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Sample records for enhances endoreduplication induced

  1. The DNA topoisomerase II catalytic inhibitor merbarone is genotoxic and induces endoreduplication

    International Nuclear Information System (INIS)

    Pastor, Nuria; Domínguez, Inmaculada; Orta, Manuel Luís; Campanella, Claudia; Mateos, Santiago; Cortés, Felipe

    2012-01-01

    In the last years a number of reports have shown that the so-called topoisomerase II (topo II) catalytic inhibitors are able to induce DNA and chromosome damage, an unexpected result taking into account that they do not stabilize topo II-DNA cleavable complexes, a feature of topo II poisons such as etoposide and amsacrine. Merbarone inhibits the catalytic activity of topo II by blocking DNA cleavage by the enzyme. While it was first reported that merbarone does not induce genotoxic effects in mammalian cells, this has been challenged by reports showing that the topo II inhibitor induces efficiently chromosome and DNA damage, and the question as to a possible behavior as a topo II poison has been put forward. Given these contradictory results, and the as yet incomplete knowledge of the molecular mechanism of action of merbarone, in the present study we have tried to further characterize the mechanism of action of merbarone on cell proliferation, cell cycle, as well as chromosome and DNA damage in cultured CHO cells. Merbarone was cytotoxic as well as genotoxic, inhibited topo II catalytic activity, and induced endoreduplication. We have also shown that merbarone-induced DNA damage depends upon ongoing DNA synthesis. Supporting this, inhibition of DNA synthesis causes reduction of DNA damage and increased cell survival.

  2. The Arabidopsis Transcription Factor AtTCP15 Regulates Endoreduplication by Modulating Expression of Key Cell-cycle Genes

    Institute of Scientific and Technical Information of China (English)

    Zi-Yu Li; Bin Li; Ai-Wu Dong

    2012-01-01

    Plant cells frequently undergo endoreduplication,a modified cell cycle in which genome is repeatedly replicated without cytokinesis.As the key step to achieve final size and function for cells,endoreduplication is prevalent during plant development.However,mechanisms to control the balance between endoreduplication and mitotic cell division are still poorly understood.Here,we show that the Arabidopsis TCP (CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF)-family transcription factor gene AtTCP15 is expressed in trichomes,as well as in rapidly dividing and vascular tissues.Expression of AtTCP15SRDX,AtTCP15 fused with a SRDX repressor domain,induces extra endoreduplication in trichomes and cotyledon cells in transgenic Arabidopsis.On the contrary,overexpression of AtTCP15 suppresses endoreduplication in trichomes and other examined cells.Misregulation of AtTCP15 affects the expression of several important genes involved in cell-cycle regulation.AtTCP15 protein binds directly to the promoter regions of CYCA2;3 and RETINOBLASTOMA-RELATED (RBR) genes,which play key roles in endoreduplication.Taken together,AtTCP15 plays an important role in regulating endoreduplication during Arabidopsis development.

  3. Evaluation of ploidy level and endoreduplication in carnation (Dianthus spp.).

    Science.gov (United States)

    Agulló-Antón, María Ángeles; Olmos, Enrique; Pérez-Pérez, José Manuel; Acosta, Manuel

    2013-03-01

    Carnation (Dianthus caryophyllus L.) is one of the fifth most important ornamental species worldwide. Many desirable plant characteristics, such as big size, adaptation under stress, and intra or interspecific hybridization capability, are dependent on plant ploidy level. We optimized a quick flow cytometry method for DNA content determination in wild and cultivated carnation samples that allowed a systematic evaluation of ploidy levels in Dianthus species. The DNA content of different carnation cultivars and wild Dianthus species was determined using internal reference standards. The precise characterization of ploidy, endoreduplication and C-value of D. caryophyllus 'Master' makes it a suitable standard cultivar for ploidy level determination in other carnation cultivars. Mixoploidy was rigorously characterized in different regions of several organs from D. caryophyllus 'Master', which combined with a detailed morphological description suggested some distinctive developmental traits of this species. Both the number of endoreduplication cycles and the proportion of endopolyploid cells were highly variable in the petals among the cultivars studied, differently to the values found in leaves. Our results suggest a positive correlation between ploidy, cell size and petal size in cultivated carnation, which should be considered in breeding programs aimed to obtain new varieties with large flowers. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Control of cell proliferation, endoreduplication, cell size, and cell death by the retinoblastoma-related pathway in maize endosperm

    KAUST Repository

    Sabelli, Paolo A.

    2013-04-22

    The endospermof cereal grains is one of the most valuable products of modern agriculture. Cereal endosperm development comprises different phases characterized by mitotic cell proliferation, endoreduplication, the accumulation of storage compounds, and programmed cell death. Although manipulation of these processes could maximize grain yield, how they are regulated and integrated is poorly understood. We show that the Retinoblastoma-related (RBR) pathway controls key aspects of endosperm development in maize. Down-regulation of RBR1 by RNAi resulted in up-regulation of RBR3-type genes, as well as the MINICHROMOSOME MAINTENANCE 2-7 gene family and PROLIFERATING CELL NUCLEAR ANTIGEN, which encode essential DNA replication factors. Both the mitotic and endoreduplication cell cycles were stimulated. Developing transgenic endosperm contained 42-58% more cells and ~70% more DNA than wild type, whereas there was a reduction in cell and nuclear sizes. In addition, cell death was enhanced. The DNA content of mature endosperm increased 43% upon RBR1 downregulation, whereas storage protein content and kernel weight were essentially not affected. Down-regulation of both RBR1 and CYCLIN DEPENDENT KINASE A (CDKA);1 indicated that CDKA;1 is epistatic to RBR1 and controls endoreduplication through an RBR1- dependent pathway. However, the repressive activity of RBR1 on downstream targets was independent from CDKA;1, suggesting diversification of RBR1 activities. Furthermore, RBR1 negatively regulated CDK activity, suggesting the presence of a feedback loop. These results indicate that the RBR1 pathway plays a major role in regulation of different processes during maize endosperm development and suggest the presence of tissue/organlevel regulation of endosperm/seed homeostasis.

  5. Effect of Blue Light on Endogenous Isopentenyladenine and Endoreduplication during Photomorphogenesis and De-Etiolation of Tomato (Solanum lycopersicum L.) Seedlings

    Science.gov (United States)

    Bergougnoux, Véronique; Zalabák, David; Jandová, Michaela; Novák, Ondřej; Wiese-Klinkenberg, Anika; Fellner, Martin

    2012-01-01

    Light is one of the most important factor influencing plant growth and development all through their life cycle. One of the well-known light-regulated processes is de-etiolation, i.e. the switch from skotomorphogenesis to photomorphogenesis. The hormones cytokinins (CKs) play an important role during the establishment of photomorphogenesis as exogenous CKs induced photomorphogenesis of dark-grown seedlings. Most of the studies are conducted on the plant model Arabidopsis, but no or few information are available for important crop species, such as tomato (Solanum lycopersicum L.). In our study, we analyzed for the first time the endogenous CKs content in tomato hypocotyls during skotomorphogenesis, photomorphogenesis and de-etiolation. For this purpose, two tomato genotypes were used: cv. Rutgers (wild-type; WT) and its corresponding mutant (7B-1) affected in its responses to blue light (BL). Using physiological and molecular approaches, we identified that the skotomorphogenesis is characterized by an endoreduplication-mediated cell expansion, which is inhibited upon BL exposure as seen by the accumulation of trancripts encoding CycD3, key regulators of the cell cycle. Our study showed for the first time that iP (isopentenyladenine) is the CK accumulated in the tomato hypocotyl upon BL exposure, suggesting its specific role in photomorphogenesis. This result was supported by physiological experiments and gene expression data. We propose a common model to explain the role and the relationship between CKs, namely iP, and endoreduplication during de-etiolation and photomorphogenesis. PMID:23049779

  6. High Concentration of Melatonin Regulates Leaf Development by Suppressing Cell Proliferation and Endoreduplication in Arabidopsis.

    Science.gov (United States)

    Wang, Qiannan; An, Bang; Shi, Haitao; Luo, Hongli; He, Chaozu

    2017-05-05

    N -acetyl-5-methoxytryptamine (Melatonin), as a crucial messenger in plants, functions in adjusting biological rhythms, stress tolerance, plant growth and development. Several studies have shown the retardation effect of exogenous melatonin treatment on plant growth and development. However, the in vivo role of melatonin in regulating plant leaf growth and the underlying mechanism are still unclear. In this study, we found that high concentration of melatonin suppressed leaf growth in Arabidopsis by reducing both cell size and cell number. Further kinetic analysis of the fifth leaves showed that melatonin remarkably inhibited cell division rate. Additionally, flow cytometic analysis indicated that melatonin negatively regulated endoreduplication during leaf development. Consistently, the expression analysis revealed that melatonin regulated the transcriptional levels of key genes of cell cycle and ribosome. Taken together, this study suggests that high concentration of melatonin negatively regulated the leaf growth and development in Arabidopsis , through modulation of endoreduplication and the transcripts of cell cycle and ribosomal key genes.

  7. Systemic control of cell division and endoreduplication by NAA and BAP by modulating CDKs in root tip cells of Allium cepa.

    Science.gov (United States)

    Tank, Jigna G; Thaker, Vrinda S

    2014-01-01

    Molecular mechanism regulated by auxin and cytokinin during endoreduplication, cell division, and elongation process is studied by using Allium cepa roots as a model system. The activity of CDK genes modulated by auxin and cytokinin during cell division, elongation, and endoreduplication process is explained in this research work. To study the significance of auxin and cytokinin in the management of cell division and endoreduplication process in plant meristematic cells at molecular level endoreduplication was developed in root tips of Allium cepa by giving colchicine treatment. There were inhibition of vegetative growth, formation of c-tumor at root tip, and development of endoreduplicated cells after colchicine treatment. This c-tumor was further treated with NAA and BAP to reinitiate vegetative growth in roots. BAP gave positive response in reinitiation of vegetative growth of roots from center of c-tumor. However, NAA gave negative response in reinitiation of vegetative growth of roots from c-tumor. Further, CDKs gene expression analysis from normal, endoreduplicated, and phytohormone (NAA or BAP) treated root tip was done and remarkable changes in transcription level of CDK genes in normal, endoreduplicated, and phytohormones treated cells were observed.

  8. Flow cytometric analysis of variation in the level of nuclear DNA endoreduplication in the cotyledons amongst Vigna radiata cultivars

    Czech Academy of Sciences Publication Activity Database

    Pal, A.; Vrána, Jan; Doležel, Jaroslav

    2004-01-01

    Roč. 57, č. 3 (2004), s. 262-266 ISSN 0008-7114 R&D Projects: GA AV ČR IBS5038104 Grant - others:Indian National Science Academy(IN) INSA Institutional research plan: CEZ:AV0Z5038910 Keywords : Cotyledon * endoreduplication * flow cytometry Subject RIV: GE - Plant Breeding Impact factor: 0.366, year: 2004

  9. Centrosome/Cell cycle uncoupling and elimination in the endoreduplicating intestinal cells of C. elegans.

    Directory of Open Access Journals (Sweden)

    Yu Lu

    Full Text Available The centrosome cycle is most often coordinated with mitotic cell division through the activity of various essential cell cycle regulators, consequently ensuring that the centriole is duplicated once, and only once, per cell cycle. However, this coupling can be altered in specific developmental contexts; for example, multi-ciliated cells generate hundreds of centrioles without any S-phase requirement for their biogenesis, while Drosophila follicle cells eliminate their centrosomes as they begin to endoreduplicate. In order to better understand how the centrosome cycle and the cell cycle are coordinated in a developmental context we use the endoreduplicating intestinal cell lineage of C. elegans to address how novel variations of the cell cycle impact this important process. In C. elegans, the larval intestinal cells undergo one nuclear division without subsequent cytokinesis, followed by four endocycles that are characterized by successive rounds of S-phase. We monitored the levels of centriolar/centrosomal markers and found that centrosomes lose their pericentriolar material following the nuclear division that occurs during the L1 stage and is thereafter never re-gained. The centrioles then become refractory to S phase regulators that would normally promote duplication during the first endocycle, after which they are eliminated during the L2 stage. Furthermore, we show that SPD-2 plays a central role in the numeral regulation of centrioles as a potential target of CDK activity. On the other hand, the phosphorylation on SPD-2 by Polo-like kinase, the transcriptional regulation of genes that affect centriole biogenesis, and the ubiquitin/proteasome degradation pathway, contribute collectively to the final elimination of the centrioles during the L2 stage.

  10. Endoreduplication intensity as a marker of seed developmental stage in the Fabaceae.

    Science.gov (United States)

    Rewers, Monika; Sliwinska, Elwira

    2012-12-01

    Flow cytometry (FCM) can be used to study cell cycle activity in developing, mature and germinating seeds. It provides information about a seed's physiological state and therefore can be used by seed growers for assessing optimal harvest times and presowing treatments. Because an augmented proportion of 4C nuclei usually is indicative of high mitotic activity, the 4C/2C ratio is commonly used to follow the progress of seed development and germination. However, its usefulness for polysomatic (i.e., containing cells with different DNA content) seeds is questioned. Changes in cell cycle/endoreduplication activity in developing seeds of five members of the Fabaceae were studied to determine a more suitable marker of seed developmental stages for polysomatic species based on FCM measurements. Seeds of Phaseolus vulgaris, Medicago sativa, Pisum sativum, Vicia sativa, and Vicia faba var. minor were collected 20, 30, 40, 50, and 60 days after flowering (DAF), embryos were isolated and the proportion of nuclei with different DNA contents in the embryo axis and cotyledon was established. The ratios 4C/2C and (Σ>2C)/2C were calculated. Dried seeds were subjected to laboratory germination tests following international seed testing association (ISTA) rules. Additionally, the absolute nuclear DNA content was estimated in the leaves of the studied species. During seed development nuclei with DNA contents from 2C to 128C were detected; the endopolyploidy pattern depended on the species, seed organ and developmental stage. The cell cycle/endoreduplication parameters correlated negatively with genome size. The (Σ>2C)/2C ratio in the cotyledons reflected the seed developmental stage and corresponded with seed germinability. Therefore, this ratio is recommended as a marker in polysomatic seed research and production instead of the 4C/2C ratio, which does not consider the occurrence of endopolyploid cells. Copyright © 2012 International Society for Advancement of Cytometry.

  11. Field enhancement induced laser ablation

    DEFF Research Database (Denmark)

    Fiutowski, Jacek; Maibohm, Christian; Kjelstrup-Hansen, Jakob

    Sub-diffraction spatially resolved, quantitative mapping of strongly localized field intensity enhancement on gold nanostructures via laser ablation of polymer thin films is reported. Illumination using a femtosecond laser scanning microscope excites surface plasmons in the nanostructures....... The accompanying field enhancement substantially lowers the ablation threshold of the polymer film and thus creates local ablation spots and corresponding topographic modifications of the polymer film. Such modifications are quantified straightforwardly via scanning electron and atomic force microscopy. Thickness...

  12. Cell division and endoreduplication play important roles in stem swelling of tuber mustard (Brassica juncea Coss. var. tumida Tsen et Lee).

    Science.gov (United States)

    Shi, H; Wang, L L; Sun, L T; Dong, L L; Liu, B; Chen, L P

    2012-11-01

    We investigated spatio-temporal variations in cell division and the occurrence of endoreduplication in cells of tuber mustard stems during development. Cells in the stem had 8C nuclei (C represents DNA content of a two haploid genome), since it is an allotetraploid species derived from diploid Brassica rapa (AA) and B. nigra (BB), thus indicating the occurrence of endoreduplication. Additionally, we observed a dynamic change of cell ploidy in different regions of the swollen stems, with a decrease in 4C proportion in P4-1 and a sharp increase in 8C cells that became the dominant cell type (86.33% at most) in the inner pith cells. Furthermore, cDNAs of 14 cell cycle genes and four cell expansion genes were cloned and their spatial transcripts analysed in order to understand their roles in stem development. The expression of most cell cycle genes peaked in regions of the outer pith (P2 or P3), some genes regulating S/G2 and G2/M (BjCDKB1;2, BjCYCB1;1 and BjCYCB1;2) significantly decrease in P5 and P6, while G1/S regulators (BjE2Fa, BjE2Fb and BjE2Fc) showed a relative high expression level in the inner pith (P5) where cells were undergoing endoreduplication. Coincidentally, BjXTH1and BjXTH2 were exclusively expressed in the endoreduplicated cells. Our results suggest that cells of outer pith regions (P2 and P3) mainly divide for cell proliferation, while cells of the inner pith expand through endoreduplication. Endoreduplication could trigger expression of BjXTH1 and BjXTH2 and thus function in cell expansion of the pith tissue. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

  13. Induced resistance: an enhancement of basal resistance?

    NARCIS (Netherlands)

    Vos, M. de; Robben, C.; Pelt, J.A. van; Loon, L.C. van; Pieterse, C.M.J.

    2002-01-01

    Upon primary pathogen attack, plants activate resistance mechanisms at the site of infection. Besides this so-called basal resistance, plants have also the ability to enhance their defensive capacity against future pathogen attack. There are at least two types of biologically induced resistance.

  14. Induced seismicity associated with enhanced geothermal system

    Energy Technology Data Exchange (ETDEWEB)

    Majer, Ernest; Majer, Ernest L.; Baria, Roy; Stark, Mitch; Oates, Stephen; Bommer, Julian; Smith, Bill; Asanuma, Hiroshi

    2006-09-26

    Enhanced Geothermal Systems (EGS) offer the potential to significantly add to the world energy inventory. As with any development of new technology, some aspects of the technology has been accepted by the general public, but some have not yet been accepted and await further clarification before such acceptance is possible. One of the issues associated with EGS is the role of microseismicity during the creation of the underground reservoir and the subsequent extraction of the energy. The primary objectives of this white paper are to present an up-to-date review of the state of knowledge about induced seismicity during the creation and operation of enhanced geothermal systems, and to point out the gaps in knowledge that if addressed will allow an improved understanding of the mechanisms generating the events as well as serve as a basis to develop successful protocols for monitoring and addressing community issues associated with such induced seismicity. The information was collected though literature searches as well as convening three workshops to gather information from a wide audience. Although microseismicity has been associated with the development of production and injection operations in a variety of geothermal regions, there have been no or few adverse physical effects on the operations or on surrounding communities. Still, there is public concern over the possible amount and magnitude of the seismicity associated with current and future EGS operations. It is pointed out that microseismicity has been successfully dealt with in a variety of non-geothermal as well as geothermal environments. Several case histories are also presented to illustrate a variety of technical and public acceptance issues. It is concluded that EGS Induced seismicity need not pose any threat to the development of geothermal resources if community issues are properly handled. In fact, induced seismicity provides benefits because it can be used as a monitoring tool to understand the

  15. Mutation induced enhanced biosynthesis of lipase | Bapiraju ...

    African Journals Online (AJOL)

    The purpose of the present investigation is to enhance production of biomedically important enzyme lipase by subjecting the indigenous lipase producing strain Rhizopus sp. BTS-24 to improvement by natural selection and random mutagenesis (UV and N-methyl-N'-nitro-N-nitroso guanidine, NTG). The isolation of mutants ...

  16. Enhancement of acetaminophen overdosage-induced hepatotoxicity ...

    African Journals Online (AJOL)

    paracetamol) overdosage-induced hepatotoxicity in three groups of albino Wistar rats. Administration of the minimum toxic dose of paracetamol (150mg/kg body weight) to animals (group II) produced significantly (P≤0.05) higher levels of alanine ...

  17. Nonlinearity induced synchronization enhancement in mechanical oscillators

    Science.gov (United States)

    Czaplewski, David A.; Lopez, Omar; Guest, Jeffrey R.; Antonio, Dario; Arroyo, Sebastian I.; Zanette, Damian H.

    2018-05-08

    An autonomous oscillator synchronizes to an external harmonic force only when the forcing frequency lies within a certain interval, known as the synchronization range, around the oscillator's natural frequency. Under ordinary conditions, the width of the synchronization range decreases when the oscillation amplitude grows, which constrains synchronized motion of micro- and nano-mechanical resonators to narrow frequency and amplitude bounds. The present invention shows that nonlinearity in the oscillator can be exploited to manifest a regime where the synchronization range increases with an increasing oscillation amplitude. The present invention shows that nonlinearities in specific configurations of oscillator systems, as described herein, are the key determinants of the effect. The present invention presents a new configuration and operation regime that enhances the synchronization of micro- and nano-mechanical oscillators by capitalizing on their intrinsic nonlinear dynamics.

  18. Endogenous Abscisic Acid Promotes Hypocotyl Growth and Affects Endoreduplication during Dark-Induced Growth in Tomato (Solanum lycopersicum L.)

    Czech Academy of Sciences Publication Activity Database

    Humplík, Jan; Bergougnoux, V.; Jandová, M.; Šimura, Jan; Pěnčík, Aleš; Tomanec, O.; Rolčík, Jakub; Novák, Ondřej; Fellner, Martin

    2015-01-01

    Roč. 10, č. 2 (2015) E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : DEPENDENT KINASE INHIBITOR * DEFICIENT MUTANT SITIENS * ARABIDOPSIS-THALIANA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

  19. Enhanced thermo-mechanical performance and strain-induced ...

    Indian Academy of Sciences (India)

    Enhanced thermo-mechanical performance and strain-induced band gap reduction of TiO2@PVC nanocomposite films ... School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Republic of Korea; School of Mechanical Engineering, Yeungnam University, Gyeongsan 712-749, Republic of Korea ...

  20. Rubrene analogues with the aggregation-induced emission enhancement behaviour

    DEFF Research Database (Denmark)

    Zhang, Xiaoxu; Sørensen, Jakob Kryger; Fu, Xiaowei

    2014-01-01

    In the light of the principle of aggregation-induced emission enhancement (AIEE), the rubrene analogue with orange light-emitting properties is designed and synthesized by substituting the phenyl side groups of rubrene with thienyl groups. To the best of our knowledge, this is the first report on...

  1. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    International Nuclear Information System (INIS)

    Jiang Erkang; Wu Lijun

    2009-01-01

    In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy α-particle irradiated and non-irradiated bystander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensitive to damage signals. Treated by c-PTIO(2-(4-carboxy-phenyl)- 4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide), a nitric oxide (NO) scavenger, the MN frequencies were effectively inhibited, showing that nitric oxide might be very important in mediating the enhanced damage. These results indicated that caffeine enhanced the low dose α-particle radiation-induced damage in irradiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE). (ion beam bioengineering)

  2. Development of microwave-enhanced spark-induced breakdown spectroscopy

    International Nuclear Information System (INIS)

    Ikeda, Yuji; Moon, Ahsa; Kaneko, Masashi

    2010-01-01

    We propose microwave-enhanced spark-induced breakdown spectroscopy with the same measurement and analysis processes as in laser-induced breakdown spectroscopy, but with a different plasma generation mechanism. The size and lifetime of the plasma generated can contribute to increased measurement accuracy and expand its applicability to industrial measurement, such as an exhaust gas analyzer for automobile engine development and its regulation, which has been hard to operate by laser at an engineering evaluation site. The use of microwaves in this application helps lower the cost, reduce the system size, and increase the ease of operation to make it commercially viable. A microwave frequency of 2.45 GHz was used to enhance the volume and lifetime of the plasma at atmospheric condition even at elevated pressure.

  3. Towards the Understanding of Induced Seismicity in Enhanced Geothermal Systems

    Energy Technology Data Exchange (ETDEWEB)

    Gritto, Roland [Array Information Technology, Greenbelt, MD (United States); Dreger, Douglas [Univ. of California, Berkeley, CA (United States); Heidbach, Oliver [Helmholtz Centre Potsdam (Germany, German Research Center for Geosciences; Hutchings, Lawrence [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-08-29

    This DOE funded project was a collaborative effort between Array Information Technology (AIT), the University of California at Berkeley (UCB), the Helmholtz Centre Potsdam - German Research Center for Geosciences (GFZ) and the Lawrence Berkeley National Laboratory (LBNL). It was also part of the European research project “GEISER”, an international collaboration with 11 European partners from six countries including universities, research centers and industry, with the goal to address and mitigate the problems associated with induced seismicity in Enhanced Geothermal Systems (EGS). The goal of the current project was to develop a combination of techniques, which evaluate the relationship between enhanced geothermal operations and the induced stress changes and associated earthquakes throughout the reservoir and the surrounding country rock. The project addressed the following questions: how enhanced geothermal activity changes the local and regional stress field; whether these activities can induce medium sized seismicity M > 3; (if so) how these events are correlated to geothermal activity in space and time; what is the largest possible event and strongest ground motion, and hence the potential hazard associated with these activities. The development of appropriate technology to thoroughly investigate and address these questions required a number of datasets to provide the different physical measurements distributed in space and time. Because such a dataset did not yet exist for an EGS system in the United State, we used current and past data from The Geysers geothermal field in northern California, which has been in operation since the 1960s. The research addressed the need to understand the causal mechanisms of induced seismicity, and demonstrated the advantage of imaging the physical properties and temporal changes of the reservoir. The work helped to model the relationship between injection and production and medium sized magnitude events that have

  4. Surface plasmon-enhanced molecular fluorescence induced by gold nanostructures

    International Nuclear Information System (INIS)

    Teng, Y.; Ueno, K.; Shi, X.; Aoyo, D.; Misawa, H.; Qiu, J.

    2012-01-01

    The authors report on surface plasmon-enhanced fluorescence of Eosin Y molecules induced by gold nanostructures. Al 2 O 3 films deposited by atomic layer deposition with sub-nanometer resolution were used as the spacer layer to control the distance between molecules and the gold surface. As the thickness of the Al 2 O 3 film increased, the fluorescence intensity first increased and then decreased. The highest enhancement factor is achieved with a 1 nm Al 2 O 3 film. However, the trend for the fluorescence lifetime is the opposite. It first decreased and then increased. The changes in the fluorescence quantum yield were also calculated. The yield shows a similar trend to the fluorescence intensity. The competition between the surface plasmon-induced increase in the radiative decay rate and the gold-induced fluorescence quenching is responsible for the observed phenomenon. In addition, this competition strongly depends on the thickness of the spacer layer between Eosin Y molecules and the gold surface. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Irradiation-enhanced and-induced mass transport

    International Nuclear Information System (INIS)

    Rehn, L.E.

    1989-01-01

    Irradiation can be used to enhance diffusion, that is, to increase the rate at which equilibrium is attained, as well as to induce nonequilibrium changes. The main factors influencing whether irradiation will drive a material toward or away from equilibrium are the initial specimen microstructure and geometry, irradiation temperature, and primary recoil spectrum. This paper summarizes known effects of irradiation temperature and primary recoil spectrum on mass transport during irradiation. In comparison to either electron or heavy-ion irradiation, it is concluded that relatively low-energy, light-ion bombardment at intermediate temperatures offers the greatest potential to enhance the rate at which equilibrium is attained. The greatest departures from equilibrium can be expected from irradiation with similar particles at very low temperatures

  6. Jeast (Saccharomyces cerevisial) mutants with enhanced induced mutagenesis

    International Nuclear Information System (INIS)

    Ivanov, E.L.; Koval'tsova, S.V.; Korolev, V.G.

    1987-01-01

    The influence of him1-1, him2-1, him3-1 and himX mutations on induction frequency and specificity of UV-induced adenine-dependent mutations in the yeast Saccharomyces cerevisiae has been. Him mutations do not render haploid cells more sensitive to the lethal action of UV-light; however, in him strains adeine-dependent mutations (ade, ade2) were induced more frequently (1.5-2-fold), as compared to the HIM strain. An analysis of the molecular nature of ade2 mutants revealed than him1-1, him2-1, and himX mutations increase specifically the yield of transitions (AT-GC and GC→AT), whereas in the him3-1, strain the yield of transversions was enhanced as well. We suggest him mutations analysed to affect specific repair pathway for mismatch correction

  7. Limitations to CO2-induced growth enhancement in pot studies.

    Science.gov (United States)

    McConnaughay, K D M; Berntson, G M; Bazzaz, F A

    1993-07-01

    Recently, it has been suggested that small pots may reduce or eliminate plant responses to enriched CO 2 atmospheres due to root restriction. While smaller pot volumes provide less physical space available for root growth, they also provide less nutrients. Reduced nutrient availability alone may reduce growth enhancement under elevated CO 2 . To investigate the relative importance of limited physical rooting space separate from and in conjunction with soil nutrients, we grew plants at ambient and double-ambient CO 2 levels in growth containers of varied volume, shape, nutrient concentration, and total nutrient content. Two species (Abutilon theophrasti, a C 3 dicot with a deep tap root andSetaria faberii, a C 4 monocot with a shallow diffuse root system) were selected for their contrasting physiology and root architecture. Shoot demography was determined weekly and biomass was determined after eight and ten weeks of growth. Increasing total nutrients, either by increasing nutrient concentration or by increasing pot size, increased plant growth. Further, increasing pot size while maintaining equal total nutrients per pot resulted in increased total biomass for both species. CO 2 -induced growth and reproductive yield enhancements were greatest in pots with high nutrient concentrations, regardless of total nutrient content or pot size, and were also mediated by the shape of the pot. CO 2 -induced growth and reproductive yield enhancements were unaffected by pot size (growth) or were greater in small pots (reproductive yield), regardless of total nutrient content, contrary to predictions based on earlier studies. These results suggest that several aspects of growth conditions within pots may influence the CO 2 responses of plants; pot size, pot shape, the concentration and total amount of nutrient additions to pots may lead to over-or underestimates of the CO 2 responses of real-world plants.

  8. Malaria-induced changes in host odors enhance mosquito attraction.

    Science.gov (United States)

    De Moraes, Consuelo M; Stanczyk, Nina M; Betz, Heike S; Pulido, Hannier; Sim, Derek G; Read, Andrew F; Mescher, Mark C

    2014-07-29

    Vector-borne pathogens may alter traits of their primary hosts in ways that influence the frequency and nature of interactions between hosts and vectors. Previous work has reported enhanced mosquito attraction to host organisms infected with malaria parasites but did not address the mechanisms underlying such effects. Here we document malaria-induced changes in the odor profiles of infected mice (relative to healthy individuals) over the course of infection, as well as effects on the attractiveness of infected hosts to mosquito vectors. We observed enhanced mosquito attraction to infected mice during a key period after the subsidence of acute malaria symptoms, but during which mice remained highly infectious. This attraction corresponded to an overall elevation in the volatile emissions of infected mice observed during this period. Furthermore, data analyses--using discriminant analysis of principal components and random forest approaches--revealed clear differences in the composition of the volatile blends of infected and healthy individuals. Experimental manipulation of individual compounds that exhibited altered emission levels during the period when differential vector attraction was observed also elicited enhanced mosquito attraction, indicating that compounds being influenced by malaria infection status also mediate vector host-seeking behavior. These findings provide important insights into the cues that mediate vector attraction to hosts infected with transmissible stages of malaria parasites, as well as documenting characteristic changes in the odors of infected individuals that may have potential value as diagnostic biomarkers of infection.

  9. Jasmonic Acid Enhances Al-Induced Root Growth Inhibition.

    Science.gov (United States)

    Yang, Zhong-Bao; He, Chunmei; Ma, Yanqi; Herde, Marco; Ding, Zhaojun

    2017-02-01

    Phytohormones such as ethylene and auxin are involved in the regulation of the aluminum (Al)-induced root growth inhibition. Although jasmonate (JA) has been reported to play a crucial role in the regulation of root growth and development in response to environmental stresses through interplay with ethylene and auxin, its role in the regulation of root growth response to Al stress is not yet known. In an attempt to elucidate the role of JA, we found that exogenous application of JA enhanced the Al-induced root growth inhibition. Furthermore, phenotype analysis with mutants defective in either JA biosynthesis or signaling suggests that JA is involved in the regulation of Al-induced root growth inhibition. The expression of the JA receptor CORONATINE INSENSITIVE1 (COI1) and the key JA signaling regulator MYC2 was up-regulated in response to Al stress in the root tips. This process together with COI1-mediated Al-induced root growth inhibition under Al stress was controlled by ethylene but not auxin. Transcriptomic analysis revealed that many responsive genes under Al stress were regulated by JA signaling. The differential responsive of microtubule organization-related genes between the wild-type and coi1-2 mutant is consistent with the changed depolymerization of cortical microtubules in coi1 under Al stress. In addition, ALMT-mediated malate exudation and thus Al exclusion from roots in response to Al stress was also regulated by COI1-mediated JA signaling. Together, this study suggests that root growth inhibition is regulated by COI1-mediated JA signaling independent from auxin signaling and provides novel insights into the phytohormone-mediated root growth inhibition in response to Al stress. © 2017 American Society of Plant Biologists. All Rights Reserved.

  10. Resonance-enhanced laser-induced plasma spectroscopy for sensitive elemental analysis: Elucidation of enhancement mechanisms

    International Nuclear Information System (INIS)

    Lui, S.L.; Cheung, N.H.

    2002-01-01

    When performing laser-induced plasma spectroscopy for elemental analysis, the analyte signal-to-noise ratio increased from four to over fifty if the plume was reheated by a dye laser pulse tuned to resonant absorption. Time-resolved studies showed that the enhancement was not due to resonance photoionization. Rather, efficient and controlled rekindling of a larger plume volume was the key mechanism. The signal-to-noise ratio further increased to over a hundred if the atmosphere was replaced by a low-pressure heavy inert gas. The ambient gas helped confine and thermally insulate the expanding vapor

  11. Enhanced stimulus-induced gamma activity in humans during propofol-induced sedation.

    Directory of Open Access Journals (Sweden)

    Neeraj Saxena

    Full Text Available Stimulus-induced gamma oscillations in the 30-80 Hz range have been implicated in a wide number of functions including visual processing, memory and attention. While occipital gamma-band oscillations can be pharmacologically modified in animal preparations, pharmacological modulation of stimulus-induced visual gamma oscillations has yet to be demonstrated in non-invasive human recordings. Here, in fifteen healthy humans volunteers, we probed the effects of the GABAA agonist and sedative propofol on stimulus-related gamma activity recorded with magnetoencephalography, using a simple visual grating stimulus designed to elicit gamma oscillations in the primary visual cortex. During propofol sedation as compared to the normal awake state, a significant 60% increase in stimulus-induced gamma amplitude was seen together with a 94% enhancement of stimulus-induced alpha suppression and a simultaneous reduction in the amplitude of the pattern-onset evoked response. These data demonstrate, that propofol-induced sedation is accompanied by increased stimulus-induced gamma activity providing a potential window into mechanisms of gamma-oscillation generation in humans.

  12. Thermal enhancement of x-ray induced DNA crosslinking

    International Nuclear Information System (INIS)

    Bowden, G.T.; Kasunic, M.; Cress, A.E.

    1982-01-01

    Ionizing radiation appears to crosslink nuclear DNA with chromosomal proteins. Important cellular processes such as transcription and DNA replication are likely to be compromised as a result of the DNA crosslinking. Heat treatment (43/sup o/C) of mouse leukemia cells (L1210) before X irradiation (50 Gy) was found to cause a doubling of the radiation-induced DNA crosslinking as measured by alkaline elution technique. By using proteinase K, a very active protease, to eliminate DNA-protein crosslinking in the alkaline elution assay, it was shown that the thermally enhanced DNA crosslinking was attributed to an increase in DNA-protein crosslinking. However, utilizing a protein radiolabel technique under conditions of increased DNA-protein crosslinking, the amount of protein left on the filter in the elution assay was not increased. These data suggest that qualitative rather than large quantitative differences in the crosslinked chromosomal proteins exist between irradiated cells and cells treated with heat prior to irradiation

  13. Improvement of boiling heat transfer by radiation induced boiling enhancement

    International Nuclear Information System (INIS)

    Imai, Yasuyuki; Okamoto, Koji; Madarame, Haruki; Takamasa, Tomoji

    2003-01-01

    For nuclear reactor systems, the critical heat flux (CHF) data is very important because it limits reactor efficiency. Improvement of CHF requires that the cooling liquid can contact the heating surface, or a high-wettability, highly hydrophilic heating surface, even if a vapor bubble layer is generated on the surface. In our previous study, we confirmed that the surface wettability changed significantly or that highly hydrophilic conditions were achieved, after irradiation of 60 Co gamma ray, by the Radiation Induced Surface Activation (RISA) phenomenon. To delineate the effect of RISA on boiling phenomena, surface wettability in a high-temperature environment and critical heat flux (CHF) of metal oxides irradiated by gamma rays were investigated. A CHF experiment in the pool boiling condition was carried out under atmospheric pressure. The heating test section made of titanium was 0.2 mm in thickness, 3 mm in height, and 60 mm in length. Oxidation of the surface was carried out by plasma jetting for 40 seconds. The test section was irradiated by 60 Co gamma ray with predetermined radiation intensity and period. The CHF of oxidized titanium was improved up to 100 percent after 800 kGy 60 Co gamma ray irradiation. We call this effect Radiation Induced Boiling Enhancement (RIBE). Before we conducted the CHF experiment, contact angles of the test pieces were measured to show the relationship between wettability and CHF. The CHF in the present experiment increases will surface wettability in the same manner as shown by Liaw and Dhir's results. (author)

  14. Noise-induced enhancement of network reciprocity in social dilemmas

    International Nuclear Information System (INIS)

    Zhang, Gui-Qing; Sun, Qi-Bo; Wang, Lin

    2013-01-01

    Highlights: • We introduce the noise-induced mechanism into the prisoner’s dilemma game. • Cooperation will be largely enhanced by introducing the noise into the calculation of fitness. • Despite the defectors prevail initially, the stressed factor still promotes the cooperation. • The mechanism studied here is helpful on different kinds of interaction networks. -- Abstract: The network reciprocity is an important dynamic rule fostering the emergence of cooperation among selfish individuals. This was reported firstly in the seminal work of Nowak and May, where individuals were arranged on the regular lattice network, and played the prisoner’s dilemma game (PDG). In the standard PDG, one often assumes that the players have perfect rationality. However, in reality, we human are far from rational agents, as we often make mistakes, and behave irrationally. Accordingly, in this work, we introduce the element of noise into the measurement of fitness, which is determined by the parameter α controlling the degree of noise. The considered noise-induced mechanism remarkably promotes the behavior of cooperation, which may be conducive to interpret the emergence of cooperation within the population

  15. Improvement of boiling heat transfer by radiation induced boiling enhancement

    International Nuclear Information System (INIS)

    Imai, Y.; Okamoto, K.; Madarame, H.; Takamasa, T.

    2003-01-01

    For nuclear reactor systems, the Critical Heat Flux (CHF) data is very important because it limits reactor efficiency. Improvement of CHF requires that the cooling liquid can contact the heating surface, or a high-wettability, highly hydrophilic heating surface, even if a vapor bubble layer is generated on the surface. In our previous study, we confirmed that the surface wettability changed significantly or that highly hydrophilic conditions were achieved, after irradiation of 60Co gamma ray, by the Radiation Induced Surface Activation (RISA) phenomenon. To delineate the effect of RISA on boiling phenomena, surface wettability in a high-temperature environment and Critical Heat Flux (CHF) of metal oxides irradiated by gamma rays were investigated. A CHF experiment in the pool boiling condition was carried out under atmospheric pressure. The heating test section made of titanium was 0.2mm in thickness, 3mm in height, and 60mm in length. Oxidation of the surfaces was carried out by plasma jetting for 40 seconds. The test section was irradiated by 60Co gamma ray with predetermined radiation intensity and period. The CHF of oxidized titanium was improved up to 100 percent after 800kGy 60Co gamma ray irradiation. We call this effect Radiation Induced Boiling Enhancement (RIBE). Before we conducted the CHF experiment, contact angles of the test pieces were measured to show the relationship between wettability and CHF. The CHF in the present experiment increases with surface wettability in the same manner as shown by Liaw and Dhir's results

  16. Enhanced heat sink with geometry induced wall-jet

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Md. Mahamudul, E-mail: sohel0991@gmail.com; Tikadar, Amitav; Bari, Fazlul; Morshed, A. K. M. M. [Department of Mechanical Engineering Bangladesh University of Engineering and Technology, Dhaka-1000. Bangladesh (Bangladesh)

    2016-07-12

    Mini-channels embedded in solid matrix have already proven to be a very efficient way of electronic cooling. Traditional mini-channel heat sinks consist of single layer of parallel channels. Although mini-channel heat sink can achieve very high heat flux, its pumping requirement for circulating liquid through the channel increase very sharply as the flow velocity increases. The pumping requirements of the heat sink can be reduced by increasing its performance. In this paper a novel approach to increase the thermal performance of the mini-channel heat sink is proposed through geometry induced wall jet which is a passive technique. Geometric irregularities along the channel length causes abrupt pressure change between the channels which causes cross flow through the interconnections thus one channel faces suction and other channel jet action. This suction and jet action disrupts boundary layer causing enhanced heat transfer performance. A CFD model has been developed using commercially available software package FLUENT to evaluate the technique. A parametric study of the velocities and the effect of the position of the wall-jets have been performed. Significant reduction in thermal resistance has been observed for wall-jets, it is also observed that this reduction in thermal resistance is dependent on the position and shape of the wall jet.

  17. Dependence of enhanced asymmetry-induced transport on collision frequency

    Science.gov (United States)

    Eggleston, D. L.

    2014-07-01

    A single-particle code with collisional effects is used to study how asymmetry-induced radial transport in a non-neutral plasma depends on collision frequency. For asymmetries of the form ϕ1(r) cos(kz) cos(ωt-lθ), two sources for the transport have been identified: resonant particles and axially trapped particles. The simulation shows that this latter type, which occurs near the radius where ω matches the azimuthal rotation frequency ωR, is usually dominant at low collision frequency ν but becomes negligible at higher ν. This behavior can be understood by noting that axially trapped particles have a lower trapping frequency than resonant particles. In the low ν (banana) regime, the radial oscillations have amplitude Δr ≈ vr/ωT, so axially trapped particles dominate, and the transport may even exceed the resonant particle plateau regime level. As ν increases, collisions start to interrupt the slower axially trapped particle oscillations, while the resonant particles are still in the banana regime, so the axially trapped particle contribution to the transport decreases. At the largest ν values, axially trapped particle transport is negligible and the observed diffusion coefficient matches that given by plateau regime resonant particle theory. Heuristic models based on these considerations give reasonable agreement with the observed scaling laws for the value of the collision frequency where axially trapped particle transport starts to decrease and for the enhancement of the diffusion coefficient produced by axially trapped particles.

  18. Dependence of enhanced asymmetry-induced transport on collision frequency

    International Nuclear Information System (INIS)

    Eggleston, D. L.

    2014-01-01

    A single-particle code with collisional effects is used to study how asymmetry-induced radial transport in a non-neutral plasma depends on collision frequency. For asymmetries of the form ϕ 1 (r) cos(kz) cos(ωt−lθ), two sources for the transport have been identified: resonant particles and axially trapped particles. The simulation shows that this latter type, which occurs near the radius where ω matches the azimuthal rotation frequency ω R , is usually dominant at low collision frequency ν but becomes negligible at higher ν. This behavior can be understood by noting that axially trapped particles have a lower trapping frequency than resonant particles. In the low ν (banana) regime, the radial oscillations have amplitude Δr ≈ v r /ω T , so axially trapped particles dominate, and the transport may even exceed the resonant particle plateau regime level. As ν increases, collisions start to interrupt the slower axially trapped particle oscillations, while the resonant particles are still in the banana regime, so the axially trapped particle contribution to the transport decreases. At the largest ν values, axially trapped particle transport is negligible and the observed diffusion coefficient matches that given by plateau regime resonant particle theory. Heuristic models based on these considerations give reasonable agreement with the observed scaling laws for the value of the collision frequency where axially trapped particle transport starts to decrease and for the enhancement of the diffusion coefficient produced by axially trapped particles

  19. Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors.

    Science.gov (United States)

    Bagley, Elena E; Hacker, Jennifer; Chefer, Vladimir I; Mallet, Christophe; McNally, Gavan P; Chieng, Billy C H; Perroud, Julie; Shippenberg, Toni S; Christie, MacDonald J

    2011-10-30

    Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal.

  20. Protocol for Addressing Induced Seismicity Associated with Enhanced Geothermal Systems

    Energy Technology Data Exchange (ETDEWEB)

    Majer, Ernie [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States); Nelson, James [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States); Robertson-Tait, Ann [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States); Savy, Jean [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States); Wong, Ivan [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States)

    2012-01-01

    This Protocol is a living guidance document for geothermal developers, public officials, regulators and the general public that provides a set of general guidelines detailing useful steps to evaluate and manage the effects of induced seismicity related to EGS projects.

  1. Nanoantenna array-induced fluorescence enhancement and reduced lifetimes

    DEFF Research Database (Denmark)

    Bakker, R. M.; Drachev, V. P.; Liu, Z.

    2008-01-01

    Enhanced fluorescence is observed from dye molecules interacting with optical nanoantenna arrays. Elliptical gold dimers form individual nanoantennae with tunable plasmon resonances depending upon the geometry of the two particles and the size of the gap between them. A fluorescent dye, Rhodamine...... 800, is uniformly embedded in a dielectric host that coats the nanoantennae. The nanoantennae act to enhance the dye absorption. In turn, emission from the dye drives the plasmon resonance of the antennae; the nanoantennae act to enhance the fluorescence signal and change the angular distribution...... of emission. These effects depend upon the overlap of the plasmon resonance with the excitation wavelength and the fluorescence emission band. A decreased fluorescence lifetime is observed along with highly polarized emission that displays the characteristics of the nanoantenna's dipole mode. Being able...

  2. Hund's Induced Fermi-Liquid Instabilities and Enhanced Quasiparticle Interactions.

    Science.gov (United States)

    De' Medici, Luca

    2017-04-21

    Hund's coupling is shown to generally favor, in a doped half-filled Mott insulator, an increase in the compressibility culminating in a Fermi-liquid instability towards phase separation. The largest effect is found near the frontier between an ordinary and an orbitally decoupled ("Hund's") metal. The increased compressibility implies an enhancement of quasiparticle scattering, thus favoring other possible symmetry breakings. This physics is shown to happen in simulations of the 122 Fe-based superconductors, possibly implying the relevance of this mechanism in the enhancement of the critical temperature for superconductivity.

  3. Disorder-induced enhancement of conductance in doped nanowires

    Institute of Scientific and Technical Information of China (English)

    Xu Ning; Wang Bao-Lin; Sun Hou-Qian; Kong Fan-Jie

    2010-01-01

    A new mechanism is proposed to explain the enhancement of conductance in doped nanowires. It is shown that the anomalous enhancement of conductance is due to surface doping. The conductance in doped nanowires increases with dopant concentration, which is qualitatively consistent with the existing experimental results. In addition, the I-V curves are linear and thus suggest that the metal electrodes make ohmic contacts to the shell-doped nanowires.The electric current increases with wire diameter (D) and decreases exponentially with wire length (L). Therefore, the doped nanowires have potential application in nanoscale electronic and optoelectronic devices.

  4. Neurotensin enhances estradiol induced DNA synthesis in immature rat uterus

    Energy Technology Data Exchange (ETDEWEB)

    Mistry, A.; Vijayan, E.

    1985-05-27

    Systemic administration of Neurotensin, a tridecapeptide, in immature rats treated with estradiol benzoate significantly enhances uterine DNA synthesis as reflected by the incorporation of /sup 3/H-thymidine. The peptide may have a direct action on the uterus. Substance P, a related peptide, had no effect on uterine DNA synthesis. 18 references, 4 tables.

  5. Evaluate the Mechanism of Enhanced Metastasis Induced by Arthritis

    Science.gov (United States)

    2012-09-01

    Genes that mediate breast ca ncer metastasis to lung . Nature 2005, 436(7050):518-524. 6. Das Roy L, Pathangey L, Tinder T, Schettini J, Gruber H...7. Das Roy L, Ghosh S, Pathangey LB, Tinder TL, Gruber HE, Mukherjee P: Collagen induced arthritis increases s econdary metastasis in MMTV-PyV

  6. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    International Nuclear Information System (INIS)

    Vilela, Luciano R.; Gobira, Pedro H.; Viana, Thercia G.; Medeiros, Daniel C.; Ferreira-Vieira, Talita H.; Doria, Juliana G.; Rodrigues, Flávia; Aguiar, Daniele C.; Pereira, Grace S.; Massessini, André R.; Ribeiro, Fabíola M.; Oliveira, Antonio Carlos P. de; Moraes, Marcio F.D.; Moreira, Fabricio A.

    2015-01-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB 1 receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB 1 receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis attenuates

  7. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Vilela, Luciano R. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Gobira, Pedro H.; Viana, Thercia G. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Medeiros, Daniel C.; Ferreira-Vieira, Talita H. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Doria, Juliana G. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Rodrigues, Flávia [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Aguiar, Daniele C. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Pereira, Grace S.; Massessini, André R. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ribeiro, Fabíola M. [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Oliveira, Antonio Carlos P. de [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moraes, Marcio F.D., E-mail: mfdm@icb.ufmg.br [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moreira, Fabricio A., E-mail: fabriciomoreira@icb.ufmg.br [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2015-08-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB{sub 1} receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB{sub 1} receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis

  8. Chill-inducing music enhances altruism in humans

    Directory of Open Access Journals (Sweden)

    Hajime eFukui

    2014-10-01

    Full Text Available Music is a universal feature of human cultures, and it has both fascinated and troubled many researchers. In this paper we show through the Dictator Game that an individual’s listening to preferred chill-inducing music may promote altruistic behavior that extends beyond the bounds of kin selection or reciprocal altruism. Participants were 22 undergraduate and postgraduate students who were divided into two groups, the In-group (IG and the Out-group (OG, and they acted as dictators. The dictators listened to their own preferred chill-inducing music, to music they disliked, or to silence, and then played the Dictator Game. In this hypothetical experiment, the dictators were given real money (which they did not keep and were asked to distribute it to the recipients, who were presented as stylized images of men and women displayed on a computer screen. The dictators played the Dictator Game both before and after listening to the music. Both male and female dictators gave more money after listening to their preferred music and less after listening to the music they disliked, whereas silence had no effect on the allocated amounts. The group to which the recipient belonged did not influence these trends. The results suggest that listening to preferred chill-inducing music promotes altruistic behavior.

