 9x10 13 ions cm -2 have been used to study the irradiation effects. It has been observed that at the fluence of 9x10 13 ions cm -2 the PVDF sample became brittle and practically it was not possible to handle it for any further measurements. The recorded UV-visible spectra show that the optical absorption increases with increasing fluence, indicating maximum absorption at 200 nm. An interesting feature of UV-visible spectra is that dips change into peaks and vice versa with increase of fluence. In the FTIR spectra, development of new peaks at 1714 and 3692 cm -1 along with disappearance of peaks at 2363 and 3025 cm -1 and shifting of peak at 2984-2974 cm -1 have been observed due to high energy irradiation, indicating the chemical changes induced by 12 C 5+ . The diffraction pattern of PVDF indicates that this polymer is semi-crystalline in nature; a large decrease in the diffraction intensity indicates decrease in crystallinity. Increase in crystallite size has also been observed due to heavy ion irradiation

  10. Combined comparative and chemical proteomics on the mechanisms of levo-tetrahydropalmatine-induced antinociception in the formalin test.

    Science.gov (United States)

    Wang, Chen; Zhou, Jiangrui; Wang, Shuowen; Ye, Mingliang; Jiang, Chunlei; Fan, Guorong; Zou, Hanfa

    2010-06-04

    This study investigated the mechanisms involved in the antinociceptive action induced by levo-tetrahydropalmatine (l-THP) in the formalin test by combined comparative and chemical proteomics. Rats were pretreated with l-THP by the oral route (40 mg/kg) 1 h before formalin injection. The antinociceptive effect of l-THP was shown in the first and second phases of the formalin test. To address the mechanisms by which l-THP inhibits formalin-induced nociception in rats, the combined comparative and chemical proteomics were applied. A novel high-throughput comparative proteomic approach based on 2D-nano-LC-MS/MS was applied to simultaneously evaluate the deregulated proteins involved in the response of l-THP treatment in formalin-induced pain rats. Thousands of proteins were identified, among which 17 proteins survived the stringent filter criteria and were further included for functional discussion. Two proteins (Neurabin-1 and Calcium-dependent secretion activator 1) were randomly selected, and their expression levels were further confirmed by Western Blots. The results matched well with those of proteomics. In the present study, we also described the development and application of l-THP immobilized beads to bind the targets. Following incubation with cellular lysates, the proteome interacting with the fixed l-THP was identified. The results of comparative and chemical proteomics were quite complementary. Although the precise roles of these identified moleculars in l-THP-induced antinociception need further study, the combined results indicated that proteins associated with signal transduction, vesicular trafficking and neurotransmitter release, energy metabolism, and ion transport play important roles in l-THP-induced antinociception in the formalin test.

  11. POSSIBLE NATURE OF THE RADIATION-INDUCED SIGNAL IN NAILS: HIGH-FIELD EPR, CONFIRMING CHEMICAL SYNTHESIS, AND QUANTUM CHEMICAL CALCULATIONS.

    Science.gov (United States)

    Tipikin, Dmitriy S; Swarts, Steven G; Sidabras, Jason W; Trompier, François; Swartz, Harold M

    2016-12-01

    Exposure of finger- and toe-nails to ionizing radiation generates an Electron Paramagnetic Resonance (EPR) signal whose intensity is dose dependent and stable at room temperature for several days. The dependency of the radiation-induced signal (RIS) on the received dose may be used as the basis for retrospective dosimetry of an individual's fortuitous exposure to ionizing radiation. Two radiation-induced signals, a quasi-stable (RIS2) and stable signal (RIS5), have been identified in nails irradiated up to a dose of 50 Gy. Using X-band EPR, both RIS signals exhibit a singlet line shape with a line width around 1.0 mT and an apparent g-value of 2.0044. In this work, we seek information on the exact chemical nature of the radiation-induced free radicals underlying the signal. This knowledge may provide insights into the reason for the discrepancy in the stabilities of the two RIS signals and help develop strategies for stabilizing the radicals in nails or devising methods for restoring the radicals after decay. In this work an analysis of high field (94 GHz and 240 GHz) EPR spectra of the RIS using quantum chemical calculations, the oxidation-reduction properties and the pH dependence of the signal intensities are used to show that spectroscopic and chemical properties of the RIS are consistent with a semiquinone-type radical underlying the RIS. It has been suggested that semiquinone radicals formed on trace amounts of melanin in nails are the basis for the RIS signals. However, based on the quantum chemical calculations and chemical properties of the RIS, it is likely that the radicals underlying this signal are generated from the radiolysis of L-3,4-dihydroxyphenylalanine (DOPA) amino acids in the keratin proteins. These DOPA amino acids are likely formed from the exogenous oxidation of tyrosine in keratin by the oxygen from the air prior to irradiation. We show that these DOPA amino acids can work as radical traps, capturing the highly reactive and unstable sulfur

  12. POSSIBLE NATURE OF THE RADIATION-INDUCED SIGNAL IN NAILS: HIGH-FIELD EPR, CONFIRMING CHEMICAL SYNTHESIS, AND QUANTUM CHEMICAL CALCULATIONS

    Science.gov (United States)

    Tipikin, Dmitriy S.; Swarts, Steven G.; Sidabras, Jason W.; Trompier, François; Swartz, Harold M.