  9. Chill-inducing music enhances altruism in humans.

    Science.gov (United States)

    Fukui, Hajime; Toyoshima, Kumiko

    2014-01-01

    Music is a universal feature of human cultures, and it has both fascinated and troubled many researchers. In this paper we show through the dictator game (DG) that an individual's listening to preferred "chill-inducing" music may promote altruistic behavior that extends beyond the bounds of kin selection or reciprocal altruism. Participants were 22 undergraduate and postgraduate students who were divided into two groups, the in-group and the out-group, and they acted as dictators. The dictators listened to their own preferred "chill-inducing" music, to music they disliked, or to silence, and then played the DG. In this hypothetical experiment, the dictators were given real money (which they did not keep) and were asked to distribute it to the recipients, who were presented as stylized images of men and women displayed on a computer screen. The dictators played the DG both before and after listening to the music. Both male and female dictators gave more money after listening to their preferred music and less after listening to the music they disliked, whereas silence had no effect on the allocated amounts. The group to which the recipient belonged did not influence these trends. The results suggest that listening to preferred "chill-inducing" music promotes altruistic behavior.

  10. Hydrogen sulfide enhances nitric oxide-induced tolerance of hypoxia in maize (Zea mays L.).

    Science.gov (United States)

    Peng, Renyi; Bian, Zhiyuan; Zhou, Lina; Cheng, Wei; Hai, Na; Yang, Changquan; Yang, Tao; Wang, Xinyu; Wang, Chongying

    2016-11-01

    Our data present H 2 S in a new role, serving as a multi-faceted transducer to different response mechanisms during NO-induced acquisition of tolerance to flooding-induced hypoxia in maize seedling roots. Nitric oxide (NO), serving as a secondary messenger, modulates physiological processes in plants. Recently, hydrogen sulfide (H 2 S) has been demonstrated to have similar signaling functions. This study focused on the effects of treatment with H 2 S on NO-induced hypoxia tolerance in maize seedlings. The results showed that treatment with the NO donor sodium nitroprusside (SNP) enhanced survival rate of submerged maize roots through induced accumulation of endogenous H 2 S. The induced H 2 S then enhanced endogenous Ca 2+ levels as well as the Ca 2+ -dependent activity of alcohol dehydrogenase (ADH), improving the capacity for antioxidant defense and, ultimately, the hypoxia tolerance in maize seedlings. In addition, NO induced the activities of key enzymes in H 2 S biosynthesis, such as L-cysteine desulfhydrases (L-CDs), O-acetyl-L-serine (thiol)lyase (OAS-TL), and β-Cyanoalanine Synthase (CAS). SNP-induced hypoxia tolerance was enhanced by the application of NaHS, but was eliminated by the H 2 S-synthesis inhibitor hydroxylamine (HA) and the H 2 S-scavenger hypotaurine (HT). H 2 S concurrently enhanced the transcriptional levels of relative hypoxia-induced genes. Together, our findings indicated that H 2 S serves as a multi-faceted transducer that enhances the nitric oxide-induced hypoxia tolerance in maize (Zea mays L.).

  11. Enhanced tunability of plasmon induced transparency in graphene strips

    International Nuclear Information System (INIS)

    Shi, Xi; Su, Xiaopeng; Yang, Yaping

    2015-01-01

    The approach of slow-light efficiency manipulation is theoretically investigated in graphene analogue of electromagnetically induced transparency (EIT) system, which cannot be realized in conventional quantum regime. In this system, two graphene strips with different Fermi energies placed side by side as radiative elements have been discussed, and the coupling strength between radiative elements and dark elements is tuned by these radiative elements. Our proposed scheme exploits the tuning of coupling strength between the radiative elements and dark elements in contrast with the existing approaches that rely on tuning the damping rates of radiative or dark elements. The transparent window and group delays can be tuned by different coupling strength without changing the geometry of structure. This manipulation can be explained using a temporal coupled-mode theory. Furthermore, the hybridized states in this EIT-like system can be manipulated by tuning the Fermi energy of radiative elements. This kind of controllable electromagnetically induced transparency has many significant potential applications in optoelectronic, photodetectors, tunable sensors, and storage of optical data regimes

  12. Phonon-induced enhancement of the energy gap and critical current of superconducting aluminum films

    International Nuclear Information System (INIS)

    Seligson, D.; Clarke, J.

    1983-01-01

    Enhancements of the energy gap Δ and the critical current I/sub c/ have been induced in thin superconducting aluminum films near the transition temperature T/sub c/ by pulses of phonons at approximately 9 GHz. In terms of the change in temperature Vertical BardeltaT/T/sub c/Vertical Bar necessary to produce the same enhancement in equilibrium, the gap enhancement increased smoothly with phonon power at fixed temperature and decreasing temperature at fixed phonon power; however, very close to T/sub c/ the enhancement rolled off. At relatively low phonon powers, the data were in good agreement with the theory of Eckern, Schmid, Schmutz, and Schoen, but at higher power levels the data fell markedly below the predictions of the theory. The critical-current enhancements in terms of Vertical BardeltaT/T/sub c/Vertical Bar were always larger than the gap enhancements at the same temperature and phonon power. At fixed phonon power the critical-current enhancements were nearly independent of temperature, except very close to T/sub c/ where the enhancement became small. The inclusion of the nonequilibrium quasiparticle distribution and the kinetic energy of the supercurrent in the theory relating the critical-current enhancement to the gap enhancement did not resolve the discrepancies between the two enhancements. It appears likely that there is an additional mechanism for critical-current enhancement that has not yet been identified

  13. Enhanced SCAP glycosylation by inflammation induces macrophage foam cell formation.

    Directory of Open Access Journals (Sweden)

    Chao Zhou

    Full Text Available Inflammatory stress promotes foam cell formation by disrupting LDL receptor feedback regulation in macrophages. Sterol Regulatory Element Binding Proteins (SREBPs Cleavage-Activating Protein (SCAP glycosylation plays crucial roles in regulating LDL receptor and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR feedback regulation. The present study was to investigate if inflammatory stress disrupts LDL receptor and HMGCoAR feedback regulation by affecting SCAP glycosylation in THP-1 macrophages. Intracellular cholesterol content was assessed by Oil Red O staining and quantitative assay. The expression of molecules controlling cholesterol homeostasis was examined using real-time quantitative RT-PCR and Western blotting. The translocation of SCAP from the endoplasmic reticulum (ER to the Golgi was detected by confocal microscopy. We demonstrated that exposure to inflammatory cytokines increased lipid accumulation in THP-1 macrophages, accompanying with an increased SCAP expression even in the presence of a high concentration of LDL. These inflammatory cytokines also prolonged the half-life of SCAP by enhancing glycosylation of SCAP due to the elevated expression of the Golgi mannosidase II. This may enhance translocation and recycling of SCAP between the ER and the Golgi, escorting more SREBP2 from the ER to the Golgi for activation by proteolytic cleavages as evidenced by an increased N-terminal of SREBP2 (active form. As a consequence, the LDL receptor and HMGCoAR expression were up-regulated. Interestingly, these effects could be blocked by inhibitors of Golgi mannosidases. Our results indicated that inflammation increased native LDL uptake and endogenous cholesterol de novo synthesis, thereby causing foam cell formation via increasing transcription and protein glycosylation of SCAP in macrophages. These data imply that inhibitors of Golgi processing enzymes might have a potential vascular-protective role in prevention of atherosclerotic foam

  14. Diagnostic performance of Contrast-enhanced CT in Pyrrolizidine Alkaloids-induced Hepatic Sinusoidal Obstructive Syndrome

    Science.gov (United States)

    Kan, Xuefeng; Ye, Jin; Rong, Xinxin; Lu, Zhiwen; Li, Xin; Wang, Yong; Yang, Ling; Xu, Keshu; Song, Yuhu; Hou, Xiaohua

    2016-01-01

    Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. Since PAs exposure is obscure and clinical presentation of HSOS is unspecific, it is challenge to establish the diagnosis of PAs-induced HSOS. Gynura segetum is one of the most wide-use herbals containing PAs. The aim of our study is to describe the features of contrast-enhanced computed tomography (CT) in gynura segetum-induced HSOS, and then determine diagnostic performance of radiological signs. We retrospectively analyzed medical records and CT images of HSOS patients (71 cases) and the controls (222 cases) enrolled from January 1, 2008, to Oct 31, 2015. The common findings of contrast CT in PAs-induced HSOS included: ascites (100%), hepatomegaly (78.87%), gallbladder wall thickening (86.96%), pleural effusion (70.42%), hepatic vein narrowing (87.32%), patchy liver enhancement (92.96%), and heterogeneous hypoattenuation (100%); of these signs, patchy enhancement and heterogeneous hypoattenuation were valuable features. Then, the result of diagnostic performance demonstrated that contrast CT possessed better performance in diagnosing PAs-induced HSOS compared with various parameters of Seattle criteria. In conclusion, the patients with PAs-induced HSOS display distinct radiologic features at CT-scan, which reveals that contrast-enhanced CT provides an effective noninvasive method for diagnosing PAs-induced HSOS. PMID:27897243

  15. Systematic investigation of resonance-induced single-harmonic enhancement in the extreme-ultraviolet range

    International Nuclear Information System (INIS)

    Ganeev, R. A.; Bom, L. B. Elouga; Kieffer, J.-C.; Ozaki, T.

    2007-01-01

    We demonstrate the intensity enhancement of single harmonics in high-order harmonic generation from laser plasma. We identified several targets (In, Sn, Sb, Cr, and Mn) that demonstrate resonance-induced enhancement of single harmonic, that are spectrally close to ionic transitions with strong oscillator strengths. We optimized and obtained enhancements of the 13th, 17th, 21st, 29th, and 33rd harmonics from the above targets, by varying the chirp of the 800 nm wavelength femtosecond laser. We also observe harmonic enhancement by using frequency-doubled pump laser (400 nm wavelength). For Mn plasma pumped by the 400 nm wavelength laser, the maximum order of the enhanced harmonic observed was the 17th order (λ=23.5 nm), which corresponds to the highest photon energy (52.9 eV) reported for an enhanced single harmonic

  16. Drinking sucrose enhances quinpirole-induced yawning in rats.

    Science.gov (United States)

    Baladi, Michelle G; Newman, Amy H; Thomas, Yvonne M; France, Charles P

    2011-12-01

    Food and drugs can activate brain dopamine systems and sensitivity to the effects of drugs acting on those systems is influenced by amount and content of food consumed. This study examined the effects of drinking sucrose on behavioral effects of the direct-acting dopamine receptor agonist quinpirole. Male Sprague-Dawley rats (n=6/group) had free access to water or 10% sucrose and quinpirole dose-response curves (yawning and hypothermia) were generated weekly for 8 weeks. Subsequently, all rats drank water for 8 weeks with quinpirole dose-response curves determined on weeks 9, 10, and 16. In rats drinking sucrose, the ascending (D3 receptor-mediated), but not descending (D2 receptor-mediated), limb of the yawning dose-response curve shifted leftward. The D3 receptor-selective antagonist PG01037 shifted the ascending limb of the dose-response curve to the right in all rats. When rats that previously drank sucrose drank water, their sensitivity to quinpirole did not return to normal. Quinpirole-induced hypothermia was not different between groups. These data show that drinking sucrose increases sensitivity to a dopamine D3, but not D2, receptor-mediated effect and that this change is long lasting. Dopamine receptors mediate the effects of many drugs and the actions of those drugs are likely impacted by dietary factors.

  17. Genetically-induced cholinergic hyper-innervation enhances taste learning

    Directory of Open Access Journals (Sweden)

    Selin eNeseliler

    2011-12-01

    Full Text Available Acute inhibition of acetylcholine (ACh has been shown to impair many forms of simple learning, and notably conditioned taste aversion (CTA. The most adhered-to theory that has emerged as a result of this work—that ACh increases a taste’s perceived novelty, and thereby its associability—would be further strengthened by evidence showing that enhanced cholinergic function improves learning above normal levels. Experimental testing of this corollary hypothesis has been limited, however, by side-effects of pharmacological ACh agonism and by the absence of a model that achieves long-term increases in cholinergic signaling. Here, we present this further test of the ACh hypothesis, making use of mice lacking the p75 pan-neurotrophin receptor gene, which show a resultant over-abundance of cholinergic neurons in subregions of the basal forebrain (BF. We first demonstrate that the p75-/- abnormality directly affects portions of the CTA circuit, locating mouse gustatory cortex (GC using a functional assay and then using immunohistochemisty to demonstrate cholinergic hyperinnervation of GC in the mutant mice—hyperinnervation that is unaccompanied by changes in cell numbers or compensatory changes in muscarinic receptor densities. We then demonstrate that both p75-/- and wild-type mice learn robust CTAs, which extinguish more slowly in the mutants. Further testing to distinguish effects on learning from alterations in memory retention demonstrate that p75-/- mice do in fact learn stronger CTAs than wild-type mice. These data provide novel evidence for the hypothesis linking ACh and taste learning.

  18. Enhancement in the photodetection of ZnO nanowires by introducing surface-roughness-induced traps

    International Nuclear Information System (INIS)

    Park, Woojin; Jo, Gunho; Hong, Woong-Ki; Yoon, Jongwon; Choe, Minhyeok; Ji, Yongsung; Kim, Geunjin; Kahng, Yung Ho; Lee, Kwanghee; Lee, Takhee; Lee, Sangchul; Wang, Deli

    2011-01-01

    We investigated the enhanced photoresponse of ZnO nanowire transistors that was introduced with surface-roughness-induced traps by a simple chemical treatment with isopropyl alcohol (IPA). The enhanced photoresponse of IPA-treated ZnO nanowire devices is attributed to an increase in adsorbed oxygen on IPA-induced surface traps. The results of this study revealed that IPA-treated ZnO nanowire devices displayed higher photocurrent gains and faster photoswitching speed than transistors containing unmodified ZnO nanowires. Thus, chemical treatment with IPA can be a useful method for improving the photoresponse of ZnO nanowire devices.

  19. Double pulse laser ablation and plasma: Laser induced breakdown spectroscopy signal enhancement

    International Nuclear Information System (INIS)

    Babushok, V.I.; DeLucia, F.C.; Gottfried, J.L.; Munson, C.A.; Miziolek, A.W.

    2006-01-01

    A review of recent results of the studies of double laser pulse plasma and ablation for laser induced breakdown spectroscopy applications is presented. The double pulse laser induced breakdown spectroscopy configuration was suggested with the aim of overcoming the sensitivity shortcomings of the conventional single pulse laser induced breakdown spectroscopy technique. Several configurations have been suggested for the realization of the double pulse laser induced breakdown spectroscopy technique: collinear, orthogonal pre-spark, orthogonal pre-heating and dual pulse crossed beam modes. In addition, combinations of laser pulses with different wavelengths, different energies and durations were studied, thus providing flexibility in the choice of wavelength, pulse width, energy and pulse sequence. The double pulse laser induced breakdown spectroscopy approach provides a significant enhancement in the intensity of laser induced breakdown spectroscopy emission lines up to two orders of magnitude greater than a conventional single pulse laser induced breakdown spectroscopy. The double pulse technique leads to a better coupling of the laser beam with the plasma plume and target material, thus providing a more temporally effective energy delivery to the plasma and target. The experimental results demonstrate that the maximum effect is obtained at some optimum separation delay time between pulses. The optimum value of the interpulse delay depends on several factors, such as the target material, the energy level of excited states responsible for the emission, and the type of enhancement process considered. Depending on the specified parameter, the enhancement effects were observed on different time scales ranging from the picosecond time level (e.g., ion yield, ablation mass) up to the hundred microsecond level (e.g., increased emission intensity for laser induced breakdown spectroscopy of submerged metal target in water). Several suggestions have been proposed to explain

  20. Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice.

    Science.gov (United States)

    Abe, Kenji; Kobayashi, Kanayo; Yoshino, Saori; Taguchi, Kyoji; Nojima, Hiroshi

    2015-04-01

    An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10-50 mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60 min was recorded and summed. We found that at 24 hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.

  1. Turbulence enhancement by ultrasonically induced gaseous cavitation in the CO2 saturated water

    International Nuclear Information System (INIS)

    Lee, Seung Youp; Choi, Young Don

    2002-01-01

    Recent primary concern for the design of high performance heat exchanger and highly integrated electronic equipment is to develop an active and creative technologies which enhance the heat transfer without obstructing the coolant flows. In this study, we found through the LDV measurement that the gaseous cavitation induced by ultrasonic vibration applied to the CO 2 saturated water in the square cross-sectioned straight duct flow enhances the turbulence much more than the case of non-ultrasonic or normal ultrasonic conditions without gaseous cavitation does. We also found that gaseous cavitation can enhance effectively the turbulent heat transfer between the heating surfaces and coolants by destructing the viscous sublayer

  2. Interleukin 17 enhances bone morphogenetic protein-2-induced ectopic bone formation

    NARCIS (Netherlands)

    Croes, M.; Kruyt, M. C.; Groen, W. M.; Van Dorenmalen, K. M.A.; Dhert, W. J.A.; Öner, F. C.; Alblas, J.

    2018-01-01

    Interleukin 17 (IL-17) stimulates the osteogenic differentiation of progenitor cells in vitro through a synergy with bone morphogenetic protein (BMP)-2. This study investigates whether the diverse responses mediated by IL-17 in vivo also lead to enhanced BMP-2-induced bone formation. Since IL-17 is

  3. Enhancing resilience of farmer seed system to climate-induced stresses

    NARCIS (Netherlands)

    Kansiime, Monica K.; Mastenbroek, Astrid

    2016-01-01

    Given the challenges facing African agriculture resulting from climate-induced stresses, building resilience is a priority. Seed systems are important for enhancing such resilience as seed security has direct links to food security, and resilient livelihoods in general. Using data from a case

  4. Persistent wind-induced enhancement of diffusive CO2 transport in a mountain forest snowpack

    Science.gov (United States)

    D. R. Bowling; W. J. Massman

    2011-01-01

    Diffusion dominates the transport of trace gases between soil and the atmosphere. Pressure gradients induced by atmospheric flow and wind interacting with topographical features cause a small but persistent bulk flow of air within soil or snow. This forcing, called pressure pumping or wind pumping, leads to a poorly quantified enhancement of gas transport beyond the...

  5. Real-time observations of mechanical stimulus-induced enhancements of mechanical properties in osteoblast cells

    International Nuclear Information System (INIS)

    Zhang Xu; Liu Xiaoli; Sun Jialun; He Shuojie; Lee, Imshik; Pak, Hyuk Kyu

    2008-01-01

    Osteoblast, playing a key role in the pathophysiology of osteoporosis, is one of the mechanical stress sensitive cells. The effects of mechanical load-induced changes of mechanical properties in osteoblast cells were studied at real-time. Osteoblasts obtained from young Wister rats were exposed to mechanical loads in different frequencies and resting intervals generated by atomic force microscopy (AFM) probe tip and simultaneously measured the changes of the mechanical properties by AFM. The enhancement of the mechanical properties was observed and quantified by the increment of the apparent Young's modulus, E * . The observed mechanical property depended on the frequency of applied tapping loads. For the resting interval is 50 s, the mechanical load-induced enhancement of E * -values disappears. It seems that the enhanced mechanical property was recover able under no additional mechanical stimulus

  6. Gamma radiation induced enhancement in the antioxidant and radioprotective activities of flavonoids

    International Nuclear Information System (INIS)

    Arul Anantha Kumar, A.; Sonwani, Swetha; Bakkiam, D.

    2018-01-01

    Recently γ-radiation has been used as a tool to induce structural changes in natural biomolecules to enhance their biological and physiological properties. Flavonoids are a family of plant derived polyphenolic compounds having considerable scientific and therapeutic importance. Structurally they are the benzo-γ-pyrone derivatives containing phenolic and pyrane rings. Flavonoid radioprotection is an intense area of research thanks to features like natural origin, effectiveness at non-toxic dose levels and lack of side effects. But till date no report is available on the effect of γ-radiation mediated enhancement in radioprotection activity of flavonoids. In view of this the present study was carried out to determine the γ-radiation induced structural changes in selected flavonoids i.e. apigenin, naringenin and genistein and also to explore the possibility of enhancement in their antioxidant and radioprotective activities

  7. Active Enhancement of Slow Light Based on Plasmon-Induced Transparency with Gain Materials.

    Science.gov (United States)

    Zhang, Zhaojian; Yang, Junbo; He, Xin; Han, Yunxin; Zhang, Jingjing; Huang, Jie; Chen, Dingbo; Xu, Siyu

    2018-06-03

    As a plasmonic analogue of electromagnetically induced transparency (EIT), plasmon-induced transparency (PIT) has drawn more attention due to its potential of realizing on-chip sensing, slow light and nonlinear effect enhancement. However, the performance of a plasmonic system is always limited by the metal ohmic loss. Here, we numerically report a PIT system with gain materials based on plasmonic metal-insulator-metal waveguide. The corresponding phenomenon can be theoretically analyzed by coupled mode theory (CMT). After filling gain material into a disk cavity, the system intrinsic loss can be compensated by external pump beam, and the PIT can be greatly fueled to achieve a dramatic enhancement of slow light performance. Finally, a double-channel enhanced slow light is introduced by adding a second gain disk cavity. This work paves way for a potential new high-performance slow light device, which can have significant applications for high-compact plasmonic circuits and optical communication.

  8. Air pollution induces enhanced mitochondrial oxidative stress in cystic fibrosis airway epithelium.

    Science.gov (United States)

    Kamdar, O; Le, Wei; Zhang, J; Ghio, A J; Rosen, G D; Upadhyay, D

    2008-10-29

    We studied the effects of airborne particulate matters (PM) on cystic fibrosis (CF) epithelium. We noted that PM enhanced human CF bronchial epithelial apoptosis, activated caspase-9 and PARP-1; and reduced mitochondrial membrane potential. Mitochondrial inhibitors (4,4-diisothiocyanatostilbene-2,2'disulfonic acid, rotenone and thenoyltrifluoroacetone) blocked PM-induced generation of reactive oxygen species and apoptosis. PM upregulated pro-apoptotic Bad, Bax, p53 and p21; and enhanced mitochondrial localization of Bax. The anti-apoptotic Bcl-2, Bcl-xl, Mcl-1 and Xiap remained unchanged; however, overexpression of Bcl-xl blocked PM-induced apoptosis. Accordingly, we provide the evidence that PM enhances oxidative stress and mitochondrial signaling mediated apoptosis via the modulation of Bcl family proteins in CF.

  9. The ER stress inducer DMC enhances TRAIL-induced apoptosis in glioblastoma

    NARCIS (Netherlands)

    van Roosmalen, Ingrid A. M.; Dos Reis, Carlos R; Setroikromo, Rita; Yuvaraj, Saravanan; Joseph, Justin V.; Tepper, Pieter G.; Kruyt, Frank A. E.; Quax, Wim J.

    2014-01-01

    Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour in humans and is highly resistant to current treatment modalities. We have explored the combined treatment of the endoplasmic reticulum (ER) stress-inducing agent 2,5-dimethyl-celecoxib (DMC) and TNF-related

  10. Hepatocyte growth factor enhances death receptor-induced apoptosis by up-regulating DR5

    International Nuclear Information System (INIS)

    Li, Yang; Fan, Xing; Goodwin, C Rory; Laterra, John; Xia, Shuli

    2008-01-01

    Hepatocyte growth factor (HGF) and its receptor c-MET are commonly expressed in malignant gliomas and embryonic neuroectodermal tumors including medulloblastoma and appear to play an important role in the growth and dissemination of these malignancies. Dependent on cell context and the involvement of specific downstream effectors, both pro- and anti-apoptotic effects of HGF have been reported. Human medulloblastoma cells were treated with HGF for 24–72 hours followed by death receptor ligand TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) for 24 hours. Cell death was measured by MTT and Annexin-V/PI flow cytometric analysis. Changes in expression levels of targets of interest were measured by Northern blot analysis, quantitative reverse transcription-PCR, Western blot analysis as well as immunoprecipitation. In this study, we show that HGF promotes medulloblastoma cell death induced by TRAIL. TRAIL alone triggered apoptosis in DAOY cells and death was enhanced by pre-treating the cells with HGF for 24–72 h prior to the addition of TRAIL. HGF (100 ng/ml) enhanced TRAIL (10 ng/ml) induced cell death by 36% (P < 0.001). No cell death was associated with HGF alone. Treating cells with PHA-665752, a specific c-Met receptor tyrosine kinase inhibitor, significantly abrogated the enhancement of TRAIL-induced cell death by HGF, indicating that its death promoting effect requires activation of its canonical receptor tyrosine kinase. Cell death induced by TRAIL+HGF was predominately apoptotic involving both extrinsic and intrinsic pathways as evidenced by the increased activation of caspase-3, 8, 9. Promotion of apoptosis by HGF occurred via the increased expression of the death receptor DR5 and enhanced formation of death-inducing signal complexes (DISC). Taken together, these and previous findings indicate that HGF:c-Met pathway either promotes or inhibits medulloblastoma cell death via pathway and context specific mechanisms

  11. Radiation-induced enhancement of enzymatic cell lysis of Micrococcus radiodurans

    International Nuclear Information System (INIS)

    Watanabe, H.; Takehisa, M.; Iizuka, H.

    1981-01-01

    The intact cells of M. radiodurans were rendered sensitive to the action of lytic enzyme (P2-2 enzyme) by irradiation. The radiation-induced enhancement of cell lysis with P2-2 enzyme was completely prevented by the addition of t-butanol and irradiation at liquid nitrogen temperature. These results indicate that the enhancement is due to indirect action resulting from OH radicals. Cell lysis by lysozyme was enhanced only when the cells were irradiated under N 2 O. The enhancement of cell lysis with lysozyme was also prevented by adding alcohols. On the other hand, when lipid components in cells were removed by extraction with n-butanol, the radiation-induced enhancement of cell lysis with P2-2 enzyme and lysozyme was not observed. From these results it is concluded that the enhancement of enzymatic cell lysis by irradiation is attributable to alteration in the lipid-rich layer of the cell wall caused by OH radicals

  12. Radiation-induced enhancement of enzymatic cell lysis of Micrococcus radiodurans

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, H.; Takehisa, M. [Japan Atomic Energy Research Inst., Takasaki, Gunma, Takasaki Radiation Chemistry Research Establishment (Japan); Iizuka, H.

    1981-10-15

    The intact cells of M. radiodurans were rendered sensitive to the action of lytic enzyme (P2-2 enzyme) by irradiation. The radiation-induced enhancement of cell lysis with P2-2 enzyme was completely prevented by the addition of t-butanol and irradiation at liquid nitrogen temperature. These results indicate that the enhancement is due to indirect action resulting from OH radicals. Cell lysis by lysozyme was enhanced only when the cells were irradiated under N{sub 2}O. The enhancement of cell lysis with lysozyme was also prevented by adding alcohols. On the other hand, when lipid components in cells were removed by extraction with n-butanol, the radiation-induced enhancement of cell lysis with P2-2 enzyme and lysozyme was not observed. From these results it is concluded that the enhancement of enzymatic cell lysis by irradiation is attributable to alteration in the lipid-rich layer of the cell wall caused by OH radicals.

  13. Enhancement of vortex induced forces and motion through surface roughness control

    Science.gov (United States)

    Bernitsas, Michael M [Saline, MI; Raghavan, Kamaldev [Houston, TX

    2011-11-01

    Roughness is added to the surface of a bluff body in a relative motion with respect to a fluid. The amount, size, and distribution of roughness on the body surface is controlled passively or actively to modify the flow around the body and subsequently the Vortex Induced Forces and Motion (VIFM). The added roughness, when designed and implemented appropriately, affects in a predetermined way the boundary layer, the separation of the boundary layer, the level of turbulence, the wake, the drag and lift forces, and consequently the Vortex Induced Motion (VIM), and the fluid-structure interaction. The goal of surface roughness control is to increase Vortex Induced Forces and Motion. Enhancement is needed in such applications as harnessing of clean and renewable energy from ocean/river currents using the ocean energy converter VIVACE (Vortex Induced Vibration for Aquatic Clean Energy).

  14. Piperine Enhances the Protective Effect of Curcumin Against 3-NP Induced Neurotoxicity: Possible Neurotransmitters Modulation Mechanism.

    Science.gov (United States)

    Singh, Shamsher; Jamwal, Sumit; Kumar, Puneet

    2015-08-01

    3-Nitropropionic acid (3-NP) is a fungal toxin well established model used for inducing symptoms of Huntington's disease. Curcumin a natural polyphenol has been reported to possess neuroprotective activity by decreasing oxidative stress. The aim of present study was to investigate neuroprotective effect of curcumin with piperine (bioavailability enhancer) against 3-NP induced neurotoxicity in rats. Administration of 3-NP (10 mg/kg for 21 days) showed loss in body weight, declined motor function and changes in biochemical (LPO, nitrite and glutathione level), neuroinflammatory (TNF-α and IL-1β level) and neurochemical (DA, NE, 5-HT, DOPAC, 5-HIAA and HVA). Chronic treatment with curcumin (25 and 50 mg/kg) and curcumin (25 mg/kg) with piperine (2.5 mg/kg) once daily for 21 days prior to 3-NP administration. All the behavioral parameters were studied at 1st, 7th, 14th, and 21st day. On 22nd day all the animals was scarified and striatum was separated. Curcumin alone and combination (25 mg/kg) with piperine (2.5 mg/kg) showed beneficial effect against 3-NP induced motor deficit, biochemical and neurochemical abnormalities in rats. Piperine (2.5 mg/kg) with curcumin (25 mg/kg) significantly enhances its protective effect as compared with curcumin alone treated group. The results of the present study indicate that protective effect of curcumin potentiated in the presence of piperine (bioavailability enhancer) against 3-NP-induced behavioral and molecular alteration.

  15. [Study of enhancement effect of laser-induced crater on plasma radiation].

    Science.gov (United States)

    Chen, Jin-Zhong; Zhang, Xiao-Ping; Guo, Qing-Lin; Su, Hong-Xin; Li, Guang

    2009-02-01

    Single pulses exported from high-energy neodymium glass laser were used to act on the same position of soil sample surface repeatedly, and the plasma emission spectra generated from sequential laser pulse action were collected by spectral recording system. The experimental results show that the laser-induced soil plasma radiation was enhanced continuously under the confinement effect of the crater walls, and the line intensities and signal-to-background ratios both had different improvements along with increasing the number of acting pulses. The photographs of the plasma image and crater appearance were taken to study the plasma shape, laser-induced crater appearance, and the mass of the ablated sample. The internal mechanism behind that laser-induced crater enhanced plasma radiation was researched. Under the sequential laser pulse action, the forming plasma as a result enlarges gradually first, leading to distortion at the trail of plasma plume, and then, its volume diminishes slowly. And also, the color of the plasma changes from buff to white gradually, which implies that the temperature increases constantly. The laser-induced crater had a regular shape, that is, the diameter increased from its bottom to top gradually, thus forming a taper. The mass of the laser-ablated substance descends along with increasing the amount of action pulse. Atomization degree of vaporized substance was improved in virtue of the crater confinement effect, Fresnel absorption produced from the crater walls reflection, and the inverse bremsstrahlung, and the plasma radiation intensity was enhanced as a result.

  16. Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G., E-mail: lhudson@salud.unm.edu

    2013-06-01

    Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the Hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations. - Highlights: • Low levels of arsenite enhance UV-induced DNA damage in human keratinocytes. • UV-initiated HPRT mutation frequency is enhanced by arsenite. • Zinc supplementation offsets DNA damage and mutation frequency enhanced by arsenite. • Zinc-dependent reduction of arsenite enhanced DNA damage is confirmed in vivo.

  17. Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum.

    Science.gov (United States)

    Mattsson, Anna; Olson, Lars; Svensson, Torgny H; Schilström, Björn

    2007-11-01

    Cholinergic dysfunction has been implicated as a putative contributing factor in the pathogenesis of schizophrenia. Recently, we showed that cholinergic denervation of the neocortex in adult rats leads to a marked increase in the behavioral response to amphetamine. The main objective of this study was to investigate if the enhanced locomotor response to amphetamine seen after cortical cholinergic denervation was paralleled by an increased amphetamine-induced release of dopamine in the nucleus accumbens and/or striatum. The corticopetal cholinergic projections were lesioned by intraparenchymal infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of adult rats. Amphetamine-induced dopamine release in the nucleus accumbens or striatum was monitored by in vivo microdialysis 2 to 3 weeks after lesioning. We found that cholinergic denervation of the rat neocortex leads to a significantly increased amphetamine-induced dopamine release in the nucleus accumbens. Interestingly, the cholinergic lesion did not affect amphetamine-induced release of dopamine in the striatum. The enhanced amphetamine-induced dopamine release in the nucleus accumbens in the cholinergically denervated rats could be reversed by administration of the muscarinic agonist oxotremorine, but not nicotine, prior to the amphetamine challenge, suggesting that loss of muscarinic receptor stimulation is likely to have caused the observed effect. The results suggest that abnormal responsiveness of dopamine neurons can be secondary to cortical cholinergic deficiency. This, in turn, might be of relevance for the pathophysiology of schizophrenia and provides a possible link between cholinergic disturbances and alteration of dopamine transmission.

  18. Genetic modification to induce CXCR2 overexpression in mesenchymal stem cells enhances treatment benefits in radiation-induced oral mucositis.

    Science.gov (United States)

    Shen, Zongshan; Wang, Jiancheng; Huang, Qiting; Shi, Yue; Wei, Zhewei; Zhang, Xiaoran; Qiu, Yuan; Zhang, Min; Wang, Yi; Qin, Wei; Huang, Shuheng; Huang, Yinong; Liu, Xin; Xia, Kai; Zhang, Xinchun; Lin, Zhengmei

    2018-02-14

    Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting. By systematically evaluating the expression patterns of chemokines in radiation/chemical-induced oral mucositis, we found that CXCL2 was highly expressed, whereas cultured MSCs negligibly express the CXCL2 receptor CXCR2. Thus, we explored the potential therapeutic benefits of the transplantation of CXCR 2 -overexpressing MSCs (MSCs CXCR2 ) for mucositis treatment. Indeed, MSCs CXCR2 exhibited enhanced targeting ability to the inflamed mucosa in radiation/chemical-induced oral mucositis mouse models. Furthermore, we found that MSC CXCR2 transplantation accelerated ulcer healing by suppressing the production of pro-inflammatory chemokines and radiogenic reactive oxygen species (ROS). Altogether, these findings indicate that CXCR2 overexpression in MSCs accelerates ulcer healing, providing new insights into cell-based therapy for radiation/chemical-induced oral mucositis.

  19. Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Hitoshi Uchiyama

    2014-09-01

    Full Text Available The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF. Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins—hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate—on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated. In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated. However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated. These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins.

  20. Heat-shock-induced enhanced reactivation of UV-irradiated Herpesvirus

    Energy Technology Data Exchange (ETDEWEB)

    Yager, J.D.; Zurlo, J.; Penn, A.L.

    1985-09-01

    The objective of this study was to compare the ability of heat shock (HS) with that of another type of cellular stress, UV irradiation, to cause the induction of enhanced viral reactivation, a process that may represent an SOS-type repair process in mammalian cells. These results indicate that, like UV irradiation, HS at levels inhibitory to cell growth induced enhanced viral reactivation in Vero cells. The results also suggest that at least two proteins in the HS protein family are not necessary for this response to occur. (Auth.). 27 refs.; 5 figs.

  1. Dye-Induced Enhancement of Optical Nonlinearity in Liquids and Liquid Crystals

    International Nuclear Information System (INIS)

    Muenster, R.; Jarasch, M.; Zhuang, X.; Shen, Y.

    1997-01-01

    Optical nonlinearity of liquid crystals (LC) in the isotropic phase can be enhanced by 1 order of magnitude by dissolving 0.1% of anthraquinone dye in the LC. The enhancement decreases by ∼30% when the LC transforms into the nematic phase. The same guest-host effect also exists in non-LC liquids. It can be explained by a model based on the change of guest-host interaction induced by optical excitations of the dye. copyright 1996 The American Physical Society

  2. Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

    Science.gov (United States)

    Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

    1993-01-01

    It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components.

  3. Design and Evaluation of Photo-Induced Biofeedback Fabric for the Enhancement in Sleeping Sense

    OpenAIRE

    Chu, Wei-Cheng; Lin, Hsin-Ju; Chiu, Shu-Ping

    2013-01-01

    Based on overcoming the sleeping obstacle for people, the purpose of this study is to design a photo-induced biofeedback fabric which is a kind of optical fiber fabric with the function of enhancing sleeping sense and to evaluate its effect. The fabrics with two layers including background layer and pattern layer were designed firstly. The pattern layers with 3 kinds of wavelengths of sine waves and the light controller with 3 kinds of flashing frequencies were then prepared. Guiding the ligh...

  4. Enhancement of four-wave mixing induced by interacting dark resonances

    International Nuclear Information System (INIS)

    Yang Weifeng; Gong Shangqing; Niu Yueping; Jin Shiqi; Xu Zhizhan

    2005-01-01

    We analyse a four-wave mixing (FWM) scheme in a five-level atomic system in which double-dark resonances are present. It is found that the enhancement of FWM in both electromagnetically induced transparency (EIT) windows can be obtained even without the condition of multiphoton resonance. Moreover, the conversion efficiency of FWM in one EIT window can be much larger than that in the other due to the presence of interacting dark resonances

  5. Saccharomyces cerevisiae mutants with enhanced induced mutation and altered mitotic gene conversion.

    Science.gov (United States)

    Ivanov, E L; Kovaltzova, S V; Korolev, V G

    1989-08-01

    We have developed a method to isolate yeast (Saccharomyces cerevisiae) mutants with enhanced induced mutagenesis based on nitrous acid-induced reversion of the ade2-42 allele. Six mutants have been isolated and designated him (high induced mutagenesis), and 4 of them were studied in more detail. The him mutants displayed enhanced reversion of the ade2-42 allele, either spontaneous or induced by nitrous acid, UV light, and the base analog 6-N-hydroxylaminopurine, but not by gamma-irradiation. It is worth noting that the him mutants turned out not to be sensitive to the lethal effects of the mutagens used. The enhancement in mutation induced by nitrous acid, UV light, and 6-N-hydroxylaminopurine has been confirmed in a forward-mutation assay (induction of mutations in the ADE1, ADE2 genes). The latter agent revealed the most apparent differences between the him mutants and the wild-type strain and was, therefore, chosen for the genetic analysis of mutants, him mutations analyzed behaved as a single Mendelian trait; complementation tests indicated 3 complementation groups (HIM1, HIM2, and HIM3), each containing 1 mutant allele. Uracil-DNA glycosylase activity was determined in crude cell extracts, and no significant differences between the wild-type and him strains were detected. Spontaneous mitotic gene conversion at the ADE2 locus is altered in him1 strains, either increased or decreased, depending on the particular heteroallelic combination. Genetic evidence strongly suggests him mutations to be involved in a process of mismatch correction of molecular heteroduplexes.

  6. Irigenin sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells.

    Science.gov (United States)

    Xu, Ying; Gao, Cheng-Cheng; Pan, Zhen-Guo; Zhou, Chuan-Wen

    2018-02-12

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promising value for cancer therapy due to its capacity to induce apoptosis in cancer cells. Nevertheless, TRAIL therapy is greatly hampered by its resistance. Irigenin (Iri), isoflavonoids, can be isolated from the rhizome of Belamcanda chinensis, and has been shown anti-cancer properties. In this study, we explored if Iri could enhance TRAIL-regulated apoptosis in TRAIL resistant gastric cancer cells. Iri significantly potentiated TRAIL-triggered cytotoxicity. Iri alone and TRAIL alone showed no effective role in apoptosis induction, whereas combined treatment with Iri and TRAIL markedly induced apoptosis in cancer cells, as evidenced by the up-regulation of cleaved Caspase-8/-9/-3 and PARP. Additionally, the sensitization to TRAIL was along with the enhancement of pro-apoptotic proteins, including FAS-associated protein with death domain (FADD), death receptor 5 (DR5) and Bax. And suppressing FADD, DR5 and Bax by si RNA significantly reduced the apoptosis and enhanced the cell viability induced by the co-application of Iri and TRAIL. Moreover, the sensitization to TRAIL was accompanied by the decrease of Cellular-FLICE inhibitory protein (c-FLIP), Bcl-2 and Survivin. Additionally, Iri could sensitize TRAIL to produce reactive oxygen species (ROS). Pre-treatment of N-acetyl-cysteine (NAC), ROS scavenger, attenuated Iri plus TRAIL-induced apoptosis and improved cell viability. Finally, combination of Iri and TRAIL inhibited tumor growth in the xenograft model. Collectively, our present study gave new insights into the effects of Iri on potentiating TRAIL-sensitivity, and suggested that Iri could be a potential candidate for sensitizer of TRAIL-resistant cancer cell treatment. Copyright © 2018. Published by Elsevier Inc.

  7. GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines.

    Science.gov (United States)

    Panka, David J; Cho, Daniel C; Atkins, Michael B; Mier, James W

    2008-01-11

    Glycogen synthase kinase-3beta (GSK-3beta) can participate in the induction of apoptosis or, alternatively, provide a survival signal that minimizes cellular injury. We previously demonstrated that the multikinase inhibitor sorafenib induces apoptosis in melanoma cell lines. In this report, we show that sorafenib activates GSK-3beta in multiple subcellular compartments and that this activation undermines the lethality of the drug. Pharmacologic inhibition and/or down-modulation of the kinase enhances sorafenib-induced apoptosis as determined by propidium iodide staining and by assessing the mitochondrial release of apoptosis-inducing factor and Smac/DIABLO. Conversely, the forced expression of a constitutively active form of the enzyme (GSK-3beta(S9A)) protects the cells from the apoptotic effects of the drug. This protective effect is associated with a marked increase in basal levels of Bcl-2, Bcl-x(L), and survivin and a diminution in the degree to which these anti-apoptotic proteins are down-modulated by sorafenib exposure. Sorafenib down-modulates the pro-apoptotic Bcl-2 family member Noxa in cells with high constitutive GSK-3beta activity. Pharmacologic inhibition of GSK-3beta prevents the disappearance of Noxa induced by sorafenib and enhances the down-modulation of Mcl-1. Down-modulation of Noxa largely eliminates the enhancing effect of GSK-3 inhibition on sorafenib-induced apoptosis. These data provide a strong rationale for the use of GSK-3beta inhibitors as adjuncts to sorafenib treatment and suggest that preservation of Noxa may contribute to their efficacy.

  8. Hypoxia-induced mitogenic factor enhances angiogenesis by promoting proliferation and migration of endothelial cells

    International Nuclear Information System (INIS)

    Tong Qiangsong; Zheng Liduan; Li Bo; Wang Danming; Huang Chuanshu; Matuschak, George M.; Li Dechun

    2006-01-01

    Our previous studies have indicated that hypoxia-induced mitogenic factor (HIMF) has angiogenic properties in an in vivo matrigel plug model and HIMF upregulates expression of vascular endothelial growth factor (VEGF) in mouse lungs and cultured lung epithelial cells. However, whether HIMF exerts angiogenic effects through modulating endothelial cell function remains unknown. In this study, mouse aortic rings cultured with recombinant HIMF protein resulted in enhanced vascular sprouting and increased endothelial cell spreading as confirmed by Dil-Ac-LDL uptake, von Willebrand factor and CD31 staining. In cultured mouse endothelial cell line SVEC 4-10, HIMF dose-dependently enhanced cell proliferation, in vitro migration and tubulogenesis, which was not attenuated by SU1498, a VEGFR2/Flk-1 receptor tyrosine kinase inhibitor. Moreover, HIMF stimulation resulted in phosphorylation of Akt, p38 and ERK1/2 kinases in SVEC 4-10 cells. Treatment of mouse aortic rings and SVEC 4-10 cells with LY294002, but not SB203580, PD098059 or U0126, abolished HIMF-induced vascular sprouting and angiogenic responses. In addition, transfection of a dominant-negative mutant of phosphatidylinositol 3-kinase (PI-3K), Δp85, blocked HIMF-induced phosphorylation of Akt, endothelial activation and tubulogenesis. These results indicate that HIMF enhances angiogenesis by promoting proliferation and migration of endothelial cells via activation of the PI-3K/Akt pathways

  9. CAMKII activation is not required for maintenance of learning-induced enhancement of neuronal excitability.

    Directory of Open Access Journals (Sweden)

    Ori Liraz

    Full Text Available Pyramidal neurons in the piriform cortex from olfactory-discrimination trained rats show enhanced intrinsic neuronal excitability that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the post-burst after-hyperpolarization (AHP which is generated by repetitive spike firing. AHP reduction is due to decreased conductance of a calcium-dependent potassium current, the sI(AHP. We have previously shown that learning-induced AHP reduction is maintained by persistent protein kinase C (PKC and extracellular regulated kinase (ERK activation. However, the molecular machinery underlying this long-lasting modulation of intrinsic excitability is yet to be fully described. Here we examine whether the CaMKII, which is known to be crucial in learning, memory and synaptic plasticity processes, is instrumental for the maintenance of learning-induced AHP reduction. KN93, that selectively blocks CaMKII autophosphorylation at Thr286, reduced the AHP in neurons from trained and control rat to the same extent. Consequently, the differences in AHP amplitude and neuronal adaptation between neurons from trained rats and controls remained. Accordingly, the level of activated CaMKII was similar in pirifrom cortex samples taken form trained and control rats. Our data show that although CaMKII modulates the amplitude of AHP of pyramidal neurons in the piriform cortex, its activation is not required for maintaining learning-induced enhancement of neuronal excitability.

  10. Platelet-collagen adhesion enhances platelet aggregation induced by binding of VWF to platelets

    International Nuclear Information System (INIS)

    Laduca, F.M.; Bell, W.R.; Bettigole, R.E.

    1987-01-01

    Ristocetin-induced platelet aggregation (RIPA) was evaluated in the presence of platelet-collagen adhesion. RIPA of normal donor platelet-rich plasma (PRP) demonstrated a primary wave of aggregation mediated by the binding of von Willebrand factor (VWF) to platelets and a secondary aggregation wave, due to a platelet-release reaction, initiated by VWF-platelet binding and inhibitable by acetylsalicylic acid (ASA). An enhanced RIPA was observed in PRP samples to which collagen had been previously added. These subthreshold concentrations of collagen, which by themselves were insufficient to induce aggregation, caused measurable platelet-collagen adhesion. Subthreshold collagen did not cause microplatelet aggregation, platelet release of [ 3 H]serotonin, or alter the dose-responsive binding of 125 I-labeled VWF to platelets, which occurred with increasing ristocetin concentrations. However, ASA inhibition of the platelet release reaction prevented collagen-enhanced RIPA. These results demonstrate that platelet-collagen adhesion altered the platelet-release reaction induced by the binding of VWF to platelets causing a platelet-release reaction at a level of VWF-platelet binding not normally initiating a secondary aggregation. These findings suggest that platelet-collagen adhesion enhances platelet function mediated by VWF

  11. Enhanced protection against Clonorchis sinensis induced by co-infection with Trichinella spiralis in rats.

    Science.gov (United States)

    Chu, K-B; Kim, S-S; Lee, S-H; Lee, H-S; Joo, K-H; Lee, J-H; Lee, Y-S; Zheng, S; Quan, F-S

    2014-10-01

    Although co-infection with multiple parasites is a frequent occurrence, changes in the humoral immune response against a pre-existing parasite induced as a result of a subsequent parasitic infection remain undetermined. Here, we utilized enzyme-linked immunosorbent assay (ELISA) to investigate antibody responses, cytokine production and enhanced resistance in Clonorchis sinensis-infected rats (Sprague-Dawley) upon Trichinella spiralis infection. Higher levels of C. sinensis-specific IgG and IgA were elicited upon T. spiralis infection, and these levels remained higher than in rats infected with C. sinensis alone. Upon subsequent infection with T. spiralis, IgG antibodies against C. sinensis appeared to be rapidly boosted at day 3, and IgA antibodies were boosted at day 7. Challenge infection of C. sinensis-infected rats with T. spiralis induced substantial mucosal IgG and IgA responses in the liver and intestine and increases in antibody-secreting plasma cells in the spleen and bone marrow. Subsequent infection also appeared to confer effective control of liver C. sinensis loads, resulting in enhanced resistance. Memory B cells generated in response to C. sinensis infection were rapidly amplified into antibody-secreting cells upon T. spiralis infection. These results indicate that enhanced C. sinensis clearance induced by co-infection is associated with systemic and mucosal IgG and IgA responses. © 2014 John Wiley & Sons Ltd.

  12. PERSONALITY DOES NOT INFLUENCE EXERCISE-INDUCED MOOD ENHANCEMENT AMONG FEMALE EXERCISERS

    Directory of Open Access Journals (Sweden)

    Andrew M. Lane

    2005-09-01

    Full Text Available The present study investigated the influence of personality on exercise-induced mood changes. It was hypothesised that (a exercise would be associated with significant mood enhancement across all personality types, (b extroversion would be associated with positive mood and neuroticism with negative mood both pre- and post-exercise, and (c personality measures would interact with exercise-induced mood changes. Participants were 90 female exercisers (M = 25.8 yr, SD = 9.0 yr who completed the Eysenck Personality Inventory (EPI once and the Brunel Mood Scale (BRUMS before and after a 60-minute exercise session. Median splits were used to group participants into four personality types: stable introverts (n = 25, stable extroverts (n = 20, neurotic introverts (n = 26, and neurotic extroverts (n = 19. Repeated measures MANOVA showed significant mood enhancement following exercise across all personality types. Neuroticism was associated with negative mood scores pre- and post-exercise but the effect of extroversion on reported mood was relatively weak. There was no significant interaction effect between exercise-induced mood enhancement and personality. In conclusion, findings lend support to the notion that exercise is associated with improved mood. However, findings show that personality did not influence this effect, although neuroticism was associated with negative mood

  13. Laser-induced electron--ion recombination used to study enhanced spontaneous recombination during electron cooling

    International Nuclear Information System (INIS)

    Schramm, U.; Wolf, A.; Schuess ler, T.; Habs, D.; Schwalm, D.; Uwira, O.; Linkemann, J.; Mueller, A.

    1997-01-01

    Spontaneous recombination of highly charged ions with free electrons in merged velocity matched electron and ion beams has been observed in earlier experiments to occur at rates significantly higher than predicted by theoretical estimates. To study this enhanced spontaneous recombination, laser induced recombination spectra were measured both in velocity matched beams and in beams with well defined relative velocities, corresponding to relative electron-ion detuning energies ranging from 1 meV up to 6.5 meV where the spontaneous recombination enhancement was found to be strongly reduced. Based on a comparison with simplified calculations, the development of the recombination spectra for decreasing detuning energies indicates additional contributions at matched velocities which could be related to the energy distribution of electrons causing the spontaneous recombination rate enhancement

  14. Muscle damage and repeated bout effect induced by enhanced eccentric squats.

    Science.gov (United States)

    Coratella, Giuseppe; Chemello, Alessandro; Schena, Federico

    2016-12-01

    Muscle damage and repeated bout effect have been studied after pure eccentric-only exercise. The aim of this study was to evaluate muscle damage and repeated bout effect induced by enhanced eccentric squat exercise using flywheel device. Thirteen healthy males volunteered for this study. Creatine kinase blood activity (CK), quadriceps isometric peak torque and muscle soreness were used as markers of muscle damage. The dependent parameters were measured at baseline, immediately after and each day up to 96 hours after the exercise session. The intervention consisted of 100 repetitions of enhanced eccentric squat exercise using flywheel device. The same protocol was repeated after 4 weeks. After the first bout, CK and muscle soreness were significantly greater (P0.05), while isometric peak torque and muscle soreness returned to values similar to baseline after respectively 48 and 72 hours. All muscle damage markers were significantly lower after second compared to first bout. The enhanced eccentric exercise induced symptoms of muscle damage up to 96 hours. However, it provided muscle protection after the second bout, performed four weeks later. Although it was not eccentric-only exercise, the enhancement of eccentric phase provided muscle protection.

  15. 8-aminoadenosine enhances radiation-induced cell death in human lung carcinoma A549 cells

    International Nuclear Information System (INIS)

    Meike, Shunsuke; Yamamori, Tohru; Yasui, Hironobu; Eitaki, Masato; Inanami, Osamu; Matsuda, Akira

    2011-01-01

    The combination of a chemotherapeutic agent and radiation is widely applied to enhance cell death in solid tumor cells in cancer treatment. The purine analogue 8-aminoadenosine (8-NH 2 -Ado) is known to be a transcription inhibitor that has proved very effective in multiple myeloma cell lines and primary indolent leukemia cells. In this report, to examine whether 8-NH 2 -Ado had the ability to enhance the radiation-induced cell killing in solid tumor cells, human lung adenocarcinoma A549 cells were irradiated in the presence and absence of 8-NH 2 -Ado. 8-NH 2 -Ado significantly increased reproductive cell death and apoptosis in A549 cells exposed to X-rays. When peptide inhibitors against caspase-3, -8, and -9 were utilized to evaluate the involvement of caspases, all inhibitors suppressed the enhancement of radiation-induced apoptosis, suggesting that not only mitochondria-mediated apoptotic signal transduction pathways but also death receptor-mediated pathways were involved in this enhancement of apoptosis. In addition, in the cells exposed to the treatment combining X-irradiation and 8-NH 2 -Ado, reduction of the intracellular ATP concentration was essential for survival, and down-regulation of the expression of antiapoptotic proteins such as survivin and X-linked inhibitor of apoptosis protein (XIAP) was observed. These results indicate that 8-NH 2 -Ado has potential not only as an anti-tumor drug for leukemia and lymphoma but also as a radiosensitizing agent for solid tumors. (author)

  16. Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis

    International Nuclear Information System (INIS)

    Bai, Xupeng; Hong, Weipeng; Cai, Peiheng; Chen, Yibei; Xu, Chuncao; Cao, Di; Yu, Weibang; Zhao, Zhongxiang; Huang, Min; Jin, Jing

    2017-01-01

    Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood. Here we demonstrated the involvement of fatty acid uptake and lipogenesis in VPA-induced hepatic steatosis in vitro and in vivo by using quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, fatty acid uptake assays, Nile Red staining assays, and Oil Red O staining assays. Specifically, we found that the expression of cluster of differentiation 36 (CD36), an important fatty acid transport, and diacylglycerol acyltransferase 2 (DGAT2) were significantly up-regulated in HepG2 cells and livers of C57B/6J mice after treatment with VPA. Furthermore, VPA treatment remarkably enhanced the efficiency of fatty acid uptake mediated by CD36, while this effect was abolished by the interference with CD36-specific siRNA. Also, VPA treatment significantly increased DGAT2 expression as a result of the inhibition of mitogen-activated protein kinase kinase (MEK) – extracellular regulated kinase (ERK) pathway; however, DGAT2 knockdown significantly alleviated VPA-induced intracellular lipid accumulation. Additionally, we also found that sterol regulatory element binding protein-1c (SREBP-1c)-mediated fatty acid synthesis may be not involved in VPA-induced hepatic steatosis. Overall, VPA-triggered over-regulation of CD36 and DGAT2 could be helpful for a better understanding of the mechanisms underlying VPA-induced hepatic steatosis and may offer novel therapeutic strategies to combat VPA-induced hepatotoxicity. - Highlights: • VPA induced hepatic steatosis and modulated genes associated with lipid metabolism. • CD36-mediated fatty acid uptake contributed to VPA-induced lipid accumulation. • PA increased the hepatic

  17. Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xupeng; Hong, Weipeng; Cai, Peiheng; Chen, Yibei; Xu, Chuncao [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou (China); Cao, Di [School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou (China); Yu, Weibang [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou (China); Zhao, Zhongxiang [School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou (China); Huang, Min [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou (China); Jin, Jing, E-mail: jinjing@mail.sysu.edu.cn [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou (China)

    2017-06-01

    Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood. Here we demonstrated the involvement of fatty acid uptake and lipogenesis in VPA-induced hepatic steatosis in vitro and in vivo by using quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, fatty acid uptake assays, Nile Red staining assays, and Oil Red O staining assays. Specifically, we found that the expression of cluster of differentiation 36 (CD36), an important fatty acid transport, and diacylglycerol acyltransferase 2 (DGAT2) were significantly up-regulated in HepG2 cells and livers of C57B/6J mice after treatment with VPA. Furthermore, VPA treatment remarkably enhanced the efficiency of fatty acid uptake mediated by CD36, while this effect was abolished by the interference with CD36-specific siRNA. Also, VPA treatment significantly increased DGAT2 expression as a result of the inhibition of mitogen-activated protein kinase kinase (MEK) – extracellular regulated kinase (ERK) pathway; however, DGAT2 knockdown significantly alleviated VPA-induced intracellular lipid accumulation. Additionally, we also found that sterol regulatory element binding protein-1c (SREBP-1c)-mediated fatty acid synthesis may be not involved in VPA-induced hepatic steatosis. Overall, VPA-triggered over-regulation of CD36 and DGAT2 could be helpful for a better understanding of the mechanisms underlying VPA-induced hepatic steatosis and may offer novel therapeutic strategies to combat VPA-induced hepatotoxicity. - Highlights: • VPA induced hepatic steatosis and modulated genes associated with lipid metabolism. • CD36-mediated fatty acid uptake contributed to VPA-induced lipid accumulation. • PA increased the hepatic

  18. Intracellular Methamphetamine Prevents the Dopamine-induced Enhancement of Neuronal Firing*

    Science.gov (United States)

    Saha, Kaustuv; Sambo, Danielle; Richardson, Ben D.; Lin, Landon M.; Butler, Brittany; Villarroel, Laura; Khoshbouei, Habibeh

    2014-01-01

    The dysregulation of the dopaminergic system is implicated in multiple neurological and neuropsychiatric disorders such as Parkinson disease and drug addiction. The primary target of psychostimulants such as amphetamine and methamphetamine is the dopamine transporter (DAT), the major regulator of extracellular dopamine levels in the brain. However, the behavioral and neurophysiological correlates of methamphetamine and amphetamine administration are unique from one another, thereby suggesting these two compounds impact dopaminergic neurotransmission differentially. We further examined the unique mechanisms by which amphetamine and methamphetamine regulate DAT function and dopamine neurotransmission; in the present study we examined the impact of extracellular and intracellular amphetamine and methamphetamine on the spontaneous firing of cultured midbrain dopaminergic neurons and isolated DAT-mediated current. In dopaminergic neurons the spontaneous firing rate was enhanced by extracellular application of amphetamine > dopamine > methamphetamine and was DAT-dependent. Amphetamine > methamphetamine similarly enhanced DAT-mediated inward current, which was sensitive to isosmotic substitution of Na+ or Cl− ion. Although isosmotic substitution of extracellular Na+ ions blocked amphetamine and methamphetamine-induced DAT-mediated inward current similarly, the removal of extracellular Cl− ions preferentially blocked amphetamine-induced inward current. The intracellular application of methamphetamine, but not amphetamine, prevented the dopamine-induced increase in the spontaneous firing of dopaminergic neurons and the corresponding DAT-mediated inward current. The results reveal a new mechanism for methamphetamine-induced dysregulation of dopaminergic neurons. PMID:24962577

  19. Ablative fractional laser enhances MAL-induced PpIX accumulation

    DEFF Research Database (Denmark)

    Haak, C S; Christiansen, K; Erlendsson, Andrés M

    2016-01-01

    BACKGROUND AND OBJECTIVES: Pretreatment of skin with ablative fractional laser enhances accumulation of topical provided photosensitizer, but essential information is lacking on the interaction between laser channel densities and pharmacokinetics. Hence our objectives were to investigate how...... (range 46-133min) induced fluorescence levels similar to curettage and 180min incubation. Furthermore, MAL 80 and 160mg/g induced similar fluorescence intensities in skin exposed to laser densities of 1, 2 and 5% (p>0.0537, 30-180min). CONCLUSION: MAL-induced protoporphyrin accumulation is augmented...... protoporphyrin accumulation was affected by laser densities, incubation time and drug concentration. METHODS: We conducted the study on the back of healthy male volunteers (n=11). Test areas were pretreated with 2940nm ablative fractional Er:YAG laser, 11.2mJ per laser channel using densities of 1, 2, 5, 10...

  20. Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Costello Joseph F

    2008-07-01

    Full Text Available Abstract Background Hypertonic saline (HTS reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury. Methods Adult male Sprague Dawley rats were used in all experiments. Series 1 examined the potential for HTS to reduce the severity of evolving oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12 or hypertonic saline (HTS, n = 12, and the extent of lung injury assessed after 6 hours. Series 2 examined the potential for HTS to enhance the resolution of oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6 or hypertonic saline (HTS, n = 6, and the extent of lung injury assessed after 6 hours. Results In Series I, HTS significantly reduced bronchoalveolar lavage (BAL neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 103 cells.ml-1]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, in Series 2, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 103 cells.ml-1], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml-1]. Conclusion These findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.

  1. Induced seismicity hazard and risk by enhanced geothermal systems: an expert elicitation approach

    Science.gov (United States)

    Trutnevyte, Evelina; Azevedo, Inês L.

    2018-03-01

    Induced seismicity is a concern for multiple geoenergy applications, including low-carbon enhanced geothermal systems (EGS). We present the results of an international expert elicitation (n = 14) on EGS induced seismicity hazard and risk. Using a hypothetical scenario of an EGS plant and its geological context, we show that expert best-guess estimates of annualized exceedance probabilities of an M ≥ 3 event range from 0.2%-95% during reservoir stimulation and 0.2%-100% during operation. Best-guess annualized exceedance probabilities of M ≥ 5 event span from 0.002%-2% during stimulation and 0.003%-3% during operation. Assuming that tectonic M7 events could occur, some experts do not exclude induced (triggered) events of up to M7 too. If an induced M = 3 event happens at 5 km depth beneath a town with 10 000 inhabitants, most experts estimate a 50% probability that the loss is contained within 500 000 USD without any injuries or fatalities. In the case of an induced M = 5 event, there is 50% chance that the loss is below 50 million USD with the most-likely outcome of 50 injuries and one fatality or none. As we observe a vast diversity in quantitative expert judgements and underlying mental models, we conclude with implications for induced seismicity risk governance. That is, we suggest documenting individual expert judgements in induced seismicity elicitations before proceeding to consensual judgements, to convene larger expert panels in order not to cherry-pick the experts, and to aim for multi-organization multi-model assessments of EGS induced seismicity hazard and risk.

  2. Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production

    International Nuclear Information System (INIS)

    Kakita, Hiroki; Aoyama, Mineyoshi; Nagaya, Yoshiaki; Asai, Hayato; Hussein, Mohamed Hamed; Suzuki, Mieko; Kato, Shin; Saitoh, Shinji; Asai, Kiyofumi

    2013-01-01

    Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1β, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N G -monomethyl-L-arginine (L-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF. - Highlights: ► Influenza-associated encephalopathy (IAE) is associated with a high mortality rate. ► Hyperimmunization in the brain is believed to be responsible for IAE

  3. Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production

    Energy Technology Data Exchange (ETDEWEB)

    Kakita, Hiroki [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Aoyama, Mineyoshi, E-mail: ao.mine@med.nagoya-cu.ac.jp [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Nagaya, Yoshiaki; Asai, Hayato [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Hussein, Mohamed Hamed [Neonatal Intensive Care Unit, Pediatric Hospital, Cairo University, Cairo 11559 (Egypt); Maternal and Child Health Department, VACSERA, 51 Wizaret El-Zeraa-Agouza, Giza 22311 (Egypt); Suzuki, Mieko [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Kato, Shin [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Saitoh, Shinji [Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2013-04-15

    Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1β, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N{sup G}-monomethyl-L-arginine (L-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF. - Highlights: ► Influenza-associated encephalopathy (IAE) is associated with a high mortality rate. ► Hyperimmunization in the brain is believed to be responsible for

  4. Cyclic mechanical stretch enhances BMP9-induced osteogenic differentiation of mesenchymal stem cells.

    Science.gov (United States)

    Song, Yang; Tang, Yinhong; Song, Jinlin; Lei, Mingxing; Liang, Panpan; Fu, Tiwei; Su, Xudong; Zhou, Pengfei; Yang, Li; Huang, Enyi

    2018-04-01

    The purpose of this study was to investigate whether mechanical stretch can enhance the bone morphogenetic protein 9 (BMP9)-induced osteogenic differentiation in MSCs. Recombinant adenoviruses were used to overexpress the BMP9 in C3H10T1/2 MSCs. Cells were seeded onto six-well BioFlex collagen I-coated plates and subjected to cyclic mechanical stretch [6% elongation at 60 cycles/minute (1 Hz)] in a Flexercell FX-4000 strain unit for up to 12 hours. Immunostaining and confocal microscope were used to detect cytoskeleton organization. Cell cycle progression was checked by flow cytometry. Alkaline phosphatase activity was measured with a Chemiluminescence Assay Kit and was quantified with a histochemical staining assay. Matrix mineralization was examined by Alizarin Red S Staining. Mechanical stretch induces cytoskeleton reorganization and inhibits cell proliferation by preventing cells entry into S phase of the cell cycle. Although mechanical stretch alone does not induce the osteogenic differentiation of C3H10T1/2 MSCs, co-stimulation with mechanical stretch and BMP9 enhances alkaline phosphatase activity. The expression of key lineage-specific regulators (e.g., osteocalcin (OCN), SRY-related HMG-box 9, and runt-related transcription factor 2) is also increased after the co-stimulation, compared to the mechanical stretch stimulation along. Furthermore, mechanical stretch augments the BMP9-mediated bone matrix mineralization of C3H10T1/2 MSCs. Our results suggest that mechanical stretch enhances BMP9-induced osteoblastic lineage specification in C3H10T1/2 MSCs.

  5. Enhanced tolerance to stretch-induced performance degradation of stretchable MnO2-based supercapacitors.

    Science.gov (United States)

    Huang, Yan; Huang, Yang; Meng, Wenjun; Zhu, Minshen; Xue, Hongtao; Lee, Chun-Sing; Zhi, Chunyi

    2015-02-04

    The performance of many stretchable electronics, such as energy storage devices and strain sensors, is highly limited by the structural breakdown arising from the stretch imposed. In this article, we focus on a detailed study on materials matching between functional materials and their conductive substrate, as well as enhancement of the tolerance to stretch-induced performance degradation of stretchable supercapacitors, which are essential for the design of a stretchable device. It is revealed that, being widely utilized as the electrode material of the stretchable supercapacitor, metal oxides such as MnO2 nanosheets have serious strain-induced performance degradation due to their rigid structure. In comparison, with conducting polymers like a polypyrrole (PPy) film as the electrochemically active material, the performance of stretchable supercapacitors can be well preserved under strain. Therefore, a smart design is to combine PPy with MnO2 nanosheets to achieve enhanced tolerance to strain-induced performance degradation of MnO2-based supercapacitors, which is realized by fabricating an electrode of PPy-penetrated MnO2 nanosheets. The composite electrodes exhibit a remarkable enhanced tolerance to strain-induced performance degradation with well-preserved performance over 93% under strain. The detailed morphology and electrochemical impedance variations are investigated for the mechanism analyses. Our work presents a systematic investigation on the selection and matching of electrode materials for stretchable supercapacitors to achieve high performance and great tolerance to strain, which may guide the selection of functional materials and their substrate materials for the next-generation of stretchable electronics.

  6. Chronic Enhancement of Serotonin Facilitates Excitatory Transcranial Direct Current Stimulation-Induced Neuroplasticity.

    Science.gov (United States)

    Kuo, Hsiao-I; Paulus, Walter; Batsikadze, Giorgi; Jamil, Asif; Kuo, Min-Fang; Nitsche, Michael A

    2016-04-01

    Serotonin affects memory formation via modulating long-term potentiation (LTP) and depression (LTD). Accordingly, acute selective serotonin reuptake inhibitor (SSRI) administration enhanced LTP-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. However, it usually takes some time for SSRI to reduce clinical symptoms such as anxiety, negative mood, and related symptoms of depression and anxiety disorders. This might be related to an at least partially different effect of chronic serotonergic enhancement on plasticity, as compared with single-dose medication. Here we explored the impact of chronic application of the SSRI citalopram (CIT) on plasticity induced by tDCS in healthy humans in a partially double-blinded, placebo (PLC)-controlled, randomized crossover study. Furthermore, we explored the dependency of plasticity induction from the glutamatergic system via N-methyl-D-aspartate receptor antagonism. Twelve healthy subjects received PLC medication, combined with anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took CIT (20 mg/day) consecutively for 35 days. During this period, four additional interventions were performed (CIT and PLC medication with anodal/cathodal tDCS, CIT and dextromethorphan (150 mg) with anodal/cathodal tDCS). Plasticity was monitored by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic application of CIT increased and prolonged the LTP-like plasticity induced by anodal tDCS for over 24 h, and converted cathodal tDCS-induced LTD-like plasticity into facilitation. These effects were abolished by dextromethorphan. Chronic serotonergic enhancement results in a strengthening of LTP-like glutamatergic plasticity, which might partially explain the therapeutic impact of SSRIs in depression and other neuropsychiatric diseases.

  7. Transactivation of bad by vorinostat-induced acetylated p53 enhances doxorubicin-induced cytotoxicity in cervical cancer cells.

    Science.gov (United States)

    Lee, Sook-Jeong; Hwang, Sung-Ook; Noh, Eun Joo; Kim, Dong-Uk; Nam, Miyoung; Kim, Jong Hyeok; Nam, Joo Hyun; Hoe, Kwang-Lae

    2014-02-14

    Vorinostat (VOR) has been reported to enhance the cytotoxic effects of doxorubicin (DOX) with fewer side effects because of the lower DOX dosage in breast cancer cells. In this study, we investigated the novel mechanism underlying the synergistic cytotoxic effects of VOR and DOX co-treatment in cervical cancer cells HeLa, CaSki and SiHa cells. Co-treatment with VOR and DOX at marginal doses led to the induction of apoptosis through caspase-3 activation, poly (ADP-ribose) polymerase cleavage and DNA micronuclei. Notably, the synergistic growth inhibition induced by the co-treatment was attributed to the upregulation of the pro-apoptotic protein Bad, as the silencing of Bad expression using small interfering RNA (siRNA) abolished the phenomenon. As siRNA against p53 did not result in an increase in acetylated p53 and the consequent upregulation of Bad, the observed Bad upregulation was mediated by acetylated p53. Moreover, a chromatin immunoprecipitation analysis showed that the co-treatment of HeLa cells with VOR and DOX increased the recruitment of acetylated p53 to the bad promoter, with consequent bad transactivation. Conversely, C33A cervical cancer cells containing mutant p53 co-treated with VOR and DOX did not exhibit Bad upregulation, acetylated p53 induction or consequent synergistic growth inhibition. Together, the synergistic growth inhibition of cervical cancer cell lines induced by co-treatment with VOR and DOX can be attributed to the upregulation of Bad, which is induced by acetylated p53. These results show for the first time that the acetylation of p53, rather than histones, is a mechanism for the synergistic growth inhibition induced by VOR and DOX co-treatments.

  8. Inducible protective processes in animal systems XV: Hyperthermia enhances the Ethyl methanesulfonate induced adaptive response in meiotic cells of grasshopper Poecilocerus pictus

    Directory of Open Access Journals (Sweden)

    R. Venu

    2016-04-01

    Conclusion: There is a protection against EMS induced anomalies by hyperthermia in in vivo P. pictus. As far as our knowledge is concerned, this is the first report to demonstrate that hyperthermia enhances the EMS induced adaptive response in in vivo meiotic cells.

  9. Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells.

    Science.gov (United States)

    Zeng, Wei; Xiao, Tao; Cai, Anlie; Cai, Weiliang; Liu, Huanhuan; Liu, Jingling; Li, Jie; Tan, Miduo; Xie, Li; Liu, Ying; Yang, Xiangcheng; Long, Yi

    2017-01-01

    Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy. We show that salidroside induced significant apoptosis in the human chondrosarcoma cell line SW1353. In addition, we demonstrate that salidroside-induced an autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II and downregulation of P62. Moreover, pharmacological or genetic blocking of autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced TFEB (Ser142) dephosphorylation, subsequently to activated TFEB nuclear translocation and increase of TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes. Importantly, we found that salidroside triggered the generation of ROS in SW1353 cells. Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB-dependent autophagy. These data demonstrate that salidroside increased TFEB-dependent autophagy by activating ROS signaling pathways in human chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent autophagy to enhance the activity of salidroside warrants further attention in treatment of human chondrosarcoma cells. © 2017 The Author(s). Published by S. Karger AG, Basel.

  10. l-Serine Enhances Light-Induced Circadian Phase Resetting in Mice and Humans.

    Science.gov (United States)

    Yasuo, Shinobu; Iwamoto, Ayaka; Lee, Sang-Il; Ochiai, Shotaro; Hitachi, Rina; Shibata, Satomi; Uotsu, Nobuo; Tarumizu, Chie; Matsuoka, Sayuri; Furuse, Mitsuhiro; Higuchi, Shigekazu

    2017-12-01

    Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 l-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before l-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of l-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: l-Serine administration enhanced light-induced phase shifts in mice (1.86-fold; P light-dark cycle by 6 h, l-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, l-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-l-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances. © 2017 American Society for Nutrition.

  11. Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis.

    Science.gov (United States)

    Bai, Xupeng; Hong, Weipeng; Cai, Peiheng; Chen, Yibei; Xu, Chuncao; Cao, Di; Yu, Weibang; Zhao, Zhongxiang; Huang, Min; Jin, Jing

    2017-06-01

    Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood. Here we demonstrated the involvement of fatty acid uptake and lipogenesis in VPA-induced hepatic steatosis in vitro and in vivo by using quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, fatty acid uptake assays, Nile Red staining assays, and Oil Red O staining assays. Specifically, we found that the expression of cluster of differentiation 36 (CD36), an important fatty acid transport, and diacylglycerol acyltransferase 2 (DGAT2) were significantly up-regulated in HepG2 cells and livers of C57B/6J mice after treatment with VPA. Furthermore, VPA treatment remarkably enhanced the efficiency of fatty acid uptake mediated by CD36, while this effect was abolished by the interference with CD36-specific siRNA. Also, VPA treatment significantly increased DGAT2 expression as a result of the inhibition of mitogen-activated protein kinase kinase (MEK) - extracellular regulated kinase (ERK) pathway; however, DGAT2 knockdown significantly alleviated VPA-induced intracellular lipid accumulation. Additionally, we also found that sterol regulatory element binding protein-1c (SREBP-1c)-mediated fatty acid synthesis may be not involved in VPA-induced hepatic steatosis. Overall, VPA-triggered over-regulation of CD36 and DGAT2 could be helpful for a better understanding of the mechanisms underlying VPA-induced hepatic steatosis and may offer novel therapeutic strategies to combat VPA-induced hepatotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 28-Homobrassinolide mitigates boron induced toxicity through enhanced antioxidant system in Vigna radiata plants.

    Science.gov (United States)

    Yusuf, Mohammad; Fariduddin, Qazi; Ahmad, Aqil

    2011-11-01

    The objective of this study was to establish relationship between boron induced oxidative stress and antioxidant system in Vigna radiata plants and also to investigate whether brassinosteroids will enhance the level of antioxidant system that could confer tolerance to the plants from the boron induced oxidative stress. The mung bean (V. radiata cv. T-44) plants were administered with 0.50, 1.0 and 2.0 mM boron at 6 d stage for 7 d along with nutrient solution. At 13 d stage, the seedlings were sprayed with deionized water (control) or 10(-8) M of 28-homobrassinolide and plants were harvested at 21 d stage to assess growth, leaf gas-exchange traits and biochemical parameters. The boron treatments diminished growth, water relations and photosynthetic attributes along with nitrate reductase and carbonic anhydrase activity in the concentration dependent manner whereas, it enhanced lipid peroxidation, electrolyte leakage, accumulation of H(2)O(2) as well as proline, and various antioxidant enzymes in the leaves of mung bean which were more pronounced at higher concentrations of boron. However, the follow-up application of 28-homobrassinolide to the boron stressed plants improved growth, water relations and photosynthesis and further enhanced the various antioxidant enzymes viz. catalase, peroxidase and superoxide dismutase and content of proline. The elevated level of antioxidant enzymes as well as proline could have conferred tolerance to the B-stressed plants resulting in improved growth, water relations and photosynthetic attributes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. 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.

  14. Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status.

    Science.gov (United States)

    Ajith, T A; Hema, U; Aswathy, M S

    2007-11-01

    A large number of xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents - proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3g/kg, p.o.) acute hepatotoxicity in rat. Aqueous extract of Z. officinale significantly protected the hepatotoxicity as evident from the activities of serum transaminase and alkaline phosphatase (ALP). Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and ALP activities were significantly (pHepatic lipid peroxidation was enhanced significantly (pofficinale (200 and 400mg/kg, p.o.) prior to acetaminophen significantly declines the activities of serum transaminases and ALP. Further the hepatic antioxidant status was enhanced in the Z. officinale plus acetaminophen treated group than the control group. The results of the present study concluded that the hepatoprotective effect of aqueous ethanol extract of Z. officinale against acetaminophen-induced acute toxicity is mediated either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity.

  15. Induced over voltage test on transformers using enhanced Z-source inverter based circuit

    Science.gov (United States)

    Peter, Geno; Sherine, Anli

    2017-09-01

    The normal life of a transformer is well above 25 years. The economical operation of the distribution system has its roots in the equipments being used. The economy being such, that it is financially advantageous to replace transformers with more than 15 years of service in the second perennial market. Testing of transformer is required, as its an indication of the extent to which a transformer can comply with the customers specified requirements and the respective standards (IEC 60076-3). In this paper, induced over voltage testing on transformers using enhanced Z source inverter is discussed. Power electronic circuits are now essential for a whole array of industrial electronic products. The bulky motor generator set, which is used to generate the required frequency to conduct the induced over voltage testing of transformers is nowadays replaced by static frequency converter. First conventional Z-source inverter, and second an enhanced Z source inverter is being used to generate the required voltage and frequency to test the transformer for induced over voltage test, and its characteristics is analysed.

  16. Tempo enhances heat-induced apoptosis by mitochondrial targeting of Bax

    International Nuclear Information System (INIS)

    Zhao, Q.-L.; Fujiwara, Y.; Kondo, T.

    2003-01-01

    A stable membrane-permeable nitroxide, Tempo, exerts an SOD-like antioxidant activity against ROS. Reportedly, Tempo inhibits ROS-induced thymocyte apoptosis, while 10 mM Tempo activates JNK1 to induce apoptosis in breast cancer cells. We have observed that nontoxic 5 mM Tempo enhances suboptimal hyperthermia (44 deg C/10 min)-induced apoptosis in U937 cells. Here we report the enhancing mechanism, focusing on activation and targeting of Bax to mitochondria and cytochrome c release. Methods: U937 cells were treated with either Tempo (5 mM, 37 deg C/10 min), heating (44 deg C/10 min), or Tempo-plus-heating, washed and incubated for various times up to 6 h, until assessing apoptosis, mitochondrial potential (ΔΨ>), and amount of superoxide by flow cytometry using Annexin V-FITC/PI, TMRM, and dihydroethidium, respectively. Bax, Bcl-2 and Bcl-XL, and cytochrome c were detected by western blotting, activated Bax was by immunoprecipitation, and ATP was by a luciferase assay. Bax targeting to and cytochrome c release from mitochorndria were also detected immunocytochemically under fluorescent microscopy. Results and Discussion: Treatment of U937 cells with 5 mM Tempo for 10 min at 37 deg C or suboptimal heating (44 deg C/ 10 min) alone did not induce apoptosis. The combined treatment with 5 mM Tempo and 44 deg C for 10 min dramatically induced ∼90% apoptosis in 6 h, as did the 44 deg C/30 min heating. During the enhanced apoptosis, cytochrome c release progressed. Although signals of Bcl-2, Bcl-XL and Bax in cell lysates were not altered, Bax was specifically activated and translocated to mitochondria after the combined treatment. Further, loss of ΔΨ>and decreases in superoxide and ATP progressed after the combined treatment, suggesting that the treatment may disturb mitochondrial electron transport. Thus, Tempo sensitizes the heat-induced apoptosis through (1) targeting of Bax to mitochondria and releasing cytochrome c, and (2) mitochondrial dysfunction

  17. Multiphase contrast-enhanced magnetic resonance imaging features of Bacillus Calmette-Guerin-induced granulomatous prostatitis in five patients

    Energy Technology Data Exchange (ETDEWEB)

    Kawada, Hiroshi; Kanematsu, Masayuki; Goshima, Satoshi; Kondo, Hiroshi; Watanabe, Haruo; Noda, Yoshifumi; Tanahashi, Yukichi; Kawai, Nobuyuki; Hoshi, Hiroaki [Gifu University Hospital, Gifu (Japan)

    2015-04-15

    To evaluate the multiphase contrast-enhanced magnetic resonance (MR) imaging features of Bacillus Calmette-Guerin (BCG)-induced granulomatous prostatitis (GP). Magnetic resonance images obtained from five patients with histopathologically proven BCG-induced GP were retrospectively analyzed for tumor location, size, signal intensity on T2-weighted images (T2WI) and diffusion-weighted images (DWI), apparent diffusion coefficient (ADC) value, and appearance on gadolinium-enhanced multiphase images. MR imaging findings were compared with histopathological findings. Bacillus Calmette-Guerin-induced GP (size range, 9-40 mm; mean, 21.2 mm) were identified in the peripheral zone in all patients. The T2WI showed lower signal intensity compared with the normal peripheral zone. The DWIs demonstrated high signal intensity and low ADC values (range, 0.44-0.68 x 10(-3) mm2/sec; mean, 0.56 x 10(-3) mm2/sec), which corresponded to GP. Gadolinium-enhanced multiphase MR imaging performed in five patients showed early and prolonged ring enhancement in all cases of GP. Granulomatous tissues with central caseation necrosis were identified histologically, which corresponded to ring enhancement and a central low intensity area on gadolinium-enhanced MR imaging. The findings on T2WI, DWI, and gadolinium-enhanced images became gradually obscured with time. Bacillus Calmette-Guerin-induced GP demonstrates early and prolonged ring enhancement on gadolinium-enhanced MR imaging which might be a key finding to differentiate it from prostate cancer.

  18. A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear.

    Science.gov (United States)

    Meyer, R M; Burgos-Robles, A; Liu, E; Correia, S S; Goosens, K A

    2014-12-01

    Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is no clear relationship between the levels of these hormones and stress-associated mental illnesses such as posttraumatic stress disorder (PTSD). Therefore, other hormones are likely to be involved in this effect of stress. Here we used a rodent model of PTSD in which rats repeatedly exposed to a stressor display heightened fear learning following auditory Pavlovian fear conditioning. Our results show that stress-related increases in circulating ghrelin, a peptide hormone, are necessary and sufficient for stress-associated vulnerability to exacerbated fear learning and these actions of ghrelin occur in the amygdala. Importantly, these actions are also independent of the classic HPA stress axis. Repeated systemic administration of a ghrelin receptor agonist enhanced fear memory but did not increase either corticotropin-releasing factor (CRF) or corticosterone. Repeated intraamygdala infusion of a ghrelin receptor agonist produced a similar enhancement of fear memory. Ghrelin receptor antagonism during repeated stress abolished stress-related enhancement of fear memory without blunting stress-induced corticosterone release. We also examined links between ghrelin and growth hormone (GH), a major downstream effector of the ghrelin receptor. GH protein was upregulated in the amygdala following chronic stress, and its release from amygdala neurons was enhanced by ghrelin receptor stimulation. Virus-mediated overexpression of GH in the amygdala was also sufficient to increase fear. Finally, virus-mediated overexpression of a GH receptor antagonist was sufficient to block the fear-enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin requires GH in the amygdala to exert fear-enhancing effects. These results suggest that ghrelin mediates a novel branch of the stress response and highlight a previously unrecognized role for ghrelin and

  19. SHI induced enhancement in green emission from nanocrystalline CdS thin films for photonic applications

    International Nuclear Information System (INIS)

    Kumar, Pragati; Saxena, Nupur; Chandra, Ramesh; Gao, Kun; Zhou, Shengqiang; Agarwal, Avinash; Singh, Fouran; Gupta, Vinay; Kanjilal, D.

    2014-01-01

    Intense green emission is reported from nanocrystalline CdS thin films grown by pulsed laser deposition. The effect of ion beam induced dense electronic excitation on luminescence property of CdS films is explored under irradiation using 70 MeV 58 Ni 6+ ions. It is found that swift heavy ion beam irradiation enhances the emission intensity by an order of 1 and broadens the emission range. This feature is extremely useful to enhance the performance of different photonic devices like light emitting diodes and lasers, as well as luminescence based sensors. To examine the role of energy relaxation process of swift heavy ions in creation/annihilation of different defect levels, multi-peaks are fitted in photoluminescence spectra using a Gaussian function. The variation of contribution of different emissions in green emission with ion fluence is studied. Origin of enhancement in green emission is supported by various characterization techniques like UV–visible absorption spectroscopy, glancing angle X-ray diffraction, micro-Raman spectroscopy and transmission electron microscopy. A possible mechanism of enhanced GE due to ion beam irradiation is proposed on the basis of existing models. -- Highlights: • Room temperature green luminescence nanocrystalline CdS thin films grown by pulsed laser deposition. • Enhanced green emission by means of swift heavy ion irradiation. • Multipeak fitting of photoluminescence spectra using a Gaussian function. • Variation of area contributed by different emissions in green emission is studied with respect to ion fluence. • Mechanism of enhanced green emission is discussed based on creation/annihilation of defects due to ion beam irradiation

  20. SHI induced enhancement in green emission from nanocrystalline CdS thin films for photonic applications

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Pragati, E-mail: pkumar.phy@gmail.com [Department of Physics, Bareilly College, Shahmat Ganj Road, Bareilly 243005, Uttar Pradesh (India); Saxena, Nupur [Inter University Accelerator Centre, Aruna Asaf Ali Marg, P.O. Box 10502, New Delhi 110067 (India); Chandra, Ramesh [Institute Instrumentation Centre, Indian Institute of Technology, Roorkee 247667 (India); Gao, Kun; Zhou, Shengqiang [Institute of Ion Beam Physics and Materials Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), P.O. Box 510119, 01314 Dresden (Germany); Agarwal, Avinash [Department of Physics, Bareilly College, Shahmat Ganj Road, Bareilly 243005, Uttar Pradesh (India); Singh, Fouran [Inter University Accelerator Centre, Aruna Asaf Ali Marg, P.O. Box 10502, New Delhi 110067 (India); Gupta, Vinay [Department of Physics and Astrophysics, Delhi University, Delhi 110007 (India); Kanjilal, D. [Inter University Accelerator Centre, Aruna Asaf Ali Marg, P.O. Box 10502, New Delhi 110067 (India)

    2014-03-15

    Intense green emission is reported from nanocrystalline CdS thin films grown by pulsed laser deposition. The effect of ion beam induced dense electronic excitation on luminescence property of CdS films is explored under irradiation using 70 MeV {sup 58}Ni{sup 6+} ions. It is found that swift heavy ion beam irradiation enhances the emission intensity by an order of 1 and broadens the emission range. This feature is extremely useful to enhance the performance of different photonic devices like light emitting diodes and lasers, as well as luminescence based sensors. To examine the role of energy relaxation process of swift heavy ions in creation/annihilation of different defect levels, multi-peaks are fitted in photoluminescence spectra using a Gaussian function. The variation of contribution of different emissions in green emission with ion fluence is studied. Origin of enhancement in green emission is supported by various characterization techniques like UV–visible absorption spectroscopy, glancing angle X-ray diffraction, micro-Raman spectroscopy and transmission electron microscopy. A possible mechanism of enhanced GE due to ion beam irradiation is proposed on the basis of existing models. -- Highlights: • Room temperature green luminescence nanocrystalline CdS thin films grown by pulsed laser deposition. • Enhanced green emission by means of swift heavy ion irradiation. • Multipeak fitting of photoluminescence spectra using a Gaussian function. • Variation of area contributed by different emissions in green emission is studied with respect to ion fluence. • Mechanism of enhanced green emission is discussed based on creation/annihilation of defects due to ion beam irradiation.

  1. Enhancing repair of radiation-induced strand breaks in cellular DNA as a radiotherapeutic potential

    International Nuclear Information System (INIS)

    Nair, C.K.K.

    2014-01-01

    Protection of mammalian organisms including man from deleterious effects of ionizing radiation is of paramount importance and development of effective approaches to combat radiation damages using non-toxic radioprotectors is of considerable interest for defence, nuclear industries, radiation accidents, space travels, etc., besides the protection of normal tissues during radiotherapy of tumours. Many synthetic as well as natural compounds have been investigated in the recent past for their efficacy to protect the biological systems from radiation induced damages. They include sulfhydryl compounds, antioxidants, plant extracts, immune-modulators, and other agents. However, the inherent toxicity of many of the synthetic agents at the effective radio-protective concentration warranted further search for safer and more effective radio-protectors. In this context, therapeutic radioprotectors which are effective on post irradiation administration are of special relevance. One of the property that can be applied while screening for such radiation protective therapeutics is their ability to enhance repair of radiation-induced lesions in cellular DNA in terms of cellular repair index based on the parameters of the DNA following comet assay. Post irradiation administration of some natural and synthetic agents have shown their potential to enhance repair of radiation-induced strand breaks in cellular DNA in mice. These include phytoceuticals such as gallic acid, sesamol etc., extracts of medicinal plants such as Andrographis panniculata, and a few synthetic compounds such as tocopherol-mono-glucoside. The talk will give an overview of the work on DNA repair enhancement by a few natural and synthetic agents. (author)

  2. Vectorization of biomacromolecules into cells using extracellular vesicles with enhanced internalization induced by macropinocytosis.

    Science.gov (United States)

    Nakase, Ikuhiko; Noguchi, Kosuke; Fujii, Ikuo; Futaki, Shiroh

    2016-10-17

    Extracellular vesicles (EVs, exosomes) are approximately 30- to 200-nm-long vesicles that have received increased attention due to their role in cell-to-cell communication. Although EVs are highly anticipated to be a next-generation intracellular delivery tool because of their pharmaceutical advantages, including non-immunogenicity, their cellular uptake efficacy is low because of the repulsion of EVs and negatively charged cell membranes and size limitations in endocytosis. Here, we demonstrate a methodology for achieving enhanced cellular EV uptake using arginine-rich cell-penetrating peptides (CPPs) to induce active macropinocytosis. The induction of macropinocytosis via a simple modification to the exosomal membrane using stearylated octaarginine, which is a representative CPP, significantly enhanced the cellular EV uptake efficacy. Consequently, effective EV-based intracellular delivery of an artificially encapsulated ribosome-inactivating protein, saporin, in EVs was attained.

  3. Resonance-enhanced laser-induced plasma spectroscopy: ambient gas effects

    International Nuclear Information System (INIS)

    Lui, S.L.; Cheung, N.H.

    2003-01-01

    When performing laser-induced plasma spectroscopy for elemental analysis, the sensitivity could be significantly enhanced if the plume was resonantly rekindled by a dye laser pulse. The extent of the enhancement was found to depend on the ambient gas. Air, nitrogen, helium, argon and xenon at pressures ranging from vacuum to 1 bar were investigated. In vacuum, the analyte signal was boosted because of reduced cooling, but it soon decayed as the plume freely expanded. By choosing the right ambient gas at the right pressure, the expanding plume could be confined as well as thermally insulated to maximize the analyte signal. For instance, an ambient of 13 mbar xenon yielded a signal-to-noise ratio of 110. That ratio was 53 when the pellet was ablated in air, and decreased further to 5 if the dye laser was tuned off resonance

  4. Knockdown of cytosolic NADP(+) -dependent isocitrate dehydrogenase enhances MPP(+) -induced oxidative injury in PC12 cells.

    Science.gov (United States)

    Yang, Eun Sun; Park, Jeen-Woo

    2011-05-01

    1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its toxic metabolite 1-methyl-4-phenylpyridium ion (MPP(+)) have been shown to induce Parkinson's disease-like symptoms as well as neurotoxicity in humans and animal species. Recently, we reported that maintenance of redox balance and cellular defense against oxidative damage are primary functions of the novel antioxidant enzyme cytosolic NADP(+) -dependent isocitrate dehydrogenase (IDPc). In this study, we examined the role of IDPc in cellular defense against MPP(+) -induced oxidative injury using PC12 cells transfected with IDPc small interfering RNA (siRNA). Our results demonstrate that MPP(+) -mediated disruption of cellular redox status, oxidative damage to cells, and apoptotic cell death were significantly enhanced by knockdown of IDPc.

  5. Macrophage activation induced by Brucella DNA suppresses bacterial intracellular replication via enhancing NO production.

    Science.gov (United States)

    Liu, Ning; Wang, Lin; Sun, Changjiang; Yang, Li; Tang, Bin; Sun, Wanchun; Peng, Qisheng

    2015-12-01

    Brucella DNA can be sensed by TLR9 on endosomal membrane and by cytosolic AIM2-inflammasome to induce proinflammatory cytokine production that contributes to partially activate innate immunity. Additionally, Brucella DNA has been identified to be able to act as a major bacterial component to induce type I IFN. However, the role of Brucella DNA in Brucella intracellular growth remains unknown. Here, we showed that stimulation with Brucella DNA promote macrophage activation in TLR9-dependent manner. Activated macrophages can suppresses wild type Brucella intracellular replication at early stage of infection via enhancing NO production. We also reported that activated macrophage promotes bactericidal function of macrophages infected with VirB-deficient Brucella at the early or late stage of infection. This study uncovers a novel function of Brucella DNA, which can help us further elucidate the mechanism of Brucella intracellular survival. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Laser induced surface structuring of Cu for enhancement of field emission properties

    Science.gov (United States)

    Akram, Mahreen; Bashir, Shazia; Jalil, Sohail Abdul; Shahid Rafique, Muhammad; Hayat, Asma; Mahmood, Khaliq

    2018-02-01

    The effect of Nd:YAG (1064 nm, 10 ns, 10 Hz) laser induced surface structuring of copper (Cu) for enhancement of field emission (FE) properties has been investigated. X-ray diffraction analysis was employed to investigate the surface structural and compositional modifications. The surface structuring was explored by scanning electron microscope investigation. FE properties were studied under UHV conditions in a parallel plate configuration of planar un-irradiated Cu anode and laser irradiated Cu cathode. The Fowler-Nordheim plots were drawn to confirm the dominance of FE behavior of the measured I-V characteristics. The obtained values of turn-on field ‘E o’, field enhancement factor ‘β’ and maximum current density ‘J max’ come out to be to be in the range of 5.5-8.5 V μm-1, 1380-2730 and 147-375 μA cm-2 respectively for the Cu samples irradiated at laser irradiance ranging from 13 to 50 GW cm-2. The observed enhancement in the FE properties has been correlated with the growth of various surface structures such as ridged protrusions, cones and pores/tiny holes. The porous morphology is found to be responsible for a significant enhancement in the FE parameters.

  7. Plasmon-Induced Selective Enhancement of Green Emission in Lanthanide-Doped Nanoparticles.

    Science.gov (United States)

    Zhang, Weina; Li, Juan; Lei, Hongxiang; Li, Baojun

    2017-12-13

    By introducing an 18 nm thick Au nanofilm, selective enhancement of green emission from lanthanide-doped (β-NaYF 4 :Yb 3+ /Er 3+ ) upconversion nanoparticles (UCNPs) is demonstrated. The Au nanofilm is deposited on a microfiber surface by the sputtering method and then covered with the UCNPs. The plasma on the surface of the Au nanofilm can be excited by launching a 980 nm wavelength laser beam into the microfiber, resulting in an enhancement of the local electric field and a strong thermal effect. A 36-fold luminescence intensity enhancement of the UCNPs at 523 nm is observed, with no obvious reduction in the photostability of the UCNPs. Further, the intensity ratios of the emissions at 523-545 nm and at 523-655 nm are enhanced with increasing pump power, which is attributed to the increasing plasmon-induced thermal effect. Therefore, the fabricated device is further demonstrated to exhibit an excellent ability in temperature sensing. By controlling the pump power and the UCNP concentration, a wide temperature range (325-811 K) and a high temperature resolution (0.035-0.046 K) are achieved in the fabricated device.

  8. Laser Induced Breakdown Spectroscopy Based on Single Beam Splitting and Geometric Configuration for Effective Signal Enhancement

    Science.gov (United States)

    Yang, Guang; Lin, Qingyu; Ding, Yu; Tian, Di; Duan, Yixiang

    2015-01-01

    A new laser induced breakdown spectroscopy (LIBS) based on single-beam-splitting (SBS) and proper optical geometric configuration has been initially explored in this work for effective signal enhancement. In order to improve the interaction efficiency of laser energy with the ablated material, a laser beam operated in pulse mode was divided into two streams to ablate/excite the target sample in different directions instead of the conventional one beam excitation in single pulse LIBS (SP-LIBS). In spatial configuration, the laser beam geometry plays an important role in the emission signal enhancement. Thus, an adjustable geometric configuration with variable incident angle between the two splitted laser beams was constructed for achieving maximum signal enhancement. With the optimized angles of 60° and 70° for Al and Cu atomic emission lines at 396.15 nm and 324.75 nm respectively, about 5.6- and 4.8-folds signal enhancements were achieved for aluminum alloy and copper alloy samples compared to SP-LIBS. Furthermore, the temporal analysis, in which the intensity of atomic lines in SP-LIBS decayed at least ten times faster than the SBS-LIBS, proved that the energy coupling efficiency of SBS-LIBS was significantly higher than that of SP-LIBS. PMID:25557721

  9. CYP 2E1 mutant mice are resistant to DDC-induced enhancement of MPTP toxicity.

    Science.gov (United States)

    Viaggi, C; Vaglini, F; Pardini, C; Sgadò, P; Caramelli, A; Corsini, G U

    2007-01-01

    In order to reach a deeper insight into the mechanism of diethyldithiocarbamate (DDC)-induced enhancement of MPTP toxicity in mice, we showed that CYP450 (2E1) inhibitors, such as diallyl sulfide (DAS) or phenylethylisothiocyanate (PIC), also potentiate the selective DA neuron degeneration in C57/bl mice. Furthermore we showed that CYP 2E1 is present in the brain and in the basal ganglia of mice (Vaglini et al., 2004). However, because DAS and PIC are not selective CYP 2E1 inhibitors and in order to provide direct evidence for CYP 2E1 involvement in the enhancement of MPTP toxicity, CYP 2E1 knockout mice (GONZ) and wild type animals (SVI) of the same genetic background were treated with MPTP or the combined DDC + MPTP treatment. In CYP 2E1 knockout mice, DDC pretreatment completely fails to enhance MPTP toxicity, although enhancement of MPTP toxicity was regularly present in the SVI control animals. The immunohistochemical study confirms our results and suggests that CYP 2E1 may have a detoxifying role.