    2016-01-01

    Exposure of finger- and toe-nails to ionizing radiation generates an Electron Paramagnetic Resonance (EPR) signal whose intensity is dose dependent and stable at room temperature for several days. The dependency of the radiation-induced signal (RIS) on the received dose may be used as the basis for retrospective dosimetry of an individual's fortuitous exposure to ionizing radiation. Two radiation-induced signals, a quasi-stable (RIS2) and stable signal (RIS5), have been identified in nails irradiated up to a dose of 50 Gy. Using X-band EPR, both RIS signals exhibit a singlet line shape with a line width around 1.0 mT and an apparent g-value of 2.0044. In this work, we seek information on the exact chemical nature of the radiation-induced free radicals underlying the signal. This knowledge may provide insights into the reason for the discrepancy in the stabilities of the two RIS signals and help develop strategies for stabilizing the radicals in nails or devising methods for restoring the radicals after decay. In this work an analysis of high field (94 GHz and 240 GHz) EPR spectra of the RIS using quantum chemical calculations, the oxidation–reduction properties and the pH dependence of the signal intensities are used to show that spectroscopic and chemical properties of the RIS are consistent with a semiquinone-type radical underlying the RIS. It has been suggested that semiquinone radicals formed on trace amounts of melanin in nails are the basis for the RIS signals. However, based on the quantum chemical calculations and chemical properties of the RIS, it is likely that the radicals underlying this signal are generated from the radiolysis of L-3,4-dihydroxyphenylalanine (DOPA) amino acids in the keratin proteins. These DOPA amino acids are likely formed from the exogenous oxidation of tyrosine in keratin by the oxygen from the air prior to irradiation. We show that these DOPA amino acids can work as radical traps, capturing the highly reactive and unstable

  13. Noise-induced multistability in chemical systems: Discrete versus continuum modeling

    Czech Academy of Sciences Publication Activity Database

    Duncan, A.; Liao, S.; Vejchodský, Tomáš; Erban, R.; Grima, R.

    2015-01-01

    Roč. 91, č. 4 (2015), s. 042111 ISSN 1539-3755 EU Projects: European Commission(XE) 328008 - STOCHDETBIOMODEL Institutional support: RVO:67985840 Keywords : chemical master equation * chemical Fokker-Planck equation * multimodality Subject RIV: BA - General Mathematics Impact factor: 2.288, year: 2014 http://journals.aps.org/pre/abstract/10.1103/PhysRevE.91.042111

  14. A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

    Science.gov (United States)

    One of the reported effects for exposure to many of the toxic industrial chemicals is DNA damage. The present study describes a simple, rapid and innovative assay to detect DNA damage resulting from exposure of surrogate DNA to toxic industrial chemicals (acrolein, allylamine, ch...

  15. Heat-induced chemical and color changes of extractive-free Black Locust (Rosinia Pseudoacacia) wood

    Science.gov (United States)

    Yao Chen; Jianmin Gao; Yongming Fan; Mandla A. Tshabalala; Nicole M. Stark

    2012-01-01

    To investigate chemical and color changes of the polymeric constituents of black locust (Robinia pseudoacacia) wood during heat treatment, extractive-free wood flour was conditioned to 30% initial moisture content (MC) and heated for 24 h at 120 °C in either an oxygen or nitrogen atmosphere. The color change was measured using the CIELAB color system. Chemical changes...

  16. Ultraviolet and chemical induced DNA repair in human cells assayed by bromodeoxyuridine photolysis or cytosine arabinoside arrest

    International Nuclear Information System (INIS)

    Regan, J.D.; Dunn, W.C.

    1979-01-01

    The bromodeoxyuridine photolysis assay of DNA damage in human cells permits an estimate of both the number of repaired regions in the DNA and the size of the average repaired region - the patch size. The antineoplastic agent arabinofuranosyl cytosine (ara-C) can also be employed to assay the magnitude of repair since this agent appears to block rejoining of single-strand incisions made in the DNA during the initial step of repair. Thus, the number of incisions can be accumulated. The ara-C effect is dependent on the presence of hydroxyurea. Both assays can be employed for the study of physical or chemical DNA damages. Results comparing these assays are presented

  17. B-lymphocytes as key players in chemical-induced asthma.

    Directory of Open Access Journals (Sweden)

    Vanessa De Vooght

    Full Text Available T-lymphocytes and B-lymphocytes are key players in allergic asthma, with B-lymphocytes producing antigen-specific immunoglobulins E (IgE. We used a mouse model of chemical-induced asthma and transferred B-lymphocytes from sensitized animals into naïve wild type mice, B-lymphocyte knock-out (B-KO mice or severe combined immunodeficiency (SCID mice. On days 1 and 8, BALB/c mice were dermally sensitized with 0.3% toluene diisocyanate (TDI (20 µl/ear. On day 15, mice were euthanized and the auricular lymph nodes isolated. B-lymphocytes (CD19(+ were separated from the whole cell suspension and 175,000 cells were injected in the tail vein of naïve wild type, B-KO or SCID mice. Three days later, the mice received a single oropharyngeal challenge with 0.01% TDI (20 µl or vehicle (acetone/olive oil (AOO (controls. Airway reactivity to methacholine and total and differential cell counts in the bronchoalveolar lavage (BAL fluid were measured 24 hours after challenge. B-lymphocytes of AOO or TDI-sensitized mice were characterized for the expression of surface markers and production of cytokines. We found that transfer of B-cells obtained from mice dermally sensitized to toluene diisocyanate (TDI into naïve wild type mice, B-KO mice or SCID mice led, within three days, to an acute asthma-like phenotype after an airway challenge with TDI. This response was specific and independent of IgE. These B-lymphocytes showed antigen presenting capacities (CD80/CD86 and CD40 and consisted of B effector (Be2- (IL-4 and Be1-lymphocytes (IFN-γ. The transferred B-lymphocytes were visualized near large airways, 24 hours after TDI challenge. Thus, B-lymphocytes can provoke an asthmatic response without the action of T-lymphocytes and without major involvement of IgE.

  18. Effect of complex polyphenols and tannins from red wine (WCPT) on chemically induced oxidative DNA damage in the rat.

    Science.gov (United States)

    Casalini, C; Lodovici, M; Briani, C; Paganelli, G; Remy, S; Cheynier, V; Dolara, P

    1999-08-01

    Flavonoids are polyphenolic antioxidants occurring in vegetables and fruits as well as beverages such as tea and wine which have been thought to influence oxidative damage. We wanted to verify whether a complex mixture of wine tannins (wine complex polyphenols and tannins, WCPT) prevent chemically-induced oxidative DNA damage in vivo. Oxidative DNA damage was evaluated by measuring the ratio of 8-hydroxy-2'-deoxyguanosine (80HdG)/ 2-deoxyguanosine (2dG) x 10(-6) in hydrolyzed DNA using HPLC coupled with electrochemical and UV detectors. We treated rats with WCPT (57 mg/kg p.o.) for 14 d, a dose 10-fold higher than what a moderate wine drinker would be exposed to. WCPT administration significantly reduced the ratio of 80HdG/2dG x 10(-6) in liver DNA obtained from rats treated with 2-nitropropane (2NP) relative to controls administered 2NP only (33. 3 +/- 2.5 vs. 44.9 +/- 3.2 x 10(-6) 2dG; micro +/- SE; p<0.05). On the contrary, pretreatment with WCPT for 10 d did not protect the colon mucosa from oxidative DNA damage induced by 1, 2-dimethylhydrazine (DMH). 2NP and DMH are hepatic and colon carcinogens, respectively, capable of inducing oxidative DNA damage. WCPT have protective action against some types of chemically-induced oxidative DNA damage in vivo.