  10. Application of terpene-induced cell for enhancing biodegradation of TCE contaminated soil

    Directory of Open Access Journals (Sweden)

    Ekawan Luepromchai

    2004-02-01

    Full Text Available Trichloroethylene (TCE, a chlorinated solvent, is a major water pollutant originating from spillage and inappropriate disposal of dry cleaning agents, degreasing solvents, and paint strippers. Due to its widespread contamination and potential health threat, remediation technology to clean-up TCE is necessary. Aerobic biodegradation of TCE is reported to occur via cometabolism, by which TCE degrading bacteria utilize other compounds such as toluene, phenol, and methane as growth substrate and enzyme inducer. Although toluene is reported to be the most effective inducer, it is regulated as a hazardous material and should not be applied to the environment. The objectives of this study were to identify an alternative enzyme inducer as well as to apply the induced bacteria for degradation of TCE in contaminated soil. We investigated the effect of terpenes, the main components in volatile essential oils of plants, on induction of TCE degradation in Rhodococcus gordoniae P3, a local Gram (+ bacterium. Selected terpenes including cumene, limonene, carvone and pinene at various concentrations were used in the study. Results from liquid culture showed that 25 mg l-1 cumeneinduced R. gordoniae P3 cells resulted in 75% degradation of 10 ppm TCE within 24 hrs. Soil microcosms were later employed to investigate the ability of cumene to enhance TCE biodegradation in the environment. There were two bioremediation treatments studied, including bioaugmentation, the inoculation of cumeneinduced R. gordoniae P3, and biostimulation, the addition of cumene to induce soil indigenous microorganisms to degrade TCE. Bioaugmentation and biostimulation were shown to accelerate TCE reduction significantly more than control treatment at the beginning of study. The results suggest that cumene-induced R. gordoniae P3 and cumene can achieve rapid TCE biodegradation.

  11. Aggregation induced emission enhancement of pyrene-appended Schiff base luminophore and its photovoltaic effect

    Energy Technology Data Exchange (ETDEWEB)

    Panda, Uttam; Roy, Suman; Mallick, Debashis [Department of Chemistry, Jadavpur University, Kolkata 700032 (India); Dalapati, Pradip [Condensed Matter Physics Research Center, Department of Physics, Jadavpur University, Kolkata 700032 (India); Biswas, Subir [Immunology Lab, Department of Zoology, University of Calcutta, Kolkata 700019 (India); Manik, Nabin Baran [Condensed Matter Physics Research Center, Department of Physics, Jadavpur University, Kolkata 700032 (India); Bhattacharyya, Arindam [Immunology Lab, Department of Zoology, University of Calcutta, Kolkata 700019 (India); Sinha, Chittaranjan, E-mail: c_r_sinha@yahoo.com [Department of Chemistry, Jadavpur University, Kolkata 700032 (India)

    2016-07-15

    Pyrene appended Schiff base, 1,3-bis-((E)-pyrene-1-ylmethyleneamino)propan-2-ol (HL), a fluorophore, shows aggregation induced emission enhancement upon addition of water in DMF (4:1, v/v) solution; the quantum yield (Φ) is increased by 0.034–0.450. Under illumination of solar radiation HL (10{sup −3} M) impregnated photovoltaic cell generates 4.4 mA/6.29 V electricity. DFT and TD-DFT computation of optimized geometry of HL has explained the photophysical properties.

  12. Glutathione depletion prevents diet-induced obesity and enhances insulin sensitivity.

    Science.gov (United States)

    Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L; Cohn, Dianne; Heywood, Elizabeth B; Bruemmer, Dennis

    2011-12-01

    Excessive accumulation of reactive oxygen species (ROS) in adipose tissue has been implicated in the development of insulin resistance and type 2 diabetes. However, emerging evidence suggests a physiologic role of ROS in cellular signaling and insulin sensitivity. In this study, we demonstrate that pharmacologic depletion of the antioxidant glutathione in mice prevents diet-induced obesity, increases energy expenditure and locomotor activity, and enhances insulin sensitivity. These observations support a beneficial role of ROS in glucose homeostasis and warrant further research to define the regulation of metabolism and energy balance by ROS.

  13. Accuracy enhancement of laser induced breakdown spectra using permittivity and size optimized plasma confinement rings.

    Science.gov (United States)

    Li, An; Guo, Shuai; Wazir, Nasrullah; Chai, Ke; Liang, Liang; Zhang, Min; Hao, Yan; Nan, Pengfei; Liu, Ruibin

    2017-10-30

    The inevitable problems in laser induced breakdown spectroscopy are matrix effect and statistical fluctuation of the spectral signal, which can be partly avoided by utilizing a proper confined unit. The dependences of spectral signal enhancement on relative permittivity were studied by varying materials to confine the plasma, which include polytetrafluoroethylene(PTFE), nylon/dacron, silicagel, and nitrile-butadiene rubber (NBR) with the relative permittivity 2.2, ~3.3, 3.6, 8~13, 15~22. We found that higher relative permittivity rings induce stronger enhancement ability, which restricts the energy dissipation of plasma better and due to the reflected electromagnetic wave from the wall of different materials, the electromagnetic field of plasma can be well confined and makes the distribution of plasma more orderly. The spectral intensities of the characteristic lines Si I 243.5 nm and Si I 263.1 nm increased approximately 2 times with relative permittivity values from 2.2 to ~20. The size dependent enhancement of PTFE was further checked and the maximum gain was realized by using a confinement ring with a diameter size of 5 mm and a height of 3 mm (D5mmH3mm), and the rings with D2mmH1mm and D3mmH2mm also show higher enhancement factor. In view of peak shift, peak lost and accidental peaks in the obtained spectra were properly treated in data progressing; the spectral fluctuation decreased drastically for various materials with different relative permittivities as confined units, which means the core of plasma is stabilized, attributing to the confinement effect. Furthermore, the quantitative analysis in coal shows wonderful results-the prediction fitting coefficient R 2 reaches 0.98 for ash and 0.99 for both volatile and carbon.

  14. Radiation-induced bystander effects enhanced by elevated sodium chloride through sensitizing cells to bystander factors

    International Nuclear Information System (INIS)

    Zhu Lingyan; Han Wei; Chen Shaopeng; Zhao Ye; Jiang Erkang; Bao Lingzhi; Pei Bei; Yang Gen; Zhao Guoping; Wang Jun; Xu An; Wu Lijun

    2008-01-01

    Radiation-induced bystander effects (RIBE) have been demonstrated to occur widely in various cell lines. However, very little data is available on the genotoxic effects of RIBE combined with other factor(s). We reported previously that with a low dose of α-particle irradiation, the fraction of γ-H2AX foci-positive cells in non-irradiated bystander cells was significantly increased under elevated NaCl culture conditions. In this study, we further investigated the functional role of NaCl in the enhancement of RIBE using a specially designed co-culture system and micronucleus (MN) test. It was shown that the MN frequency was not increased significantly by elevated NaCl (9.0 g/L) alone or by medium exposure. However, with 1.0 cGy α-particle irradiation, the induced MN frequency increased significantly in both irradiated and non-irradiated bystander regions. Additional studies showed that elevated NaCl made the non-irradiated bystander cells more vulnerable to bystander factors. Furthermore, it was found that the induced MN frequency in cells both in irradiated and non-irradiated bystander regions was weakened when the hypertonic medium was changed to normotonic medium for 2 h before irradiation. Such observations were quite similar to the co-effect of NaCl and hydrogen peroxide (H 2 O 2 ), indicating that elevated NaCl might sensitize non-irradiated cells to bystander factors-induced oxidative stress

  15. Enhanced photosynthetic capacity and antioxidant potential mediate brassinosteriod-induced phenanthrene stress tolerance in tomato

    International Nuclear Information System (INIS)

    Ahammed, Golam Jalal; Li, Xin; Xia, Xiao-Jian; Shi, Kai; Zhou, Yan-Hong; Yu, Jing-Quan

    2015-01-01

    Photosynthesis, the basal manufacturing process in the earth is habitually restricted by airborne micropollutants such as phenanthrene (PHE). Here, we show that 24-epibrassinolide (EBR), a bioactive plant steroid is able to keep higher photosynthetic capacity consistently for a long period under a shoot-imposed PHE stress in tomato. EBR-promoted photosynthetic capacity and efficiency eventually resulted in a 37.5% increase of biomass under PHE stress. As primary response, transcripts of antioxidant genes were remarkably induced by EBR in PHE-treated plants. Activities of antioxidant and detoxification enzymes were also enhanced by EBR. Notably, EBR-induced higher antioxidant potential was associated with reduced levels of H 2 O 2 and O 2 · — , resulting in a 32.7% decrease of content of malondialdehyde in the end of experiment and relatively healthy chloroplast ultrastructure in EBR + PHE treatment compared with PHE alone. These results indicate that EBR alleviates shoot-imposed PHE phytotoxicity by maintaining a consistently higher photosynthetic capacity and antioxidant potential in tomato. - Highlights: • PHE mist spray gradually inhibits photosynthesis and eventually reduces biomass. • EBR maintains a consistently higher photosynthesis even under PHE stress. • EBR upregulates expression of antioxidant genes as initial response to PHE stress. • EBR reduces oxidative stress by constantly activating strong antioxidant potential. • EBR-induced efficient neutralization of ROS protects chloroplast ultrastructure. - 24-epibrassinolide protects tomato plants from airborne phenanthrene-induced damages by maintaining a consistently higher photosynthetic capacity and antioxidant potential

  16. Blockage of JNK pathway enhances arsenic trioxide-induced apoptosis in human keratinocytes

    International Nuclear Information System (INIS)

    Huang, H.-S.; Liu, Z.-M.; Hong, D.-Y.

    2010-01-01

    Arsenic is well known as a carcinogen predisposing humans to some severe diseases and also as an effective medicine for treating acute promyelocytic leukemia, syphilis, and psoriasis. Multiple active mechanisms, including cell cycle arrest and apoptosis, have been proposed in therapy; however, the opposing effects of arsenic remain controversial. Our previous study found that arsenic trioxide (ATO)-induced activation of p21 WAF1/CIP1 (p21) led to A431 cell death through the antagonistic effects of the signaling of ERK1/2 and JNK1. In the current study, the inhibitory effects of JNK1 on ATO-induced p21 expression were explored. Over-expression of JNK1 in A431 cells could inhibit p21 expression, which was associated with HDAC1 and TGIF. Using the GST pull-down assay and fluorescence resonance energy transfer analysis, N-terminal domain (amino acids 1-108) of TGIF, critical to its binding with c-Jun, was found. Using reporter assays, requirement of the C-terminal domain (amino acids 138-272) of TGIF to suppress ATO-induced p21 expression was observed. Thus, the domains of TGIF that carried out its inhibitory effects on p21 were identified. Finally, treatment with JNK inhibitor SP600125 could enhance ATO-induced apoptosis of HaCaT keratinocytes by using flow cytometry.

  17. Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

    Science.gov (United States)

    Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

    2016-03-01

    Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Nör

    2014-02-01

    Full Text Available Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs. These unique cells, named here cancer stem cells (CSCs, proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B cells and observed that cisplatin treatment increased (P = .0013 the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDHhighCD44high]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1 and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatinsensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDHhighCD44high immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3 phosphorylation (indicative of stemness was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK phosphorylation (indicative of differentiation processes was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs

  19. Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Chieri [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi, E-mail: tsuyo-i@huhs.ac.jp [Division of Pharmacotherapy, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer We investigated the role of S1P signaling for osteoblast differentiation. Black-Right-Pointing-Pointer Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. Black-Right-Pointing-Pointer S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. Black-Right-Pointing-Pointer MEK/ERK signaling is a pathway underlying S1P signaling for osteoblast differentiation. -- Abstract: We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated signaling induced proliferation and prostaglandin productions by synovial cells from rheumatoid arthritis (RA) patients. In the present study we investigated the role of S1P receptor-mediated signaling for osteoblast differentiation. We investigated osteoblast differentiation using C2C12 myoblasts, a cell line derived from murine satellite cells. Osteoblast differentiation was induced by the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast differentiation was determined by osteoblast-specific transcription factor, Runx2 mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was examined by Western blotting. Osteocalcin production by C2C12 cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2-stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect of FTY was stronger than that of S1P. S1P receptor-mediated signaling on osteoblast differentiation was inhibited by addition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results indicate that S1P

  20. Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation

    International Nuclear Information System (INIS)

    Sato, Chieri; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime

    2012-01-01

    Highlights: ► We investigated the role of S1P signaling for osteoblast differentiation. ► Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. ► S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. ► MEK/ERK signaling is a pathway underlying S1P signaling for osteoblast differentiation. -- Abstract: We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated signaling induced proliferation and prostaglandin productions by synovial cells from rheumatoid arthritis (RA) patients. In the present study we investigated the role of S1P receptor-mediated signaling for osteoblast differentiation. We investigated osteoblast differentiation using C2C12 myoblasts, a cell line derived from murine satellite cells. Osteoblast differentiation was induced by the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast differentiation was determined by osteoblast-specific transcription factor, Runx2 mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was examined by Western blotting. Osteocalcin production by C2C12 cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2-stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect of FTY was stronger than that of S1P. S1P receptor-mediated signaling on osteoblast differentiation was inhibited by addition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results indicate that S1P receptor-mediated signaling plays a crucial role for osteoblast differentiation.

  1. Micropore-induced capillarity enhances bone distribution in vivo in biphasic calcium phosphate scaffolds.

    Science.gov (United States)

    Rustom, Laurence E; Boudou, Thomas; Lou, Siyu; Pignot-Paintrand, Isabelle; Nemke, Brett W; Lu, Yan; Markel, Mark D; Picart, Catherine; Wagoner Johnson, Amy J

    2016-10-15

    The increasing demand for bone repair solutions calls for the development of efficacious bone scaffolds. Biphasic calcium phosphate (BCP) scaffolds with both macropores and micropores (MP) have improved healing compared to those with macropores and no micropores (NMP), but the role of micropores is unclear. Here, we evaluate capillarity induced by micropores as a mechanism that can affect bone growth in vivo. Three groups of cylindrical scaffolds were implanted in pig mandibles for three weeks: MP were implanted either dry (MP-Dry), or after submersion in phosphate buffered saline, which fills pores with fluid and therefore suppresses micropore-induced capillarity (MP-Wet); NMP were implanted dry. The amount and distribution of bone in the scaffolds were quantified using micro-computed tomography. MP-Dry had a more homogeneous bone distribution than MP-Wet, although the average bone volume fraction, BVF‾, was not significantly different for these two groups (0.45±0.03 and 0.37±0.03, respectively). There was no significant difference in the radial bone distribution of NMP and MP-Wet, but the BVF‾, of NMP was significantly lower among the three groups (0.25±0.02). These results suggest that micropore-induced capillarity enhances bone regeneration by improving the homogeneity of bone distribution in BCP scaffolds. The explicit design and use of capillarity in bone scaffolds may lead to more effective treatments of large and complex bone defects. The increasing demand for bone repair calls for more efficacious bone scaffolds and calcium phosphate-based materials are considered suitable for this application. Macropores (>100μm) are necessary for bone ingrowth and vascularization. However, studies have shown that microporosity (micropore-induced capillarity had the potential to enhance bone growth in vivo. This work illustrates the positive effects of capillarity on bone regeneration in vivo; it demonstrates that micropore-induced capillarity significantly

  2. 3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells.

    Science.gov (United States)

    Liu, Zhe; Sun, Yiming; Hong, Haiyu; Zhao, Surong; Zou, Xue; Ma, Renqiang; Jiang, Chenchen; Wang, Zhiwei; Li, Huabin; Liu, Hao

    2015-01-01

    Increasing evidence demonstrates that the hexokinase inhibitor 3-bromopyruvate (3-BrPA) induces the cell apoptotic death by inhibiting ATP generation in human cancer cells. Interestingly, some tumor cell lines are less sensitive to 3-BrPA-induced apoptosis than others. Moreover, the molecular mechanism of 3-BrPA-trigged apoptosis is unclear. In the present study, we examined the effects of 3-BrPA on the viability of the breast cancer cell lines MDA-MB-231 and MCF-7. We further investigated the potential roles of monocarboxylate transporter 1 (MCT1) in drug accumulation and efflux of breast cancer cells. Finally, we explored whether 3-BrPA enhanced daunorubicin (DNR)-induced cytotoxicity through regulation of MCT1 in breast cancer cells. MTT and colony formation assays were used to measure cell viability. Western blot analysis, flow cytometric analysis and fluorescent microscopy were used to determine the molecular mechanism of actions of MCT1 in different breast cancer cell lines. Whole-body bioluminescence imaging was used to investigate the effect of 3-BrPA in vivo. We found that 3-BrPA significantly inhibited cell growth and induced apoptosis in MCF-7 cell line, but not in MDA-MB-231 cells. Moreover, we observed that 3-BrPA efficiently enhanced DNR-induced cytotoxicity in MCF-7 cells by inhibiting the activity of ATP-dependent efflux pumps. We also found that MCT1 overexpression increased the efficacy of 3-BrPA in MDA-MB-231 cells. 3-BrPA markedly suppressed subcutaneous tumor growth in combination with DNR in nude mice implanted with MCF-7 cells. Lastly, our whole-body bioluminescence imaging data indicated that 3-BrPA promoted DNR accumulation in tumors. These findings collectively suggest that 3-BrPA enhanced DNR antitumor activity in breast cancer cells involved MCT-1, suggesting that inhibition of glycolysis could be an effective therapeutic approach for breast cancer treatment.

  3. Optimal autaptic and synaptic delays enhanced synchronization transitions induced by each other in Newman–Watts neuronal networks

    International Nuclear Information System (INIS)

    Wang, Baoying; Gong, Yubing; Xie, Huijuan; Wang, Qi

    2016-01-01

    Highlights: • Optimal autaptic delay enhanced synchronization transitions induced by synaptic delay in neuronal networks. • Optimal synaptic delay enhanced synchronization transitions induced by autaptic delay. • Optimal coupling strength enhanced synchronization transitions induced by autaptic or synaptic delay. - Abstract: In this paper, we numerically study the effect of electrical autaptic and synaptic delays on synchronization transitions induced by each other in Newman–Watts Hodgkin–Huxley neuronal networks. It is found that the synchronization transitions induced by synaptic delay vary with varying autaptic delay and become strongest when autaptic delay is optimal. Similarly, the synchronization transitions induced by autaptic delay vary with varying synaptic delay and become strongest at optimal synaptic delay. Also, there is optimal coupling strength by which the synchronization transitions induced by either synaptic or autaptic delay become strongest. These results show that electrical autaptic and synaptic delays can enhance synchronization transitions induced by each other in the neuronal networks. This implies that electrical autaptic and synaptic delays can cooperate with each other and more efficiently regulate the synchrony state of the neuronal networks. These findings could find potential implications for the information transmission in neural systems.

  4. TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner

    Science.gov (United States)

    Badmann, A; Langsch, S; Keogh, A; Brunner, T; Kaufmann, T; Corazza, N

    2012-01-01

    Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic alterations. Although hepatocytes represent the main target of the cytotoxic effect of paracetamol overdose, perturbations within the endothelium involving morphological changes of liver sinusoidal endothelial cells (LSECs) have also been described in paracetamol-induced liver disease. Recently, we have shown that paracetamol-induced liver damage is synergistically enhanced by the TRAIL signaling pathway. As LSECs are constantly exposed to activated immune cells expressing death ligands, including TRAIL, we investigated the effect of TRAIL on paracetamol-induced LSEC death. We here demonstrate for the first time that TRAIL strongly enhances paracetamol-mediated LSEC death with typical features of apoptosis. Inhibition of caspases using specific inhibitors resulted in a strong reduction of cell death. TRAIL appears to enhance paracetamol-induced LSEC death via the activation of the pro-apoptotic BH3-only proteins Bid and Bim, which initiate the mitochondrial apoptotic pathway. Taken together this study shows that the liver endothelial layer, mainly LSECs, represent a direct target of the cytotoxic effect of paracetamol and that activation of TRAIL receptor synergistically enhances paracetamol-induced LSEC death via the mitochondrial apoptotic pathway. TRAIL-mediated acceleration of paracetamol-induced cell death may thus contribute to the pathogenesis of paracetamol-induced liver damage. PMID:23254290

  5. Intermittent hypercapnia induces long-lasting ventilatory plasticity to enhance CO2 responsiveness to overcome dysfunction

    Science.gov (United States)

    Mosher, Bryan Patrick

    The ability of the brain to detect (central CO2 chemosensitivity) and respond to (central CO2 chemoresponsiveness) changes in tissue CO2/pH, is a homeostatic process essential for mammalian life. Dysfunction of the serotonin (5-HT) mechanisms compromises ventilatory CO 2 chemosensitivity/responsiveness and may enhance vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). The laboratory of Dr. Michael Harris has shown medullary raphe contributions to central chemosensitivity involving both 5-HT- and gamma-aminobutyric acid (GABA)-mediated mechanisms. I tested the hypothesis that postnatal exposure to mild intermittent hypercapnia (IHc) induces respiratory plasticity, due in part to strengthening of bicuculline- and saclofen-sensitive mechanisms (GABAA and GABAB receptor antagonists respectively). Rats were exposed to IHc-pretreatment (8 cycles of 5 % CO2) for 5 days beginning at postnatal day 12 (P12). I subsequently assessed CO2 responsiveness using an in situ perfused brainstem preparation. Hypercapnic responses were determined with and without pharmacological manipulation. In addition, IHc-pretreatment effectiveness was tested for its ability to overcome dysfunction in the CO2 responsiveness induced by a dietary tryptophan restriction. This dysfunctional CO2 responsiveness has been suggested to arise from a chronic, partial 5-HT reduction imparted by the dietary restriction. Results show IHc-pretreatment induced plasticity sufficient for CO2 responsiveness despite removal of otherwise critical ketanserin-sensitive mechanisms. CO2 responsiveness following IHc-pretreatment was absent if ketanserin was combined with bicuculline and saclofen, indicating that the plasticity was dependent upon bicuculline- and saclofen-sensitive mechanisms. IHc--induced plasticity was also capable of overcoming the ventilatory defects associated with maternal dietary restriction. Duration of IHc-induced plasticity was also investigated and found to last far into

  6. Aluminium doping induced enhancement of p-d coupling in ZnO

    International Nuclear Information System (INIS)

    Cong, G W; Peng, W Q; Wei, H Y; Liu, X L; Wu, J J; Han, X X; Zhu, Q S; Wang, Z G; Ye, Z Z; Lu, J G; Zhu, L P; Qian, H J; Su, R; Hong, C H; Zhong, J; Ibrahim, K; Hu, T D

    2006-01-01

    Valence-band type Auger lines in Al doped and undoped ZnO were comparatively studied with the corresponding core level x-ray photoelectron spectrography (XPS) spectra as references. Then the shift trend of energy levels in the valence band was that p and p-s-d states move upwards but e and p-d states downwards with increasing Al concentration. The decreased energy of the Zn 3d state is larger than the increased energy of the O 2p state, indicating the lowering of total energy. This may indicate that Al doping could induce the enhancement of p-d coupling in ZnO, which originates from stronger Al-O hybridization. The shifts of these states and the mechanism were confirmed by valence band XPS spectra and O K-edge x-ray absorption spectrography (XAS) spectra. Finally, some previously reported phenomena are explained based on the Al doping induced enhancement of p-d coupling

  7. Enhanced neutrophil chemotactic activity after bronchial challenge in subjects with grain dust-induced asthma.

    Science.gov (United States)

    Park, H S; Jung, K S

    1998-03-01

    There have been few reports suggesting involvement of neutrophils in induction of bronchoconstriction after inhalation of grain dust. To understand the role of neutrophils in pathogenesis of grain dust-induced asthma. We observed serum neutrophil chemotactic activity during grain dust-bronchoprovocation tests in six asthmatic subjects with positive bronchial challenges (group I). They were compared with those of six symptomatic subjects from the same workplace with negative bronchial challenges (group II). After grain dust inhalation, serum neutrophil chemotactic activity significantly increased at 30 minutes (P = .028), and then decreased to baseline level at 240 minutes (P = .028) in five subjects of group I having isolated early asthmatic responses. Enhanced neutrophil chemotactic activity was persistent for up to 240 minutes in one asthmatic subject having both early and late asthmatic responses. There was, however, no significant change in serum neutrophil chemotactic activity during bronchial challenges in subjects of group II. Pre-incubation of sera with anti-interleukin-8 (IL-8) antibody did not affect the neutrophil chemotactic activity results of group I subjects. These results suggest that enhanced neutrophil chemotactic activity distinct from IL-8 may contribute to significant bronchoconstriction induced by grain dust.

  8. MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Andrea Turner

    Full Text Available The Map kinase Activating Death Domain containing protein (MADD isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.

  9. Halogenated salicylaldehyde azines: The heavy atom effect on aggregation-induced emission enhancement properties

    International Nuclear Information System (INIS)

    Chen, Xiao-tong; Tong, Ai-jun

    2014-01-01

    This study investigates the heavy-atom effect (HAE) on aggregation-induced emission enhancement (AIEE) properties of salicylaldehyde azines. For this purpose, a series of halogenated salicylaldehyde azine derivatives, namely, chloro-salicylaldehyde azine (1), bromo-salicylaldehyde azine (2) and iodo-salicylaldehyde azine (3) are synthesized. 1 and 2 display typical AIEE characteristics of salicylaldehyde azine compounds; whereas for the iodo-substituent in 3, is found to be effective “external” heavy atom quenchers to salicylaldehyde azine fluorescence in aggregated state. Based on its weak fluorescence in aggregated state and relative strong fluorescence in dispersed state, 3 can also be applied as a turn-on fluorescence probe for egg albumin detection attributed to hydrophobic interaction. -- Highlights: • This study investigates the heavy-atom effect (HAE) on aggregation-induced emission enhancement (AIEE) properties of salicylaldehyde azines. • Chloro- and bromo-salicylaldehyde display typical AIEE properties of salicylaldehyde azine, whereas the iodo-substitute quenches AIEE in aggregated state. • Iodo-salicylaldehyde can be applied as a turn-on fluorescence probe for egg albumin detection attributed to hydrophobic interaction

  10. Repair in schizosaccharomyces pombe as measured by recovery from caffeine enhancement of radiation-induced lethality

    International Nuclear Information System (INIS)

    Gentner, N.E.; Werner, M.M.

    1975-01-01

    Inhibition of DNA repair by caffeine is manifested in Schizosaccharomyces pombe wild-type cells as an enhancement of UV- or γ-irradiation-induced lethality. The progress of DNA repair processes involving one or more caffeine-sensitive steps may be conveniently followed by measuring the concomitant decrease of this lethal enhancement effect. By measuring, during post-irradiation incubation, the ability of cells to overcome susceptibility to repair inhibition by caffeine, we have determined the time course and requirements for repair in S. pombe. Recovery began immediately and took 150-200 min after γ-irradiation and more than 500 min after UV-irradiation, for exposures which gave about 10% survival in the absence of caffeine. An incubation medium capable of supporting growth was required for caffeine-sensitive repair; no recovery occurred under liquid holding conditions. Survival curves after various recovery times indicated that a logarithmic phase cell population was homogeneous with respect to caffeine-sensitive repair of both UV- and γ-ray-induced damage. Recovery from caffeine inhibition was compared for cells of different physiological states (logarithmic and stationary phase); although the importance of the physiological state was not the same for the two types of radiation, recovery was found to occur more rapidly in the more radiation-resistant state, in each case. (orig.) [de

  11. Inducing half-metallicity with enhanced stability in zigzag graphene nanoribbons via fluorine passivation

    Energy Technology Data Exchange (ETDEWEB)

    Jaiswal, Neeraj K., E-mail: neerajkjaiswal@gmail.com [Discipline of Physics, Indian Institute of Information Technology Design & Manufacturing, Jabalpur 482005 (India); Tyagi, Neha [Department of Applied Physics, Delhi Technological University, Delhi 110042 (India); Kumar, Amit [Discipline of Physics, Indian Institute of Information Technology Design & Manufacturing, Jabalpur 482005 (India); Srivastava, Pankaj [Nanomaterials Research Group, ABV-Indian Institute of Information Technology & Management, Gwalior 474015 (India)

    2017-02-28

    Highlights: • F passivated zigzag graphene nanoribbon (F-ZGNR) are more favorable than pristine ones. • External electric field induces half metallicity in F-ZGNR. • The observed half metallicity is independent of ribbon widths. • Enhanced stability makes F-ZGNR preferable over pristine ribbon. - Abstract: Half metals are the primary ingredients for the realization of novel spintronic devices. In the present work, by employing density functional theory based first-principles calculation, we predict half metallic behavior in fluorine passivated zigzag graphene nanoribbons (F-ZGNR). Four different structures have been investigated viz. one edge F passivated ZGNR (F-ZGNR-1), both edges F passivated ZGNR (F-ZGNR-2), F passivation on alternate sites in first configuration (alt-1) and F passivation on alternate sites in second configuration (alt-2). Interestingly, it is noticed that F passivation is analogous to H passivation (pristine), however, F-ZGNR are reckoned energetically more stable than pristine ones. An spin induced band gap is noticed for all F-ZGNR irrespective of their widths although its magnitude is slightly less than the pristine counterparts. With an external transverse electric field, ribbons undergo semiconducting to half metallic transformation. The observed half metallic character with enhanced stability present F-ZGNR as a better candidate than pristine ZGNR towards the realization of upcoming spintronic devices.

  12. Gold nanoparticles enhance the X-ray-induced degradation of human centrin 2 protein

    Energy Technology Data Exchange (ETDEWEB)

    Brun, Emilie [Laboratoire de Chimie Physique, CNRS UMR 8000, Universite Paris-Sud 11, Bat. 350, 91405 Orsay Cedex (France); Duchambon, Patricia; Blouquit, Yves [INSERM U759, Imagerie Integrative, Campus Universitaire d' Orsay, Bat. 112, Institut Curie, Centre de Recherche, Laboratoire R. Latarjet, Campus Universitaire d' Orsay, 91405 Orsay Cedex (France); Keller, Gerard [UMR CNRS 8612, Physico-Chimie-Pharmacotechnie-Biopharmacie, Universite Paris 11, Faculte de Pharmacie, 5 rue Jean-Baptiste Clement, 92296 Chatenay-Malabry (France); Sanche, Leon [Groupe en Sciences des Radiations, Departement de Medecine Nucleaire et Radiobiologie, Faculte de Medecine, Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4 (Canada); Sicard-Roselli, Cecile [Laboratoire de Chimie Physique, CNRS UMR 8000, Universite Paris-Sud 11, Bat. 350, 91405 Orsay Cedex (France)], E-mail: cecile.sicard@u-psud.fr

    2009-03-15

    In the war against cancer, radiotherapy is a prominent tool but counterbalanced by the fact that it also induces damages in healthy tissues. Nanotechnologies could open a new possibility to decrease these side effects. In particular, gold nanoparticles (GNPs) could be used as radio-sensitizers. As the role of proteins in the processes leading to cell death cannot be neglected, their radio-sensitization by GNPs is of great interest. This is particularly true in the case of the human centrin 2 protein, which has been proposed to be involved in DNA repair processes. To investigate this effect, we quantified for the first time the degradation of this protein in a gold colloidal solution when submitted to X-rays. We showed that the X-ray-induced degradation of the human centrin 2 protein is enhanced 1.5-fold in the presence of GNPs, even though no covalent bond exists between protein and GNPs. Among the conditions tested, the maximum enhancement was found with the higher GNP:protein ratio of 2x10{sup -4} and with the higher X-ray energy of 49 keV.

  13. Clotrimazole enhances lysis of human erythrocytes induced by t-BHP.

    Science.gov (United States)

    Lisovskaya, Irene L; Shcherbachenko, Irina M; Volkova, Rimma I; Ataullakhanov, Fazoil I

    2009-08-14

    Clotrimazole (CLT) is an antifungal and antimalarial agent also effective as a Gardos channel inhibitor. In addition, CLT possesses antitumor properties. Recent data provide evidence that CLT forms a complex with heme (hemin), which produces a more potent lytic effect than heme alone. This study addressed the effect of CLT on the lysis of normal human erythrocytes induced by tert-butyl hydroperoxide (t-BHP). For the first time, it was shown that 10 microM CLT significantly enhanced the lytic effect of t-BHP on erythrocytes in both Ca(2+)-containing and Ca(2+)-free media, suggesting that the effect is not related to Gardos channels. CLT did not affect the rate of free radical generation, the kinetics of GSH degradation, methemoglobin formation and TBARS generation; therefore, we concluded that CLT does not cause additional oxidative damage to erythrocytes treated with t-BHP. It is tempted to speculate that CLT enhances t-BHP-induced changes in erythrocyte volume and lysis largely by forming a complex with hemin released during hemoglobin oxidation in erythrocytes: the CLT-hemin complex destabilizes the cell membrane more potently than hemin alone. If so, the effect of CLT on cell membrane damage during free-radical oxidation may be used to increase the efficacy of antitumor therapy.

  14. Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia

    Directory of Open Access Journals (Sweden)

    Rodrigo eIturriaga

    2014-12-01

    Full Text Available The carotid body (CB plays a main role in the maintenance of the oxygen homeostasis. The hypoxic stimulation of the CB increases the chemosensory discharge, which in turn elicits reflex sympathetic, cardiovascular and ventilatory adjustments. An exacerbate carotid chemosensory activity has been associated with human sympathetic-mediated diseases such as hypertension, insulin resistance, heart failure and obstructive sleep apnea (OSA. Indeed, the CB chemosensory discharge becomes tonically hypereactive in experimental models of OSA and heart failure. Chronic intermittent hypoxia (CIH, a main feature of OSA, enhances CB chemosensory baseline discharges in normoxia and in response to hypoxia, inducing sympathetic overactivity and hypertension. Oxidative stress, increased levels of ET-1, Angiotensin II and pro-inflammatory cytokines, along with a reduced production of NO in the CB, have been associated with the enhanced carotid chemosensory activity. In this review, we will discuss new evidence supporting a main role for the CB chemoreceptor in the autonomic and cardiorespiratory alterations induced by intermittent hypoxia, as well as the molecular mechanisms involved in the CB chemosensory potentiation.

  15. Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia

    Science.gov (United States)

    Iturriaga, Rodrigo; Andrade, David C.; Del Rio, Rodrigo

    2014-01-01

    The carotid body (CB) plays a main role in the maintenance of the oxygen homeostasis. The hypoxic stimulation of the CB increases the chemosensory discharge, which in turn elicits reflex sympathetic, cardiovascular, and ventilatory adjustments. An exacerbate carotid chemosensory activity has been associated with human sympathetic-mediated diseases such as hypertension, insulin resistance, heart failure, and obstructive sleep apnea (OSA). Indeed, the CB chemosensory discharge becomes tonically hypereactive in experimental models of OSA and heart failure. Chronic intermittent hypoxia (CIH), a main feature of OSA, enhances CB chemosensory baseline discharges in normoxia and in response to hypoxia, inducing sympathetic overactivity and hypertension. Oxidative stress, increased levels of ET-1, Angiotensin II and pro-inflammatory cytokines, along with a reduced production of NO in the CB, have been associated with the enhanced carotid chemosensory activity. In this review, we will discuss new evidence supporting a main role for the CB chemoreceptor in the autonomic and cardiorespiratory alterations induced by intermittent hypoxia, as well as the molecular mechanisms involved in the CB chemosensory potentiation. PMID:25520668

  16. Histone peptide AKRHRK enhances H2O2-induced DNA damage and alters its site specificity

    International Nuclear Information System (INIS)

    Midorikawa, Kaoru; Murata, Mariko; Kawanishi, Shosuke

    2005-01-01

    Histone proteins are involved in compaction of DNA and the protection of cells from oxygen toxicity. However, several studies have demonstrated that the metal-binding histone reacts with H 2 O 2 , leading to oxidative damage to a nucleobase. We investigated whether histone can accelerate oxidative DNA damage, using a minimal model for the N-terminal tail of histone H4, CH 3 CO-AKRHRK-CONH 2 , which has a metal-binding site. This histone peptide enhanced DNA damage induced by H 2 O 2 and Cu(II), especially at cytosine residues, and induced additional DNA cleavage at the 5'-guanine of GGG sequences. The peptide also enhanced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine and ESR spin-trapping signal from H 2 O 2 and Cu(II). Cyclic redox reactions involving histone-bound Cu(II) and H 2 O 2 , may give rise to multiple production of radicals leading to multiple hits in DNA. It is noteworthy that the histone H4 peptide with specific sequence AKRHRK can cause DNA damage rather than protection under metal-overloaded condition

  17. PI3K inhibition enhances doxorubicin-induced apoptosis in sarcoma cells.

    Directory of Open Access Journals (Sweden)

    Diana Marklein

    Full Text Available We searched for a drug capable of sensitization of sarcoma cells to doxorubicin (DOX. We report that the dual PI3K/mTOR inhibitor PI103 enhances the efficacy of DOX in several sarcoma cell lines and interacts with DOX in the induction of apoptosis. PI103 decreased the expression of MDR1 and MRP1, which resulted in DOX accumulation. However, the enhancement of DOX-induced apoptosis was unrelated to DOX accumulation. Neither did it involve inhibition of mTOR. Instead, the combination treatment of DOX plus PI103 activated Bax, the mitochondrial apoptosis pathway, and caspase 3. Caspase 3 activation was also observed in xenografts of sarcoma cells in nude mice upon combination of DOX with the specific PI3K inhibitor GDC-0941. Although the increase in apoptosis did not further impact on tumor growth when compared to the efficient growth inhibition by GDC-0941 alone, these findings suggest that inhibition of PI3K may improve DOX-induced proapoptotic effects in sarcoma. Taken together with similar recent studies of neuroblastoma- and glioblastoma-derived cells, PI3K inhibition seems to be a more general option to sensitize tumor cells to anthracyclines.

  18. Valproic acid induces cutaneous wound healing in vivo and enhances keratinocyte motility.

    Directory of Open Access Journals (Sweden)

    Soung-Hoon Lee

    Full Text Available BACKGROUND: Cutaneous wound healing is a complex process involving several signaling pathways such as the Wnt and extracellular signal-regulated kinase (ERK signaling pathways. Valproic acid (VPA is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VPA on cutaneous wound healing is unknown. METHODS AND FINDINGS: We created full-thickness wounds on the backs of C3H mice and then applied VPA. After 7 d, we observed marked healing and reduced wound size in VPA-treated mice. In the neo-epidermis of the wounds, β-catenin and markers for keratinocyte terminal differentiation were increased after VPA treatment. In addition, α-smooth muscle actin (α-SMA, collagen I and collagen III in the wounds were significantly increased. VPA induced proliferation and suppressed apoptosis of cells in the wounds, as determined by Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining analyses, respectively. In vitro, VPA enhanced the motility of HaCaT keratinocytes by activating Wnt/β-catenin, ERK and phosphatidylinositol 3-kinase (PI3-kinase/Akt signaling pathways. CONCLUSIONS: VPA enhances cutaneous wound healing in a murine model and induces migration of HaCaT keratinocytes.

  19. Gold nanoparticles enhance the X-ray-induced degradation of human centrin 2 protein

    International Nuclear Information System (INIS)

    Brun, Emilie; Duchambon, Patricia; Blouquit, Yves; Keller, Gerard; Sanche, Leon; Sicard-Roselli, Cecile

    2009-01-01

    In the war against cancer, radiotherapy is a prominent tool but counterbalanced by the fact that it also induces damages in healthy tissues. Nanotechnologies could open a new possibility to decrease these side effects. In particular, gold nanoparticles (GNPs) could be used as radio-sensitizers. As the role of proteins in the processes leading to cell death cannot be neglected, their radio-sensitization by GNPs is of great interest. This is particularly true in the case of the human centrin 2 protein, which has been proposed to be involved in DNA repair processes. To investigate this effect, we quantified for the first time the degradation of this protein in a gold colloidal solution when submitted to X-rays. We showed that the X-ray-induced degradation of the human centrin 2 protein is enhanced 1.5-fold in the presence of GNPs, even though no covalent bond exists between protein and GNPs. Among the conditions tested, the maximum enhancement was found with the higher GNP:protein ratio of 2x10 -4 and with the higher X-ray energy of 49 keV

  20. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis.

    Science.gov (United States)

    Jain, S K; Gill, M S; Pawar, H S; Suresh, Sarasija

    2014-09-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (Parthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.

  1. 2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

    Science.gov (United States)

    Miller, E. S.; Bates, R. A.; Koebel, D. A.; Fuchs, B. B.; Sonnenfeld, G.

    1998-01-01

    Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

  2. Asian sand dust enhances ovalbumin-induced eosinophil recruitment in the alveoli and airway of mice

    International Nuclear Information System (INIS)

    Hiyoshi, Kyoko; Ichinose, Takamichi; Sadakane, Kaori; Takano, Hirohisa; Nishikawa, Masataka; Mori, Ikuko; Yanagisawa, Rie; Yoshida, Seiichi; Kumagai, Yoshito; Tomura, Shigeo; Shibamoto, Takayuki

    2005-01-01

    Asian sand dust (ASD) containing sulfate (SO 4 2- ) reportedly causes adverse respiratory health effects but there is no experimental study showing the effect of ASD toward allergic respiratory diseases. The effects of ASD and ASD plus SO 4 2- toward allergic lung inflammation induced by ovalbumin (OVA) were investigated in this study. ICR mice were administered intratracheally with saline; ASD alone (sample from Shapotou desert); and ASD plus SO 4 2- (ASD-SO 4 ); OVA+ASD; OVA+ASD-SO 4 . ASD or ASD-SO 4 alone caused mild nutrophilic inflammation in the bronchi and alveoli. ASD and ASD-SO 4 increased pro-inflammatory mediators, such as Keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-1 alpha, in bronchoalveolar lavage fluids (BALF). ASD and ASD-SO 4 enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. However, a further increase of eosinophils by addition of SO 4 2- was not observed. The two sand dusts synergistically increased interleukin-5 (IL-5) and monocyte chemotactic protein-1 (MCP-1), which were associated with OVA, in BALF. However, the increased levels of IL-5 were lower in the OVA+ASD-SO 4 group than in the OVA+ASD group. ASD caused the adjuvant effects to specific-IgG1 production by OVA, but not to specific-IgE. These results suggest that the enhancement of eosinophil recruitment in the lung is mediated by synergistically increased IL-5 and MCP-1. IgG1 antibodies may play an important role in the enhancement of allergic reaction caused by OVA and sand dust. However, extra sulfate may not contribute to an increase of eosinophils

  3. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase

    Science.gov (United States)

    Rajfer, R. A.; Kilic, A.; Neviaser, A. S.; Schulte, L. M.; Hlaing, S. M.; Landeros, J.; Ferrini, M. G.; Ebramzadeh, E.

    2017-01-01

    Objectives We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Materials and Methods Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry. Results When compared with the control group, the COMB-4 group exhibited 46% higher maximum strength (t-test, p = 0.029) and 92% higher stiffness (t-test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42. Conclusion This study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression. Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:–97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2. PMID:28188129

  4. Respiratory syncytial virus infections enhance cigarette smoke induced COPD in mice.

    Directory of Open Access Journals (Sweden)

    Robert F Foronjy

    Full Text Available Respiratory syncytial viral (RSV infections are a frequent cause of chronic obstructive pulmonary disease (COPD exacerbations, which are a major factor in disease progression and mortality. RSV is able to evade antiviral defenses to persist in the lungs of COPD patients. Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established. Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice. RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice. This infiltration of cells was most pronounced around the vasculature and bronchial airways. By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure. Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z expression. In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure. RSV and smoke exposure also reduced protein phosphatase 2A (PP2A and protein tyrosine phosphates (PTP1B expression and activity. This is significant as these phosphatases counter smoke-induced inflammation and protease expression. Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice. Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression.

  5. Possible involvement of ROS generation in vorinostat pretreatment induced enhancement of the antibacterial activity of ciprofloxacin

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    Masadeh MM

    2017-10-01

    Full Text Available Majed M Masadeh,1 Karem H Alzoubi,2 Sayer I Al-azzam,2 Ahlam M Al-buhairan3 1Department of Pharmaceutical Technology, 2Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia Abstract: The mechanism underlying ciprofloxacin action involves interference with transcription and replication of bacterial DNA and, thus, the induction of double-strand breaks in DNA. It also involves elevated oxidative stress, which might contribute to bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. The current work investigated a possible interactive effect of vorinostat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA (ATCC 43300, and Streptococcus pneumoniae (ATCC 25923. The antibacterial activity of ciprofloxacin, with or without pretreatment of bacterial cells by vorinostat, was examined using the disc diffusion procedure and determination of the minimum inhibitory concentration (MIC and zones of inhibition of bacterial growth. All tested bacterial strains showed sensitivity to ciprofloxacin. When pretreated with vorinostat, significantly larger zones of inhibition and smaller MIC values were observed in all bacterial strains compared to those treated with ciprofloxacin alone. In correlation, generation of reactive oxygen species (ROS induced by the antibacterial action of ciprofloxacin was enhanced by treatment of bacterial cells with vorinostat. Results showed the possible agonistic properties of vorinostat when used together with ciprofloxacin. This could be related to the

  6. Caffeine may enhance orthodontic tooth movement through increasing osteoclastogenesis induced by periodontal ligament cells under compression.

    Science.gov (United States)

    Yi, Jianru; Yan, Boxi; Li, Meile; Wang, Yu; Zheng, Wei; Li, Yu; Zhao, Zhihe

    2016-04-01

    Caffeine is the kernel component of coffee and has multiple effects on bone metabolism. Here we aimed to investigate the effects of caffeine intake on orthodontic tooth movement (OTM). (1) In the in vivo study, two groups comprising 15 randomly assigned rats each underwent orthodontic treatment. One group ingested caffeine at 25mg/kg body weight per day and the other, plain water. After 3 weeks, the degree of tooth movement and effect on the periodontium were assessed. (2) In the in vitro study, we established a model mimicking the essential bioprocess of OTM, which contained a periodontal ligament tissue model (PDLtm), and a co-culture system of osteoblasts (OBs) and osteoclast precursors (pre-OCs). After being subjected to static compressive force with or without caffeine administration, the conditioned media from the PDLtm were used for the OB/pre-OC co-cultures to induce osteoclastogenesis. (1) In vivo, the caffeine group displayed a significantly greater rate of tooth movement than the control. The alveolar bone mineral density and bone volume fraction were similar between the two groups; however, immunohistochemical staining showed that the caffeine group had significantly more TRAP(+) osteoclasts and higher RANKL expression in the compressed periodontium. (2) In vitro, caffeine at 0.01mM significantly enhanced the compression-induced expression of RANKL and COX-2, as well as prostaglandin E2 production in the PDLtm. Furthermore, the "caffeine+compression"-conditioned media induced significantly more TRAP(+) OC formation when compared with compression alone. Daily intake of caffeine, at least at some specific dosage, may enhance OTM through increasing osteoclastogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation.

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    Jun-Il Kang

    Full Text Available Repetitive visual training paired with electrical activation of cholinergic projections to the primary visual cortex (V1 induces long-term enhancement of cortical processing in response to the visual training stimulus. To better determine the receptor subtypes mediating this effect the selective pharmacological blockade of V1 nicotinic (nAChR, M1 and M2 muscarinic (mAChR or GABAergic A (GABAAR receptors was performed during the training session and visual evoked potentials (VEPs were recorded before and after training. The training session consisted of the exposure of awake, adult rats to an orientation-specific 0.12 CPD grating paired with an electrical stimulation of the basal forebrain for a duration of 1 week for 10 minutes per day. Pharmacological agents were infused intracortically during this period. The post-training VEP amplitude was significantly increased compared to the pre-training values for the trained spatial frequency and to adjacent spatial frequencies up to 0.3 CPD, suggesting a long-term increase of V1 sensitivity. This increase was totally blocked by the nAChR antagonist as well as by an M2 mAChR subtype and GABAAR antagonist. Moreover, administration of the M2 mAChR antagonist also significantly decreased the amplitude of the control VEPs, suggesting a suppressive effect on cortical responsiveness. However, the M1 mAChR antagonist blocked the increase of the VEP amplitude only for the high spatial frequency (0.3 CPD, suggesting that M1 role was limited to the spread of the enhancement effect to a higher spatial frequency. More generally, all the drugs used did block the VEP increase at 0.3 CPD. Further, use of each of the aforementioned receptor antagonists blocked training-induced changes in gamma and beta band oscillations. These findings demonstrate that visual training coupled with cholinergic stimulation improved perceptual sensitivity by enhancing cortical responsiveness in V1. This enhancement is mainly mediated by n

  8. Study of xenon binding in cryptophane-A using laser-induced NMR polarization enhancement

    International Nuclear Information System (INIS)

    Luhmer, M.; Goodson, B.M.; Song, Y.Q.; Laws, D.D.; Kaiser, L.; Pines, A.; Lawrence Berkeley National Lab., CA

    1999-01-01

    Xenon is chemically inert, yet exhibits NMR parameters that are highly sensitive to its chemical environment. Considerable work has therefore capitalized on the utility of 129 Xe (I = 1/2) as a magnetic resonance probe of molecules, materials, and biological systems. In solution, spin-polarization transfer between laser-polarized xenon and the hydrogen nuclei of nearby molecules leads to signal enhancements in the resolved 1 H NMR spectrum, offering new opportunities for probing the chemical environment of xenon atoms. Following binding of laser-polarized xenon to molecules of cryptophane-A, selective enhancements of the 1 H NMR signals were observed. A theoretical framework for the interpretation of such experimental results is provided, and the spin polarization-induced nuclear Overhauser effects are shown to yield information about the molecular environment of xenon. The observed selective 1 H enhancements allowed xenon-proton internuclear distances to be estimated. These distances reveal structural characteristics of the complex, including the preferred molecular conformations adopted by cryptophane-A upon binding of xenon

  9. C3d enhanced DNA vaccination induced humoral immune response to glycoprotein C of pseudorabies virus

    International Nuclear Information System (INIS)

    Tong Tiezhu; Fan Huiying; Tan Yadi; Xiao Shaobo; Ling Jieyu; Chen Huanchun; Guo Aizhen

    2006-01-01

    Murine C3d were utilized to enhance immunogenicity of pseudorabies virus (PrV) gC DNA vaccination. Three copies of C3d and four copies of CR2-binding domain M28 4 were fused, respectively, to truncated gC gene encoding soluble glycoprotein C (sgC) in pcDNA3.1. BALB/c mice were, respectively, immunized with recombinant plasmids, blank vector, and inactivated vaccine. The antibody ELISA titer for sgC-C3d 3 DNA was 49-fold more than that for sgC DNA, and the neutralizing antibody obtained 8-fold rise. Protection of mice from death after lethal PrV (316 LD 5 ) challenge was augmented from 25% to 100%. Furthermore, C3d fusion increased Th2-biased immune response by inducing IL-4 production. The IL-4 level for sgC-C3d 3 DNA immunization approached that for the inactivated vaccine. Compared to C3d, M28 enhanced sgC DNA immunogenicity to a lesser extent. In conclusion, we demonstrated that murine C3d fusion significantly enhanced gC DNA immunity by directing Th1-biased to a balanced and more effective Th1/Th2 response

  10. Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats

    International Nuclear Information System (INIS)

    Winocour, P.D.; Colwell, J.A.

    1985-01-01

    Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, the authors used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. The authors conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis

  11. Enhancement of esculetin on Taxol-induced apoptosis in human hepatoma HepG2 cells

    International Nuclear Information System (INIS)

    Kuo, H.-C.; Lee, H.-J.; Hu, C.-C.; Shun, H.-I; Tseng, T.-H.

    2006-01-01

    The potential use of low dose chemotherapy has been appealing since lower dosages are more attainable during cancer therapy and cause less toxicity in patients. Combination therapy of Taxol, a promising frontline chemotherapy agent, with natural anti-tumor agents that are considerably less toxic with a capability of activating additional apoptotic signals or inhibiting survival signals may provide a rational molecular basis for novel chemotherapeutic strategies. Esculetin, a well-known lipoxygenase inhibitor, showed an inhibitory effect on the cell cycle progression of HL-60 cells in our previous study. In this report, the effects of a concomitant administration of esculetin and Taxol were investigated in human hepatoma HepG2 cells. Firstly, esculetin alone could exert an antiproliferation effect together with an inhibitory effect on the activation of ERKs and p38 MAPK. As compared to the treatment with Taxol only, a co-administration with esculetin and Taxol could result in a further enhancement of apoptosis as revealed by DNA fragmentation assay and Annexin-V-based assay. Meanwhile, immunoblotting analysis also showed that the co-administration of esculetin and Taxol could increase the expression of Bax and the cytosolic release of cytochrome C and enhance the expression of Fas and Fas ligand while the activation of caspase-8 and caspase-3 was also increased. Finally, the ERK cascade was proven to be involved in the enhancement of esculetin on the Taxol-induced apoptosis

  12. Solvent induced fluorescence enhancement of graphene oxide studied by ultrafast spectroscopy

    Science.gov (United States)

    Zhao, Litao; Chen, Jinquan; He, Xiaoxiao; Yu, Xiantong; Yan, Shujun; Zhang, Sanjun; Pan, Haifeng; Xu, Jianhua

    2018-05-01

    Femtosecond transient absorption (TA) spectroscopy combined with picosecond time resolved fluorescence (TRF) were used to reveal the fluorescence kinetics of graphene oxide (GO) in water, ethanol and water-ethanol mixtures. Size-independent fluorescence of GO were observed in water, and pH-dependent fluorescence spectra could be fitted well by a triple emission relaxation with peaks around 440 nm, 500 nm, and 590 nm respectively. The results indicate that polycyclic aromatic hydrocarbons (PAHs) linked by oxygen-containing functional groups dominate GO's fluorescence emission. GO's fluorescence quantum yield was measured to be 2.8% in ethanol but 1.2% in water. The three decay components fluorescence decay, as well as the transient absorption dynamics with an offset, confirmed this solvent induced fluorescence enhancement. GO's Raman spectral signals showed that GO in ethanol has a smaller average size of PAHs than that of GO in water. Therefore, besides other enhancement effects reported in literatures, we proposed that solvents could also change the size of PAHs, resulting in a photoluminescence enhancement. Our experimental data demonstrates that GO's quantum yield could be up to 2.8% in water and 8.4% in ethanol and this observation may help ones to improve GO's photoluminescence efficiency as well as its applications in solution.

  13. Enhancement of Aggregation-Induced Emission by Introducing Multiple o-Carborane Substitutions into Triphenylamine

    Directory of Open Access Journals (Sweden)

    Kenta Nishino

    2017-11-01

    Full Text Available The enhancement of aggregation-induced emission (AIE is presented on the basis of the strategy for improving solid-state luminescence by employing multiple o-carborane substituents. We synthesized the modified triphenylamines with various numbers of o-carborane units and compared their optical properties. From the optical measurements, the emission bands from the twisted intramolecular charge transfer (TICT state were obtained from the modified triphenylamines. It was notable that emission efficiencies of the multi-substituted triphenylamines including two or three o-carborane units were enhanced 6- to 8-fold compared to those of the mono-substituted triphenylamine. According to mechanistic studies, it was proposed that the single o-carborane substitution can load the AIE property via the TICT mechanism. It was revealed that the additional o-carborane units contribute to improving solid-state emission by suppressing aggregation-caused quenching (ACQ. Subsequently, intense AIEs were obtained. This paper presents a new role of the o-carborane substituent in the enhancement of AIEs.

  14. Plasmon resonance-induced photoluminescence enhancement of CdTe/Cds quantum dots thin films

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongyu [Nanjing University of Posts and Telecommunications, Nanjing 210003 (China); National Laboratory of Solid State Microstructure and School of Electronic Science and Engineering, Nanjing University, Nanjing 210093 (China); Xu, Ling, E-mail: xuling@nju.edu.cn [National Laboratory of Solid State Microstructure and School of Electronic Science and Engineering, Nanjing University, Nanjing 210093 (China); Wu, Yangqing; Xu, Jun; Ma, Zhongyuan; Chen, Kunji [National Laboratory of Solid State Microstructure and School of Electronic Science and Engineering, Nanjing University, Nanjing 210093 (China)

    2016-11-30

    Highlights: • CdTe/CdS quantum dots/Au nano-rods nano-composite films were fabricated. • PL intensity of the quantum dots films was enhanced due to Au nanorods. • Internal quantum efficiency increased due to localized surface plasmon resonance. • The lifetimes of quantum dots films decreased after interaction with Au nano-rods. - Abstract: CdTe/CdS quantum dots/Au nano-rods nano-composite films were fabricated on planar Si substrates. The optical properties of all samples were investigated and the corresponding simulations were studied. It was found that the photoluminescence intensity of the CdTe/CdS quantum dots films was enhanced about 9-fold after the incorporation of Au nano-rods, the internal quantum efficiency increased from 24.3% to 35.2% due to the localized surface plasmon resonance. The time-resolved luminescence decay curves showed that the lifetimes of CdTe/CdS quantum dots films decreased to 2.8 ns after interaction with Au nano-rods. The results of finite-difference time-domain simulation indicated that Au nano-rods induced the localization of electric field, which enhanced the PL intensity of quantum dots films in the vicinity of Au nano-rods.

  15. Design and Evaluation of Photo-Induced Biofeedback Fabric for the Enhancement in Sleeping Sense

    Directory of Open Access Journals (Sweden)

    Wei-Cheng Chu

    2013-01-01

    Full Text Available Based on overcoming the sleeping obstacle for people, the purpose of this study is to design a photo-induced biofeedback fabric which is a kind of optical fiber fabric with the function of enhancing sleeping sense and to evaluate its effect. The fabrics with two layers including background layer and pattern layer were designed firstly. The pattern layers with 3 kinds of wavelengths of sine waves and the light controller with 3 kinds of flashing frequencies were then prepared. Guiding the light into the optical fiber, it will emit out of the optical fiber and stimulate our visual system to change the form of brain wave. Finally, EEG and sleeping scale were applied to evaluate the effect of enhancing sleeping sense. The results were shown that human’s brain wave can be changed from sober status to shallow-sleeping status and the effect of enhancing sleeping sense can be achieved for all pattern layers in frequencies of 0, 5 and 10 Hz. Furthermore, female is more significant than male and participants age from 30 to 49 are the most significant. Besides, the stronger the participant’s stress is, the more significant the sleeping sense is.

  16. Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells

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    Manpreet S. Chahal

    2010-07-01

    Full Text Available Phospholipase D2 (PLD2 generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

  17. Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells.

    Science.gov (United States)

    Chahal, Manpreet S; Brauner, Daniel J; Meier, Kathryn E

    2010-07-02

    Phospholipase D2 (PLD2) generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR) can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

  18. Lymphocytes from wasted mice express enhanced spontaneous and {gamma}-ray-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E. [Argonne National Lab., IL (United States)]|[Loyola Univ. Medical Center, Maywood, IL (United States); Chang-Liu, Chin-Mei [Argonne National Lab., IL (United States); Chung, Jen; Libertin, C.R. [Loyola Univ. Medical Center, Maywood, IL (United States)

    1993-09-01

    Mice bearing the autosomal recessive mutation wasted (wst/wst) display a disease pattern including faulty repair of DNA damage in lymphocytes after radiation exposure, neurologic abnormalities, and immunodeficiency. Many of the features of this mouse model have suggested a premature or increased spontaneous frequency of apoptosis in thymocytes; past work has shown an inability to establish cultured T cell lines, an abnormally high death rate of stimulated T cells in culture, and an increased sensitivity of T cells to the killing effects of ionizing radiations in wst/wst mice relative to controls. The experiments reported here were designed to examine splenic and thymic lymphocytes from wasted and control mice for signs of early apoptosis. Our results revealed enhanced expression of Rp-8 mRNA (associated with apoptosis) in thymic lymphocytes and reduced expression in splenic lymphocytes of wst/wst mice relative to controls; expression of Rp-2 and Td-30 mRNA (induced during apoptosis) were not detectable in spleen or thymus. Higher spontaneous DNA fragmentation was observed in wasted mice than in controls; however, {gamma}-ray-induced DNA fragmentation peaked at a lower dose and occurred to a greater extent in wasted mice relative to controls. These results provide evidence for high spontaneous and {gamma}-ray-induced apoptosis in T cells of wasted mice as a mechanism underlying the observed lymphocyte and DNA repair abnormalities.

  19. Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation.

    Science.gov (United States)

    Miyata, Kenichi; Takemoto, Ai; Okumura, Sakae; Nishio, Makoto; Fujita, Naoya

    2017-06-22

    Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin to malignant progression has been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, ectopic expression of podoplanin promoted cell growth in vivo and facilitated intratumoral platelet activation. Consistently, LSCC cells evoked podoplanin-mediated platelet aggregation (PMPA), and the releasates from platelets during PMPA promoted the growth of LSCC cells in vitro. Phospho-receptor-tyrosine-kinase array analysis revealed that epidermal growth factor receptor (EGFR) phosphorylation of LSCC cells was responsible for the growth promotion induced by platelet releasates. Treatment with an antiplatelet agent or podoplanin-neutralizing antibody depressed the growth of an LSCC tumour xenograft via suppression of EGFR phosphorylation. These results suggested that podoplanin in LSCC enhanced cell growth by inducing PMPA in vivo and contributed to malignant progression.

  20. Role of ACNU-induced cell cycle perturbations in enhancing effect on radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Naoto (Niigata Univ. (Japan). Brain Research Inst.)

    1992-05-01

    The cell cycle perturbations induced by ACNU and their role in enhancing effect on radiotherapy were studied using C[sub 6] rat glioma cells. The cell cycle perturbations were analyzed with flow cytometry from 3 to 72 hours after ACNU treatment. The major effect of ACNU on cell cycle progression was G[sub 2]M accumulation. Alteration of the DNA histograms after exposure to ACNU (10, 25 [mu]g/ml) showed common features; the G[sub 2]M accumulation increased to a maximum at 24 hr, remained by 30 hr, then decreased gradually. From these analyses, the temporal course of accumulation to G[sub 2]M phase of cell cycle in the presence of ACNU (10, 25 [mu]g/ml) was demonstrated. To examine whether the G[sub 2]M accumulation induced by ACNU is responsible for the potentiation of irradiation, the following study was performed. Cells were irradiated (6 Gy) at various time intervals after ACNU treatment (25 [mu]g/ml, 1 hr), and posttreatment survival was assessed by colony forming assay. All survival values obtained from the combination treatment schedules were normalized for the ACNU cell kill and then compared with the survival value obtained after irradiation alone. It appeared that combined treatment had a similar synergistic effect in all combination schedules. From these studies, it was concluded that the G[sub 2]M accumulation induced by ACNU would not be the partial synchronization as the mechanism responsible for the potentiation of irradiation. (author).

  1. Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

    Science.gov (United States)

    Viswanathan, Kavitha; Dhabhar, Firdaus S.

    2005-04-01

    Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

  2. Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells

    Directory of Open Access Journals (Sweden)

    Miaki Uzu

    2015-05-01

    Full Text Available Connexin (Cx makes up a type of intercellular channel called gap junction (GJ. GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43 (the most ubiquitous Cx subtype expression on sunitinib (SU-induced cytotoxicity in malignant mesothelioma (MM cells. Increased Cx43 expression in an MM cell line (H28 improved the ability of SU to inhibit receptor tyrosine kinase (RTK signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells.

  3. Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues

    Science.gov (United States)

    Robinson, Mike J.F.; Anselme, Patrick; Suchomel, Kristen; Berridge, Kent C.

    2015-01-01

    Amphetamine and stress can sensitize mesolimbic dopamine-related systems. In Pavlovian autoshaping, repeated exposure to uncertainty of reward prediction can enhance motivated sign-tracking or attraction to a discrete reward-predicting cue (lever CS+), as well as produce cross-sensitization to amphetamine. However, it remains unknown how amphetamine-sensitization or repeated restraint stress interact with uncertainty in controlling CS+ incentive salience attribution reflected in sign-tracking. Here rats were tested in three successive phases. First, different groups underwent either induction of amphetamine sensitization or repeated restraint stress, or else were not sensitized or stressed as control groups (either saline injections only, or no stress or injection at all). All next received Pavlovian autoshaping training under either certainty conditions (100% CS-UCS association) or uncertainty conditions (50% CS-UCS association and uncertain reward magnitude). During training, rats were assessed for sign-tracking to the lever CS+ versus goal-tracking to the sucrose dish. Finally, all groups were tested for psychomotor sensitization of locomotion revealed by an amphetamine challenge. Our results confirm that reward uncertainty enhanced sign-tracking attraction toward the predictive CS+ lever, at the expense of goal-tracking. We also report that amphetamine sensitization promoted sign-tracking even in rats trained under CS-UCS certainty conditions, raising them to sign-tracking levels equivalent to the uncertainty group. Combining amphetamine sensitization and uncertainty conditions together did not add together to elevate sign-tracking further above the relatively high levels induced by either manipulation alone. In contrast, repeated restraint stress enhanced subsequent amphetamine-elicited locomotion, but did not enhance CS+ attraction. PMID:26076340

  4. Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues.

    Science.gov (United States)

    Robinson, Mike J F; Anselme, Patrick; Suchomel, Kristen; Berridge, Kent C

    2015-08-01

    Amphetamine and stress can sensitize mesolimbic dopamine-related systems. In Pavlovian autoshaping, repeated exposure to uncertainty of reward prediction can enhance motivated sign-tracking or attraction to a discrete reward-predicting cue (lever-conditioned stimulus; CS+), as well as produce cross-sensitization to amphetamine. However, it remains unknown how amphetamine sensitization or repeated restraint stress interact with uncertainty in controlling CS+ incentive salience attribution reflected in sign-tracking. Here rats were tested in 3 successive phases. First, different groups underwent either induction of amphetamine sensitization or repeated restraint stress, or else were not sensitized or stressed as control groups (either saline injections only, or no stress or injection at all). All next received Pavlovian autoshaping training under either certainty conditions (100% CS-UCS association) or uncertainty conditions (50% CS-UCS association and uncertain reward magnitude). During training, rats were assessed for sign-tracking to the CS+ lever versus goal-tracking to the sucrose dish. Finally, all groups were tested for psychomotor sensitization of locomotion revealed by an amphetamine challenge. Our results confirm that reward uncertainty enhanced sign-tracking attraction toward the predictive CS+ lever, at the expense of goal-tracking. We also reported that amphetamine sensitization promoted sign-tracking even in rats trained under CS-UCS certainty conditions, raising them to sign-tracking levels equivalent to the uncertainty group. Combining amphetamine sensitization and uncertainty conditions did not add together to elevate sign-tracking further above the relatively high levels induced by either manipulation alone. In contrast, repeated restraint stress enhanced subsequent amphetamine-elicited locomotion, but did not enhance CS+ attraction. (c) 2015 APA, all rights reserved).

  5. Optimal emission enhancement in orthogonal double-pulse laser-induced breakdown spectroscopy

    International Nuclear Information System (INIS)

    Sanginés, R.; Contreras, V.; Sobral, H.; Robledo-Martinez, A.

    2015-01-01

    Orthogonal double-pulse (DP) laser-induced breakdown spectroscopy (LIBS) was performed using reheating and pre-ablative configurations. The ablation pulse power density was varied by two orders of magnitude and the DP experiments were carried out for a wide range of interpulse delays. For both DP-LIBS schemes, the signal enhancement was evaluated with respect to the corresponding single-pulse (SP) LIBS as a function of the interpulse delay. The reheating scheme shows a sharp maximum signal enhancement of up to 200-fold for low ablative power densities (0.4 GW cm −2 ); however, for power densities larger than 10 GW cm −2 this configuration did not improve the SP outcome. On the other hand, a more uniform signal enhancement of about 4–6 was obtained for the pre-ablative scheme nearly independently of the used ablative power density. In terms of the signal-to-noise ratio (SNR) the pre-ablative scheme shows a monotonic increment with the ablative power density. Whereas the reheating configuration reaches a maximum at 2.2 GW cm −2 , its enhancement effect collapses markedly for fluencies above 10 GW cm −2 . - Highlights: • Comparison of reheating and pre-ablative double-pulse LIBS was done using a wide range of ablation power densities. • Experimental parameters that could achieve optimal signal-to-noise ratio were investigated. • A reheating scheme is better for low-ablation power densities. • A pre-ablative configuration is better for high-ablation power densities

  6. Enhanced basophil histamine release and neutrophil chemotactic activity predispose grain dust-induced airway obstruction.

    Science.gov (United States)

    Park, H; Jung, K; Kang, K; Nahm, D; Cho, S; Kim, Y

    1999-04-01

    The pathogenic mechanism of grain dust (GD)-induced occupational asthma (OA) remains unclear. To understand further the mechanism of GD-induced OA. Fifteen employees working in a same GD industry, complaining of work-related respiratory symptoms, were enrolled and were divided into two groups according to the GD-bronchoprovocation test (BPT) result: six positive responders were grouped as group III, nine negative responders as group II and five healthy controls as group I. Serum GD-specific immunoglobulin (Ig)E (sIgE), specific IgG (sIgG) and specific IgG4 (sIgG4) antibodies were detected by enzyme-linked immunosorbent assay. Basophil histamine release was measured by the autofluorometric method, and changes of serum neutrophil chemotactic activity were observed by the Boyden chamber method. For clinical parameters such as degree of airway hyperresponsiveness to methacholine, duration of respiratory symptoms, exposure duration, and prevalences of serum sIgE, sIgG and sIgG4 antibodies, there were no significant differences between group II and III (P > 0.05, respectively). Serum neutrophil chemotactic activity increased significantly at 30 min and decreased at 240 min after the GD-BPT in group III subjects (P 0.05). Basophil histamine release induced by GD was significantly higher in group III than those of group I or group II (P < 0.05, respectively), while minimal release of anti-IgG4 antibodies was noted in all three groups. These results suggest that enhanced basophil histamine release and serum neutrophil chemotactic activity might contribute to the development of GD-induced occupational asthma.

  7. Radiation-induced bystander effects enhanced by elevated sodium chloride through sensitizing cells to bystander factors

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Lingyan; Han Wei; Chen Shaopeng; Zhao Ye; Jiang Erkang; Bao Lingzhi; Pei Bei; Yang Gen; Zhao Guoping; Wang Jun; Xu An [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, Anhui (China); Wu Lijun [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, Anhui (China)], E-mail: ljw@ipp.ac.cn

    2008-09-26

    Radiation-induced bystander effects (RIBE) have been demonstrated to occur widely in various cell lines. However, very little data is available on the genotoxic effects of RIBE combined with other factor(s). We reported previously that with a low dose of {alpha}-particle irradiation, the fraction of {gamma}-H2AX foci-positive cells in non-irradiated bystander cells was significantly increased under elevated NaCl culture conditions. In this study, we further investigated the functional role of NaCl in the enhancement of RIBE using a specially designed co-culture system and micronucleus (MN) test. It was shown that the MN frequency was not increased significantly by elevated NaCl (9.0 g/L) alone or by medium exposure. However, with 1.0 cGy {alpha}-particle irradiation, the induced MN frequency increased significantly in both irradiated and non-irradiated bystander regions. Additional studies showed that elevated NaCl made the non-irradiated bystander cells more vulnerable to bystander factors. Furthermore, it was found that the induced MN frequency in cells both in irradiated and non-irradiated bystander regions was weakened when the hypertonic medium was changed to normotonic medium for 2 h before irradiation. Such observations were quite similar to the co-effect of NaCl and hydrogen peroxide (H{sub 2}O{sub 2}), indicating that elevated NaCl might sensitize non-irradiated cells to bystander factors-induced oxidative stress.

  8. Field-induced cluster spin glass and inverse symmetry breaking enhanced by frustration

    Science.gov (United States)

    Schmidt, M.; Zimmer, F. M.; Magalhaes, S. G.

    2018-03-01

    We consider a cluster disordered model to study the interplay between short- and long-range interactions in geometrically frustrated spin systems under an external magnetic field (h). In our approach, the intercluster long-range disorder (J) is analytically treated to get an effective cluster model that is computed exactly. The clusters follow a checkerboard lattice with first-neighbor (J1) and second-neighbor (J2) interactions. We find a reentrant transition from the cluster spin-glass (CSG) state to a paramagnetic (PM) phase as the temperature decreases for a certain range of h. This inverse symmetry breaking (ISB) appears as a consequence of both quenched disorder with frustration and h, that introduce a CSG state with higher entropy than the polarized PM phase. The competitive scenario introduced by antiferromagnetic (AF) short-range interactions increases the CSG state entropy, leading to continuous ISB transitions and enhancing the ISB regions, mainly in the geometrically frustrated case (J1 =J2). Remarkably, when strong AF intracluster couplings are present, field-induced CSG phases can be found. These CSG regions are strongly related to the magnetization plateaus observed in this cluster disordered system. In fact, it is found that each field-induced magnetization jump brings a CSG region. We notice that geometrical frustration, as well as cluster size, play an important role in the magnetization plateaus and, therefore, are also relevant in the field-induced glassy states. Our findings suggest that competing interactions support ISB and field-induced CSG phases in disordered cluster systems under an external magnetic field.

  9. Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xuchen Cao; Bowen Liu; Wenfeng Cao; Weiran Zhang; Fei Zhang; Hongmeng Zhao; Ran Meng

    2013-01-01

    Apigenin (4',5,7-trihydroxyflavone) is a member of the flavone subclass of flavonoids present in fruits and vegetables.The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated.Cell proliferation and viability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays.Flow cytometry,fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy,and the role of autophagy was assessed using autophagy inhibitors.Apigenin dose-and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines.The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3,PARP cleavage and Bax/Bcl-2 ratios.The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis.In addition,the apigenin-treated cells exhibited autophagy,as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles (AVOs)by flow cytometry.Furthermore,the results of the Western blot analysis revealed that the level of LC3-Ⅱ,the processed form of LC3-Ⅰ,was increased.Treatment with the autophagy inhibitor,3-methyladenine (3-MA),significantly enhanced the apoptosis induced by apigenin,which was accompanied by an increase in the level of PARP cleavage.Similar results were also confirmed by flow cytometry and fluorescence microscopy.These results indicate that apigenin has apoptosis-and autophagy-inducing effects in breast cancer cells.Autophagy plays a cyto-protective role in apigenin-induced apoptosis,and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.

  10. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    Science.gov (United States)

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

    2015-01-01

    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  11. Arsenite enhances tumor necrosis factor-α-induced expression of vascular cell adhesion molecule-1

    International Nuclear Information System (INIS)

    Tsou, T.-C.; Yeh, Szu Ching; Tsai, E.-M.; Tsai, F.-Y.; Chao, H.-R.; Chang, Louis W.

    2005-01-01

    Epidemiological studies demonstrated a high association of vascular diseases with arsenite exposure. We hypothesize that arsenite potentiates the effect of proinflammatory cytokines on vascular endothelial cells, and hence contributes to atherosclerosis. In this study, we investigated the effect of arsenite and its induction of glutathione (GSH) on vascular cell adhesion molecule-1 (VCAM-1) protein expression in human umbilical vein endothelial cells (HUVECs) in response to tumor necrosis factor-α (TNF-α), a typical proinflammatory cytokine. Our study demonstrated that arsenite pretreatment potentiated the TNF-α-induced VCAM-1 expression with up-regulations of both activator protein-1 (AP-1) and nuclear factor-κB (NF-κB). To elucidate the role of GSH in regulation of AP-1, NF-κB, and VCAM-1 expression, we employed L-buthionine (S,R)-sulfoximine (BSO), a specific γ-glutamylcysteine synthetase (γ-GCS) inhibitor, to block intracellular GSH synthesis. Our investigation revealed that, by depleting GSH, arsenite attenuated the TNF-α-induced VCAM-1 expression as well as a potentiation of AP-1 and an attenuation of NF-κB activations by TNF-α. Moreover, we found that depletion of GSH would also attenuate the TNF-α-induced VCAM-1 expression with a down-regulation of the TNF-α-induced NF-κB activation and without significant effect on AP-1. On the other hand, the TNF-α-induced VCAM-1 expression could be completely abolished by inhibition of AP-1 or NF-κB activity, suggesting that activation of both AP-1 and NF-κB was necessary for VCAM-1 expression. In summary, we demonstrate that arsenite enhances the TNF-α-induced VCAM-1 expression in HUVECs via regulation of AP-1 and NF-κB activities in a GSH-sensitive manner. Our present study suggested a potential mechanism for arsenite in the induction of vascular inflammation and vascular diseases via modulating the actions of proinflammatory cytokines

  12. RAD9 deficiency enhances radiation induced bystander DNA damage and transcriptomal response

    International Nuclear Information System (INIS)

    Ghandhi, Shanaz A; Ponnaiya, Brian; Panigrahi, Sunil K; Hopkins, Kevin M; Cui, Qingping; Hei, Tom K; Amundson, Sally A; Lieberman, Howard B

    2014-01-01

    Radiation induced bystander effects are an important component of the overall response of cells to irradiation and are associated with human health risks. The mechanism responsible includes intra-cellular and inter-cellular signaling by which the bystander response is propagated. However, details of the signaling mechanism are not well defined. We measured the bystander response of Mrad9 +/+ and Mrad9 −/− mouse embryonic stem cells, as well as human H1299 cells with inherent or RNA interference-mediated reduced RAD9 levels after exposure to 1 Gy α particles, by scoring chromosomal aberrations and micronuclei formation, respectively. In addition, we used microarray gene expression analyses to profile the transcriptome of directly irradiated and bystander H1299 cells. We demonstrated that Mrad9 null enhances chromatid aberration frequency induced by radiation in bystander mouse embryonic stem cells. In addition, we found that H1299 cells with reduced RAD9 protein levels showed a higher frequency of radiation induced bystander micronuclei formation, compared with parental cells containing inherent levels of RAD9. The enhanced bystander response in human cells was associated with a unique transcriptomic profile. In unirradiated cells, RAD9 reduction broadly affected stress response pathways at the mRNA level; there was reduction in transcript levels corresponding to genes encoding multiple members of the UVA-MAPK and p38MAPK families, such as STAT1 and PARP1, suggesting that these signaling mechanisms may not function optimally when RAD9 is reduced. Using network analysis, we found that differential activation of the SP1 and NUPR1 transcriptional regulators was predicted in directly irradiated and bystander H1299 cells. Transcription factor prediction analysis also implied that HIF1α (Hypoxia induced factor 1 alpha) activation by protein stabilization in irradiated cells could be a negative predictor of the bystander response, suggesting that local hypoxic stress

  13. Heat transfer enhancement induced by electrically generated convection in a plane layer of dielectric liquid

    International Nuclear Information System (INIS)

    Traoré, P; Wu, J; Romat, H; Louste, C; Perez, A; Koulova, D

    2012-01-01

    The electro-thermo-convective motion in a plane horizontal dielectric liquid layer subjected to simultaneous action of electric field and thermal gradient is numerically investigated. We consider the case of a strong unipolar charge injection C = 10 from above or below. Therefore in this context, we only take into account the Coulomb force, disregarding the dielectric one. The effect of the electric field on the heat transfer is analyzed through the characterization of the time history of the Nusselt number as well as its evolution according to the characteristic dimensionless electric parameter T. It is demonstrated that the electric effects dominate the buoyancy ones resulting in an electrically induced convection which significantly enhance the heat transfer.

  14. Giant Pressure-Induced Enhancement of Seebeck Coefficient and Thermoelectric Efficiency in SnTe

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Jason; Kumar, Ravhi; Park, Changyong; Kenney-Benson, Curtis; Cornelius, Andrew; Velisavljevic, Nenad (CIW); (LANL); (UNLV)

    2017-10-30

    The thermoelectric properties of polycrystalline SnTe have been measured up to 4.5 GPa at 330 K. SnTe shows an enormous enhancement in Seebeck coefficient, greater than 200 % after 3 GPa, which correlates to a known pressure-induced structural phase transition that is observed through simultaneous in situ X-ray diffraction measurement. Electrical resistance and relative changes to the thermal conductivity were also measured, enabling the determination of relative changes in the dimensionless figure of merit (ZT), which increases dramatically after 3 GPa, reaching 350 % of the lowest pressure ZT value. The results demonstrate a fundamental relationship between structure and thermoelectric behaviours and suggest that pressure is an effective tool to control them.

  15. Little enhancement of meal-induced glucagon-like peptide 1 secretion in Japanese

    DEFF Research Database (Denmark)

    Yabe, Daisuke; Kuroe, Akira; Lee, Soushou

    2010-01-01

    with or without type 2 diabetes (T2DM). Seventeen Japanese healthy controls and 18 age-matched and untreated patients with T2DM of short duration participated in the present study. Fasting levels of total GPL-1 were similar between the two groups (approximately 15 pM), and intact GLP-1 levels were considerably...... are considerably low in the Japanese and that meal-induced enhancement of GLP-1 secretion is negligible in the Japanese. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00010.x, 2010).......Although glucose-dependent insulinotropic polypeptide (GIP) levels have been characterized previously, GLP-1 levels in Asians remain unclear. Here, we investigate total and intact levels of GLP-1, as well as GIP during oral glucose and meal tolerance tests (OGTT and MTT) in Japanese patients...

  16. Induced-Charge Enhancement of the Diffusion Potential in Membranes with Polarizable Nanopores.

    Science.gov (United States)

    Ryzhkov, I I; Lebedev, D V; Solodovnichenko, V S; Shiverskiy, A V; Simunin, M M

    2017-12-01

    When a charged membrane separates two salt solutions of different concentrations, a potential difference appears due to interfacial Donnan equilibrium and the diffusion junction. Here, we report a new mechanism for the generation of a membrane potential in polarizable conductive membranes via an induced surface charge. It results from an electric field generated by the diffusion of ions with different mobilities. For uncharged membranes, this effect strongly enhances the diffusion potential and makes it highly sensitive to the ion mobilities ratio, electrolyte concentration, and pore size. Theoretical predictions on the basis of the space-charge model extended to polarizable nanopores fully agree with experimental measurements in KCl and NaCl aqueous solutions.

  17. Sandblasting induced stress release and enhanced adhesion strength of diamond films deposited on austenite stainless steel

    Science.gov (United States)

    Li, Xiao; Ye, Jiansong; Zhang, Hangcheng; Feng, Tao; Chen, Jianqing; Hu, Xiaojun

    2017-08-01

    We firstly used sandblasting to treat austenite stainless steel and then deposited a Cr/CrN interlayer by close field unbalanced magnetron sputtering on it. After that, diamond films were prepared on the interlayer. It is found that the sandblasting process induces phase transition from austenite to martensite in the surface region of the stainless steel, which decreases thermal stress in diamond films due to lower thermal expansion coefficient of martensite phase compared with that of austenite phase. The sandblasting also makes stainless steel's surface rough and the Cr/CrN interlayer film inherits the rough surface. This decreases the carburization extent of the interlayer, increases nucleation density and modifies the stress distribution. Due to lower residual stress and small extent of the interlayer's carburization, the diamond film on sandblast treated austenite stainless steel shows enhanced adhesion strength.

  18. Field enhancement of multiphoton induced luminescence processes in ZnO nanorods

    Science.gov (United States)

    Hyyti, Janne; Perestjuk, Marko; Mahler, Felix; Grunwald, Rüdiger; Güell, Frank; Gray, Ciarán; McGlynn, Enda; Steinmeyer, Günter

    2018-03-01

    The near-ultraviolet photoluminescence of ZnO nanorods induced by multiphoton absorption of unamplified Ti:sapphire pulses is investigated. Power dependence measurements have been conducted with an adaptation of the ultrashort pulse characterization method of interferometric frequency-resolved optical gating. These measurements enable the separation of second harmonic and photoluminescence bands due to their distinct coherence properties. A detailed analysis yields fractional power dependence exponents in the range of 3-4, indicating the presence of multiple nonlinear processes. The range in measured exponents is attributed to differences in local field enhancement, which is supported by independent photoluminescence and structural measurements. Simulations based on Keldysh theory suggest contributions by three- and four-photon absorption as well as avalanche ionization in agreement with experimental findings.

  19. Einstein-Podolsky-Rosen entanglement via nonlinear processes enhanced by electromagnetically induced transparency

    International Nuclear Information System (INIS)

    Cheng Guangling; Hu Xiangming; Zhong Wenxue

    2009-01-01

    We show that Einstein-Podolsky-Rosen (EPR) light entanglement is obtainable via the resonant nonlinear interactions enhanced by electromagnetically induced transparency. A three-level system is used as a unified model, where two metastable states are coupled to each other via microwave, or Raman, or two-photon transition, and the upper metastable state is coupled to the excited state. A pair of inner sidebands is amplified as optical cavity modes via the transition from the excited state to the other metastable state. The analysis is presented by using the dressed-atom squeezed-transformed-mode approach. For a proper ratio of the amplitudes of the applied fields, the sum of the variances for two EPR-like operators approaches zero, which corresponds to EPR entanglement.

  20. Virtual nature environment with nature sound exposure induce stress recovery by enhanced parasympathetic activity

    DEFF Research Database (Denmark)

    Annerstedt, Matilda; Jönsson, Peter; Wallergård, Mattias

    2013-01-01

    . The group that recovered in virtual nature without sound and the control group displayed no particular autonomic activation or deactivation. The results demonstrate a potential mechanistic link between nature, the sounds of nature, and stress recovery, and suggest the potential importance of virtual reality......Experimental research on stress recovery in natural environments is limited, as is study of the effect of sounds of nature. After inducing stress by means of a virtual stress test, we explored physiological recovery in two different virtual natural environments (with and without exposure to sounds...... of nature) and in one control condition. Cardiovascular data and saliva cortisol were collected. Repeated ANOVA measurements indicated parasympathetic activation in the group subjected to sounds of nature in a virtual natural environment, suggesting enhanced stress recovery may occur in such surroundings...

  1. Hyperthermia enhances radiosensitivity of colorectal cancer cells through ROS inducing autophagic cell death.

    Science.gov (United States)

    Ba, Ming-Chen; Long, Hui; Wang, Shuai; Wu, Yin-Bing; Zhang, Bo-Huo; Yan, Zhao-Fei; Yu, Fei-Hong; Cui, Shu-Zhong

    2018-04-01

    Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC). After four weeks of treatment, cancer growth inhibition, rate and mitochondrial membrane potential were measured with MTT and JC-1 assays, respectively, while ROS were estimated fluorimetrically. The relationship of these parameters to expressions of autophagy-related genes Beclin1, LC3B, and mTOR was analyzed. Gene expression was measured by Real-Time polymerase chain reaction (RT-PCR). There were significant increases in ROS levels and mitochondrial membrane potential in the HT + RT group. ROS levels in the HT + RT group increased more significantly than in any other group. In contrast, ROS levels in the HT + RT + NAC group were significantly decreased relative to the HT + RT group. The number of autophagic bodies in HT + RT group was higher than that of mock group. There were significant increases in the expression of Beclin1 and LC3B genes, while mTOR expression was significantly decreased in the HT + CT group. Treatment with NAC reversed the pattern of these changes. These results indicate that HT enhances the radiosensitivity of colorectal cancer cells to RT through ROS inducing autophagic cell death. © 2017 Wiley Periodicals, Inc.

  2. Enhancement of nitrite on heme-induced oxidative reactions: A potential toxicological implication.

    Science.gov (United States)

    Lu, Naihao; Chen, Wei; Zhu, Jingjie; Peng, Yi-Yuan

    2012-02-01

    Evidence to support the role of heme as major inducers of oxidative damage is increasingly present. Nitrite (NO(2)(-)) is one of the major end products of NO metabolism. Although the biological significance of heme/NO(2)(-)-mediated protein tyrosine nitration is a subject of great interest, the important roles of NO(2)(-) on heme-dependent redox reaction have been greatly underestimated. In this study, we investigated the influence of NO(2)(-) on heme -dependent oxidative reactions. It was found that NO(2)(-) had the capacity to act as a reducing agent to remove high oxidation states of heme iron. In the reduction of ferryl heme to ferric heme, NO(2)(-) was oxidized to a nitrating agent NO(2), and subsequently, tyrosine residues in bovine serum albumin (BSA) were nitrated. However, the presence of NO(2)(-) surprisingly exerted pro-oxidant effect on heme-H(2)O(2)-induced formation of BSA carbonyls at lower concentrations and enhanced the loss of HepG2 cell viability dose-dependently, which was probably due to the ability of this inorganic compound to efficiently enhance the peroxidase activity and oxidative degradation of heme. These data provide novel evidence that the dietary intake and experimental use of NO(2)(-) in vivo and in vitro would possess the pro-oxidant activity through interfering in heme-dependent oxidative reactions. Besides the classic role in protein tyrosine nitration, the deleterious effects on heme redox reactions may provide new insights into the toxicological implications of NO(2)(-) with cellular heme proteins. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Hippocampal histone acetylation regulates object recognition and the estradiol-induced enhancement of object recognition.

    Science.gov (United States)

    Zhao, Zaorui; Fan, Lu; Fortress, Ashley M; Boulware, Marissa I; Frick, Karyn M

    2012-02-15

    Histone acetylation has recently been implicated in learning and memory processes, yet necessity of histone acetylation for such processes has not been demonstrated using pharmacological inhibitors of histone acetyltransferases (HATs). As such, the present study tested whether garcinol, a potent HAT inhibitor in vitro, could impair hippocampal memory consolidation and block the memory-enhancing effects of the modulatory hormone 17β-estradiol E2. We first showed that bilateral infusion of garcinol (0.1, 1, or 10 μg/side) into the dorsal hippocampus (DH) immediately after training impaired object recognition memory consolidation in ovariectomized female mice. A behaviorally effective dose of garcinol (10 μg/side) also significantly decreased DH HAT activity. We next examined whether DH infusion of a behaviorally subeffective dose of garcinol (1 ng/side) could block the effects of DH E2 infusion on object recognition and epigenetic processes. Immediately after training, ovariectomized female mice received bilateral DH infusions of vehicle, E2 (5 μg/side), garcinol (1 ng/side), or E2 plus garcinol. Forty-eight hours later, garcinol blocked the memory-enhancing effects of E2. Garcinol also reversed the E2-induced increase in DH histone H3 acetylation, HAT activity, and levels of the de novo methyltransferase DNMT3B, as well as the E2-induced decrease in levels of the memory repressor protein histone deacetylase 2. Collectively, these findings suggest that histone acetylation is critical for object recognition memory consolidation and the beneficial effects of E2 on object recognition. Importantly, this work demonstrates that the role of histone acetylation in memory processes can be studied using a HAT inhibitor.

  4. Thermo-responsive polymeric nanoparticles for enhancing neuronal differentiation of human induced pluripotent stem cells.

    Science.gov (United States)

    Seo, Hye In; Cho, Ann-Na; Jang, Jiho; Kim, Dong-Wook; Cho, Seung-Woo; Chung, Bong Geun

    2015-10-01

    We report thermo-responsive retinoic acid (RA)-loaded poly(N-isopropylacrylamide)-co-acrylamide (PNIPAM-co-Am) nanoparticles for directing human induced pluripotent stem cell (hiPSC) fate. Fourier transform infrared spectroscopy and (1)H nuclear magnetic resonance analysis confirmed that RA was efficiently incorporated into PNIAPM-co-Am nanoparticles (PCANs). The size of PCANs dropped with increasing temperatures (300-400 nm at room temperature, 80-90 nm at 37°C) due to its phase transition from hydrophilic to hydrophobic. Due to particle shrinkage caused by this thermo-responsive property of PCANs, RA could be released from nanoparticles in the cells upon cellular uptake. Immunocytochemistry and quantitative real-time polymerase chain reaction analysis demonstrated that neuronal differentiation of hiPSC-derived neuronal precursors was enhanced after treatment with 1-2 μg/ml RA-loaded PCANs. Therefore, we propose that this PCAN could be a potentially powerful carrier for effective RA delivery to direct hiPSC fate to neuronal lineage. The use of induced pluripotent stem cells (iPSCs) has been at the forefront of research in the field of regenerative medicine, as these cells have the potential to differentiate into various terminal cell types. In this article, the authors utilized a thermo-responsive polymer, Poly(N-isopropylacrylamide) (PNIPAM), as a delivery platform for retinoic acid. It was shown that neuronal differentiation could be enhanced in hiPSC-derived neuronal precursor cells. This method may pave a way for future treatment of neuronal diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Flavanol-rich cocoa consumption enhances exercise-induced executive function improvements in humans.

    Science.gov (United States)

    Tsukamoto, Hayato; Suga, Tadashi; Ishibashi, Aya; Takenaka, Saki; Tanaka, Daichi; Hirano, Yoshitaka; Hamaoka, Takafumi; Goto, Kazushige; Ebi, Kumiko; Isaka, Tadao; Hashimoto, Takeshi

    2018-02-01

    Aerobic exercise is known to acutely improve cognitive functions, such as executive function (EF) and memory function (MF). Additionally, consumption of flavanol-rich cocoa has been reported to acutely improve cognitive function. The aim of this study was to determine whether high cocoa flavanol (CF; HCF) consumption would enhance exercise-induced improvement in cognitive function. To test this hypothesis, we examined the combined effects of HCF consumption and moderate-intensity exercise on EF and MF during postexercise recovery. Ten healthy young men received either an HCF (563 mg of CF) or energy-matched low CF (LCF; 38 mg of CF) beverage 70 min before exercise in a single-blind counterbalanced manner. The men then performed moderate-intensity cycling exercise at 60% of peak oxygen uptake for 30 min. The participants performed a color-word Stroop task and face-name matching task to evaluate EF and MF, respectively, during six time periods throughout the experimental session. EF significantly improved immediately after exercise compared with before exercise in both conditions. However, EF was higher after HCF consumption than after LCF consumption during all time periods because HCF consumption improved EF before exercise. In contrast, HCF consumption and moderate-intensity exercise did not improve MF throughout the experiment. The present findings demonstrated that HCF consumption before moderate-intensity exercise could enhance exercise-induced improvement in EF, but not in MF. Therefore, we suggest that the combination of HCF consumption and aerobic exercise may be beneficial for improving EF. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Combination of silicon nitride and porous silicon induced optoelectronic features enhancement of multicrystalline silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Rabha, Mohamed Ben; Dimassi, Wissem; Gaidi, Mounir; Ezzaouia, Hatem; Bessais, Brahim [Laboratoire de Photovoltaique, Centre de Recherches et des Technologies de l' Energie, Technopole de Borj-Cedria, BP 95, 2050 Hammam-Lif (Tunisia)

    2011-06-15

    The effects of antireflection (ARC) and surface passivation films on optoelectronic features of multicrystalline silicon (mc-Si) were investigated in order to perform high efficiency solar cells. A double layer consisting of Plasma Enhanced Chemical Vapor Deposition (PECVD) of silicon nitride (SiN{sub x}) on porous silicon (PS) was achieved on mc-Si surfaces. It was found that this treatment decreases the total surface reflectivity from about 25% to around 6% in the 450-1100 nm wavelength range. As a result, the effective minority carrier diffusion length, estimated from the Laser-beam-induced current (LBIC) method, was found to increase from 312 {mu}m for PS-treated cells to about 798 {mu}m for SiN{sub x}/PS-treated ones. The deposition of SiN{sub x} was found to impressively enhance the minority carrier diffusion length probably due to hydrogen passivation of surface, grain boundaries and bulk defects. Fourier Transform Infrared Spectroscopy (FTIR) shows that the vibration modes of the highly suitable passivating Si-H bonds exhibit frequency shifts toward higher wavenumber, depending on the x ratio of the introduced N atoms neighbors. (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  7. DNA Tetrahedron Delivery Enhances Doxorubicin-Induced Apoptosis of HT-29 Colon Cancer Cells

    Science.gov (United States)

    Zhang, Guiyu; Zhang, Zhiyong; Yang, Junen

    2017-08-01

    As a nano-sized drug carrier with the advantage of modifiability and proper biocompatibility, DNA tetrahedron (DNA tetra) delivery is hopeful to enhance the inhibitory efficiency of nontargeted anticancer drugs. In this investigation, doxorubicin (Dox) was assembled to a folic acid-modified DNA tetra via click chemistry to prepare a targeted antitumor agent. Cellular uptake efficiency was measured via fluorescent imaging. Cytotoxicity, inhibition efficiency, and corresponding mechanism on colon cancer cell line HT-29 were evaluated by MTT assay, cell proliferation curve, western blot, and flow cytometry. No cytotoxicity was induced by DNA tetra, but the cellular uptake ratio increased obviously resulting from the DNA tetra-facilitated penetration through cellular membrane. Accordingly, folic acid-DNA tetra-Dox markedly increased the antitumor efficiency with increased apoptosis levels. In details, 100 μM was the effective concentration and a 6-h incubation period was needed for apoptosis induction. In conclusion, nano-sized DNA tetrahedron was a safe and effective delivery system for Dox and correspondingly enhanced the anticancer efficiency.

  8. Pimecrolimus enhances TLR2/6-induced expression of antimicrobial peptides in keratinocytes.

    Science.gov (United States)

    Büchau, Amanda S; Schauber, Jürgen; Hultsch, Thomas; Stuetz, Anton; Gallo, Richard L

    2008-11-01

    Calcineurin inhibitors are potent inhibitors of T-cell-receptor mediated activation of the adaptive immune system. The effects of this class of drug on the innate immune response system are not known. Keratinocytes are essential to innate immunity in skin and rely on toll-like receptors (TLRs) and antimicrobial peptides to appropriately recognize and respond to injury or microbes. In this study we examined the response of cultured human keratinocytes to pimecrolimus. We observed that pimecrolimus enhances distinct expression of cathelicidin, CD14, and human beta-defensin-2 and beta-defensin-3 in response to TLR2/6 ligands. Some of these responses were further enhanced by 1,25 vitamin D3. Pimecrolimus also increased the functional capacity of keratinocytes to inhibit growth of Staphylococcus aureus and decreased TLR2/6-induced expression of IL-10 and IL-1beta. Furthermore, pimecrolimus inhibited nuclear translocation of NFAT and NF-kappaB in keratinocytes. These observations uncover a previously unreported function for pimecrolimus in cutaneous innate host defense.