  19. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

    NARCIS (Netherlands)

    Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

    Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were

  20. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak

    2013-09-01

    Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.

  1. Induced mutations in chickpea (Cicer arietinum L.) I. comparative mutagenic effectiveness and efficiency of physical & chemical mutagens

    International Nuclear Information System (INIS)

    Kharkwal, M.C.

    1998-01-01

    Mutagenic effectiveness usually means the rate of mutation as related to dose. Mutagenic efficiency refers to the mutation rate in relation to damage. Studies on comparative mutagenic effectiveness and efficiency of two physical (gamma rays and fast neutrons) and two chemical mutagens (NMU and EMS) on two desi (G 130 & H 214), one kabuli (C 104) and one green seeded (L 345) chickpea (Cicer arietinum L.) have been reported. The treatments included three doses each of gamma rays (400, 500 and 600 Gy) and fast neutrons (5, 10 and 15 Gy) and two concentrations with two different durations of two chemical mutagens, NMU 0.01% 20h and 0.02% 8h) and EMS (0.1% 20h and 0.2% 8h). Results indicated that chemical mutagens, particularly NMU are not only more effective but also efficient than physical mutagens in inducing mutations in chickpea. Mutagenic effectiveness and efficiency showed differential behaviour depending upon mutagen and varietal type. Chemical mutagens were more efficient than physical in inducing cholorophyll as well as viable and total number of mutations. Among the mutagens NMU was the most potent, while in the physical, gamma rays were more effective. Out of four mutagens, NMU was the most effective and efficient in inducing a high frequency and wide spectrum of chlorophyll mutations in the M2 followed by fast neutrons. While gamma rays showed least effectiveness, EMS was least efficient mutagens. Major differences in the mutagenic response of the four cultivars were observed. The varieties of desi type were more resistant towards mutagenic treatment than kabuli and green seeded type

  2. Noise-induced multistability in chemical systems: Discrete versus continuum modeling

    Czech Academy of Sciences Publication Activity Database

    Duncan, A.; Liao, S.; Vejchodský, Tomáš; Erban, R.; Grima, R.

    2015-01-01

    Roč. 91, č. 4 (2015), s. 042111 ISSN 1539-3755 EU Projects: European Commission(XE) 328008 - STOCHDETBIOMODEL Institutional support: RVO:67985840 Keywords : chemical master equation * chemical Fokker-Planck equation * multimodality Subject RIV: BA - General Mathematics Impact factor: 2.288, year: 2014 http://journals. aps .org/pre/abstract/10.1103/PhysRevE.91.042111

  3. [Revealing the chemical changes of tea cell wall induced by anthracnose with confocal Raman microscopy].

    Science.gov (United States)

    Li, Xiao-li; Luo, Liu-bin; Hu, Xiao-qian; Lou, Bing-gan; He, Yong

    2014-06-01

    Healthy tea and tea infected by anthracnose were first studied by confocal Raman microscopy to illustrate chemical changes of cell wall in the present paper. Firstly, Raman spectra of both healthy and infected sample tissues were collected with spatial resolution at micron-level, and ultrastructure of healthy and infected tea cells was got from scanning electron microscope. These results showed that there were significant changes in Raman shift and Raman intensity between healthy and infected cell walls, indicating that great differences occurred in chemical compositions of cell walls between healthy and infected samples. In details, intensities at many Raman bands which were closely associated with cellulose, pectin, esters were reduced after infection, revealing that the content of chemical compounds such as cellulose, pectin, esters was decreased after infection. Subsequently, chemical imaging of both healthy and infected tea cell walls were realized based on Raman fingerprint spectra of cellulose and microscopic spatial structure. It was found that not only the content of cellulose was reduced greatly after infection, but also the ordered structure of cellulose was destroyed by anthracnose infection. Thus, confocal Raman microscopy was shown to be a powerful tool to detect the chemical changes in cell wall of tea caused by anthracnose without any chemical treatment or staining. This research firstly applied confocal Raman microscopy in phytopathology for the study of interactive relationship between host and pathogen, and it will also open a new way for intensive study of host-pathogen at cellular level.

  4. Protective effects of black rice bran against chemically-induced inflammation of mouse skin

    Science.gov (United States)

    We investigated the inhibitory effects of black rice (cv. LK1-3-6-12-1-1) bran against 12-O-tetradecanolylphorbol-13-acetate (TPA)-induced skin edema and 2,4-dinitroflurobenzene (DNFB)-induced allergic contact dermatitis (ACD) in inflammatory mouse models. We also determined the effects of the bran...

  5. The Load and Time Dependence of Chemical Bonding-Induced Frictional Ageing of Silica at the Nanoscale

    Science.gov (United States)

    Tian, K.; Gosvami, N. N.; Goldsby, D. L.; Carpick, R. W.