  9. Salinity induced oxidative stress enhanced biofuel production potential of microalgae Scenedesmus sp. CCNM 1077.

    Science.gov (United States)

    Pancha, Imran; Chokshi, Kaumeel; Maurya, Rahulkumar; Trivedi, Khanjan; Patidar, Shailesh Kumar; Ghosh, Arup; Mishra, Sandhya

    2015-01-01

    Microalgal biomass is considered as potential feedstock for biofuel production. Enhancement of biomass, lipid and carbohydrate contents in microalgae is important for the commercialization of microalgal biofuels. In the present study, salinity stress induced physiological and biochemical changes in microalgae Scenedesmus sp. CCNM 1077 were studied. During single stage cultivation, 33.13% lipid and 35.91% carbohydrate content was found in 400 mM NaCl grown culture. During two stage cultivation, salinity stress of 400 mM for 3 days resulted in 24.77% lipid (containing 74.87% neutral lipid) along with higher biomass compared to single stage, making it an efficient strategy to enhance biofuel production potential of Scenedesmus sp. CCNM 1077. Apart from biochemical content, stress biomarkers like hydrogen peroxide, lipid peroxidation, ascorbate peroxidase, proline and mineral contents were also studied to understand the role of reactive oxygen species (ROS) mediated lipid accumulation in microalgae Scenedesmus sp. CCNM 1077. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Effects of Saccade Induced Retrieval Enhancement on conceptual and perceptual tests of explicit & implicit memory.

    Science.gov (United States)

    Parker, Andrew; Powell, Daniel; Dagnall, Neil

    2018-03-01

    The effects of saccadic horizontal (bilateral) eye movements upon tests of both conceptual and perceptual forms of explicit and implicit memory were investigated. Participants studied a list of words and were then assigned to one of four test conditions: conceptual explicit, conceptual implicit, perceptual explicit, or perceptual implicit. Conceptual tests comprised category labels with either explicit instructions to recall corresponding examples from the study phase (category-cued recall), or implicit instructions to generate any corresponding examples that spontaneously came to mind (category-exemplar generation). Perceptual tests comprised of word-fragments with either explicit instructions to complete these with study items (word-fragment-cued recall), or implicit instructions to complete each fragment with the first word that simply 'popped to mind' (word-fragment completion). Just prior to retrieval, participants were required to engage in 30 s of bilateral vs. no eye movements. Results revealed that saccadic horizontal eye movements enhanced performance in only the conceptual explicit condition, indicating that Saccade-Induced Retrieval Enhancement is a joint function of conceptual and explicit retrieval mechanisms. Findings are discussed from both a cognitive and neuropsychological perspective, in terms of their potential functional and neural underpinnings. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

    Science.gov (United States)

    Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

    2017-11-01

    Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Compressive strain induced enhancement in thermoelectric-power-factor in monolayer MoS2 nanosheet

    International Nuclear Information System (INIS)

    Dimple; Jena, Nityasagar; De Sarkar, Abir

    2017-01-01

    Strain and temperature induced tunability in the thermoelectric properties in monolayer MoS 2 (ML-MoS 2 ) has been demonstrated using density functional theory coupled to semi-classical Boltzmann transport theory. Compressive strain, in general and uniaxial compressive strain (along the zig-zag direction), in particular, is found to be most effective in enhancing the thermoelectric power factor, owing to the higher electronic mobility and its sensitivity to lattice compression along this direction. Variation in the Seebeck coefficient and electronic band gap with strain is found to follow the Goldsmid–Sharp relation. n-type doping is found to raise the relaxation time-scaled thermoelectric power factor higher than p-type doping and this divide widens with increasing temperature. The relaxation time-scaled thermoelectric power factor in optimally n-doped ML-MoS 2 is found to undergo maximal enhancement under the application of 3% uniaxial compressive strain along the zig-zag direction, when both the ( direct ) electronic band gap and the Seebeck coefficient reach their maximum, while the electron mobility drops down drastically from 73.08 to 44.15 cm 2 V −1 s −1 . Such strain sensitive thermoelectric responses in ML-MoS 2 could open doorways for a variety of applications in emerging areas in 2D-thermoelectrics, such as on-chip thermoelectric power generation and waste thermal energy harvesting. (paper)

  13. Frequency-Dependent Enhancement of Fluid Intelligence Induced by Transcranial Oscillatory Potentials

    Energy Technology Data Exchange (ETDEWEB)

    Santarnecchi, Emiliano [Univ. of Siena (Italy). Dept. of Medicine, Surgery and Neuroscience; Polizzotto, Nicola Riccardo [Univ. of Pittsburgh, PA (United States). Dept. of Psychiatry; Godone, Marco [Univ. of Siena (Italy). Dept. of Medicine, Surgery and Neuroscience; Giovannelli, Fabio [San Giovanni di Dio Hospital, Florence (Italy). Complex Unit of Neurology; Feurra, Matteo [Univ. of Siena (Italy). Dept. of Medicine, Surgery and Neuroscience; Matzen, Laura [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rossi, Alessandro [Univ. of Siena (Italy). Dept. of Medicine, Surgery and Neuroscience; Rossi, Simone [Univ. of Siena (Italy). Dept. of Medicine, Surgery and Neuroscience

    2013-08-05

    Everyday problem solving requires the ability to go beyond experience by efficiently encoding and manipulating new information, i.e., fluid intelligence (Gf) [1]. Performance in tasks involving Gf, such as logical and abstract reasoning, has been shown to rely on distributed neural networks, with a crucial role played by prefrontal regions [2]. Synchronization of neuronal activity in the gamma band is a ubiquitous phenomenon within the brain; however, no evidence of its causal involvement in cognition exists to date [3]. Here, we show an enhancement of Gf ability in a cognitive task induced by exogenous rhythmic stimulation within the gamma band. Imperceptible alternating current [4] delivered through the scalp over the left middle frontal gyrus resulted in a frequency-specific shortening of the time required to find the correct solution in a visuospatial abstract reasoning task classically employed to measure Gf abilities (i.e., Raven’s matrices) [5]. Crucially, gamma-band stimulation (γ-tACS) selectively enhanced performance only on more complex trials involving conditional/logical reasoning. The finding presented here supports a direct involvement of gamma oscillatory activity in the mechanisms underlying higher-order human cognition.

  14. Fruit-Enhanced Resistance to Microbial Infection Induced by Selective Laser Excitation

    Directory of Open Access Journals (Sweden)

    Alicia G. Gonzálvez

    2013-01-01

    Full Text Available Table grapes were irradiated with laser pulses at two different wavelengths: one selected at 302.1 nm, that is, resonant with the transresveratrol biphoton absorption band, and another selected at 300 nm, that is a nonresonant wavelength where trans-resveratrol two-photon absorption is negligible. Attenuated total reflectance Fourier transformed infrared spectroscopic analyses of the irradiated grapes' skin showed an enhancement of polyphenols' content when the resonant wavelength was employed. Furthermore, microbiological analysis performed with nontreated (control, nonresonant, and resonantly irradiated grapes demonstrated how the last samples developed a significantly lower number of colony forming units. Since the only difference between the two (resonant and nonresonant irradiation conditions was just a couple of nanometres in the employed UV-B laser wavelengths, the germicidal effect should be considered very similar. As a result, the observed difference in the table grape resistance to microbial infection was attributed to a wavelength-dependent-induced photochemistry. Finally, the potentiality of this method to enhance the postharvest health status of table grapes is remarked.

  15. Ethanol enhances GABA-induced 36Cl-influx in primary spinal cord cultured neurons

    International Nuclear Information System (INIS)

    Ticku, M.K.; Lowrimore, P.; Lehoullier, P.

    1986-01-01

    Ethanol has a pharmacological profile similar to other centrally acting drugs, which facilitate GABAergic transmission. GABA is known to produce its effects by increasing the conductance to Cl- ions. In this study, we have examined the effect of ethanol on GABA-induced 36Cl-influx in primary spinal cord cultured neurons. GABA produces a concentration-dependent, and saturable effect on 36Cl-influx in these neurons. Ethanol potentiates the effect of GABA on 36Cl-influx in these neurons. GABA (20 microM) increased the 36Cl-influx by 75% over the basal value, and in the presence of 50 mM ethanol, the observed increase was 142%. Eadie-Hoffstee analysis of the saturation curves indicated that ethanol decreases the Km value of GABA (10.6 microM to 4.2 microM), and also increases the Vmax. Besides potentiating the effect of GABA, ethanol also appears to have a direct effect in the absence of added GABA. These results suggest that ethanol enhances GABA-induced 36Cl-influx and indicate a role of GABAergic system in the actions of ethanol. These results also support the behavioral and electrophysiological studies, which have implicated GABA systems in the actions of ethanol. The potential mechanism(s) and the role of direct effect of ethanol is not clear at this time, but is currently being investigated

  16. Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorouracil and cyclophosphamide.

    Science.gov (United States)

    Agrawal, Siddarth; Łuc, Mateusz; Ziółkowski, Piotr; Agrawal, Anil Kumar; Pielka, Ewa; Walaszek, Kinga; Zduniak, Krzysztof; Woźniak, Marta

    2017-06-01

    The study was designed to evaluate the potential use of insulin for cancer-specific treatment. Insulin-induced sensitivity of MCF-7 breast cancer cells to chemotherapeutic agents 5-fluorouracil and cyclophosphamide was evaluated. To investigate and establish the possible mechanisms of this phenomenon, we assessed cell proliferation, induction of apoptosis, activation of apoptotic and autophagic pathways, expression of glucose transporters 1 and 3, formation of reactive oxygen species, and wound-healing assay. Additionally, we reviewed the literature regarding theuse of insulin in cancer-specific treatment. We found that insulin increases the cytotoxic effect of 5-fluorouracil and cyclophosphamide in vitro up to two-fold. The effect was linked to enhancement of apoptosis, activation of apoptotic and autophagic pathways, and overexpression of glucose transporters 1 and 3 as well as inhibition of cell proliferation and motility. We propose a model for insulin-induced sensitization process. Insulin acts as a sensitizer of cancer cells to cytotoxic therapy through various mechanisms opening a possibility for metronomic insulin-based treatments.

  17. Kokumi Substances, Enhancers of Basic Tastes, Induce Responses in Calcium-Sensing Receptor Expressing Taste Cells

    Science.gov (United States)

    Maruyama, Yutaka; Yasuda, Reiko; Kuroda, Motonaka; Eto, Yuzuru

    2012-01-01

    Recently, we reported that calcium-sensing receptor (CaSR) is a receptor for kokumi substances, which enhance the intensities of salty, sweet and umami tastes. Furthermore, we found that several γ-glutamyl peptides, which are CaSR agonists, are kokumi substances. In this study, we elucidated the receptor cells for kokumi substances, and their physiological properties. For this purpose, we used Calcium Green-1 loaded mouse taste cells in lingual tissue slices and confocal microscopy. Kokumi substances, applied focally around taste pores, induced an increase in the intracellular Ca2+ concentration ([Ca2+]i) in a subset of taste cells. These responses were inhibited by pretreatment with the CaSR inhibitor, NPS2143. However, the kokumi substance-induced responses did not require extracellular Ca2+. CaSR-expressing taste cells are a different subset of cells from the T1R3-expressing umami or sweet taste receptor cells. These observations indicate that CaSR-expressing taste cells are the primary detectors of kokumi substances, and that they are an independent population from the influenced basic taste receptor cells, at least in the case of sweet and umami. PMID:22511946

  18. alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-, but not beta-amyloid-induced neurotoxicity.

    Science.gov (United States)

    de Fiebre, Nancyellen C; de Fiebre, Christopher M

    2005-01-03

    The alpha7 subtype of nicotinic acetylcholine receptor (nAChR) has been implicated as a potential site of action for two neurotoxins, ethanol and the Alzheimer's disease related peptide, beta-amyloid. Here, we utilized primary neuronal cultures of cerebral cortex from alpha7 nAChR null mutant mice to examine the role of this receptor in modulating the neurotoxic properties of subchronic, "binge" ethanol and beta-amyloid. Knockout of the alpha7 nAChR gene selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related fashion. Susceptibility of cultures to beta-amyloid induced toxicity, however, was unaffected by alpha7 nAChR gene null mutation. Further, beta-amyloid did not inhibit the binding of the highly alpha7-selective radioligand, [(125)I]alpha-bungarotoxin. On the other hand, in studies in Xenopus oocytes ethanol efficaciously inhibited alpha7 nAChR function. These data suggest that alpha7 nAChRs modulate the neurotoxic effects of binge ethanol, but not the neurotoxicity produced by beta-amyloid. It is hypothesized that inhibition of alpha7 nAChRs by ethanol provides partial protection against the neurotoxic properties of subchronic ethanol.

  19. Enhancement of synaptic transmission induced by BDNF in cultured cortical neurons

    Science.gov (United States)

    He, Jun; Gong, Hui; Zeng, Shaoqun; Li, Yanling; Luo, Qingming

    2005-03-01

    Brain-derived neurotrophic factor (BDNF), like other neurotrophins, has long-term effects on neuronal survival and differentiation; furthermore, BDNF has been reported to exert an acute potentiation of synaptic activity and are critically involved in long-term potentiation (LTP). We found that BDNF rapidly induced potentiation of synaptic activity and an increase in the intracellular Ca2+ concentration in cultured cortical neurons. Within minutes of BDNF application to cultured cortical neurons, spontaneous firing rate was dramatically increased as were the frequency and amplitude of excitatory spontaneous postsynaptic currents (EPSCs). Fura-2 recordings showed that BDNF acutely elicited an increase in intracellular calcium concentration ([Ca2+]c). This effect was partially dependent on [Ca2+]o; The BDNF-induced increase in [Ca2+]c can not be completely blocked by Ca2+-free solution. It was completely blocked by K252a and partially blocked by Cd2+ and TTX. The results demonstrate that BDNF can enhances synaptic transmission and that this effect is accompanied by a rise in [Ca2+]c that requires two route: the release of Ca2+ from intracellular calcium stores and influx of extracellular Ca2+ through voltage-dependent Ca2+ channels in cultured cortical neurons.

  20. The Extract of Lycium depressum Stocks Enhances Wound Healing in Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Naji, Siamak; Zarei, Leila; Pourjabali, Masoumeh; Mohammadi, Rahim

    2017-06-01

    In diabetes, impaired wound healing and other tissue abnormalities are considered major concerns. The aim of the present study was to assess the wound-healing activity of methanolic extracts of the extract of Lycium depressum leaves. A total of 60 healthy male Wistar diabetic rats weighing approximately 160 to 180 g and 7 weeks of age were randomized into 10 groups for incision and excision wound models: sham surgery group (SHAM), including creation of wounds and no treatment; base formulation group (FG) with creation of wounds and application of base formulation ointment; treatment group 1 (TG1) with 1 g of powder extract of the plant material in ointment; treatment group 2 (TG2) with 2 g; and treatment group 4 (TG3) with 4 g of powder extract of the plant material in ointment. A wound was induced by an excision- and incision-based wound model in male rats. The mature green leaves of L depressum were collected and authenticated. Extractions of dried leaves were carried out. For wound-healing activity, the extracts were applied topically in the form of ointment and compared with control groups. The healing of the wound was assessed based on excision, incision, hydroxyproline estimation, and biomechanical and biochemical studies. The extract of L depressum leaves enhanced wound contraction, decreased epithelialization time, increased hydroxyproline content, and improved mechanical indices and histological characteristics in treatment groups compared with SHAM and FG ( P healing in a diabetes induced model.

  1. Extracts of human atherosclerotic lesions modify LDL inducing enhanced macrophage uptake

    International Nuclear Information System (INIS)

    Hoff, H.F.; O'Neill, J.

    1986-01-01

    Both an LDL-like fraction isolated from human aortic plaques and LDL incubated with cultured aortic endothelial or smooth muscle cells have been shown to be internalized by macrophages in vitro in an unregulated fashion leading to foam cell formation. Lipid peroxidation induced by free radicals released from cells was shown to be responsible for cell-modified LDL. The authors incubated LDL with a supernatant fraction of leached, i.e. non-homogenized, extracts of aortic plaques for one hour at 37 0 C, to determine whether extracellular components present in arteries were also capable of modifying LDL. Extract-treated LDL showed the following changes relative to untreated LDL: 1) increased electrophretic mobility, 2) altered pattern of B-100 on SDS-PAGE, i.e. presence of a doublet with higher M/sub r/ than B-100, and 3) enhanced uptake by cultured mouse peritoneal macrophages as measured by increased degradation of 125 I-LDL, and increased stimulation of cholesterol esterification using 14 C-oleate. Extracts from homogenized plaques and grossly normal intima induced similar changes. The modification was tissue specific in that extracts of arteries but not of liver, muscle or skin modified LDL. Protease degradation of LDL during incubation was probably not responsible since inhibitors did not prevent modification. It is possible that products of lipid peroxidation present in extracellular lipid of arteries may propagate free radicals or be incorporated into LDL, leading to modifications similar to those found in cell-modified LDL

  2. Host-Induced Silencing of Pathogenicity Genes Enhances Resistance to Fusarium oxysporum Wilt in Tomato.

    Science.gov (United States)

    Bharti, Poonam; Jyoti, Poonam; Kapoor, Priya; Sharma, Vandana; Shanmugam, V; Yadav, Sudesh Kumar

    2017-08-01

    This study presents a novel approach of controlling vascular wilt in tomato by RNAi expression directed to pathogenicity genes of Fusarium oxysporum f. sp. lycopersici. Vascular wilt of tomato caused by Fusarium oxysporum f. sp. lycopersici leads to qualitative and quantitative loss of the crop. Limitation in the existing control measures necessitates the development of alternative strategies to increase resistance in the plants against pathogens. Recent findings paved way to RNAi, as a promising method for silencing of pathogenicity genes in fungus and provided effective resistance against fungal pathogens. Here, two important pathogenicity genes FOW2, a Zn(II)2Cys6 family putative transcription regulator, and chsV, a putative myosin motor and a chitin synthase domain, were used for host-induced gene silencing through hairpinRNA cassettes of these genes against Fusarium oxysporum f. sp. lycopersici. HairpinRNAs were assembled in appropriate binary vectors and transformed into tomato plant targeting FOW2 and chsV genes, for two highly pathogenic strains of Fusarium oxysporum viz. TOFOL-IHBT and TOFOL-IVRI. Transgenic tomatoes were analyzed for possible attainment of resistance in transgenic lines against fungal infection. Eight transgenic lines expressing hairpinRNA cassettes showed trivial disease symptoms after 6-8 weeks of infection. Hence, the host-induced posttranscriptional gene silencing of pathogenicity genes in transgenic tomato plants has enhanced their resistance to vascular wilt disease caused by Fusarium oxysporum.

  3. Ghrelin enhances cue-induced bar pressing for high fat food.

    Science.gov (United States)

    St-Onge, Veronique; Watts, Alexander; Abizaid, Alfonso

    2016-02-01

    Ghrelin is an orexigenic hormone produced by the stomach that acts on growth hormone secretagogue receptors (GHSRs) both peripherally and centrally. The presence of GHSRs in the ventral tegmental area (VTA) suggests that ghrelin signaling at this level may increase the incentive value of palatable foods as well as other natural and artificial rewards. The present investigation sought to determine if ghrelin plays a role in relapse to such foods following a period of abstinence. To achieve this, thirty-six male Long Evans rats were trained to press a lever to obtain a high fat chocolate food reward on a fixed ratio schedule of 1. Following an extinction period during which lever presses were not reinforced, rats were implanted with a cannula connected to a minipump that continuously delivered ghrelin, a GHSR antagonist ([d-Lys-3]-GHRP-6), or saline in the VTA for 14days. One week later, food reward-associated cues, food reward priming, and an overnight fast were used to induce reinstatement of the lever pressing response. Our results indicate that intra-VTA ghrelin enhances cue-induced reinstatement of responses for palatable food pellets. To the extent that the reinstatement paradigm is considered a valid model of relapse in humans, this suggests that ghrelin signaling facilitates relapse to preferred foods in response to food cues through GHSR signaling in the VTA. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Cognitive enhancing of pineapple extract and juice in scopolamine-induced amnesia in mice

    Science.gov (United States)

    Momtazi-borojeni, Amir Abbas; Sadeghi-Aliabadi, Hojjat; Rabbani, Mohammed; Ghannadi, Alireza; Abdollahi, Elham

    2017-01-01

    The objective of the present study was to evaluate the cognitive enhancing of pineapple juice and ethanolic extract in scopolamine-induced cognitive deficit mice. The ethanolic extract of pineapple (Ananas comosus (L.) Merr.) was prepared by maceration method and its juice was obtained by a homogenizer. Object recognition task was used to evaluate the mice memory. Exploration time in the first and second trial was recorded. The differences in exploration time between a familiar and a novel object in the second trial were taken as a memory index. Animals were randomly assigned into 15 groups of 6 each including: control group (normal saline + vehicle), positive control group (scopolamine + rivastigmine), seven experimental groups (received scopolamine alone or scopolamine + ethanolic extract of pineapple in different doses), six other experimental groups were treated by ethanolic extract or juice of pineapple in different doses. Scopolamine (100 μL, 1 mg/kg, i.p.) and pineapple juice or extract (50, 75 and 100 mg/kg, i.p.) were administered 40 and 30 min before starting the second trial in the experimental groups. Object discrimination was impaired after scopolamine administration. Results showed that juice and ethanolic extract of pineapple significantly restored object recognition ability in mice treated with scopolamine. These finding suggested that pineapple had a protective role against scopolamine-induced amnesia, indicating its ability in management of cognitive disorders. PMID:28626484

  5. Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood.

    Science.gov (United States)

    Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

    2011-09-21

    Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12-17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Plant nodulation inducers enhance horizontal gene transfer of Azorhizobium caulinodans symbiosis island.

    Science.gov (United States)

    Ling, Jun; Wang, Hui; Wu, Ping; Li, Tao; Tang, Yu; Naseer, Nawar; Zheng, Huiming; Masson-Boivin, Catherine; Zhong, Zengtao; Zhu, Jun

    2016-11-29

    Horizontal gene transfer (HGT) of genomic islands is a driving force of bacterial evolution. Many pathogens and symbionts use this mechanism to spread mobile genetic elements that carry genes important for interaction with their eukaryotic hosts. However, the role of the host in this process remains unclear. Here, we show that plant compounds inducing the nodulation process in the rhizobium-legume mutualistic symbiosis also enhance the transfer of symbiosis islands. We demonstrate that the symbiosis island of the Sesbania rostrata symbiont, Azorhizobium caulinodans, is an 87.6-kb integrative and conjugative element (ICE Ac ) that is able to excise, form a circular DNA, and conjugatively transfer to a specific site of gly-tRNA gene of other rhizobial genera, expanding their host range. The HGT frequency was significantly increased in the rhizosphere. An ICE Ac -located LysR-family transcriptional regulatory protein AhaR triggered the HGT process in response to plant flavonoids that induce the expression of nodulation genes through another LysR-type protein, NodD. Our study suggests that rhizobia may sense rhizosphere environments and transfer their symbiosis gene contents to other genera of rhizobia, thereby broadening rhizobial host-range specificity.

  7. The enhancement mechanism of wine-processed Radix Scutellaria on NTG-induced migraine rats.

    Science.gov (United States)

    Cui, Cheng-Long; He, Xin; Dong, Cui-Lan; Song, Zi-Jing; Ji, Jun; Wang, Xue; Wang, Ling; Wang, Jiao-Ying; Du, Wen-Juan; Wang, Chong-Zhi; Yuan, Chun-Su; Guo, Chang-Run; Zhang, Chun-Feng

    2017-07-01

    To elucidate the increasing dissolution and enhancement mechanism of wine-processed Radix Scutellaria (RS) by fractal theory in nitroglycerin (NTG)-induced migraine rats. We prepared three RS from the process with 10% (S1), 15% (S2), 20% (S3) (v/m) rice wine. Mercury intrusion porosimetry and scanning electron microscope were employed to explore the internal structure of RS and the components dissolution of RS was analyzed by HPLC. Rats were randomly allocated into following groups and orally given different solutions for 10days: normal group (NOR, normal saline), model group (MOD, normal saline), Tianshu capsule group (TSC, 0.425mg/kg), ibuprofen group (IBU, 0.0821mg/kg), crude RS group (CRU, 1.04mg/kg) and wine-processed RS group (WP, 1.04mg/kg) followed by bolus subcutaneously injection of NTG (10mg/kg) to induce migraine model except NOR. Biochemical indexes (nitric oxide-NO, calcitonin-gene-related peptide-CGRP, and endothelin-ET) and c-fos positive cells were measured with commercial kits and immunohistochemical method, separately. Total surface area significantly increased in wine-processed RS (pWine-processed RS could be a promising candidate medicine for migraine treatment due to its increased component dissolution. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Enhanced salt-induced antioxidative responses involve a contribution of polyamine biosynthesis in grapevine plants.

    Science.gov (United States)

    Ikbal, Fatima Ezzohra; Hernández, José Antonio; Barba-Espín, Gregorio; Koussa, Tayeb; Aziz, Aziz; Faize, Mohamed; Diaz-Vivancos, Pedro

    2014-06-15

    The possible involvement of polyamines in the salt stress adaptation was investigated in grapevine (Vitis vinifera L.) plantlets focusing on photosynthesis and oxidative metabolism. Salt stress resulted in the deterioration of plant growth and photosynthesis, and treatment of plantlets with methylglyoxal-bis(guanylhydrazone) (MGBG), a S-adenosylmethionine decarboxylase (SAMDC) inhibitor, enhanced the salt stress effect. A decrease in PSII quantum yield (Fv/Fm), effective PSII quantum yield (Y(II)) and coefficient of photochemical quenching (qP) as well as increases in non-photochemical quenching (NPQ) and its coefficient (qN) was observed by these treatments. Salt and/or MGBG treatments also triggered an increase in lipid peroxidation and reactive oxygen species (ROS) accumulation as well as an increase of superoxide dismutase (SOD) and peroxidase (POX) activities, but not ascorbate peroxidase (APX) activity. Salt stress also resulted in an accumulation of oxidized ascorbate (DHA) and a decrease in reduced glutathione. MGBG alone or in combination with salt stress increased monodehydroascorbate reductase (MDHAR), SOD and POX activities and surprisingly no accumulation of DHA was noticed following treatment with MGBG. These salt-induced responses correlated with the maintaining of high level of free and conjugated spermidine and spermine, whereas a reduction of agmatine and putrescine levels was observed, which seemed to be amplified by the MGBG treatment. These results suggest that maintaining polyamine biosynthesis through the enhanced SAMDC activity in grapevine leaf tissues under salt stress conditions could contribute to the enhanced ROS scavenging activity and a protection of photosynthetic apparatus from oxidative damages. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. Resveratrol-induced apoptosis is enhanced in low pH environments associated with cancer.

    Science.gov (United States)

    Shamim, Uzma; Hanif, Sarmad; Albanyan, Abdulmajeed; Beck, Frances W J; Bao, Bin; Wang, Zhiwei; Banerjee, Sanjeev; Sarkar, Fazlul H; Mohammad, Ramzi M; Hadi, Sheikh M; Azmi, Asfar S

    2012-04-01

    Many critical factors such as hypoxia, nutrient deficiency, activation of glycolytic pathway/Warburg effect contribute to the observed low pH in tumors compared to normal tissue. Studies suggest that such tumor specific acidic environment can be exploited for the development of therapeutic strategies against cancer. Independent observations show reduction in pH of mammalian cells undergoing internucleosomal DNA fragmentation and apoptosis. As such, our group has extensively demonstrated that anticancer mechanisms of different plant polyphenols involve mobilization of endogenous copper and consequent internucleosomal DNA breakage. Copper is redox active metal, an essential component of chromatin and is sensitive to subtle pH changes in its microenvironment. Here we explored whether, acidic pH promotes growth inhibition, apoptosis, and DNA damaging capacity of chemopreventive agent resveratrol. Our results reveal that growth inhibition and internucleosomal DNA fragmentation induced apoptosis in Capan-2 and Panc-28 pancreatic cancer cell lines (and not in normal HPDE cells) by resveratrol is enhanced at lower pH. Using comet assay, we further demonstrate that DNA breakage by resveratrol is enhanced with acidification. Membrane permeable copper specific chelator neocuproine (and not iron chelator orthophenanthroline) abrogated growth inhibition and apoptosis by resveratrol. Western blot results show enhanced activation of DNA laddering marker H2.aX by resveratrol at acidic pH that was reversed by neocuproine and not by orthophenanthroline. Our findings provide irrevocable proof that low pH environment can be turned into tumor weakness and assist in eradication of cancer cells by resveratrol. Copyright © 2011 Wiley Periodicals, Inc.

  10. Carboplatin enhances the production and persistence of radiation-induced DNA single-strand breaks

    International Nuclear Information System (INIS)

    Yang, L.; Douple, E.B.; O'Hara, J.A.; Wang, H.J.

    1995-01-01

    Fluorometric analysis of DNA unwinding and alkaline elution were used to investigate the production and persistence of DNA single-strand breaks (SSBs) in Chinese hamster V79 and xrs-5 cells treated with the chemotherapeutic agent carboplatin in combination with radiation. Carboplatin was administered to cells before irradiation in hypoxic conditions, or the drug was added immediately after irradiation during the postirradiation recovery period in air. The results of DNA unwinding studies suggest that carboplatin enhances the production of radiation-induced SSBs in hypoxic V79 cells and xrs-5 cells by a factor of 1.86 and 1.83, respectively, when combined with radiation compared to the SSBs produced by irradiation alone. Carboplatin alone did not produce a measureable number of SSBs. Alkaline elution profiles also indicated that the rate of elution of SSBs was higher in cells treated with the carboplatin is present after irradiation and during the postirradiation recovery period, the rejoining of radiation-induced SSBs by a factor of 1.46 in V79 cells with 20 Gy irradiation and by a factor of 2.02 in xrs-5 cells with 20 Gy irradiation. When carboplatin is present after irradiation and during the postirradiation recovery period, the rejoining of radiation-induced SSBs is inhibited during this postirradiation incubation period (radiopotentiation) with a relative inhibition factor at 1 h postirradiation of 1.25 in V79 cells and 1.15 in xrs-5 cells. An increased production and persistence of SSBs resulting from the interaction of carboplatin with radiation may be an important step in the mechanism responsible for the potentiated cell killing previously from studies in animal tumors and in cultured cells. 31 refs., 7 figs

  11. Nanoparticle-Enhanced Laser Induced Breakdown Spectroscopy for the noninvasive analysis of transparent samples and gemstones.

    Science.gov (United States)

    Koral, C; Dell'Aglio, M; Gaudiuso, R; Alrifai, R; Torelli, M; De Giacomo, A

    2018-05-15

    In this paper, Nanoparticle-Enhanced Laser Induced Breakdown Spectroscopy is applied to transparent samples and gemstones with the aim to overcome the laser induced damage on the sample. We propose to deposit a layer of AuNPs on the sample surface by drying a colloidal solution before ablating the sample with a 532 nm pulsed laser beam. This procedure ensures that the most significant fraction of the beam, being in resonance with the AuNP surface plasmon, is mainly absorbed by the NP layer, which in turn results the breakdown to be induced on NPs rather than on the sample itself. The fast explosion of the NPs and the plasma induction allow the ablation and the transfer in the plasma phase of the portion of sample surface where the NPs were placed. The employed AuNPs are prepared in milliQ water without the use of any chemical stabilizers by Pulsed Laser Ablation in Liquids (PLAL), in order to obtain a strict control of composition and impurities, and to limit possible spectral interferences (except from Au emission lines). Therefore with this technique it is possible to obtain, together with the emission signal of Au (coming from atomized NPs), the emission spectrum of the sample, by limiting or avoiding the direct interaction of the laser pulse with the sample itself. This approach is extremely useful for the elemental analysis by laser ablation of high refractive index samples, where the laser pulse on an untreated surface can otherwise penetrate inside the sample, generate breakdown events below the superficial layer, and consequently cause cracks and other damage. The results obtained with NELIBS on high refractive index samples like glasses, tourmaline, aquamarine and ruby are very promising, and demonstrate the potentiality of this approach for precious gemstones analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Cytosine arabinoside enhancement of gamma irradiation induced mutations in human T-lymphocytes

    International Nuclear Information System (INIS)

    O'Neill, J.P.; Sullivan, L.M.; Hunter, T.C.; Nicklas, J.A.

    1991-01-01

    The frequency of 6-thioguanine resistant (TGr) mutants induced in human G0 phase T-lymphocytes by 200 cGy of gamma irradiation is greatly enhanced by incubation with cytosine arabinoside (ara-C) after irradiation. The mutant frequency increased with increasing incubation time in ara-C for up to 2 hr. This mutation induction required a phenotypic expression time of 5-8 days mass culture growth, similar to that found with mutants induced by 300 cGy of irradiation alone. Southern blot analysis of 40 isolated mutant clones revealed 8 independent mutations by T-cell receptor (TCR) gene rearrangement patterns. Four of these eight showed hprt gene structural alterations (0.50). An alternative method to allow phenotypic expression was developed to minimize the isolation of hprt/TCR sibling mutants. The use of in situ expression in the microtiter dish wells resulted in the isolation of 17 independent mutations in 19 mutant clones. Ten of these 17 mutations showed hprt structural alterations (0.59). The high fraction of mutations involving structural alterations detected by Southern blot analysis is consistent with the known induction of chromosome aberrations by irradiation plus ara-C treatment. We propose that both the increase in Mf and the increase in the incidence of hprt gene structural alterations are due to the accumulation of strand breaks in repairing regions of DNA under these conditions of ara-C induced inhibition of repair. We further propose that upon release of the ara-C inhibition, these repairing regions can interact to yield both gene mutations and chromosome aberrations

  13. 14-Day thawed plasma retains clot enhancing properties and inhibits tPA-induced fibrinolysis.

    Science.gov (United States)

    Huebner, Benjamin R; Moore, Ernest E; Moore, Hunter B; Shepherd-Singh, Raymond; Sauaia, Angela; Stettler, Gregory R; Nunns, Geoffrey R; Silliman, Christopher C

    2017-11-01

    Plasma-first resuscitation attenuates trauma-induced coagulopathy (TIC); however, the logistics of plasma-first resuscitation require thawed plasma (TP) be readily available due to the obligatory thawing time of fresh frozen plasma (FFP). The current standard is storage of TP for up to 5 days at 4°C, based on factor levels at outdate, for use in patients at risk for TIC, but there remains a 2.2% outdated wastage rate. However, the multitude of plasma proteins in attenuating TIC remains unknown. We hypothesize that TP retains the ability to enhance clotting and reduce tPA-induced fibrinolysis at 14-day storage. FFP was thawed and stored at 4°C at the following intervals: 14, 10, 7, 5, 3, and 1-day prior to the experiment. Healthy volunteers underwent blood draws followed by 50% dilution with TP stored at previously mentioned intervals as well as FFP, normal saline (NS), albumin, and whole blood (WB) control. Samples underwent tPA-modified (75 ng/mL) thrombelastography (TEG) with analysis of R-time, angle, maximum amplitude (MA), and LY30. TEG properties did not change significantly over the thawed storage. 14-day TP retained the ability to inhibit tPA-induced hyperfibrinolysis (median LY30% 9.6%) similar to FFP (5.6%), WB (14.6%), and superior to albumin (59.3%) and NS (58.1%). 14-day TP also retained faster clot formation (median angle, 66.2°) and superior clot strength (MA, 61.5 mm) to albumin (34.8°, 21.6 mm) and NS (41.6°, 32.2 mm). TP plasma stored for 14 days retains clot-enhancing ability and resistance to clot degradation similar to FFP. A clinical trial is needed to validate these in vitro results. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Inhibition of autophagy enhances DNA damage-induced apoptosis by disrupting CHK1-dependent S phase arrest

    Energy Technology Data Exchange (ETDEWEB)

    Liou, Jong-Shian; Wu, Yi-Chen; Yen, Wen-Yen; Tang, Yu-Shuan [Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, ROC (China); Kakadiya, Rajesh B.; Su, Tsann-Long [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, ROC (China); Yih, Ling-Huei, E-mail: lhyih@gate.sinica.edu.tw [Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, ROC (China)

    2014-08-01

    DNA damage has been shown to induce autophagy, but the role of autophagy in the DNA damage response and cell fate is not fully understood. BO-1012, a bifunctional alkylating derivative of 3a-aza-cyclopenta[a]indene, is a potent DNA interstrand cross-linking agent with anticancer activity. In this study, BO-1012 was found to reduce DNA synthesis, inhibit S phase progression, and induce phosphorylation of histone H2AX on serine 139 (γH2AX) exclusively in S phase cells. Both CHK1 and CHK2 were phosphorylated in response to BO-1012 treatment, but only depletion of CHK1, but not CHK2, impaired BO-1012-induced S phase arrest and facilitated the entry of γH2AX-positive cells into G2 phase. CHK1 depletion also significantly enhanced BO-1012-induced cell death and apoptosis. These results indicate that BO-1012-induced S phase arrest is a CHK1-dependent pro-survival response. BO-1012 also resulted in marked induction of acidic vesicular organelle (AVO) formation and microtubule-associated protein 1 light chain 3 (LC3) processing and redistribution, features characteristic of autophagy. Depletion of ATG7 or co-treatment of cells with BO-1012 and either 3-methyladenine or bafilomycin A1, two inhibitors of autophagy, not only reduced CHK1 phosphorylation and disrupted S phase arrest, but also increased cleavage of caspase-9 and PARP, and cell death. These results suggest that cells initiate S phase arrest and autophagy as pro-survival responses to BO-1012-induced DNA damage, and that suppression of autophagy enhances BO-1012-induced apoptosis via disruption of CHK1-dependent S phase arrest. - Highlights: • Autophagy inhibitors enhanced the cytotoxicity of a DNA alkylating agent, BO-1012. • BO-1012-induced S phase arrest was a CHK1-dependent pro-survival response. • Autophagy inhibition enhanced BO-1012 cytotoxicity via disrupting the S phase arrest.

  15. Fano-induced spontaneous emission enhancement of molecule placed in a cluster of asymmetrically-arranged metallic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Le, Khai Q., E-mail: khai.lequang@hoasen.edu.vn [Faculty of Science and Technology, Hoa Sen University, Ho Chi Minh (Viet Nam); Department of Electrical Engineering, University of Minnesota, Duluth, MN 55812 (United States); Bai, Jing [Department of Electrical Engineering, University of Minnesota, Duluth, MN 55812 (United States); Nguyen, H.P.T. [Department of Electrical and Computer Engineering, New Jersey Institute of Technology, NJ 07102 (United States)

    2016-05-15

    We demonstrate that plasmonic Fano resonance significantly boosts spontaneous emission rate of a single emitter, e.g. atom, molecule and quantum dot, over a moderately broad emission spectrum. An emission enhancement of up to 140 times compared to the system with no external inclusion at tunable frequencies is achieved, providing a new complementary enhancement mechanism. Fano resonance is induced in clusters of four asymmetric-arranged nanoparticles with ultra-small inter-particle gaps. It is shown to play a dominant role in light-emitting enhancement, mediated by combined localized surface plasmon resonances.

  16. Protection of halogenated DNA from strand breakage and sister-chromatid exchange induced by the topoisomerase I inhibitor camptothecin

    International Nuclear Information System (INIS)

    Orta, Manuel Luis; Mateos, Santiago; Cantero, Gloria; Wolff, Lisa J.; Cortes, Felipe

    2008-01-01

    The fundamental nuclear enzyme DNA topoisomerase I (topo I), cleaves the double-stranded DNA molecule at preferred sequences within its recognition/binding sites. We have recently reported that when cells incorporate halogenated nucleosides analogues of thymidine into DNA, it interferes with normal chromosome segregation, as shown by an extraordinarily high yield of endoreduplication, and results in a protection against DNA breakage induced by the topo II poison m-AMSA [F. Cortes, N. Pastor, S. Mateos, I. Dominguez, The nature of DNA plays a role in chromosome segregation: endoreduplication in halogen-substituted chromosomes, DNA Repair 2 (2003) 719-726; G. Cantero, S. Mateos, N. Pastor; F. Cortes, Halogen substitution of DNA protects from poisoning of topoisomerase II that results in DNA double-strand breaks (DSBs), DNA Repair 5 (2006) 667-674]. In the present investigation, we have assessed whether the presence of halogenated nucleosides in DNA diminishes the frequency of interaction of topo I with DNA and thus the frequency with which the stabilisation of cleavage complexes by the topo I poison camptothecin (CPT) takes place, in such a way that it protects from chromosome breakage and sister-chromatid exchange. This protective effect is shown to parallel a loss in halogen-substituted cells of the otherwise CPT-increased catalytic activity bound to DNA

  17. Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

    Science.gov (United States)

    Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

    2009-11-01

    Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

  18. Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors.

    Science.gov (United States)

    McGraw, Kathy L; Basiorka, Ashley A; Johnson, Joseph O; Clark, Justine; Caceres, Gisela; Padron, Eric; Heaton, Ruth; Ozawa, Yukiyasu; Wei, Sheng; Sokol, Lubomir; List, Alan F

    2014-01-01

    Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS). Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR) signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size). Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q) MDS.

  19. Error-enhancing robot therapy to induce motor control improvement in childhood onset primary dystonia

    Directory of Open Access Journals (Sweden)

    Casellato Claudia

    2012-07-01

    Full Text Available Abstract Background Robot-generated deviating forces during multijoint reaching movements have been applied to investigate motor control and to tune neuromotor adaptation. Can the application of force to limbs improve motor learning? In this framework, the response to altered dynamic environments of children affected by primary dystonia has never been studied. Methods As preliminary pilot study, eleven children with primary dystonia and eleven age-matched healthy control subjects were asked to perform upper limb movements, triangle-reaching (three directions and circle-writing, using a haptic robot interacting with ad-hoc developed task-specific visual interfaces. Three dynamic conditions were provided, null additive external force (A, constant disturbing force (B and deactivation of the additive external force again (C. The path length for each trial was computed, from the recorded position data and interaction events. Results The results show that the disturbing force affects significantly the movement outcomes in healthy but not in dystonic subjects, already compromised in the reference condition: the external alteration uncalibrates the healthy sensorimotor system, while the dystonic one is already strongly uncalibrated. The lack of systematic compensation for perturbation effects during B condition is reflected into the absence of after-effects in C condition, which would be the evidence that CNS generates a prediction of the perturbing forces using an internal model of the environment. The most promising finding is that in dystonic population the altered dynamic exposure seems to induce a subsequent improvement, i.e. a beneficial after-effect in terms of optimal path control, compared with the correspondent reference movement outcome. Conclusions The short-time error-enhancing training in dystonia could represent an effective approach for motor performance improvement, since the exposure to controlled dynamic alterations induces a refining

  20. Sialoadhesin expressed on IFN-induced monocytes binds HIV-1 and enhances infectivity.

    Directory of Open Access Journals (Sweden)

    Hans Rempel

    2008-04-01

    Full Text Available HIV-1 infection dysregulates the immune system and alters gene expression in circulating monocytes. Differential gene expression analysis of CD14(+ monocytes from subjects infected with HIV-1 revealed increased expression of sialoadhesin (Sn, CD169, Siglec 1, a cell adhesion molecule first described in a subset of macrophages activated in chronic inflammatory diseases.We analyzed sialoadhesin expression on CD14(+ monocytes by flow cytometry and found significantly higher expression in subjects with elevated viral loads compared to subjects with undetectable viral loads. In cultured CD14(+ monocytes isolated from healthy individuals, sialoadhesin expression was induced by interferon-alpha and interferon-gamma but not tumor necrosis factor-alpha. Using a stringent binding assay, sialoadhesin-expressing monocytes adsorbed HIV-1 through interaction with the sialic acid residues on the viral envelope glycoprotein gp120. Furthermore, monocytes expressing sialoadhesin facilitated HIV-1 trans infection of permissive cells, which occurred in the absence of monocyte self-infection.Increased sialoadhesin expression on CD14(+ monocytes occurred in response to HIV-1 infection with maximum expression associated with high viral load. We show that interferons induce sialoadhesin in primary CD14(+ monocytes, which is consistent with an antiviral response during viremia. Our findings suggest that circulating sialoadhesin-expressing monocytes are capable of binding HIV-1 and effectively delivering virus to target cells thereby enhancing the distribution of HIV-1. Sialoadhesin could disseminate HIV-1 to viral reservoirs during monocyte immunosurveillance or migration to sites of inflammation and then facilitate HIV-1 infection of permissive cells.

  1. Alcohol enhances oxysterol-induced apoptosis in human endothelial cells by a calcium-dependent mechanism.

    Science.gov (United States)

    Spyridopoulos, I; Wischhusen, J; Rabenstein, B; Mayer, P; Axel, D I; Fröhlich, K U; Karsch, K R

    2001-03-01

    Controversy exists about the net effect of alcohol on atherogenesis. A protective effect is assumed, especially from the tannins and phenolic compounds in red wine, owing to their inhibition of low density lipoprotein (LDL) oxidation. However, increased atherogenesis occurs in subjects with moderate to heavy drinking habits. The purpose of this study was to investigate the influence of alcohol in combination with oxysterols on the endothelium. Cultured human arterial endothelial cells (HAECs) served as an in vitro model to test the cellular effects of various oxysterols. Oxysterols (7beta-hydroxycholesterol, 7-ketocholesterol, and cholesterol-5,6-epoxides), which are assumed to be the most toxic constituents of oxidized LDL, induced apoptosis in HAECs through calcium mobilization followed by activation of caspase-3. Ethanol, methanol, isopropanol, tert-butanol, and red wine all potentiated oxysterol-induced cell death up to 5-fold, paralleled by further induction of caspase-3. The alcohol effect occurred in a dose-dependent manner and reached a plateau at 0.05% concentration. Alcohol itself did not affect endothelial cell viability, nor did other solvents such as dimethyl sulfoxide mimic the alcohol effect. So far as the physiologically occurring oxysterols are concerned, this effect was apparent only for oxysterols oxidized at the steran ring. The possibility of alcohol facilitating the uptake of oxysterols into the cell was not supported by the data from an uptake study with radiolabeled compounds. Finally, alcohol in combination with oxysterols did cause a dramatic increase in cytosolic calcium influx. Blockage of calcium influx by the calcium channel blocker aurintricarboxylic acid or the calcium chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid abrogated the alcohol-mediated enhancement of oxysterol toxicity. We describe for the first time a mechanistic concept explaining possible adverse effects of alcohol in conjunction with

  2. Enhanced electrocatalytic CO2 reduction via field-induced reagent concentration

    Science.gov (United States)

    Liu, Min; Pang, Yuanjie; Zhang, Bo; de Luna, Phil; Voznyy, Oleksandr; Xu, Jixian; Zheng, Xueli; Dinh, Cao Thang; Fan, Fengjia; Cao, Changhong; de Arquer, F. Pelayo García; Safaei, Tina Saberi; Mepham, Adam; Klinkova, Anna; Kumacheva, Eugenia; Filleter, Tobin; Sinton, David; Kelley, Shana O.; Sargent, Edward H.

    2016-09-01

    Electrochemical reduction of carbon dioxide (CO2) to carbon monoxide (CO) is the first step in the synthesis of more complex carbon-based fuels and feedstocks using renewable electricity. Unfortunately, the reaction suffers from slow kinetics owing to the low local concentration of CO2 surrounding typical CO2 reduction reaction catalysts. Alkali metal cations are known to overcome this limitation through non-covalent interactions with adsorbed reagent species, but the effect is restricted by the solubility of relevant salts. Large applied electrode potentials can also enhance CO2 adsorption, but this comes at the cost of increased hydrogen (H2) evolution. Here we report that nanostructured electrodes produce, at low applied overpotentials, local high electric fields that concentrate electrolyte cations, which in turn leads to a high local concentration of CO2 close to the active CO2 reduction reaction surface. Simulations reveal tenfold higher electric fields associated with metallic nanometre-sized tips compared to quasi-planar electrode regions, and measurements using gold nanoneedles confirm a field-induced reagent concentration that enables the CO2 reduction reaction to proceed with a geometric current density for CO of 22 milliamperes per square centimetre at -0.35 volts (overpotential of 0.24 volts). This performance surpasses by an order of magnitude the performance of the best gold nanorods, nanoparticles and oxide-derived noble metal catalysts. Similarly designed palladium nanoneedle electrocatalysts produce formate with a Faradaic efficiency of more than 90 per cent and an unprecedented geometric current density for formate of 10 milliamperes per square centimetre at -0.2 volts, demonstrating the wider applicability of the field-induced reagent concentration concept.