    2015-12-01

    Rate and state friction (RSF) laws are empirical relationships that describe the frictional behavior of rocks and other materials in experiments, and reproduce a variety of observed natural behavior when employed in earthquake models. A pervasive observation from rock friction experiments is the linear increase of static friction with the log of contact time, or 'ageing'. Ageing is usually attributed to an increase in real area of contact associated with asperity creep. However, recent atomic force microscopy (AFM) experiments demonstrate that ageing of nanoscale silica-silica contacts is due to progressive formation of interfacial chemical bonds in the absence of plastic deformation, in a manner consistent with the multi-contact ageing behavior of rocks [Li et al., 2011]. To further investigate chemical bonding-induced ageing, we explored the influence of normal load (and thus contact normal stress) and contact time on ageing. Experiments that mimic slide-hold-slide rock friction experiments were conducted in the AFM for contact loads and hold times ranging from 23 to 393 nN and 0.1 to 100 s, respectively, all in humid air (~50% RH) at room temperature. Experiments were conducted by sequentially sliding the AFM tip on the sample at a velocity V of 0.5 μm/s, setting V to zero and holding the tip stationary for a given time, and finally resuming sliding at 0.5 μm/s to yield a peak value of friction followed by a drop to the sliding friction value. Chemical bonding-induced ageing, as measured by the peak friction minus the sliding friction, increases approximately linearly with the product of normal load and the log of the hold time. Theoretical studies of the roles of reaction energy barriers in nanoscale ageing indicate that frictional ageing depends on the total number of reaction sites and the hold time [Liu & Szlufarska, 2012]. We combine chemical kinetics analyses with contact mechanics models to explain our results, and develop a new approach for curve

  6. Gene Expression Patterns during the Early Stages of Chemically Induced Larval Metamorphosis and Settlement of the Coral Acropora millepora

    Science.gov (United States)

    Siboni, Nachshon; Abrego, David; Motti, Cherie A.; Tebben, Jan; Harder, Tilmann

    2014-01-01

    The morphogenetic transition of motile coral larvae into sessile primary polyps is triggered and genetically programmed upon exposure to environmental biomaterials, such as crustose coralline algae (CCA) and bacterial biofilms. Although the specific chemical cues that trigger coral larval morphogenesis are poorly understood there is much more information available on the genes that play a role in this early life phase. Putative chemical cues from natural biomaterials yielded defined chemical samples that triggered different morphogenetic outcomes: an extract derived from a CCA-associated Pseudoalteromonas bacterium that induced metamorphosis, characterized by non-attached metamorphosed juveniles; and two fractions of the CCA Hydrolithon onkodes (Heydrich) that induced settlement, characterized by attached metamorphosed juveniles. In an effort to distinguish the genes involved in these two morphogenetic transitions, competent larvae of the coral Acropora millepora were exposed to these predictable cues and the expression profiles of 47 coral genes of interest (GOI) were investigated after only 1 hour of exposure using multiplex RT–qPCR. Thirty-two GOI were differentially expressed, indicating a putative role during the early regulation of morphogenesis. The most striking differences were observed for immunity-related genes, hypothesized to be involved in cell recognition and adhesion, and for fluorescent protein genes. Principal component analysis of gene expression profiles resulted in separation between the different morphogenetic cues and exposure times, and not only identified those genes involved in the early response but also those which influenced downstream biological changes leading to larval metamorphosis or settlement. PMID:24632854

  7. New method for estimating clustering of DNA lesions induced by physical/chemical mutagens using fluorescence anisotropy.

    Science.gov (United States)

    Akamatsu, Ken; Shikazono, Naoya; Saito, Takeshi

    2017-11-01

    We have developed a new method for estimating the localization of DNA damage such as apurinic/apyrimidinic sites (APs) on DNA using fluorescence anisotropy. This method is aimed at characterizing clustered DNA damage produced by DNA-damaging agents such as ionizing radiation and genotoxic chemicals. A fluorescent probe with an aminooxy group (AlexaFluor488) was used to label APs. We prepared a pUC19 plasmid with APs by heating under acidic conditions as a model for damaged DNA, and subsequently labeled the APs. We found that the observed fluorescence anisotropy (r obs ) decreases as averaged AP density (λ AP : number of APs per base pair) increases due to homo-FRET, and that the APs were randomly distributed. We applied this method to three DNA-damaging agents, 60 Co γ-rays, methyl methanesulfonate (MMS), and neocarzinostatin (NCS). We found that r obs -λ AP relationships differed significantly between MMS and NCS. At low AP density (λ AP  < 0.001), the APs induced by MMS seemed to not be closely distributed, whereas those induced by NCS were remarkably clustered. In contrast, the AP clustering induced by 60 Co γ-rays was similar to, but potentially more likely to occur than, random distribution. This simple method can be used to estimate mutagenicity of ionizing radiation and genotoxic chemicals. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model

    Energy Technology Data Exchange (ETDEWEB)

    Sirenko, Oksana, E-mail: oksana.sirenko@moldev.com [Molecular Devices, LLC, Sunnyvale, CA (United States); Grimm, Fabian A. [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Ryan, Kristen R. [Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Iwata, Yasuhiro; Chiu, Weihsueh A. [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Parham, Frederick [Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Wignall, Jessica A. [ICF, Fairfax, VA (United States); Anson, Blake [Cellular Dynamics International, Madison, WI (United States); Cromwell, Evan F. [Protein Fluidics, Inc., Burlingame, CA (United States); Behl, Mamta [Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Rusyn, Ivan [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Tice, Raymond R. [Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)

    2017-05-01

    An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs. Human induced pluripotent stem cell-derived cardiomyocytes were exposed in concentration-response for 30 min or 24 h and effects on cardiomyocyte beating and cellular and mitochondrial toxicity were assessed by kinetic measurements of intracellular Ca{sup 2+} flux and high-content imaging using the nuclear dye Hoechst 33342, the cell viability marker Calcein AM, and the mitochondrial depolarization probe JC-10. More than half of the tested chemicals exhibited effects on cardiomyocyte beating after 30 min of exposure. In contrast, after 24 h, effects on cell beating without concomitant cytotoxicity were observed in about one third of the compounds. Concentration-response data for in vitro bioactivity phenotypes visualized using the Toxicological Prioritization Index (ToxPi) showed chemical class-specific clustering of environmental chemicals, including pesticides, flame retardants, and polycyclic aromatic hydrocarbons. For environmental chemicals with human exposure predictions, the activity-to-exposure ratios between modeled blood concentrations and in vitro bioactivity were between one and five orders of magnitude. These findings not only demonstrate that some ubiquitous environmental pollutants might have the potential at high exposure levels to alter cardiomyocyte function, but also indicate similarities in the mechanism of these effects both within and among chemicals and classes. - Highlights:

  9. In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model

    International Nuclear Information System (INIS)

    Sirenko, Oksana; Grimm, Fabian A.; Ryan, Kristen R.; Iwata, Yasuhiro; Chiu, Weihsueh A.; Parham, Frederick; Wignall, Jessica A.; Anson, Blake; Cromwell, Evan F.; Behl, Mamta; Rusyn, Ivan; Tice, Raymond R.