  3. Enhanced efficiency of plasma acceleration in the laser-induced cavity pressure acceleration scheme

    International Nuclear Information System (INIS)

    Badziak, J; Rosiński, M; Jabłoński, S; Pisarczyk, T; Chodukowski, T; Parys, P; Rączka, P; Krousky, E; Ullschmied, J; Liska, R; Kucharik, M

    2015-01-01

    Among various methods for the acceleration of dense plasmas the mechanism called laser-induced cavity pressure acceleration (LICPA) is capable of achieving the highest energetic efficiency. In the LICPA scheme, a projectile placed in a cavity is accelerated along a guiding channel by the laser-induced thermal plasma pressure or by the radiation pressure of an intense laser radiation trapped in the cavity. This arrangement leads to a significant enhancement of the hydrodynamic or electromagnetic forces driving the projectile, relative to standard laser acceleration schemes. The aim of this paper is to review recent experimental and numerical works on LICPA with the emphasis on the acceleration of heavy plasma macroparticles and dense ion beams. The main experimental part concerns the research carried out at the kilojoule sub-nanosecond PALS laser facility in Prague. Our measurements performed at this facility, supported by advanced two-dimensional hydrodynamic simulations, have demonstrated that the LICPA accelerator working in the long-pulse hydrodynamic regime can be a highly efficient tool for the acceleration of heavy plasma macroparticles to hyper-velocities and the generation of ultra-high-pressure (>100 Mbar) shocks through the collision of the macroparticle with a solid target. The energetic efficiency of the macroparticle acceleration and the shock generation has been found to be significantly higher than that for other laser-based methods used so far. Using particle-in-cell simulations it is shown that the LICPA scheme is highly efficient also in the short-pulse high-intensity regime and, in particular, may be used for production of intense ion beams of multi-MeV to GeV ion energies with the energetic efficiency of tens of per cent, much higher than for conventional laser acceleration schemes. (paper)

  4. Repeated Microneedle Stimulation Induces Enhanced Hair Growth in a Murine Model.

    Science.gov (United States)

    Kim, Yoon Seob; Jeong, Kwan Ho; Kim, Jung Eun; Woo, Young Jun; Kim, Beom Joon; Kang, Hoon

    2016-10-01

    Microneedle is a method that creates transdermal microchannels across the stratum corneum barrier layer of skin. No previous study showed a therapeutic effect of microneedle itself on hair growth by wounding. The aim of this study is to investigate the effect of repeated microwound formed by microneedle on hair growth and hair growth-related genes in a murine model. A disk microneedle roller was applied to each group of mice five times a week for three weeks. First, to identify the optimal length and cycle, microneedles of lengths of 0.15 mm, 0.25 mm, 0.5 mm, and 1 mm and cycles of 3, 6, 10, and 13 cycles were applied. Second, the effect of hair growth and hair-growth-related genes such as Wnt3a, β-catenin, vascular endothelial growth factor (VEGF), and Wnt10b was observed using optimized microneedle. Outcomes were observed using visual inspection, real-time polymerase chain reaction, and immunohistochemistry. We found that the optimal length and cycle of microneedle treatment on hair growth was 0.25 mm/10 cycles and 0.5 mm/10 cycles. Repeated microneedle stimulation promoted hair growth, and it also induced the enhanced expression of Wnt3a, β-catenin, VEGF, and Wnt10b. Our study provides evidence that microneedle stimulation can induce hair growth via activation of the Wnt/β-catenin pathway and VEGF. Combined with the drug delivery effect, we believe that microneedle stimulation could lead to new approaches for alopecia.

  5. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

    Directory of Open Access Journals (Sweden)

    Chia-Yu Chang

    2015-01-01

    Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

  6. Dopamine mediated iron release from ferritin is enhanced at higher temperatures: Possible implications for fever-induced Parkinson's disease

    International Nuclear Information System (INIS)

    Babincova, Melania; Babinec, Peter

    2005-01-01

    A new molecular mechanism is proposed to explain the pathogenesis of fever-induced Parkinson's disease. This proposal is based on dopamine and 6-hydroxydopamine-mediated free iron release from ferritin magnetic nanoparticles, which is enhanced at higher temperatures, and which may lead to substantial peroxidation and injury of lipid biomembranes of the substantia nigra in the brain

  7. Drug ‘‘supersaturation’’ states induced by polymeric micelles and liposomes: A mechanistic investigation into permeability enhancements

    DEFF Research Database (Denmark)

    Di Cagno, Massimiliano; Luppi, Barbara

    2013-01-01

    The objective of this study was to investigate if the increase in apparent solubility induced by liposomalization or micellization of the poorly soluble drug hydrocortisone (HC) would lead to an enhancement of its permeability through biological membranes. For this purpose phosphatidylcholine...

  8. Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs)

    International Nuclear Information System (INIS)

    Li, Qing; Guo, Dong; Dong, Zhongqi; Zhang, Wei; Zhang, Lei; Huang, Shiew-Mei; Polli, James E.; Shu, Yan

    2013-01-01

    The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists, such as ondansetron, should be investigated in patients. - Highlights: • Nephrotoxicity significantly limits clinical use of the chemotherapeutic cisplatin

  9. Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs)

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qing [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Guo, Dong [Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Dong, Zhongqi [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Zhang, Wei [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Zhang, Lei; Huang, Shiew-Mei [Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD (United States); Polli, James E. [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Shu, Yan, E-mail: yshu@rx.umaryland.edu [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States)

    2013-11-15

    The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT{sub 3}) receptor antagonists, such as ondansetron, should be investigated in patients. - Highlights: • Nephrotoxicity significantly limits clinical use of the chemotherapeutic

  10. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    International Nuclear Information System (INIS)

    Rashid, Kahkashan; Sil, Parames C.

    2015-01-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  11. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Rashid, Kahkashan; Sil, Parames C., E-mail: parames@jcbose.ac.in

    2015-02-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  12. Interaction of processes may explain induced seismicity after shut-in in Enhanced Geothermal Systems

    Science.gov (United States)

    De Simone, Silvia; Carrera, Jesus; Vilarrasa, Victor

    2015-04-01

    Deep fluid injection is a necessary operation in several engineering sectors, like geothermal energy production, natural gas storage, CO2 storage, etc. The seismicity associated to these activities has, in some occasions, reached unexpected magnitude, raising public concern. Moreover, the occurrence of such seismicity after the injection shut-in pointed out the incompleteness of the knowledge and the inability of fully managing these processes. On the other hand, the growing attention toward clean energy makes it clear that we cannot abandon these procedures, which have a huge potential. Therefore, deeply understanding the mechanisms that induce seismicity is crucial. In this study we consider hydraulic stimulation of deep geothermal systems and analyze the mechanisms that may induce or trigger seismicity. Given that the basic mechanism is fluid pressure increase, secondary triggering processes have been studied. In detail, we attempt to identify the potential mechanisms that may trigger seismicity in the post-injection phase, when the overpressure decreases. These mechanisms have been investigated with a coupled and uncoupled approach, in order to understand the individual effects of each one and the effects of the interactions between them on the reservoir stability. Besides fluid overpressure, another relevant process is the temperature variation. Indeed, in the case of enhanced geothermal systems, the temperature contrast between the injected cold fluid and the deep hot reservoir is great and induces thermal stress, which sensibly affects the in-situ stress field. Therefore, we have studied overpressure and temperature effects by means of analytic solutions and by means of hydro-mechanical and thermo-hydro-mechanical numerical simulations. Results show that in fractured rocks the spatial variability of hydraulic and mechanic parameters provokes no isotropic variation of the tensional field, in response to pressure and temperature perturbations. Another

  13. Silencing of cytosolic NADP+-dependent isocitrate dehydrogenase gene enhances ethanol-induced toxicity in HepG2 cells.

    Science.gov (United States)

    Yang, Eun Sun; Lee, Su-Min; Park, Jeen-Woo

    2010-07-01

    It has been shown that acute and chronic alcohol administrations increase the production of reactive oxygen species, lower cellular antioxidant levels and enhance oxidative stress in many tissues. We recently reported that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) functions as an antioxidant enzyme by supplying NADPH to the cytosol. Upon exposure to ethanol, IDPc was susceptible to the loss of its enzyme activity in HepG2 cells. Transfection of HepG2 cells with an IDPc small interfering RNA noticeably downregulated IDPc and enhanced the cells' vulnerability to ethanol-induced cytotoxicity. Our results suggest that suppressing the expression of IDPc enhances ethanol-induced toxicity in HepG2 cells by further disruption of the cellular redox status.

  14. Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not adolescent rats susceptible to diet-induced obesity

    Science.gov (United States)

    Oginsky, Max F.; Maust, Joel D.; Corthell, John T.; Ferrario, Carrie R.

    2015-01-01

    Rationale Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. Objectives We determined whether there are differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity, and basal differences in the striatal neuron function in adult and adolescent obesity-prone and obesity-resistant rats. Methods Susceptible and resistant outbred rats were identified based on “junk-food” diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). Results In rats that became obese after eating “junk-food”, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ~60% at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Conclusions Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals; and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats. PMID:26612617

  15. Fusobacterium nucleatum-Induced Impairment of Autophagic Flux Enhances the Expression of Proinflammatory Cytokines via ROS in Caco-2 Cells.

    Directory of Open Access Journals (Sweden)

    Bin Tang

    Full Text Available Fusobacterium nucleatum (F. nucleatum plays a critical role in gastrointestinal inflammation. However, the exact mechanism by which F. nucleatum contributes to inflammation is unclear. In the present study, it was revealed that F. nucleatum could induce the production of proinflammatory cytokines (IL-8, IL-1β and TNF-α and reactive oxygen species (ROS in Caco-2 colorectal adenocarcinoma cells. Furthermore, ROS scavengers (NAC or Tiron could decrease the production of proinflammatory cytokines during F. nucleatum infection. In addition, we observed that autophagy is impaired in Caco-2 cells after F. nucleatum infection. The production of proinflammatory cytokines and ROS induced by F. nucleatum was enhanced with either autophagy pharmacologic inhibitors (3-methyladenine, bafilomycin A1 or RNA interference in essential autophagy genes (ATG5 or ATG12 in Caco-2 cells. Taken together, these results indicate that F. nucleatum-induced impairment of autophagic flux enhances the expression of proinflammatory cytokines via ROS in Caco-2 Cells.

  16. Strain-Induced Enhancement of the Electron Energy Relaxation in Strongly Correlated Superconductors

    Directory of Open Access Journals (Sweden)

    C. Gadermaier

    2014-03-01

    Full Text Available We use femtosecond optical spectroscopy to systematically measure the primary energy relaxation rate Γ_{1} of photoexcited carriers in cuprate and pnictide superconductors. We find that Γ_{1} increases monotonically with increased negative strain in the crystallographic a axis. Generally, the Bardeen-Shockley deformation potential theorem and, specifically, pressure-induced Raman shifts reported in the literature suggest that increased negative strain enhances electron-phonon coupling, which implies that the observed direct correspondence between a and Γ_{1} is consistent with the canonical assignment of Γ_{1} to the electron-phonon interaction. The well-known nonmonotonic dependence of the superconducting critical temperature T_{c} on the a-axis strain is also reflected in a systematic dependence T_{c} on Γ_{1}, with a distinct maximum at intermediate values (∼16  ps^{−1} at room temperature. The empirical nonmonotonic systematic variation of T_{c} with the strength of the electron-phonon interaction provides us with unique insight into the role of electron-phonon interaction in relation to the mechanism of high-T_{c} superconductivity as a crossover phenomenon.

  17. Enhancement of photovoltaic response in multilayer MoS2 induced by plasma doping.

    Science.gov (United States)

    Wi, Sungjin; Kim, Hyunsoo; Chen, Mikai; Nam, Hongsuk; Guo, L Jay; Meyhofer, Edgar; Liang, Xiaogan

    2014-05-27

    Layered transition-metal dichalcogenides hold promise for making ultrathin-film photovoltaic devices with a combination of excellent photovoltaic performance, superior flexibility, long lifetime, and low manufacturing cost. Engineering the proper band structures of such layered materials is essential to realize such potential. Here, we present a plasma-assisted doping approach for significantly improving the photovoltaic response in multilayer MoS2. In this work, we fabricated and characterized photovoltaic devices with a vertically stacked indium tin oxide electrode/multilayer MoS2/metal electrode structure. Utilizing a plasma-induced p-doping approach, we are able to form p-n junctions in MoS2 layers that facilitate the collection of photogenerated carriers, enhance the photovoltages, and decrease reverse dark currents. Using plasma-assisted doping processes, we have demonstrated MoS2-based photovoltaic devices exhibiting very high short-circuit photocurrent density values up to 20.9 mA/cm(2) and reasonably good power-conversion efficiencies up to 2.8% under AM1.5G illumination, as well as high external quantum efficiencies. We believe that this work provides important scientific insights for leveraging the optoelectronic properties of emerging atomically layered two-dimensional materials for photovoltaic and other optoelectronic applications.

  18. ΔNp73 enhances promoter activity of TGF-β induced genes.

    Directory of Open Access Journals (Sweden)

    Maarten Niemantsverdriet

    Full Text Available The p53 homolog p73 is frequently overexpressed in cancers. Especially the transactivation domain truncated isoform ΔNp73 has oncogenic properties and its upregulation is associated with poor patient survival. It has been shown that ΔNp73 has an inhibitory effect on the transactivation capacity of p53 and other p73 isoforms. Here, we confirm this finding but surprisingly find that ΔNp73 may also stimulate the expression of TGF-β signaling targets. Promoter-reporter analysis indicated that the presence of Smad Binding Elements (SBE in the promoter is sufficient for stimulation of gene expression by ΔNp73. TGF-β signaling was less efficient in ΔNp73 downregulated cells, whereas tetracycline induced ΔNp73 increased expression of endogenous TGF-β regulated genes PAI-1 and Col1a1. Pull-down assays with SBE DNA suggest that ΔNp73 enhances smad3/4 binding to SBEs, thereby stimulating TGF-β signaling. Chromatin immunoprecipitation assays confirmed a direct interaction between ΔNp73 and SBE. Given the role of TGF-β signaling in carcinogenesis, tumor invasion and metastasis via targets like PAI-1 and Col1a1, our data suggest a model on how this effect of ΔNp73 could be a contributing factor in cancer progression.

  19. Vitamin D enhances omega-3 polyunsaturated fatty acids-induced apoptosis in breast cancer cells.

    Science.gov (United States)

    Yang, Jing; Zhu, Shenglong; Lin, Guangxiao; Song, Ci; He, Zhao

    2017-08-01

    Breast cancer is a leading type of cancer in women and generally classified into three subtypes of ER + /PR + , HER2 + and triple negative. Both omega-3 polyunsaturated fatty acids and vitamin D 3 play positive role in the reduction of breast cancer incidence. However, whether combination of omega-3 polyunsaturated fatty acids and vitamin D 3 has stronger protective effect on breast carcinogenesis still remains unknown. In this study, we show that the combination of ω-3 free fatty acids (ω-3 FFAs) and 1α, 25-dihydroxy-vitamin D 3 (VD 3 ) dramatically enhances cell apoptosis among three subtypes of breast cancer cell lines. Bcl-2 and total PARP protein levels are decreased in combined treatment MCF-7 and SK-BR-3 cells. Caspase signals play a vital role in cell apoptosis induced by combination. Moreover, Raf-MAPK signaling pathway is involved in the apoptosis induction by combination of ω-3 FFAs+VD 3 . These results demonstrate that the induction of cell apoptosis by combined treatment is dependent on different signaling pathways in three subtypes of breast cancer cell lines. © 2017 International Federation for Cell Biology.

  20. Pyrene-Phosphonate Conjugate: Aggregation-Induced Enhanced Emission, and Selective Fe3+ Ions Sensing Properties

    Directory of Open Access Journals (Sweden)

    Sachin D. Padghan

    2017-08-01

    Full Text Available A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE properties in water/acetonitrile (ACN solutions. Dynamic light scattering (DLS characterization revealed that the aggregates of receptor 1 at 80% water fraction have an average size of ≈142 nm. Field emission scanning electron microscopy (FE-SEM analysis confirmed the formation of spherical aggregates upon solvent evaporation. The sensing properties of receptor 1 were investigated by UV-vis, fluorescence emission spectroscopy, and other optical methods. Among the tested metal ions, receptor 1 is capable of recognizing the Fe3+ ion selectively. The changes in spectral measurements were explained on the basis of complex formation. The composition of receptor 1 and Fe3+ ions was determined by using Job’s plot and found to be 1:1. The receptor 1–Fe3+ complex showed a reversible UV-vis response in the presence of EDTA.

  1. Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake

    Science.gov (United States)

    Ensign, Laura M.; Hoen, Timothy; Maisel, Katharina; Cone, Richard; Hanes, Justin

    2013-01-01

    Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that administration of hypotonic solutions would induce fluid uptake that could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We found that hypotonic formulations markedly increased the rate at which small molecule drugs and muco-inert nanoparticles (mucus-penetrating particles, or MPP), but not conventional mucoadhesive nanparticles (CP), reached the vaginal epithelial surface in vivo in mice. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that drugs or MPP in isotonic formulations failed to reach efficiently. However, hypotonic formulations caused unencapsulated “free” drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for localized sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. In contrast, as we previously demonstrated, hypotonic delivery of drug via MPP led to better long-term retention and protection in the vagina. Importantly, we demonstrate that slightly hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. Hypotonic formulations for vaginal drug delivery via MPP may significantly improve prevention and treatment of reproductive tract diseases and disorders. PMID:23769419

  2. Attenuated RANKL-induced cytotoxicity by Portulaca oleracea ethanol extract enhances RANKL-mediated osteoclastogenesis.

    Science.gov (United States)

    Erkhembaatar, Munkhsoyol; Choi, Eun-Joo; Lee, Hak-Yong; Lee, Choong Hun; Lee, Young-Rae; Kim, Min Seuk

    2015-07-14

    Portulaca oleracea (PO) has been widely used as traditional medicine because of its pharmacological activities. However, the effects of PO on osteoclasts that modulate bone homeostasis are still elusive. In this study, we examined the effects of PO ethanol extract (POEE) on receptor activator of nuclear factor-κB ligand (RANKL)-mediated Ca(2+) mobilization, nuclear factor of activated T-cell c1 (NFATc1) amplification, tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cell (MNC) formation, and cytotoxicity. Our results demonstrated that POEE suppressed RANKL-induced Ca(2+) oscillations by inhibition of Ca(2+) release from internal Ca(2+) stores, resulting in reduction of NFATc1 amplification. Notably, POEE attenuated RANKL-mediated cytotoxicity and cleavage of polyadenosine 5'-diphosphate-ribose polymerase (PARP), resulted in enhanced formation of TRAP+ MNCs. These results present in vitro effects of POEE on RANKL-mediated osteoclastogenesis and suggest the possible use of PO in treating bone disorders, such as osteopetrosis.

  3. Alanine Enhances Aminoglycosides-Induced ROS Production as Revealed by Proteomic Analysis

    Directory of Open Access Journals (Sweden)

    Jin-zhou Ye

    2018-01-01

    Full Text Available Metabolite-enabled killing of antibiotic-resistant pathogens by antibiotics is an attractive strategy to manage antibiotic resistance. Our previous study demonstrated that alanine or/and glucose increased the killing efficacy of kanamycin on antibiotic-resistant bacteria, whose action is through up-regulating TCA cycle, increasing proton motive force and enhancing antibiotic uptake. Despite the fact that alanine altered several metabolic pathways, other mechanisms could be potentially involved in alanine-mediated kanamycin killing of bacteria which remains to be explored. In the present study, we adopted proteomic approach to analyze the proteome changes induced by exogenous alanine. Our results revealed that the expression of three outer membrane proteins was altered and the deletion of nagE and fadL decreased the intracellular kanamycin concentration, implying their possible roles in mediating kanamycin transport. More importantly, the integrated analysis of proteomic and metabolomic data pointed out that alanine metabolism could connect to riboflavin metabolism that provides the source for reactive oxygen species (ROS production. Functional studies confirmed that alanine treatment together with kanamycin could promote ROS production that in turn potentiates the killing of antibiotic-resistant bacteria. Further investigation showed that alanine repressed the transcription of antioxidant-encoding genes, and alanine metabolism to riboflavin metabolism connected with riboflavin metabolism through TCA cycle, glucogenesis pathway and pentose phosphate pathway. Our results suggest a novel mechanism by which alanine facilitates kanamycin killing of antibiotic-resistant bacteria via promoting ROS production.

  4. Cognitive Performance Enhancement Induced by Caffeine, Carbohydrate and Guarana Mouth Rinsing during Submaximal Exercise

    Directory of Open Access Journals (Sweden)

    Laura Pomportes

    2017-06-01

    Full Text Available The aim of this study was to investigate the influence of serial mouth rinsing (MR with nutritional supplements on cognitive performance (i.e., cognitive control and time perception during a 40-min submaximal exercise. Twenty-four participants completed 4 counterbalanced experimental sessions, during which they performed MR with either placebo (PL, carbohydrate (CHO: 1.6 g/25 mL, guarana complex (GUAc: 0.4 g/25 mL or caffeine (CAF: 67 mg/25 mL before and twice during exercise. The present study provided some important new insights regarding the specific changes in cognitive performance induced by nutritional supplements. The main results were: (1 CHO, CAF and GUA MR likely led participants to improve temporal performance; (2 CAF MR likely improved cognitive control; and (3 CHO MR led to a likely decrease in subjective perception of effort at the end of the exercise compared to PL, GUA and CAF. Moreover, results have shown that performing 40-min submaximal exercise enhances information processing in terms of both speed and accuracy, improves temporal performance and does not alter cognitive control. The present study opens up new perspectives regarding the use of MR to optimize cognitive performance during physical exercise.

  5. Pathogen-induced maternal effects result in enhanced immune responsiveness across generations.

    Science.gov (United States)

    Rosengaus, Rebeca B; Hays, Nicole; Biro, Colette; Kemos, James; Zaman, Muizz; Murray, Joseph; Gezahegn, Bruck; Smith, Wendy

    2017-05-01

    Parental investment theory postulates that adults can accurately perceive cues from their surroundings, anticipate the needs of future offspring based on those cues, and selectively allocate nongenetic resources to their progeny. Such context-dependent parental contributions can result in phenotypically variable offspring. Consistent with these predictions, we show that bacterially exposed Manduca sexta mothers oviposited significantly more variable embryos (as measured by mass, volume, hatching time, and hatching success) relative to naïve and control mothers. By using an in vivo "clearance of infection" assay, we also show that challenged larvae born to heat-killed- or live- Serratia -injected mothers, supported lower microbial loads and cleared the infection faster than progeny of control mothers. Our data support the notion that mothers can anticipate the future pathogenic risks and immunological needs of their unborn offspring, providing progeny with enhanced immune protection likely through transgenerational immune priming. Although the inclusion of live Serratia into oocytes does not appear to be the mechanism by which mothers confer protection to their young, other mechanisms, including epigenetic modifications in the progeny due to maternal pathogenic stress, may be at play. The adaptive nature of maternal effects in the face of pathogenic stress provides insights into parental investment, resource allocation, and life-history theories and highlights the significant role that pathogen-induced maternal effects play as generators and modulators of evolutionary change.

  6. Transients of the electromagnetically-induced-transparency-enhanced refractive Kerr nonlinearity: Theory

    International Nuclear Information System (INIS)

    Pack, M. V.; Camacho, R. M.; Howell, J. C.

    2006-01-01

    We present a theory describing the transients and rise times of the refractive Kerr nonlinearity which is enhanced using electromagnetically induced transparency (EIT). We restrict our analysis to the case of a pulsed signal field with continuous-wave EIT fields, and all fields are well below saturation. These restrictions enable the reduction of an EIT Kerr, four-level, density-matrix equation to a two-level Bloch-vector equation which has a simple and physically intuitive algebraic solution. The physically intuitive picture of a two-level Bloch vector provides insights that are easily generalized to more complex and experimentally realistic models. We consider generalization to the cases of Doppler broadening, many-level EIT systems (we consider the D1 line of 87 Rb), and optically thick media. For the case of optically thick media we find that the rise time of the refractive EIT Kerr effect is proportional to the optical thickness. The rise time of the refractive EIT Kerr effect sets important limitations for potential few-photon applications

  7. Metallic behavior and enhanced adsorption energy of graphene on BN layer induced by Cu(111) substrate

    International Nuclear Information System (INIS)

    Hashmi, Arqum; Hong, Jisang

    2014-01-01

    We have investigated the adsorption properties and the electronic structure of graphene/BN and graphene/BN/Cu(111) systems by using van der Waals density functional theory. The ground-state adsorption site of graphene on BN/Cu(111) is found to be the same as that of graphene/BN. The Cu(111) substrate did not induce a significant change in the geometrical feature of graphene/BN. However, the adsorption energy of graphene on BN/Cu(111) is observed to be enhanced due to the Cu(111) substrate. In addition, we have found that the graphene layer displays a weak metallic character in graphene/BN/Cu(111) whereas an energy band gap is observed in the graphene in the graphene/BN bilayer system. Therefore, we have found that the metallic Cu(111) substrate affects the electronic structure and adsorption properties of graphene on BN/Cu(111), although it has no significant effect on the geometrical features.

  8. Drug perfusion enhancement in tissue model by steady streaming induced by oscillating microbubbles.

    Science.gov (United States)

    Oh, Jin Sun; Kwon, Yong Seok; Lee, Kyung Ho; Jeong, Woowon; Chung, Sang Kug; Rhee, Kyehan

    2014-01-01

    Drug delivery into neurological tissue is challenging because of the low tissue permeability. Ultrasound incorporating microbubbles has been applied to enhance drug delivery into these tissues, but the effects of a streaming flow by microbubble oscillation on drug perfusion have not been elucidated. In order to clarify the physical effects of steady streaming on drug delivery, an experimental study on dye perfusion into a tissue model was performed using microbubbles excited by acoustic waves. The surface concentration and penetration length of the drug were increased by 12% and 13%, respectively, with streaming flow. The mass of dye perfused into a tissue phantom for 30s was increased by about 20% in the phantom with oscillating bubbles. A computational model that considers fluid structure interaction for streaming flow fields induced by oscillating bubbles was developed, and mass transfer of the drug into the porous tissue model was analyzed. The computed flow fields agreed with the theoretical solutions, and the dye concentration distribution in the tissue agreed well with the experimental data. The computational results showed that steady streaming with a streaming velocity of a few millimeters per second promotes mass transfer into a tissue. © 2013 Published by Elsevier Ltd.

  9. Transcriptional Enhancers Induce Insertional Gene Deregulation Independently From the Vector Type and Design

    Science.gov (United States)

    Maruggi, Giulietta; Porcellini, Simona; Facchini, Giulia; Perna, Serena K; Cattoglio, Claudia; Sartori, Daniela; Ambrosi, Alessandro; Schambach, Axel; Baum, Christopher; Bonini, Chiara; Bovolenta, Chiara; Mavilio, Fulvio; Recchia, Alessandra

    2009-01-01

    The integration characteristics of retroviral (RV) vectors increase the probability of interfering with the regulation of cellular genes, and account for a tangible risk of insertional mutagenesis in treated patients. To assess the potential genotoxic risk of conventional or self-inactivating (SIN) γ-RV and lentiviral (LV) vectors independently from the biological consequences of the insertion event, we developed a quantitative assay based on real-time reverse transcriptase—PCR on low-density arrays to evaluate alterations of gene expression in individual primary T-cell clones. We show that the Moloney leukemia virus long terminal repeat (LTR) enhancer has the strongest activity in both a γ-RV and a LV vector context, while an internal cellular promoter induces deregulation of gene expression less frequently, at a shorter range and to a lower extent in both vector types. Downregulation of gene expression was observed only in the context of LV vectors. This study indicates that insertional gene activation is determined by the characteristics of the transcriptional regulatory elements carried by the vector, and is largely independent from the vector type or design. PMID:19293778

  10. Cognitive Performance Enhancement Induced by Caffeine, Carbohydrate and Guarana Mouth Rinsing during Submaximal Exercise.

    Science.gov (United States)

    Pomportes, Laura; Brisswalter, Jeanick; Casini, Laurence; Hays, Arnaud; Davranche, Karen

    2017-06-09

    The aim of this study was to investigate the influence of serial mouth rinsing (MR) with nutritional supplements on cognitive performance (i.e., cognitive control and time perception) during a 40-min submaximal exercise. Twenty-four participants completed 4 counterbalanced experimental sessions, during which they performed MR with either placebo (PL), carbohydrate (CHO: 1.6 g/25 mL), guarana complex (GUAc: 0.4 g/25 mL) or caffeine (CAF: 67 mg/25 mL) before and twice during exercise. The present study provided some important new insights regarding the specific changes in cognitive performance induced by nutritional supplements. The main results were: (1) CHO, CAF and GUA MR likely led participants to improve temporal performance; (2) CAF MR likely improved cognitive control; and (3) CHO MR led to a likely decrease in subjective perception of effort at the end of the exercise compared to PL, GUA and CAF. Moreover, results have shown that performing 40-min submaximal exercise enhances information processing in terms of both speed and accuracy, improves temporal performance and does not alter cognitive control. The present study opens up new perspectives regarding the use of MR to optimize cognitive performance during physical exercise.

  11. High salt intake enhances swim stress-induced PVN vasopressin cell activation and active stress coping.

    Science.gov (United States)

    Mitchell, N C; Gilman, T L; Daws, L C; Toney, G M

    2018-07-01

    Stress contributes to many psychiatric disorders; however, responsivity to stressors can vary depending on previous or current stress exposure. Relatively innocuous heterotypic (differing in type) stressors can summate to result in exaggerated neuronal and behavioral responses. Here we investigated the ability of prior high dietary sodium chloride (salt) intake, a dehydrating osmotic stressor, to enhance neuronal and behavioral responses of mice to an acute psychogenic swim stress (SS). Further, we evaluated the contribution of the osmo-regulatory stress-related neuropeptide arginine vasopressin (VP) in the hypothalamic paraventricular nucleus (PVN), one of only a few brain regions that synthesize VP. The purpose of this study was to determine the impact of high dietary salt intake on responsivity to heterotypic stress and the potential contribution of VPergic-mediated neuronal activity on high salt-induced stress modulation, thereby providing insight into how dietary (homeostatic) and environmental (psychogenic) stressors might interact to facilitate psychiatric disorder vulnerability. Salt loading (SL) with 4% saline for 7 days was used to dehydrate and osmotically stress mice prior to exposure to an acute SS. Fluid intake and hematological measurements were taken to quantify osmotic dehydration, and serum corticosterone levels were measured to index stress axis activation. Immunohistochemistry (IHC) was used to stain for the immediate early gene product c-Fos to quantify effects of SL on SS-induced activation of neurons in the PVN and extended amygdala - brain regions that are synaptically connected and implicated in responding to osmotic stress and in modulation of SS behavior, respectively. Lastly, the role of VPergic PVN neurons and VP type 1 receptor (V1R) activity in the amygdala in mediating effects of SL on SS behavior was evaluated by quantifying c-Fos activation of VPergic PVN neurons and, in functional experiments, by nano-injecting the V1R selective

  12. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Ming-Huan [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Institute of Neuroscience, National Changchi University, Taipei, Taiwan (China); Chung, Shiang-Sheng [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Department of Pharmacy, Yuli Veterans Hospital, Hualien, Taiwan (China); Stoker, Astrid K.; Markou, Athina [Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (United States); Chen, Hwei-Hsien, E-mail: hwei@nhri.org.tw [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China)

    2012-12-01

    Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene-induced

  13. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

    International Nuclear Information System (INIS)

    Chan, Ming-Huan; Chung, Shiang-Sheng; Stoker, Astrid K.; Markou, Athina; Chen, Hwei-Hsien

    2012-01-01

    Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene-induced

  14. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  15. Re-expression of ARHI (DIRAS3) induces autophagy in breast cancer cells and enhances the inhibitory effect of paclitaxel

    International Nuclear Information System (INIS)

    Zou, Chun-Fang; Yu, Yinhua; Jia, Luoqi; Jin, Hongyan; Yao, Ming; Zhao, Naiqing; Huan, Jin; Lu, Zhen; Bast, Robert C Jr; Feng, Youji

    2011-01-01

    ARHI is a Ras-related imprinted gene that inhibits cancer cell growth and motility. ARHI is downregulated in the majority of breast cancers, and loss of its expression is associated with its progression from ductal carcinoma in situ (DCIS) to invasive disease. In ovarian cancer, re-expression of ARHI induces autophagy and leads to autophagic death in cell culture; however, ARHI re-expression enables ovarian cancer cells to remain dormant when they are grown in mice as xenografts. The purpose of this study is to examine whether ARHI induces autophagy in breast cancer cells and to evaluate the effects of ARHI gene re-expression in combination with paclitaxel. Re-expression of ARHI was achieved by transfection, by treatment with trichostatin A (TSA) or by a combination of TSA and 5-aza-2'-deoxycytidine (DAC) in breast cancer cell cultures and by liposomal delivery of ARHI in breast tumor xenografts. ARHI re-expression induces autophagy in breast cancer cells, and ARHI is essential for the induction of autophagy. When ARHI was re-expressed in breast cancer cells treated with paclitaxel, the growth inhibitory effect of paclitaxel was enhanced in both the cell culture and the xenografts. Although paclitaxel alone did not induce autophagy in breast cancer cells, it enhanced ARHI-induced autophagy. Conversely, ARHI re-expression promoted paclitaxel-induced apoptosis and G2/M cell cycle arrest. ARHI re-expression induces autophagic cell death in breast cancer cells and enhances the inhibitory effects of paclitaxel by promoting autophagy, apoptosis, and G2/M cell cycle arrest

  16. Temporal dependence of the enhancement of material removal in femtosecond-nanosecond dual-pulse laser-induced breakdown spectroscopy

    International Nuclear Information System (INIS)

    Scaffidi, Jon; Pearman, William; Carter, J. Chance; Colston, Bill W. Jr.; Angel, S. Michael

    2004-01-01

    Despite the large neutral atomic and ionic emission enhancements that have been noted in collinear and orthogonal dual-pulse laser-induced breakdown spectroscopy, the source or sources of these significant signal and signal-to-noise ratio improvements have yet to be explained. In the research reported herein, the combination of a femtosecond preablative air spark and a nanosecond ablative pulse yields eightfold and tenfold material removal improvement for brass and aluminum, respectively, but neutral atomic emission is enhanced by only a factor of 3-4. Additionally, temporal correlation between enhancement of material removal and of atomic emission is quite poor, suggesting that the atomic-emission enhancements noted in the femtosecond-nanosecond pulse configuration result in large part from some source other than simple improvement in material removal

  17. Twenty-fold plasmon-induced enhancement of radiative emission rate in silicon nanocrystals embedded in silicon dioxide

    International Nuclear Information System (INIS)

    Gardelis, S; Gianneta, V.; Nassiopoulou, A.G

    2016-01-01

    We report on a 20-fold enhancement of the integrated photoluminescence (PL) emission of silicon nanocrystals, embedded in a matrix of silicon dioxide, induced by excited surface plasmons from silver nanoparticles, which are located in the vicinity of the silicon nanocrystals and separated from them by a silicon dioxide layer of a few nanometers. The electric field enhancement provided by the excited surface plasmons increases the absorption cross section and the emission rate of the nearby silicon nanocrystals, resulting in the observed enhancement of the photoluminescence, mainly attributed to a 20-fold enhancement in the emission rate of the silicon nanocrystals. The observed remarkable improvement of the PL emission makes silicon nanocrystals very useful material for photonic, sensor and solar cell applications.

  18. A novel cold-inducible zinc finger protein from soybean, SCOF-1, enhances cold tolerance in transgenic plants.

    Science.gov (United States)

    Kim, J C; Lee, S H; Cheong, Y H; Yoo, C M; Lee, S I; Chun, H J; Yun, D J; Hong, J C; Lee, S Y; Lim, C O; Cho, M J

    2001-02-01

    Cold stress on plants induces changes in the transcription of cold response genes. A cDNA clone encoding C2H2-type zinc finger protein, SCOF-1, was isolated from soybean. The transcription of SCOF-1 is specifically induced by low temperature and abscisic acid (ABA) but not by dehydration or high salinity. Constitutive overexpression of SCOF-1 induced cold-regulated (COR) gene expression and enhanced cold tolerance of non-acclimated transgenic Arabidopsis and tobacco plants. SCOF-1 localized to the nucleus but did not bind directly to either C-repeat/dehydration (CRT/DRE) or ABA responsive element (ABRE), cis-acting DNA regulatory elements present in COR gene promoters. However, SCOF-1 greatly enhanced the DNA binding activity of SGBF-1, a soybean G-box binding bZIP transcription factor, to ABRE in vitro. SCOF-1 also interacted with SGBF-1 in a yeast two-hybrid system. The SGBF-1 transactivated the beta-glucuronidase reporter gene driven by the ABRE element in Arabidopsis leaf protoplasts. Furthermore, the SCOF-1 enhanced ABRE-dependent gene expression mediated by SGBF-1. These results suggest that SCOF-1 may function as a positive regulator of COR gene expression mediated by ABRE via protein-protein interaction, which in turn enhances cold tolerance of plants.

  19. SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition.

    Science.gov (United States)

    Jia, Zhuqing; Wang, Jiaji; Shi, Qiong; Liu, Siyu; Wang, Weiping; Tian, Yuyao; Lu, Qin; Chen, Ping; Ma, Kangtao; Zhou, Chunyan

    2016-02-01

    Sepsis-induced cardiac apoptosis is one of the major pathogenic factors in myocardial dysfunction. As it enhances numerous proinflammatory factors, lipopolysaccharide (LPS) is considered the principal mediator in this pathological process. However, the detailed mechanisms involved are unclear. In this study, we attempted to explore the mechanisms involved in LPS-induced cardiomyocyte apoptosis. We found that LPS stimulation inhibited microRNA (miR)-499 expression and thereby upregulated the expression of SOX6 and PDCD4 in neonatal rat cardiomyocytes. We demonstrate that SOX6 and PDCD4 are target genes of miR-499, and they enhance LPS-induced cardiomyocyte apoptosis by activating the BCL-2 family pathway. The apoptosis process enhanced by overexpression of SOX6 or PDCD4, was rescued by the cardiac-abundant miR-499. Overexpression of miR-499 protected the cardiomyocytes against LPS-induced apoptosis. In brief, our results demonstrate the existence of a miR-499-SOX6/PDCD4-BCL-2 family pathway in cardiomyocytes in response to LPS stimulation.

  20. Persistent attenuation and enhancement of the earthworm main muscle contraction generator response induced by repeated stimulation of a peripheral neuron

    Directory of Open Access Journals (Sweden)

    Y.C. Chang

    1998-10-01

    Full Text Available Responses evoked in the earthworm, Amynthas hawayanus, main muscle contraction generator M-2 (postsynaptic mechanical-stimulus-sensitive neuron by threshold mechanical stimuli in 2-s intertrial intervals (ITI were used as the control or unconditioned responses (UR. Their attenuation induced by decreasing these intervals in non-associative conditioning and their enhancement induced by associating the unconditioned stimuli (US to a train of short (0.1 s hyperpolarizing electrical substitutive conditioning stimuli (SCS in the Peri-Kästchen (PK neuron were measured in four parameters, i.e., peak numbers (N and amplitude (averaged from 120 responses, sum of these amplitudes (SAMP and the highest peak amplitude (V over a period of 4 min. Persistent attenuation similar to habituation was induced by decreasing the control ITI to 0.5 s and 2.0 s in non-associative conditioning within less than 4 min. Dishabituation was induced by randomly pairing one of these habituated US to an electrical stimulus in the PK neuron. All four parameters of the UR were enhanced by forward (SCS-US, but not backward (US-SCS, association of the US with 25, 100 and 250-Hz trains of SCS with 40-ms interstimulus intervals (ISI for 4 min and persisted for another 4 min after turning off the SCS. The enhancement of these parameters was proportional to the SCS frequencies in the train. No UR was evoked by the SCS when the US was turned off after 4 min of classical conditioning.

  1. The p53-reactivating small-molecule RITA enhances cisplatin-induced cytotoxicity and apoptosis in head and neck cancer.

    Science.gov (United States)

    Roh, Jong-Lyel; Ko, Jung Ho; Moon, Soo Jin; Ryu, Chang Hwan; Choi, Jun Young; Koch, Wayne M

    2012-12-01

    We evaluated whether the restoration of p53 function by the p53-reactivating small molecule RITA (reactivation of p53 and induction of tumor cell apoptosis enhances cisplatin-induced cytotoxicity and apoptosis in head-and-neck cancer (HNC). RITA induced prominent accumulation and reactivation of p53 in a wild-type TP53-bearing HNC cell line. RITA showed maximal growth suppression in tumor cells showing MDM2-dependent p53 degradation. RITA promoted apoptosis in association with upregulation of p21, BAX, and cleaved caspase-3; notably, the apoptotic response was blocked by pifithrin-α, demonstrating its p53 dependence. With increasing concentrations, RITA strongly induced apoptosis rather than G2-phase arrest. In combination therapy, RITA enhanced cisplatin-induced growth inhibition and apoptosis of HNC cells invitro and in vivo. Our data suggest that the restoration of p53 tumor-suppressive function by RITA enhances the cytotoxicity and apoptosis of cisplatin, an action that may offer an attractive strategy for treating HNC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Spectral Induced Polarization (SIP) monitoring during Microbial Enhanced Oil Recovery (MEOR)

    Science.gov (United States)

    Heenan, J. W.; Ntarlagiannis, D.; Slater, L. D.

    2010-12-01

    Jeffrey Heenan, Dimitrios Ntarlagiannis, Lee Slater Department of Earth and Environmental Sciences, Rutgers University, Newark NJ Microbial Enhanced Oil Recovery (MEOR) is an established, cost effective, method for enhancing tertiary oil recovery. Although not commonly used for shallow heavy oils, it could be a viable alternative since it can offer sustainable economic recovery and minimal environmental impact. A critical component of successful MEOR treatments is accurate, real time monitoring of the biodegradation processes resulting from the injection of microbial communities into the formation; results of recent biogeophysical research suggest that minimally-invasive geophysical methods could significantly contribute to such monitoring efforts. Here we present results of laboratory experiments, to assess the sensitivity of the spectral induced polarization method (SIP) to MEOR treatments. We used heavy oil, obtained from a shallow oilfield in SW Missouri, to saturate three sand columns. We then followed common industry procedures,and used a commercially available microbial consortia, to treat the oil columns. The active MEOR experiments were performed in duplicate while a control column maintained similar conditions, without promoting microbial activity and oil degradation. We monitored the SIP signatures, between 0.001 Hz and 1000 Hz, for a period of six months. To support the geophysical measurements we also monitored common geochemical parameters, including pH, Eh and fluid conductivity, and collected weekly fluid samples from the outflow and inflow for further analysis; fluid samples were analyzed to confirm that microbes actively degraded the heavy oils in the column while destructive analysis of the solid materials was performed upon termination of the experiment. Preliminary analysis of the results suggests that SIP is sensitive to MEOR processes. In both inoculated columns we recorded an increase in the low frequency polarization with time; measureable

  3. Variability induced by the MR imager in dynamic contrast-enhanced imaging of the prostate.

    Science.gov (United States)

    Brunelle, S; Zemmour, C; Bratan, F; Mège-Lechevallier, F; Ruffion, A; Colombel, M; Crouzet, S; Sarran, A; Rouvière, O

    2018-04-01

    To evaluate the variability induced by the imager in discriminating high-grade (Gleason≥7) prostate cancers (HGC) using dynamic contrast-enhanced MRI. We retrospectively selected 3T MRIs with temporal resolution<10 seconds and comprising T1 mapping from a prospective radiologic-pathologic database of patients treated by prostatectomy. Ktrans, Kep, Ve and Vp were calculated for each lesion seen on MRI using the Weinmann arterial input function (AIF) and three patient-specific AIFs measured in the right and left iliac arteries in pixels in the center of the lumen (psAIF-ST) or manually selected by two independent readers (psAIF-R1 and psAIF-R2). A total of 43 patients (mean age, 63.6±4.9 [SD]; range: 48-72 years) with 100 lesions on MRI (55 HGC) were selected. MRIs were performed on imager A (22 patients, 49 lesions) or B (21 patients, 51 lesions) from two different manufacturers. Using the Weinmann AIF, Kep (P=0.005), Ve (P=0.04) and Vp (P=0.01) significantly discriminated HCG. After adjusting on tissue classes, the imager significantly influenced the values of Kep (P=0.049) and Ve (P=0.007). Using patient-specific AIFs, Vp with psAIF-ST (P=0.008) and psAIF-R2 (P=0.04), and Kep with psAIF-R1 (P=0.03) significantly discriminated HGC. After adjusting on tissue classes, types of patient-specific AIF and side of measurement, the imager significantly influenced the values of Ktrans (P=0.0002), Ve (P=0.0072) and Vp (P=0.0003). For all AIFs, the diagnostic value of pharmacokinetic parameters remained unchanged after adjustment on the imager, with stable odds ratios. The imager induced variability in the absolute values of pharmacokinetic parameters but did not change their diagnostic performance. Copyright © 2018 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  4. Zinc salt enhances gastroprotective activity of risperidone in indomethacin-induced gastric ulcer.

    Science.gov (United States)

    Oluwole, F S; Onwuchekwa, C

    2016-09-01

    Zinc has been reported to mediate cellular responses to injury by producing cytoprotection via the scavenging of reactive oxygen species. Anti-stress medications are generally anti-psychotic drugs and anti- depressants. Some Anti-psychotic drugs such as risperidone have been reported to possess anti-ulcer activity. Risperidone as an antipsychotic drug blocks several neurotransmitter systems including dopaminergic, adrenergic, histaminergic and serotonergic pathways. The study investigated the antiulcer activity of Zinc Chloride (ZnCl(2)) in combination with risperidone in male Wistar rats. The animals were divided into two groups of twenty animals each for ZnCl(2) and risperidone groups. Each group was further divided into four subgroups. ZnCl(2) was administered orally at 20mg/kg, 40mg/kg and 80mg/kg to a subgroup, while 80mg/kg of ZnCl(2) was administered in combination with risperidone (0.1mg/kg, 0.3mg/kg and 0.5mg/kg) orally once daily for 21 days. The controls were treated with distilled water. Ulcer was induced using indomethacin. Histology of the stomach tissues was prepared with PAS and H& E stains. Ulcer score and ulcer area were assessed using standard methods. Data were analysed using student t-test and Graphpad Prism 5. There were decreases in ulcer scores using the different doses of ZnCl, (20mg/kg, 40mg/kg and 80mg/kg). Also using the highest dose ZnCl(2) (80mg/ kg) and different doses of risperidone there were decreases in ulcer scores compared to the control. This effect of the risperidone showed a significant dose- dependent reduction. The effect ZnCl(2), and risperidone were also reflected in the ulcer area and in the histology. These findings suggest that ZnCl(2), enhances the gastroprotective activity ofrisperidone in indomethacin- induced gastric ulcer. However, more detailed studies are necessary to confirm the relevance of this finding and its implications in clinical settings.

  5. Enhancement of ATRA-induced differentiation of neuroblastoma cells with LOX/COX inhibitors: an expression profiling study

    Directory of Open Access Journals (Sweden)

    Hermanova Marketa

    2010-05-01

    Full Text Available Abstract Background We performed expression profiling of two neuroblastoma cell lines, SK-N-BE(2 and SH-SY5Y, after combined treatment with all-trans retinoic acid (ATRA and inhibitors of lipoxygenases (LOX and cyclooxygenases (COX. This study is a continuation of our previous work confirming the possibility of enhancing ATRA-induced cell differentiation in these cell lines by the application of LOX/COX inhibitors and brings more detailed information concerning the mechanisms of the enhancement of ATRA-induced differentiation of neuroblastoma cells. Methods Caffeic acid, as an inhibitor of 5-lipoxygenase, and celecoxib, as an inhibitor on cyclooxygenase-2, were used in this study. Expression profiling was performed using Human Cancer Oligo GEArray membranes that cover 440 cancer-related genes. Results Cluster analyses of the changes in gene expression showed the concentration-dependent increase in genes known to be involved in the process of retinoid-induced neuronal differentiation, especially in cytoskeleton remodeling. These changes were detected in both cell lines, and they were independent of the type of specific inhibitors, suggesting a common mechanism of ATRA-induced differentiation enhancement. Furthermore, we also found overexpression of some genes in the same cell line (SK-N-BE(2 or SH-SY5Y after combined treatment with both ATRA and CA, or ATRA and CX. Finally, we also detected that gene expression was changed after treatment with the same inhibitor (CA or CX in combination with ATRA in both cell lines. Conclusions Obtained results confirmed our initial hypothesis of the common mechanism of enhancement in ATRA-induced cell differentiation via inhibition of arachidonic acid metabolic pathway.

  6. Enhancement of ATRA-induced differentiation of neuroblastoma cells with LOX/COX inhibitors: an expression profiling study.

    Science.gov (United States)

    Chlapek, Petr; Redova, Martina; Zitterbart, Karel; Hermanova, Marketa; Sterba, Jaroslav; Veselska, Renata

    2010-05-11

    We performed expression profiling of two neuroblastoma cell lines, SK-N-BE(2) and SH-SY5Y, after combined treatment with all-trans retinoic acid (ATRA) and inhibitors of lipoxygenases (LOX) and cyclooxygenases (COX). This study is a continuation of our previous work confirming the possibility of enhancing ATRA-induced cell differentiation in these cell lines by the application of LOX/COX inhibitors and brings more detailed information concerning the mechanisms of the enhancement of ATRA-induced differentiation of neuroblastoma cells. Caffeic acid, as an inhibitor of 5-lipoxygenase, and celecoxib, as an inhibitor on cyclooxygenase-2, were used in this study. Expression profiling was performed using Human Cancer Oligo GEArray membranes that cover 440 cancer-related genes. Cluster analyses of the changes in gene expression showed the concentration-dependent increase in genes known to be involved in the process of retinoid-induced neuronal differentiation, especially in cytoskeleton remodeling. These changes were detected in both cell lines, and they were independent of the type of specific inhibitors, suggesting a common mechanism of ATRA-induced differentiation enhancement. Furthermore, we also found overexpression of some genes in the same cell line (SK-N-BE(2) or SH-SY5Y) after combined treatment with both ATRA and CA, or ATRA and CX. Finally, we also detected that gene expression was changed after treatment with the same inhibitor (CA or CX) in combination with ATRA in both cell lines. Obtained results confirmed our initial hypothesis of the common mechanism of enhancement in ATRA-induced cell differentiation via inhibition of arachidonic acid metabolic pathway.