    2017-01-01

    An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs. Human induced pluripotent stem cell-derived cardiomyocytes were exposed in concentration-response for 30 min or 24 h and effects on cardiomyocyte beating and cellular and mitochondrial toxicity were assessed by kinetic measurements of intracellular Ca 2+ flux and high-content imaging using the nuclear dye Hoechst 33342, the cell viability marker Calcein AM, and the mitochondrial depolarization probe JC-10. More than half of the tested chemicals exhibited effects on cardiomyocyte beating after 30 min of exposure. In contrast, after 24 h, effects on cell beating without concomitant cytotoxicity were observed in about one third of the compounds. Concentration-response data for in vitro bioactivity phenotypes visualized using the Toxicological Prioritization Index (ToxPi) showed chemical class-specific clustering of environmental chemicals, including pesticides, flame retardants, and polycyclic aromatic hydrocarbons. For environmental chemicals with human exposure predictions, the activity-to-exposure ratios between modeled blood concentrations and in vitro bioactivity were between one and five orders of magnitude. These findings not only demonstrate that some ubiquitous environmental pollutants might have the potential at high exposure levels to alter cardiomyocyte function, but also indicate similarities in the mechanism of these effects both within and among chemicals and classes. - Highlights:

  10. Use of the enhanced frog embryo teratogenesis assay-Xenopus (FETAX) to determine chemically-induced phenotypic effects.

    Science.gov (United States)

    Hu, Lingling; Zhu, Jingmin; Rotchell, Jeanette M; Wu, Lijiao; Gao, Jinjuan; Shi, Huahong

    2015-03-01

    The frog embryo teratogenesis assay-Xenopus (FETAX) is an established method for the evaluation of the developmental toxicities of chemicals. To develop an enhanced FETAX that is appropriate for common environmental contaminants, we exposed Xenopus tropicalis embryos to eight compounds, including tributyltin, triphenyltin, CdCl2, pyraclostrobin, picoxystrobin, coumoxystrobin, all-trans-retinoic acid and 9-cis-retinoic acid. Multiple malformations were induced in embryos particularly following exposure to tributyltin, triphenyltin and pyraclostrobin at environmentally relevant concentrations. Based on the range of observed malformations, we proposed a phenotypic assessment method with 20 phenotypes and a 0-5 scoring system. This derived index exhibited concentration-dependent relationships for all of the chemicals tested. Furthermore, the phenotype profiles were characteristic of the different tested chemicals. Our results indicate that malformation phenotypes can be quantitatively integrated with the primary endpoints in conventional FETAX assessments to allow for increased sensitivity and measurement of quantitative effects and to provide indicative mechanistic information for each tested chemical. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Ameliorative Effects of Neurolytic Celiac Plexus Block on Stress and ...

    African Journals Online (AJOL)

    Keywords: Neurolytic celiac plexus block, Cytokine, Nuclear translocation, Partial hepatectomy, Stress, ... International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index ... inflammatory reactions, leading to over-activation.

  12. Chemical effects induced by dissolving γ-irradiated alkali halides in aqueous nitrate, permanganate and chromate solutions

    International Nuclear Information System (INIS)

    Phansalkar, V.K.; Bapat, L.; Ravishankar, D.

    1982-01-01

    Dissolution of γ-irradiated alkali halides in aqueous solutions of sodium nitrate, potassium permanganate and potassium chromate at neutral pH induces chemical changes leading to the formation of NO 2 - in nitrate, Mn(IV) and Cr(III) species in permanganate and chromate solutions, respectively. Further, the studies on nitrate and permanganate systems show that the amount of NO 2 - and Mn(IV) formed grows by increasing the dose of γ-irradiation of the salt and the amount of irradiated salt. Moreover, the extent of chemical changes effected by irradiated chlorides has been found to be more than that of bromides. The mesh size of the irradiated salt and the presence of scavengers like I - and methanol in the system, affects the yield of NO 2 - . (author)

  13. Investigation of chemical vapour deposition diamond detectors by X-ray micro-beam induced current and X-ray micro-beam induced luminescence techniques

    International Nuclear Information System (INIS)

    Olivero, P.; Manfredotti, C.; Vittone, E.; Fizzotti, F.; Paolini, C.; Lo Giudice, A.; Barrett, R.; Tucoulou, R.

    2004-01-01

    Tracking detectors have become an important ingredient in high-energy physics experiments. In order to survive the harsh detection environment of the large hadron collider (LHC), trackers need to have special properties. They must be radiation hard, provide fast collection of charge, be as thin as possible and remove heat from readout electronics. The unique properties of diamond allow it to fulfill these requirements. In this work we present an investigation of the charge transport and luminescence properties of 'detector grade' artificial chemical vapour deposition (CVD) diamond devices developed within the CERN RD42 collaboration, performed by means of X-ray micro-beam induced current collection (XBICC) and X-ray micro-beam induced luminescence (XBIL) techniques. XBICC technique allows quantitative estimates of the transport parameters of the material to be evaluated and mapped with micrometric spatial resolution. In particular, the high resolution and sensitivity of the technique has allowed a quantitative study of the inhomogeneity of the charge transport parameter defined as the product of mobility and lifetime for both electron and holes. XBIL represents a technique complementary to ion beam induced luminescence (IBIL), which has already been used by our group, since X-ray energy loss profile in the material is different from that of MeV ions. X-ray induced luminescence maps have been performed simultaneously with induced photocurrent maps, to correlate charge transport and induced luminescence properties of diamond. Simultaneous XBICC and XBIL maps exhibit features of partial complementarity that have been interpreted on the basis of considerations on radiative and non-radiative recombination processes which compete with charge transport efficiency

  14. Preventive effect of chemical peeling on ultraviolet induced skin tumor formation.

    Science.gov (United States)

    Abdel-Daim, Mohamed; Funasaka, Yoko; Kamo, Tsuneyoshi; Ooe, Masahiko; Matsunaka, Hiroshi; Yanagita, Emmy; Itoh, Tomoo; Nishigori, Chikako

    2010-10-01

    Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. We assessed the photochemopreventive effect of several clinically used chemical peeling agents on the ultraviolet (UV)-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, 10% or 35% trichloroacetic acid (TCA) in distilled water at the right back of UV-irradiated hairless mice every 2 weeks in case of glycolic acid, salicylic acid, and 10% TCA and every 4 weeks in case of 35% TCA for totally 18 weeks after the establishment of photoaged mice by irradiation with UVA+B range light three times a week for 10 weeks at a total dose of 420 J/cm(2) at UVA and 9.6 J/cm(2) at UVB. Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of P53 expression, and mRNA expression of cyclooxygenase (COX)-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also non-treated area. Peeling suppressed clonal retention of p53 positive abnormal cells and reduced mRNA expression of COX-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid, and TCA could serve tumor prevention by removing photodamaged cells. Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Systematic review of the use of the lymphocyte cytokinesis-block micronucleus assay to measure DNA damage induced by exposure to polycyclic aromatic hydrocarbons

    Czech Academy of Sciences Publication Activity Database

    Šrám, Radim; Švecová, Vlasta; Rössnerová, Andrea

    2016-01-01

    Roč. 770, oct - dec (2016), s. 162-169 ISSN 1383-5742 R&D Projects: GA ČR(CZ) GA13-13458S Institutional support: RVO:68378041 Keywords : cytokinesis blocked micronuclei * peripheral blood lymphocytes * polycyclic aromatic hydrocarbons Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 5.500, year: 2016

  16. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Douglas class were classified in [3]; they are unilateral block shifts of arbitrary block size (i.e. dim H(n) can be anything). However, no examples of irreducible homogeneous bilateral block shifts of block size larger than 1 were known until now.

  17. Characterization of Chemically Induced Liver Injuries Using Gene Co-Expression Modules

    Science.gov (United States)

    2014-09-16

    evaluated the periportal fibrosis gene signature in the GEO dataset - GSE13747 [34]. In this dataset, liver fibrosis was induced by bile duct ...dataset, liver fibrosis was induced by bile duct ligation. Figure 10-D shows the observed correlation between log-ratios of periportal fibrosis...at 15 days of exposure obtained from TG-GATEs, and D) liver fibrosis produced by bile duct ligation obtained from GSE13747. doi:10.1371/journal.pone

  18. Characterization of root agravitropism induced by genetic, chemical, and developmental constraints

    International Nuclear Information System (INIS)

    Moore, R.; Fondren, W.M.; Marcum, H.

    1987-01-01

    The patterns and rates of organelle redistribution in columella (i.e., putative statocyte) cells of agravitropic agt mutants of Zea mays are not significantly different from those of columella cells in graviresponsive roots. Graviresponsive roots of Z. mays are characterized by a strongly polar movement of 45 Ca 2+ across the root tip from the upper to the lower side. Horizontally-oriented roots of agt mutants exhibit only a minimal polar transport of 45 Ca 2+ . Exogenously-induced asymmetries of Ca result in curvature of agt roots toward the Ca source. A similar curvature can be induced by a Ca asymmetry in normally nongraviresponsive (i.e., lateral) roots of Phaseolus vulgaris. Similarly, root curvature can be induced by placing the roots perpendicular to an electric field. This electrotropism increase with (1) currents between 8-35 mA, and (2) time between 1-9 hr when the current is constant. Electrotropism is reduced significantly by treating roots with triiodobenzoic acid (TIBA), an inhibitor of auxin transport. These results suggest that (1) if graviperception occurs via the sedimentation of amyloplasts in columella cells, then nongraviresponsive roots apparently sense gravity as do graviresponsive roots, (2) exogenously induced asymmetries of a gravitropic effector (i.e., Ca) can induce curvature of normally nongraviresponsive roots, (3) the gravity-induced downward movement of exogenously-applied 45 Ca 2+ across tips of graviresponsive roots does not occur in nongraviresponsive roots, (4) placing roots in an electrical field (i.e., one favoring the movement of ions such as Ca 2+ ) induces root curvature and (5) electrically-induced curvature is apparently dependent on auxin transport. These result are discussed relative to a model to account for the lack of graviresponsiveness by these roots

  19. Designing block copolymer architectures for targeted membrane performance

    KAUST Repository

    Dorin, Rachel Mika; Phillip, William A.; Sai, Hiroaki; Werner, Jö rg; Elimelech, Menachem; Wiesner, Ulrich

    2014-01-01

    Using a combination of block copolymer self-assembly and non-solvent induced phase separation, isoporous ultrafiltration membranes were fabricated from four poly(isoprene-b-styrene-b-4-vinylpyridine) triblock terpolymers with similar block volume

  20. Identification of vapor-phase chemical warfare agent simulants and rocket fuels using laser-induced breakdown spectroscopy

    International Nuclear Information System (INIS)

    Stearns, Jaime A.; McElman, Sarah E.; Dodd, James A.

    2010-01-01

    Application of laser-induced breakdown spectroscopy (LIBS) to the identification of security threats is a growing area of research. This work presents LIBS spectra of vapor-phase chemical warfare agent simulants and typical rocket fuels. A large dataset of spectra was acquired using a variety of gas mixtures and background pressures and processed using partial least squares analysis. The five compounds studied were identified with a 99% success rate by the best method. The temporal behavior of the emission lines as a function of chamber pressure and gas mixture was also investigated, revealing some interesting trends that merit further study.

  1. Identification of vapor-phase chemical warfare agent simulants and rocket fuels using laser-induced breakdown spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Stearns, Jaime A.; McElman, Sarah E.; Dodd, James A.

    2010-05-01

    Application of laser-induced breakdown spectroscopy (LIBS) to the identification of security threats is a growing area of research. This work presents LIBS spectra of vapor-phase chemical warfare agent simulants and typical rocket fuels. A large dataset of spectra was acquired using a variety of gas mixtures and background pressures and processed using partial least squares analysis. The five compounds studied were identified with a 99% success rate by the best method. The temporal behavior of the emission lines as a function of chamber pressure and gas mixture was also investigated, revealing some interesting trends that merit further study.

  2. Comparison between cytogenetic damage induced in human lymphocytes by environmental chemicals or radiation

    Energy Technology Data Exchange (ETDEWEB)

    Cebulska-Wasilewska, A. [Institute of Nuclear Physics, Cracow (Poland)

    1997-12-31

    Author compared cytogenetic effects of chemicals (benzene and the member at benzene related compounds) and ionizing radiation on the human lymphocytes. Levels of various types of cytogenetic damage observed among people from petroleum plants workers groups are similar to the levels of damages detected in the blood of people suspected of the accidental exposure to a radiation source

  3. Comparison between cytogenetic damage induced in human lymphocytes by environmental chemicals or radiation

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.

    1997-01-01

    Author compared cytogenetic effects of chemicals (benzene and the member at benzene related compounds) and ionizing radiation on the human lymphocytes. Levels of various types of cytogenetic damage observed among people from petroleum plants workers groups are similar to the levels of damages detected in the blood of people suspected of the accidental exposure to a radiation source

  4. A FLUORESCENCE-BASED SCREENING ASSAY FOR DNA DAMAGE INDUCED BY GENOTOXIC INDUSTRIAL CHEMICALS

    Science.gov (United States)

    The possibility of deliberate or accidental release of toxic chemicals in industrial, commercial or residential settings has indicated a need for rapid, cost-effective and versatile monitoring methods to prevent exposures to humans and ecosystems. Because many toxic industrial c...

  5. Optimizing chemically induced resistance in tomato against Botrytis cinerea

    DEFF Research Database (Denmark)

    Luna, Estrella; Beardon, Emily G; Ravnskov, Sabine

    2016-01-01

    repressed plant growth at higher concentrations of the chemicals, which was particularly pronounced in hydroponically grown plants after BABA treatment. Both seed coating with BABA, and seedling treatments with BABA or JA, did not affect AMF root colonization in soil-grown tomato. Our study has identified...

  6. COMPARISON OF CHEMICAL-INDUCED CHANGES IN PROLIFERATION AND APOPTOSIS IN HUMAN AND MOUSE NEUROPROGENITOR CELLS.

    Science.gov (United States)

    There is a need to develop rapid and efficient models for screening chemicals for their potential to cause developmental neurotoxicity. Use of in vitro neuronal models, including human cells, is one approach that allows for timely, cost-effective toxicity screening. The present s...

  7. Comparison of Chemical-induced Changes in Proliferation and Apoptosis in Human and Mouse Neuroprogenitor Cells.***

    Science.gov (United States)

    There is a need to develop rapid and efficient models to screen chemicals for their potential to cause developmental neurotoxicity. Use of in vitro neuronal models, including human cells, is one approach that allows for timely, cost-effective toxicity screening. The present study...

  8. Aggregate formation in a freshwater bacterial strain induced by growth state and conspecific chemical cues

    Czech Academy of Sciences Publication Activity Database

    Blom, J. F.; Horňák, Karel; Šimek, Karel; Pernthaler, J.

    2010-01-01

    Roč. 12, č. 9 (2010), s. 2486-2495 ISSN 1462-2912 R&D Projects: GA ČR(CZ) GA206/08/0015 Institutional research plan: CEZ:AV0Z60170517 Keywords : aggregate formation * Sphingobium sp. * chemical cues * growth state Subject RIV: EE - Microbiology, Virology Impact factor: 5.537, year: 2010

  9. A plant-based chemical genomics screen for the identification of flowering inducers

    NARCIS (Netherlands)

    Fiers, Martijn; Hoogenboom, Jorin; Brunazzi, Alice; Wennekes, Tom; Angenent, Gerco C; Immink, Richard G H

    2017-01-01

    BACKGROUND: Floral timing is a carefully regulated process, in which the plant determines the optimal moment to switch from the vegetative to reproductive phase. While there are numerous genes known that control flowering time, little information is available on chemical compounds that are able to

  10. Femtosecond laser induced and controlled chemical reaction of carbon monoxide and hydrogen

    CSIR Research Space (South Africa)

    Du Plessis, A

    2011-07-01

    Full Text Available Results from experiments aimed at bimolecular chemical reaction control of CO and H2 at room temperature and pressure, without any catalyst, using shaped femtosecond laser pulses are presented. A stable reaction product (CO2) was measured after...

  11. ArF Laser -Induced Chemical Vapour Deposition of Polythiene Films from Carbon Disulfide

    Czech Academy of Sciences Publication Activity Database

    Tomovska, R.; Bastl, Zdeněk; Vorlíček, Vladimír; Vacek, Karel; Šubrt, Jan; Plzák, Zbyněk; Pola, Josef

    2003-01-01

    Roč. 107, č. 36 (2003), s. 9793-9801 ISSN 1089-5647 R&D Projects: GA MŠk ME 612 Institutional research plan: CEZ:AV0Z4032918; CEZ:AV0Z4040901 Keywords : laser photolysis * ArF * chemical vapour deposition Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.679, year: 2003

  12. Effect of mouse strain in a model of chemical-induced respiratory allergy.

    Science.gov (United States)

    Nishino, Risako; Fukuyama, Tomoki; Watanabe, Yuko; Kurosawa, Yoshimi; Ueda, Hideo; Kosaka, Tadashi

    2014-01-01

    The inhalation of many types of chemicals is a leading cause of allergic respiratory diseases, and effective protocols are needed for the detection of environmental chemical-related respiratory allergies. In our previous studies, we developed a method for detecting environmental chemical-related respiratory allergens by using a long-term sensitization-challenge protocol involving BALB/c mice. In the current study, we sought to improve our model by characterizing strain-associated differences in respiratory allergic reactions to the well-known chemical respiratory allergen glutaraldehyde (GA). According to our protocol, BALB/c, NC/Nga, C3H/HeN, C57BL/6N, and CBA/J mice were sensitized dermally with GA for 3 weeks and then challenged with intratracheal or inhaled GA at 2 weeks after the last sensitization. The day after the final challenge, all mice were euthanized, and total serum IgE levels were assayed. In addition, immunocyte counts, cytokine production, and chemokine levels in the hilar lymph nodes (LNs) and bronchoalveolar lavage fluids (BALF) were also assessed. In conclusion, BALB/c and NC/Nga mice demonstrated markedly increased IgE reactions. Inflammatory cell counts in BALF were increased in the treated groups of all strains, especially BALB/c, NC/Nga, and CBA/J strains. Cytokine levels in LNs were increased in all treated groups except for C3H/HeN and were particularly high in BALB/c and NC/Nga mice. According to our results, we suggest that BALB/c and NC/Nga are highly susceptible to respiratory allergic responses and therefore are good candidates for use in our model for detecting environmental chemical respiratory allergens.

  13. Chemical hybridizing agent SQ-1-induced male sterility in Triticum aestivum L.: a comparative analysis of the anther proteome.

    Science.gov (United States)

    Liu, Hongzhan; Zhang, Gaisheng; Wang, Junsheng; Li, Jingjing; Song, Yulong; Qiao, Lin; Niu, Na; Wang, Junwei; Ma, Shoucai; Li, Lili

    2018-01-05

    Heterosis is widely used to increase the yield of many crops. However, as wheat is a self-pollinating crop, hybrid breeding is not so successful in this organism. Even though male sterility induced by chemical hybridizing agents is an important aspect of crossbreeding, the mechanisms by which these agents induce male sterility in wheat is not well understood. We performed proteomic analyses using the wheat Triticum aestivum L.to identify those proteins involved in physiological male sterility (PHYMS) induced by the chemical hybridizing agent CHA SQ-1. A total of 103 differentially expressed proteins were found by 2D-PAGE and subsequently identified by MALDI-TOF/TOF MS/MS. In general, these proteins had obvious functional tendencies implicated in carbohydrate metabolism, oxidative stress and resistance, protein metabolism, photosynthesis, and cytoskeleton and cell structure. In combination with phenotypic, tissue section, and bioinformatics analyses, the identified differentially expressed proteins revealed a complex network behind the regulation of PHYMS and pollen development. Accordingly, we constructed a protein network of male sterility in wheat, drawing relationships between the 103 differentially expressed proteins and their annotated biological pathways. To further validate our proposed protein network, we determined relevant physiological values and performed real-time PCR assays. Our proteomics based approach has enabled us to identify certain tendencies in PHYMS anthers. Anomalies in carbohydrate metabolism and oxidative stress, together with premature tapetum degradation, may be the cause behind carbohydrate starvation and male sterility in CHA SQ-1 treated plants. Here, we provide important insight into the mechanisms underlying CHA SQ-1-induced male sterility. Our findings have practical implications for the application of hybrid breeding in wheat.

  14. Chemical composition and cardiovascular effects induced by the essential oil of Cymbopogon citratus DC. Stapf, Poaceae, in rats

    Directory of Open Access Journals (Sweden)

    Flávia V. Moreira

    2010-08-01

    Full Text Available Cymbopogon citratus DC. Stapf, Poaceae, is used in the folk medicine for hypertension treatment. This work investigated the chemical composition and cardiovascular effects in rats of C. citratus essential oil (EOCC. A phytochemical screening demonstrated the presence of eight constituents, being geranial the major compound (43.08%. In rats, EOCC (1, 5, 10, and 20 mg/kg, i.v. induced transient hypotension and bradycardia that were attenuated by atropine and sodium thiopental, but not by L-NAME or indomethacin. In rings of rat superior mesenteric artery pre-contracted with phenylephrine, EOCC (1 to 3000 µg/mL induced relaxation that was not affected after removal of the endothelium, after TEA or in rings pre-contracted with KCl (80 mM. Furthermore, EOCC (1000 µg/mL was not able to induce additional effect on maximal relaxation of nifedipine (10 µM. In conclusions, EOCC induces hypotension, possibly by reduction in vascular resistance caused by inhibition of the Ca2+ influx, and bradycardia probably due to an activation of cardiac muscarinic receptors.

  15. Influence of caffeine on chromosome lesions induced by chemical mutagens and radiation. 2

    International Nuclear Information System (INIS)

    Dimitrov, B.

    1977-01-01

    The modifying influence of caffeine on γ-ray induced chromosome lesions was studied by chromosome aberration anaysis. Caffeine was applied as a pre- and post-treatment agent following seed (G 1 ) and root meristem (G 2 and S) irradiation of C.capillaris. The frequency of chromosome aberrations induced in G 1 was changed neither by post- nor by pre-treatment with caffeine. This fact proves the lack of caffeine modifying effect. Applied as a post-treatment agent caffeine enhances considerably the frequency of chromosome aberrations induced in root meristem cells. This is especially valid for G 2 irradiated cells, while in S cells no synergistic effect was established between induced chromosome lesions and caffeine. The enhancement of chromosome aberration frequency produced in G 2 shows a clearly manifested dependence on the time (moment) of caffeine application post irradiation. Most considerable enhancement was obtained following post-treatment with caffeine immediately after irradiation. In the following intervals - 15 and 30 min - it decreases progressively, while after 60, 180 and 300 min no enhancing effect is observed. The probable causes for the manifestation and the lack of synergistic effect between chromosome lesions induced in the various mitotic cycle phases and caffeine are discussed. (author)

  16. Testing block subdivision algorithms on block designs

    Science.gov (United States)

    Wiseman, Natalie; Patterson, Zachary

    2016-01-01

    Integrated land use-transportation models predict future transportation demand taking into account how households and firms arrange themselves partly as a function of the transportation system. Recent integrated models require parcels as inputs and produce household and employment predictions at the parcel scale. Block subdivision algorithms automatically generate parcel patterns within blocks. Evaluating block subdivision algorithms is done by way of generating parcels and comparing them to those in a parcel database. Three