  7. ADRA2B deletion variant selectively predicts stress-induced enhancement of long-term memory in females.

    Science.gov (United States)

    Zoladz, Phillip R; Kalchik, Andrea E; Hoffman, Mackenzie M; Aufdenkampe, Rachael L; Lyle, Sarah M; Peters, David M; Brown, Callie M; Cadle, Chelsea E; Scharf, Amanda R; Dailey, Alison M; Wolters, Nicholas E; Talbot, Jeffery N; Rorabaugh, Boyd R

    2014-10-01

    Clarifying the mechanisms that underlie stress-induced alterations of learning and memory may lend important insight into susceptibility factors governing the development of stress-related psychological disorders, such as post-traumatic stress disorder (PTSD). Previous work has shown that carriers of the ADRA2B Glu(301)-Glu(303) deletion variant exhibit enhanced emotional memory, greater amygdala responses to emotional stimuli and greater intrusiveness of traumatic memories. We speculated that carriers of this deletion variant might also be more vulnerable to stress-induced enhancements of long-term memory, which would implicate the variant as a possible susceptibility factor for traumatic memory formation. One hundred and twenty participants (72 males, 48 females) submerged their hand in ice cold (stress) or warm (no stress) water for 3min. Immediately afterwards, they studied a list of 42 words varying in emotional valence and arousal and then completed an immediate free recall test. Twenty-four hours later, participants' memory for the word list was examined via free recall and recognition assessments. Stressed participants exhibiting greater heart rate responses to the stressor had enhanced recall on the 24-h assessment. Importantly, this enhancement was independent of the emotional nature of the learned information. In contrast to previous work, we did not observe a general enhancement of memory for emotional information in ADRA2B deletion carriers. However, stressed female ADRA2B deletion carriers, particularly those exhibiting greater heart rate responses to the stressor, did demonstrate greater recognition memory than all other groups. Collectively, these findings implicate autonomic mechanisms in the pre-learning stress-induced enhancement of long-term memory and suggest that the ADRA2B deletion variant may selectively predict stress effects on memory in females. Such findings lend important insight into the physiological mechanisms underlying stress

  8. Aging enhances the vulnerability of mesenchymal stromal cells to uniaxial tensile strain-induced apoptosis.

    Science.gov (United States)

    McKayed, Katey; Prendergast, Patrick J; Campbell, Veronica A

    2016-02-08

    Mechanical priming can be employed in tissue engineering strategies to control the fate and differentiation pattern of mesenchymal stromal cells. This is relevant to regenerative medicine whereby mechanical cues can promote the regeneration of a specific tissue type from mesenchymal precursors. The ability of cells to respond to mechanical forces is dependent upon mechanotransduction pathways that involve membrane-associated proteins, such as integrins. During the aging process changes in the mechanotransduction machinery may influence how cells from aged individuals respond to mechanical priming. In this study mesenchymal stromal cells were prepared from young adult and aged rats and exposed to uniaxial tensile strain at 5% and 10% for 3 days, or 2.5% for 7 days. Application of 5% tensile strain had no impact on cell viability. In contrast, application of 10% tensile strain evoked apoptosis and the strain-induced apoptosis was significantly higher in the mesenchymal stromal cells prepared from the aged rats. In parallel to the age-related difference in cellular responsiveness to strain, an age-related decrease in expression of α2 integrin and actin, and enhanced lipid peroxidation was observed. This study demonstrates that mesenchymal stem cells from aged animals have an altered membrane environment, are more vulnerable to the pro-apoptotic effects of 10% tensile strain and less responsive to the pro-osteogenic effects of 2.5% tensile strain. Thus, it is essential to consider how aged cells respond to mechanical stimuli in order to identify optimal mechanical priming strategies that minimise cell loss, particularly if this approach is to be applied to an aged population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Mechanism of salt-induced activity enhancement of a marine-derived laccase, Lac15.

    Science.gov (United States)

    Li, Jie; Xie, Yanan; Wang, Rui; Fang, Zemin; Fang, Wei; Zhang, Xuecheng; Xiao, Yazhong

    2018-04-01

    Laccase (benzenediol: oxygen oxidoreductases, EC1.10.3.2) is a multi-copper oxidase capable of oxidizing a variety of phenolic and other aromatic organic compounds. The catalytic power of laccase makes it an attractive candidate for potential applications in many areas of industry including biodegradation of organic pollutants and synthesis of novel drugs. Most laccases are vulnerable to high salt and have limited applications. However, some laccases are not only tolerant to but also activated by certain concentrations of salt and thus have great application potential. The mechanisms of salt-induced activity enhancement of laccases are unclear as yet. In this study, we used dynamic light scattering, size exclusion chromatography, analytical ultracentrifugation, intrinsic fluorescence emission, circular dichroism, ultraviolet-visible light absorption, and an enzymatic assay to investigate the potential correlation between the structure and activity of the marine-derived laccase, Lac15, whose activity is promoted by low concentrations of NaCl. The results showed that low concentrations of NaCl exert little influence on the protein structure, which was partially folded in the absence of the salt; moreover, the partially folded rather than the fully folded state seemed to be favorable for enzyme activity, and this partially folded state was distinctive from the so-called 'molten globule' occasionally observed in active enzymes. More data indicated that salt might promote laccase activity through mechanisms involving perturbation of specific local sites rather than a change in global structure. Potential binding sites for chloride ions and their roles in enzyme activity promotion are proposed.

  10. Cilostazol enhances atorvastatin-induced vasodilation of female rat aorta during aging.

    Science.gov (United States)

    Nurullahoğlu-Atalık, K E; Kutlu, S; Solak, H; Koca, R Özen

    2017-09-01

    Statins have cholesterol-independent effects including an increased vascular nitric oxide activity and are commonly used by patients with cardiovascular disease. Such patients frequently have cardiovascular diseases, which may be treated with cilostazol, a platelet aggregation inhibitor. This study was designed to investigate whether combined use of cilostazol would increase the inhibitory effect of statin on vascular smooth muscle and how maturation would affect these responses. Female Wistar rats, aged 3-4 months (young) and 14-15 months (adult), were sacrificed by cervical dislocation and the thoracic aorta was dissected and cut into 3- to 4-mm-long rings. The rings were mounted under a resting tension of 1 g in a 20-ml organ bath filled with Krebs-Henseleit solution. Rings were precontracted with phenylephrine (10 -6  M), and the presence of endothelium was confirmed with acetylcholine (10 -6  M). Then, the concentration-response curves were obtained for atorvastatin alone (10 -10 to 3 × 10 -4  M; control) and in the presence of cilostazol (10 -6  M) in young and adult rat aortas. This experimental protocol was also carried out in aorta rings, which had been pretreated with N G -nitro-l-arginine methyl ester (l-NAME, 10 -4  M). Atorvastatin induced concentration-dependent relaxations in young and adult rat thoracic aorta rings precontracted with phenylephrine. The pIC 50 value of atorvastatin was significantly decreased in adult rat aortas. In addition, pretreatment of aortas with cilostazol enhanced the potency of atorvastatin in both young and adult aortas. Incubation with l-NAME did not completely eliminate the relaxations to atorvastatin in the presence of cilostazol. These results suggest that combined application of cilostazol with atorvastatin was significantly more potent than atorvastatin alone. Combined drug therapy may be efficacious in delaying the occurrence of cardiovascular events.

  11. Signal enhancement in collinear double-pulse laser-induced breakdown spectroscopy applied to different soils

    Energy Technology Data Exchange (ETDEWEB)

    Nicolodelli, Gustavo, E-mail: gunicolodelli@hotmail.com [Embrapa Instrumentation, Rua XV de Novembro, 1452, CEP 13560-970 São Carlos, SP (Brazil); Senesi, Giorgio Saverio, E-mail: giorgio.senesi@imip.cnr.it [Institute of Inorganic Methodologies and Plasmas, CNR, Bari, 70126 Bari (Italy); Romano, Renan Arnon, E-mail: renan.romano@gmail.com [Embrapa Instrumentation, Rua XV de Novembro, 1452, CEP 13560-970 São Carlos, SP (Brazil); Physics Institute of São Carlos, University of São Paulo, IFSC-USP, Av. Trabalhador são-carlense, 400 Pq. Arnold Schimid, 13566-590 São Carlos, SP (Brazil); Oliveira Perazzoli, Ivan Luiz de, E-mail: ivanperazzoli@hotmail.com [Embrapa Instrumentation, Rua XV de Novembro, 1452, CEP 13560-970 São Carlos, SP (Brazil); Milori, Débora Marcondes Bastos Pereira, E-mail: debora.milori@embrapa.br [Embrapa Instrumentation, Rua XV de Novembro, 1452, CEP 13560-970 São Carlos, SP (Brazil)

    2015-09-01

    Laser-induced breakdown spectroscopy (LIBS) is a well-known consolidated analytical technique employed successfully for the qualitative and quantitative analysis of solid, liquid, gaseous and aerosol samples of very different nature and origin. Several techniques, such as dual-pulse excitation setup, have been used in order to improve LIBS's sensitivity. The purpose of this paper was to optimize the key parameters as excitation wavelength, delay time and interpulse, that influence the double pulse (DP) LIBS technique in the collinear beam geometry when applied to the analysis at atmospheric air pressure of soil samples of different origin and texture from extreme regions of Brazil. Additionally, a comparative study between conventional single pulse (SP) LIBS and DP LIBS was performed. An optimization of DP LIBS system, choosing the correct delay time between the two pulses, was performed allowing its use for different soil types and the use of different emission lines. In general, the collinear DP LIBS system improved the analytical performances of the technique by enhancing the intensity of emission lines of some elements up to about 5 times, when compared with conventional SP-LIBS, and reduced the continuum emission. Further, the IR laser provided the best performance in re-heating the plasma. - Highlights: • The correct choice of the delay time between the two pulses is crucial for the DP system. • An optimization of DP LIBS system was performed allowing its use for different soil and the use of different emission lines. • The DP LIBS system improved the analytical performances of the technique up to about 5 times, when compared with SP LIBS. • The IR laser provided the best performance in re-heating the plasma.

  12. Enhanced mucosal re-epithelialization induced by short chain fatty acids in experimental colitis

    Directory of Open Access Journals (Sweden)

    Aguilar-Nascimento J.E.

    1999-01-01

    Full Text Available The short chain fatty acids (SCFA are the best nutrients for the colonocytes. Glucose is poorly used as a fuel but may be transformed into SCFA by colonic bacteria. The aim of this study was to investigate the effect of SCFA or glucose on experimental colitis. Colitis was induced in 30 Wistar rats by colonic instillation of 4% acetic acid. Five days later they were randomized to receive twice a day colonic lavage containing saline (controls, N = 10, 10% hypertonic glucose (N = 10 or SCFA (N = 10 until day 8 when they were killed. At autopsy, the colon was removed and weighed and the mucosa was evaluated macro- and microscopically and stripped out for DNA assay. Data are reported as mean ± SD or median [range] as appropriate. All animals lost weight but there was no difference between groups. Colon weight was significantly lower in the SCFA group (3.8 ± 0.5 g than in the control (5.3 ± 2.1 g and glucose (5.2 ± 1.3 g groups (P<0.05. Macroscopically, the severity of inflammation was less in SCFA (grade 2 [1-5] than in control (grade 9 [4-10] and glucose-treated (grade 9 [2-10] animals (P<0.01. Microscopically, ulceration of the mucosa was more severe in the glucose and control groups than in the SCFA group. The DNA content of the mucosa of SCFA-treated animals (8.2 [5.0-20.2] mg/g of tissue was higher than in glucose-treated (5.1 [4.2-8.5] mg/g of tissue; P<0.01 and control (6.2 [4.5-8.9] mg/g of tissue; P<0.05 animals. We conclude that SCFA may enhance mucosal re-epithelialization in experimental colitis, whereas hypertonic glucose is of no benefit.

  13. The use of manganese-enhanced magnetic resonance imaging in rat radiation-induced optic neuropathy

    International Nuclear Information System (INIS)

    Guan Xiyin; Wang Jiazhou; Zhou Lijun; Zhu Guopei

    2014-01-01

    Objective: To establish a rat model of radiation-induced optic neuropathy (RION) by delivering a single radiation dose to the optic chiasm. The aim of our study was to analysis the feasibility and effectiveness of manganese-enhanced magnetic resonance imaging (MEMRI) in RION. Methods: 34 Wistar rats were randomized to the control group(4 rats), the 2-month group(5 rats), the 4-month group(4 rats) and the 6-month group(11 rats) according to the different feeding period after irradiation. MEMRI scan were performed when the respective feeding periods of all groups expired. The rats were then killed for histological studies with hematoxylin and eosin stain, Luxol Fast Blue stain, and electron microscopy analysis. Results: The ratio of RION in the four groups were 0/3, 1/5, 2/4 and 11/11, respectively(χ"2 = 15.443, P < 0.05). There was an inverse correlation between the relative optical density value in the LFB stain and the interval between irradiation and pathological examination(R = -0.643, P < 0.05). The number of glial cells in the HE stain in the four groups were 194±65, 234±19, 124±11 and 345±98, respectively(R = 0.590, P < 0.05). When compared MEMRI scan with the corresponding histological examination, we found that there was loss of signals of optic nerve on MEMRI imaging in one of 5 rats in the 2-month group, while no significant histological difference was found between this rat and the others. Conclusions: RION can be non-invasively detected and semi-quantitative analysed by MEMRI scan. Moreover, RION can be early diagnosed by MEMRI scan which is capable to show physiological change in advance of pathological change. (authors)

  14. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage.

    Directory of Open Access Journals (Sweden)

    Katja Storch

    Full Text Available Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

  15. Priming of cowpea volatile emissions with defense inducers enhances the plant's attractiveness to parasitoids when attacked by caterpillars.

    Science.gov (United States)

    Sobhy, Islam S; Bruce, Toby Ja; Turlings, Ted Cj

    2018-04-01

    The manipulation of herbivore-induced volatile organic compounds (HI-VOCs) via the application of the inducers benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester (BTH) and laminarin (β-1,3-glucan) is known to enhance the attractiveness of caterpillar-damaged cotton and maize plants to parasitoids. To test if this is also the case for legumes, we treated cowpea (Vigna unguiculata var. unguiculata) with these inducers and studied the effects on HI-VOC emissions and the attraction of three generalist endoparasitoids. After the inducers had been applied and the plants subjected to either real or mimicked herbivory by Spodoptera littoralis caterpillars, females of the parasitoids Campoletis sonorensis and Microplitis rufiventris showed a strong preference for BTH-treated plants, whereas Cotesia females were strongly attracted to both BTH- and laminarin-treated plants with real or mimicked herbivory. Treated plants emitted more of certain HI-VOCs, but considerably less indole and linalool and less of several sesquiterpenes. Multivariate data analysis revealed that enhanced wasp attraction after treatment was correlated with high relative concentrations of nonanal, α-pinene, (E)-β-ocimene and (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), and with low relative concentrations of indole, (S)-linalool and (E)-β-farnesene. Inducer treatments had no significant effect on leaf consumption by the caterpillars. Our findings confirm that treating cowpea plants with inducers can enhance their attractiveness to biological control agents. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  16. Stattic Enhances Radiosensitivity and Reduces Radio-Induced Migration and Invasion in HCC Cell Lines through an Apoptosis Pathway

    Directory of Open Access Journals (Sweden)

    Gang Xu

    2017-01-01

    Full Text Available Purpose. Signal transducer and activator of transcription factor 3 (STAT3 is involved in tumorigenesis, development, and radioresistance of many solid tumors. The aim of this study is to investigate the effects of stattic (an inhibitor of STAT3 on the radiosensitivity and radio-induced migration and invasion ability in hepatocellular carcinoma (HCC cell lines. Methods. HCC cells were treated with stattic, and cell survival rate was analyzed through CCK-8 assay. Radiosensitivity was evaluated using cloning formation analysis; STAT3, p-STAT3, and apoptosis related proteins were detected by western blot. Radio-induced migration and invasion ability in HCC cells were analyzed by wound-healing assay and transwell test. Results. Stattic inhibits the expression of p-STAT3 and reduces cell survival in a dose-dependent manner in HCC cell lines, and the IC50 values for Hep G2, Bel-7402, and SMMC-7721 are 2.94 μM, 2.5 μM, and 5.1 μM, respectively. Cloning formation analysis shows that stattic enhances the radiosensitivity of HCC cells. Wound-healing assay and transwell test show that stattic inhibits radio-induced migration and invasion. Further study indicates that stattic promotes radio-induce apoptosis through regulating the expression of apoptosis related proteins in HCC cells. Conclusion. Stattic enhances radiosensitivity and reduces radio-induced migration and invasion ability in HCC cells probably through apoptosis pathway.

  17. Enhanced Cross-Phase Modulation Based on a Double Electromagnetically Induced Transparency in a Four-Level Tripod Atomic System

    International Nuclear Information System (INIS)

    Li Shujing; Yang Xudong; Cao Xuemin; Zhang Chunhong; Xie Changde; Wang Hai

    2008-01-01

    We report experimental observations on the simultaneous electromagnetically induced transparency (EIT) effects for probe and trigger fields (double EIT) as well as the enhanced cross-phase modulation (XPM) between the two fields in a four-level tripod EIT system of the D1 line of 87 Rb atoms. The XPM coefficients (larger than 2x10 -5 cm 2 /W) and the accompanying transmissions (higher than 60%) are measured at a slight detuning of the probe field from the exact EIT-resonance condition. The system and enhanced cross-Kerr nonlinearities presented here can be applied to quantum information processes

  18. Infection-Induced Retrotransposon-Derived Noncoding RNAs Enhance Herpesviral Gene Expression via the NF-κB Pathway.

    Directory of Open Access Journals (Sweden)

    John Karijolich

    Full Text Available Short interspersed nuclear elements (SINEs are highly abundant, RNA polymerase III-transcribed noncoding retrotransposons that are silenced in somatic cells but activated during certain stresses including viral infection. How these induced SINE RNAs impact the host-pathogen interaction is unknown. Here we reveal that during murine gammaherpesvirus 68 (MHV68 infection, rapidly induced SINE RNAs activate the antiviral NF-κB signaling pathway through both mitochondrial antiviral-signaling protein (MAVS-dependent and independent mechanisms. However, SINE RNA-based signaling is hijacked by the virus to enhance viral gene expression and replication. B2 RNA expression stimulates IKKβ-dependent phosphorylation of the major viral lytic cycle transactivator protein RTA, thereby enhancing its activity and increasing progeny virion production. Collectively, these findings suggest that SINE RNAs participate in the innate pathogen response mechanism, but that herpesviruses have evolved to co-opt retrotransposon activation for viral benefit.

  19. Inhibition of inducible heat shock protein-70 (hsp72 enhances bortezomib-induced cell death in human bladder cancer cells.

    Directory of Open Access Journals (Sweden)

    Wei Qi

    Full Text Available The proteasome inhibitor bortezomib (Velcade is a promising new agent for bladder cancer therapy, but inducible cytoprotective mechanisms may limit its potential efficacy. We used whole genome mRNA expression profiling to study the effects of bortezomib on stress-induced gene expression in a panel of human bladder cancer cell lines. Bortezomib induced strong upregulation of the inducible HSP70 isoforms HSPA1A and HSPA1B isoforms of Hsp72 in 253J B-V and SW780 (HSPA1A(high cells, but only induced the HSPA1B isoform in UM-UC10 and UM-UC13 (HSPA1A(low cells. Bortezomib stimulated the binding of heat shock factor-1 (HSF1 to the HSPA1A promoter in 253JB-V but not in UM-UC13 cells. Methylation-specific PCR revealed that the HSPA1A promoter was methylated in the HSPA1A(low cell lines (UM-UC10 and UM-UC13, and exposure to the chromatin demethylating agent 5-aza-2'-deoxycytidine restored HSPA1A expression. Overexpression of Hsp72 promoted bortezomib resistance in the UM-UC10 and UM-UC13 cells, whereas transient knockdown of HSPA1B further sensitized these cells to bortezomib, and exposure to the chemical HSF1 inhibitor KNK-437 promoted bortezomib sensitivity in the 253J B-V cells. Finally, shRNA-mediated stable knockdown of Hsp72 in 253J B-V promoted sensitivity to bortezomib in vitro and in tumor xenografts in vivo. Together, our results provide proof-of-concept for using Hsp72 inhibitors to promote bortezomib sensitivity in bladder cancers and suggest that selective targeting of HSPA1B could produce synthetic lethality in tumors that display HSPA1A promoter methylation.

  20. Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells.

    Science.gov (United States)

    Lim, Sung-Chul; Jeon, Ho Jong; Kee, Keun Hong; Lee, Mi Ja; Hong, Ran; Han, Song Iy

    2017-05-01

    Andrographolide, a natural compound isolated from Andrographis paniculata , has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL). Exposure of GC cells to andrographolide altered the expression level of several growth-inhibiting and apoptosis-regulating proteins, including death receptors. It was demonstrated that activity of the TRAIL-R2 (DR5) pathway was critical in the development of andrographolide-mediated rhTRAIL sensitization, since its inhibition significantly reduced the extent of apoptosis induced by the combination of rhTRAIL and andrographolide. In addition, andrographolide increased reactive oxygen species (ROS) generation in a dose-dependent manner. N-acetyl cysteine prevented andrographolide-mediated DR5 induction and the apoptotic effect induced by the combination of rhTRAIL and andrographolide. Collectively, the present study demonstrated that andrographolide enhances TRAIL-induced apoptosis through induction of DR5 expression. This effect appears to involve ROS generation in GCs.

  1. Significant efficiency enhancement in thin film solar cells using laser beam-induced graphene transparent conductive electrodes

    OpenAIRE

    Thekkekara, L. V.; Cai, Bouyan

    2018-01-01

    Thin film solar cells have been attractive for decades in advanced green technology platforms due to its possibilities to be integrated with buildings and on-chip applications. However, the bottleneck issues involved to consider the current solar cells as a major electricity source includes the lower efficiencies and cost-effectiveness. We numerically demonstrate the concept of the absorption enhancement in thin-film amorphous silicon solar cells using the laser beam-induced graphene material...

  2. Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice

    Directory of Open Access Journals (Sweden)

    Zhao Meng

    2012-07-01

    Full Text Available Abstract Background Oxaliplatin, a platinum-based chemotherapeutic agent, causes an unusual acute peripheral neuropathy. Oxaliplatin-induced acute peripheral neuropathy appears in almost all patients rapidly after infusion, and is triggered or exacerbated by cold, while its mechanisms are poorly understood. In this study, the involvement of thermosensitive transient receptor potential channels (TRPA1, TRPM8 and TRPV1 in oxaliplatin-induced acute hypersensitivity was investigated in mice. Results A single intraperitoneal administration of oxaliplatin (1–10 mg/kg induced cold but not mechanical hypersensitivity within 2 h in a dose-dependent manner. Infusion of the oxaliplatin metabolite, oxalate (1.7 mg/kg, also induced acute cold hypersensitivity, while another platinum-based chemotherapeutic agent, cisplatin (5 mg/kg, or the non-platinum-containing chemotherapeutic agent, paclitaxel (6 mg/kg failed to induce mechanical or cold hypersensitivity. The oxaliplatin-induced acute cold hypersensitivity was abolished by the TRPA1 antagonist HC-030031 (100 mg/kg and by TRPA1 deficiency. The nocifensive behaviors evoked by intraplantar injections of allyl-isothiocyanate (AITC; TRPA1 agonist were significantly enhanced in mice treated for 2 h with oxaliplatin (1–10 mg/kg in a dose-dependent manner, while capsaicin (TRPV1 agonist-evoked nocifensive behaviors were not affected. Menthol (TRPM8/TRPA1 agonist-evoked nocifensive-like behaviors were also enhanced by oxaliplatin pretreatment, which were inhibited by TRPA1 deficiency. Similarly, oxalate enhanced, but neither cisplatin nor paclitaxel affected AITC-evoked nocifensive behaviors. Pretreatment of cultured mouse dorsal root ganglia (DRG neurons with oxaliplatin (30–300 μM for 1, 2, or 4 h significantly increased the number of AITC-sensitive neurons in a concentration-dependent manner whereas there was no change in the number of menthol- or capsaicin-sensitive neurons

  3. In situ generated CdS nanostructure induced enhanced photoluminescence from Dy{sup 3+} ions doped dielectric nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Dey, Chirantan; Karmakar, Basudeb [Glass Science and Technology Section, Glass Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata (India)

    2017-08-15

    We report CdS nanostructure induced enhanced photoluminescence (PL) from Dy{sup +3}:CdS co-doped dielectric-nanocomposites synthesized by the conventional melt-quench technique. CdS nanocrystals (NCs) were synthesized as in situ within the dielectric medium and their growth was controlled by heat treatment duration. Nanoparticles were investigated with absorption spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and Raman spectroscopy. The experimentally obtained sizes of the NCs are found to increase from 5-11 nm to 50-80 nm. Bandgap enhancement for the carrier confinement was found to alter within the range of 0.20-0.38 eV. Phonon confinement effect has been confirmed by blue shifting of Raman peak for CdS NCs at 303 cm{sup -1}. Enhanced highly intense sharp PL peak at 576 nm was detected, and different parameters associated with the PL enhancement including energy transfer from CdS NCs to Dy{sup 3+} ions have been studied. This PL enhancement was steered by varying CdS NC sizes. Enhanced PL of these nanocomposites finds their potential applications as gain medium in the field of solid state lasers. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. The Role of Hydrogen-Enhanced Strain-Induced Lattice Defects on Hydrogen Embrittlement Susceptibility of X80 Pipeline Steel

    Science.gov (United States)

    Hattori, M.; Suzuki, H.; Seko, Y.; Takai, K.

    2017-08-01

    Studies to date have not completely determined the factors influencing hydrogen embrittlement of ferrite/bainite X80 pipeline steel. Hydrogen embrittlement susceptibility was evaluated based on fracture strain in tensile testing. We conducted a thermal desorption analysis to measure the amount of tracer hydrogen corresponding to that of lattice defects. Hydrogen embrittlement susceptibility and the amount of tracer hydrogen significantly increased with decreasing crosshead speed. Additionally, a significant increase in the formation of hydrogen-enhanced strain-induced lattice defects was observed immediately before the final fracture. In contrast to hydrogen-free specimens, the fracture surface of the hydrogen-charged specimens exhibited shallower dimples without nuclei, such as secondary phase particles. These findings indicate that the presence of hydrogen enhanced the formation of lattice defects, particularly just prior to the occurrence of final fracture. This in turn enhanced the formation of shallower dimples, thereby potentially causing premature fracture of X80 pipeline steel at lower crosshead speeds.

  5. Inducible Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis in the Olfactory Bulb and Improves Olfactory Function

    Science.gov (United States)

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M.; Xu, Lihong; Storm, Daniel R.

    2015-01-01

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. PMID:25995470

  6. Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition.

    Directory of Open Access Journals (Sweden)

    Sarah L Sherrington

    2017-05-01

    Full Text Available Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this "unmasking" of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.

  7. Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition

    Science.gov (United States)

    Sorsby, Eleanor; Mahtey, Nabeel; Brown, Ian

    2017-01-01

    Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection. PMID:28542528

  8. Enhancing the efficacy of AREDS antioxidants in light-induced retinal degeneration.

    Science.gov (United States)

    Wong, Paul; Markey, M; Rapp, C M; Darrow, R M; Ziesel, A; Organisciak, D T

    2017-01-01

    week of supplemental AREDS plus carnosic acid resulted in higher levels of rod and cone cell proteins, and higher levels of retinal DNA than for AREDS alone. Rhodopsin regeneration was unaffected by the rosemary treatment. Retinal gene array analysis showed reduced expression of medium- wavelength opsin 1 and arrestin C in the high-light reared rats versus the low-light rats. The transition of rats from low cyclic light to a high cyclic light environment resulted in the differential expression of 280 gene markers, enriched for genes related to inflammation, apoptosis, cytokine, innate immune response, and receptors. Rosemary, zinc oxide plus rosemary, and AREDS plus rosemary suppressed 131, 241, and 266 of these genes (respectively) in high-light versus low-light animals and induced a small subset of changes in gene expression that were independent of light rearing conditions. Long-term environmental light intensity is a major determinant of retinal gene and protein expression, and of visual cell survival following acute photooxidative insult. Rats preconditioned by high-light rearing exhibit lower levels of cone opsin mRNA and protein, and lower mCAR protein, than low-light reared animals, but greater retention of retinal DNA and proteins following photooxidative damage. Rosemary enhanced the protective efficacy of AREDS and led to the greatest effect on the retinal genome in animals reared in high environmental light. Chronic administration of rosemary antioxidants may be a useful adjunct to the therapeutic benefit of AREDS in slowing disease progression in AMD.

  9. Porphyromonas gingivalis hydrogen sulfide enhances methyl mercaptan-induced pathogenicity in mouse abscess formation.

    Science.gov (United States)

    Nakamura, Suguru; Shioya, Koki; Hiraoka, B Yukihiro; Suzuki, Nao; Hoshino, Tomonori; Fujiwara, Taku; Yoshinari, Nobuo; Ansai, Toshihiro; Yoshida, Akihiro

    2018-04-01

    Porphyromonas gingivalis produces hydrogen sulfide (H2S) from l-cysteine. However, the role of H2S produced by P. gingivalis in periodontal inflammation is unclear. In this study, we identified the enzyme that catalyses H2S production from l-cysteine and analysed the role of H2S using a mouse abscess model. The enzyme identified was identical to methionine γ-lyase (PG0343), which produces methyl mercaptan (CH3SH) from l-methionine. Therefore, we analysed H2S and CH3SH production by P. gingivalis W83 and a PG0343-deletion mutant (ΔPG0343) with/without l-cysteine and/or l-methionine. The results indicated that CH3SH is produced constitutively irrespective of the presence of l-methionine, while H2S was greatly increased by both P. gingivalis W83 and ΔPG0343 in the presence of l-cysteine. In contrast, CH3SH production by ΔPG0343 was absent irrespective of the presence of l-methionine, and H2S production was eliminated in the absence of l-cysteine. Thus, CH3SH and H2S production involves different substrates, l-methionine or l-cysteine, respectively. Based on these characteristics, we analysed the roles of CH3SH and H2S in abscess formation in mice by P. gingivalis W83 and ΔPG0343. Abscess formation by P. gingivalis W83, but not ΔPG0343, differed significantly in the presence and absence of l-cysteine. In addition, the presence of l-methionine did not affect the size of abscesses generated by P. gingivalis W83 and ΔPG0343. Therefore, we conclude that H2S produced by P. gingivalis does not induce inflammation; however, H2S enhances inflammation caused by CH3SH. Thus, these results suggest the H2S produced by P. gingivalis plays a supportive role in inflammation caused by methionine γ-lyase.

  10. Subchronic JP-8 jet fuel exposure enhances vulnerability to noise-induced hearing loss in rats.

    Science.gov (United States)

    Fechter, L D; Fisher, J W; Chapman, G D; Mokashi, V P; Ortiz, P A; Reboulet, J E; Stubbs, J E; Lear, A M; McInturf, S M; Prues, S L; Gearhart, C A; Fulton, S; Mattie, D R

    2012-01-01

    Both laboratory and epidemiological studies published over the past two decades have identified the risk of excess hearing loss when specific chemical contaminants are present along with noise. The objective of this study was to evaluate the potency of JP-8 jet fuel to enhance noise-induced hearing loss (NIHL) using inhalation exposure to fuel and simultaneous exposure to either continuous or intermittent noise exposure over a 4-wk exposure period using both male and female Fischer 344 rats. In the initial study, male (n = 5) and female (n = 5) rats received inhalation exposure to JP-8 fuel for 6 h/d, 5 d/wk for 4 wk at concentrations of 200, 750, or 1500 mg/m³. Parallel groups of rats also received nondamaging noise (constant octave band noise at 85 dB(lin)) in combination with the fuel, noise alone (75, 85, or 95 dB), or no exposure to fuel or noise. Significant concentration-related impairment of auditory function measured by distortion product otoacoustic emissions (DPOAE) and compound action potential (CAP) threshold was seen in rats exposed to combined JP-8 plus noise exposure when JP-8 levels of 1500 mg/m³ were presented with trends toward impairment seen with 750 mg/m³ JP-8 + noise. JP-8 alone exerted no significant effect on auditory function. In addition, noise was able to disrupt the DPOAE and increase auditory thresholds only when noise exposure was at 95 dB. In a subsequent study, male (n = 5 per group) and female (n = 5 per group) rats received 1000 mg/m³ JP-8 for 6 h/d, 5 d/wk for 4 wk with and without exposure to 102 dB octave band noise that was present for 15 min out of each hour (total noise duration 90 min). Comparisons were made to rats receiving only noise, and thosereceiving no experimental treatment. Significant impairment of auditory thresholds especially for high-frequency tones was identified in the male rats receiving combined treatment. This study provides a basis for estimating excessive hearing loss under

  11. Residual Stress Induced Mechanical Property Enhancement in Steel Encapsulated Light Metal Matrix Composites

    Science.gov (United States)

    Fudger, Sean James

    Macro hybridized systems consisting of steel encapsulated light metal matrix composites (MMCs) were produced with the goal of creating a low cost/light weight composite system with enhanced mechanical properties. MMCs are frequently incorporated into advanced material systems due to their tailorable material properties. However, they often have insufficient ductility for many structural applications. The macro hybridized systems take advantage of the high strength, modulus, and damage tolerance of steels and high specific stiffness and low density of MMCs while mitigating the high density of steels and the poor ductility of MMCs. Furthermore, a coefficient of thermal expansion (CTE) mismatch induced residual compressive stress method is utilized as a means of improving the ductility of the MMCs and overall efficiency of the macro hybridized systems. Systems consisting of an A36, 304 stainless steel, or NitronicRTM 50 stainless steel shell filled with an Al-SiC, Al-Al2O3, or Mg-B4C MMC are evaluated in this work. Upon cooling from processing temperatures, residual strains are generated due to a CTE mismatch between each of the phases. The resulting systems offer higher specific properties and a more structurally efficient system can be attained. Mechanical testing was performed and improvements in yield stress, ultimate tensile stress, and ductility were observed. However, the combination of these dissimilar materials often results in the formation of intermetallic compounds. In certain loading situations, these typically brittle intermetallic layers can result in degraded performance. X-ray Diffraction (XRD), X-ray Energy Dispersive Spectroscopy (EDS), and Electron Backscatter Diffraction (EBSD) are utilized to characterize the intermetallic layer formation at the interface between the steel and MMC. As the residual stress condition in each phase has a large impact on the mechanical property improvement, accurate quantification of these strains/stresses is

  12. Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem.

    Science.gov (United States)

    Shibasaki, Masahiro; Ishii, Kazunori; Masukawa, Daiki; Ando, Koji; Ikekubo, Yuiko; Ishikawa, Yutori; Shibasaki, Yumiko; Mori, Tomohisa; Suzuki, Tsutomu

    2014-09-05

    Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days. mGlu5 receptor protein levels were significantly increased after treatment with zolpidem for 7 days, and this change was accompanied by the up-regulation of phospholipase Cβ1 and calcium/calmodulin-dependent protein kinase IIα, which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that mGlu5 receptor is directly involved in dopamine-related behavior in mice following chronic treatment with zolpidem, we measured morphine-induced hyperlocomotion after chronic treatment with zolpidem in the presence or absence of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem significantly enhanced morphine-induced hyperlocomotion, this enhancement of morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5 receptor antagonist MPEP. These results suggest that chronic treatment with zolpidem caused neural plasticity in response to activation of the mesolimbic dopaminergic system accompanied by an increase in mGlu5 receptor. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. COGNITIVE-ENHANCING PROPERTIES OF MORINDA LUCIDA (RUBIACEAE) AND PELTOPHORUM PTEROCARPUM (FABACEAE) IN SCOPOLAMINE-INDUCED AMNESIC MICE.

    Science.gov (United States)

    O, Elufioye Taiwo; Halimah A, Hameed

    2017-01-01

    Cognitive disorders associated with aging have been successfully managed by African traditional medical practitioners using various plants. This study evaluated the cognitive enhancing potentials of Morinda lucida (L) Rubiaceae and Peltophorum pterocarpum (DC) ex. K Heyne in scopolamine induced amnesic animals. The anti-amnesic activity of the ethyl acetate extracts of Morinda lucida and Peltophorum pterocarpum at doses of 4 mg/kg, 6 mg/kg and 8 mg/kg were assessed in scopolamine induced amnesic mice using Morris water maze test model. Effect of the extracts on the histology of the hippocampus was also evaluated. The ethyl acetate extract of Morinda lucida and Peltophorum pterocarpum ameliorated scopolamine induced memory deficit in the animals under study. There was no effect of the extract on the histology of the hippocampus. However, there was an increase in the density of cells in the hippocampus of treated group as compared to the untreated. Morinda lucida and Peltophorum pterocarpum showed considerable enhancement of cognition in scopolamine induced amnesic mice.

  14. Fatty acid synthase as a factor required for exercise-induced cognitive enhancement and dentate gyrus cellular proliferation.

    Directory of Open Access Journals (Sweden)

    Nataliya E Chorna

    Full Text Available Voluntary running is a robust inducer of adult hippocampal neurogenesis. Given that fatty acid synthase (FASN, the key enzyme for de novo fatty acid biosynthesis, is critically involved in proliferation of embryonic and adult neural stem cells, we hypothesized that FASN could mediate both exercise-induced cell proliferation in the subgranular zone (SGZ of the dentate gyrus (DG and enhancement of spatial learning and memory. In 20 week-old male mice, voluntary running-induced hippocampal-specific upregulation of FASN was accompanied also by hippocampal-specific accumulation of palmitate and stearate saturated fatty acids. In experiments addressing the functional role of FASN in our experimental model, chronic intracerebroventricular (i.c.v. microinfusions of C75, an irreversible FASN inhibitor, and significantly impaired exercise-mediated improvements in spatial learning and memory in the Barnes maze. Unlike the vehicle-injected mice, the C75 group adopted a non-spatial serial escape strategy and displayed delayed escape latencies during acquisition and memory tests. Furthermore, pharmacologic blockade of FASN function with C75 resulted in a significant reduction, compared to vehicle treated controls, of the number of proliferative cells in the DG of running mice as measured by immunoreactive to Ki-67 in the SGZ. Taken together, our data suggest that FASN plays an important role in exercise-mediated cognitive enhancement, which might be associated to its role in modulating exercise-induced stimulation of neurogenesis.

  15. Estradiol induces dendritic spines by enhancing glutamate release independent of transcription: A mechanism for organizational sex differences

    Science.gov (United States)

    Schwarz, Jaclyn M.; Liang, Shu-Ling; Thompson, Scott M.; McCarthy, Margaret M.

    2008-01-01

    SUMMARY The naturally occurring sex difference in dendritic spine number on hypothalamic neurons offers a unique opportunity to investigate mechanisms establishing synaptic patterning during perinatal sensitive periods. A major advantage of the model is the ability to treat neonatal females with estradiol to permanently induce the male phenotype. During the development of other systems, exuberant innervation is followed by activity-dependent pruning necessary for elimination of spurious synapses. In contrast, we demonstrate that estradiol-induced organization in the hypothalamus involves the induction of new synapses on dendritic spines. Activation of estrogen receptors by estradiol triggers a non-genomic activation of PI3 kinase that results in enhanced glutamate release from presynaptic neurons. Subsequent activation of ionotropic glutamate receptors activates MAP kinases inducing dendritic spine formation. These results reveal a trans-neuronal mechanism by which estradiol acts during a sensitive period to establish a profound and lasting sex difference in hypothalamic synaptic patterning. PMID:18498739

  16. Genetic toxicology of metal compounds. II. Enhancement of ultraviolet light-induced mutagenesis in Escherichia coli WP2

    International Nuclear Information System (INIS)

    Rossman, T.G.; Molina, M.

    1986-01-01

    Salts of metals which are carcinogenic, noncarcinogenic, or of unknown carcinogenicity were assayed for their abilities to modulate ultraviolet (UV)-induced mutagenesis in Escherichia coli WP2. In addition to the previously reported comutagenic effect of arsenite, salts of three other compounds were found to enhance UV mutagenesis. CuCl 2 , MnCl 2 (and a small effect by KMnO 4 ), and NaMoO 4 acted as comutagens in E coli WP2, which has wild-type DNA repair capability, but were much less comutagenic in the repair deficient strain WP2/sub s/ (uvrA). The survival of irradiated or unirradiated cells was not affected by these compounds. No effects on UV mutagenesis were seen for 16 other metal compounds. We suggest that the comutagenic effects might occur either via metal-induced decreases in the fidelity of repair replication or via metal-induced depurination

  17. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Jeong, Soyeon; Shin, Soyeon; Lim, Kyu [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Infection Signaling Network Research Center, Chungnam National University, Daejeon (Korea, Republic of); Heo, Jun Young, E-mail: junyoung3@gmail.com [Brainscience Institute, Chungnam National University, Daejeon (Korea, Republic of); Kweon, Gi Ryang, E-mail: mitochondria@cnu.ac.kr [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Infection Signaling Network Research Center, Chungnam National University, Daejeon (Korea, Republic of)

    2015-01-30

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

  18. Chrysin enhances doxorubicin-induced cytotoxicity in human lung epithelial cancer cell lines: The role of glutathione

    Energy Technology Data Exchange (ETDEWEB)

    Brechbuhl, Heather M. [Pediatrics, National Jewish Health, Denver, Colorado (United States); Kachadourian, Remy; Min, Elysia [Department of Medicine, National Jewish Health, Denver, Colorado (United States); Chan, Daniel [Medical Oncology, University of Colorado Denver Health Sciences Center (United States); Day, Brian J., E-mail: dayb@njhealth.org [Department of Medicine, University of Colorado Denver Health Sciences Center (United States); Immunology, University of Colorado Denver Health Sciences Center (United States); Pharmaceutical Sciences, University of Colorado Denver Health Sciences Center (United States); Department of Medicine, National Jewish Health, Denver, Colorado (United States)

    2012-01-01

    We hypothesized that flavonoid-induced glutathione (GSH) efflux through multi-drug resistance proteins (MRPs) and subsequent intracellular GSH depletion is a viable mechanism to sensitize cancer cells to chemotherapies. This concept was demonstrated using chrysin (5–25 μM) induced GSH efflux in human non-small cell lung cancer lines exposed to the chemotherapeutic agent, doxorubicin (DOX). Treatment with chrysin resulted in significant and sustained intracellular GSH depletion and the GSH enzyme network in the four cancer cell types was predictive of the severity of chrysin induced intracellular GSH depletion. Gene expression data indicated a positive correlation between basal MRP1, MRP3 and MRP5 expression and total GSH efflux before and after chrysin exposure. Co-treating the cells for 72 h with chrysin (5–30 μM) and DOX (0.025–3.0 μM) significantly enhanced the sensitivity of the cells to DOX as compared to 72-hour DOX alone treatment in all four cell lines. The maximum decrease in the IC{sub 50} values of cells treated with DOX alone compared to co-treatment with chrysin and DOX was 43% in A549 cells, 47% in H157 and H1975 cells and 78% in H460 cells. Chrysin worked synergistically with DOX to induce cancer cell death. This approach could allow for use of lower concentrations and/or sensitize cancer cells to drugs that are typically resistant to therapy. -- Graphical abstract: Possible mechanisms by which chrysin enhances doxorubicin-induced toxicity in cancer cells. Highlights: ► Chyrsin sustains a significant depletion of GSH levels in lung cancer cells. ► Chyrsin synergistically potentiates doxorubicin-induced cancer cell cytotoxicity. ► Cancer cell sensitivity correlated with GSH and MRP gene network expression. ► This approach could allow for lower side effects and targeting resistant tumors.

  19. Noradrenergic Activation of the Basolateral Amygdala Enhances Object Recognition Memory and Induces Chromatin Remodeling in the Insular Cortex

    Directory of Open Access Journals (Sweden)

    Hassiba eBeldjoud

    2015-04-01

    Full Text Available It is well established that arousal-induced memory enhancement requires noradrenergic activation of the basolateral complex of the amygdala (BLA and modulatory influences on information storage processes in its many target regions. While this concept is well accepted, the molecular basis of such BLA effects on neural plasticity changes within other brain regions remains to be elucidated. The present study investigated whether noradrenergic activation of the BLA after object recognition training induces chromatin remodeling through histone post-translational modifications in the insular cortex (IC, a brain region that is importantly involved in object recognition memory. Male Sprague–Dawley rats were trained on an object recognition task, followed immediately by bilateral microinfusions of norepinephrine (1.0 µg or saline administered into the BLA. Saline-treated control rats exhibited poor 24-h retention, whereas norepinephrine treatment induced robust 24-h object recognition memory. Most importantly, this memory-enhancing dose of norepinephrine induced a global reduction in the acetylation levels of histone H3 at lysine 14, H2B and H4 in the IC 1 h later, whereas it had no effect on the phosphorylation of histone H3 at serine 10 or tri-methylation of histone H3 at lysine 27. Norepinephrine administered into the BLA of non-trained control rats did not induce any changes in the histone marks investigated in this study. These findings indicate that noradrenergic activation of the BLA induces training-specific effects on chromatin remodeling mechanisms, and presumably gene transcription, in its target regions, which may contribute to the understanding of the molecular mechanisms of stress and emotional arousal effects on memory consolidation.

  20. Studies on the mechanisms underlying amiloride enhancement of 3,4-methylenedioxymethamphetamine-induced serotonin depletion in rats.

    Science.gov (United States)

    Goñi-Allo, Beatriz; Puerta, Elena; Hervias, Isabel; Di Palma, Richard; Ramos, Maria; Lasheras, Berta; Aguirre, Norberto

    2007-05-21

    Amiloride and several of its congeners known to block the Na(+)/Ca(2+) and/or Na(+)/H(+) antiporters potentiate methamphetamine-induced neurotoxicity without altering methamphetamine-induced hyperthermia. We now examine whether amiloride also exacerbates 3,4-methylenedioxymethamphetamine (MDMA)-induced long-term serotonin (5-HT) loss in rats. Amiloride (2.5 mg/kg, every 2 h x 3, i.p.) given at ambient temperature 30 min before MDMA (5 mg/kg, every 2 h x 3, i.p.), markedly exacerbated long-term 5-HT loss. However, in contrast to methamphetamine, amiloride also potentiated MDMA-induced hyperthermia. Fluoxetine (10 mg/kg i.p.) completely protected against 5-HT depletion caused by the MDMA/amiloride combination without significantly altering the hyperthermic response. By contrast, the calcium channel antagonists flunarizine or diltiazem did not afford any protection. Findings with MDMA and amiloride were extended to the highly selective Na(+)/H(+) exchange inhibitor dimethylamiloride, suggesting that the potentiating effects of amiloride are probably mediated by the blockade of Na(+)/H(+) exchange. When the MDMA/amiloride combination was administered at 15 degrees C hyperthermia did not develop and brain 5-HT concentrations remained unchanged 7 days later. Intrastriatal perfusion of MDMA (100 microM for 8 h) in combination with systemic amiloride caused a small depletion of striatal 5-HT content in animals made hyperthermic but not in the striatum of normothermic rats. These data suggest that enhancement of MDMA-induced 5-HT loss caused by amiloride or dimethylamiloride depends on their ability to enhance MDMA-induced hyperthermia. We hypothesise that blockade of Na(+)/H(+) exchange could synergize with hyperthermia to render 5-HT terminals more vulnerable to the toxic effects of MDMA.

  1. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    International Nuclear Information System (INIS)

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik; Jeong, Soyeon; Shin, Soyeon; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-01-01

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis

  2. Enhancement of S1P-induced contractile response in detrusor smooth muscle of rats having cystitis.

    Science.gov (United States)

    Anjum, Irfan; Denizalti, Merve; Kandilci, Hilmi Burak; Durlu-Kandilci, Nezahat Tugba; Sahin-Erdemli, Inci

    2017-11-05

    Interstitial cystitis is a chronic disease characterized by lower abdominal pain and some nonspecific symptoms including an increase in urinary frequency and urgency. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that controls smooth muscle tone via G-protein coupled receptors (S1P 1-3 receptors). S1P production is known to take place both in physiological states and some pathological situations, such as in overactive bladder syndrome. The intracellular mechanism of S1P-induced contractile response was investigated in β-escin permeabilized detrusor smooth muscle of rats having cyclophosphamide-induced cystitis. The bladder was isolated from rats and detrusor smooth muscle strips were permeabilized with β-escin. S1P (50µM)-induced contraction and calcium sensitization response were significantly increased in cystitis. S1P-induced augmented contractile response was inhibited by S1P 2 receptor antagonist JTE-013 and S1P 3 receptor antagonist suramin. S1P 2 receptor protein expressions were increased in cystitis, where no change was observed in S1P 3 expressions between control and cystitis groups. S1P-induced contraction was reduced by Rho kinase (ROCK) inhibitor Y-27632 and protein kinase C (PKC) inhibitor GF-109203X in both control and cystitis group. S1P-induced increased calcium sensitization response was decreased by ROCK inhibitor and PKC inhibitor in cystitis. Our findings provide the first evidence that interstitial cystitis triggers S1P-induced increase in intracellular calcium in permeabilized detrusor smooth muscle of female rats. Both S1P 2 and S1P 3 receptors are involved in S1P mediated enhanced contractile response. The augmentation in S1P-induced contraction in interstitial cystitis involves both PKC and ROCK pathways of calcium sensitization. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine

    International Nuclear Information System (INIS)

    Ke, J.-J.; Chen, H.-I.; Jen, C.J.; Kuo, Y.-M.; Cherng, C.G.; Tsai, Y.-P.N.; Ho, M.-C.; Tsai, C.-W.; Lung Yu

    2008-01-01

    We hereby report that repeated administration of ketamine (350 mg/kg in total) and methamphetamine (30 mg/kg in total) causes specific glutamatergic and dopaminergic neuron deficits, respectively, in adult mouse brain. Acute ketamine did not affect basal body temperature or the later methamphetamine-induced hyperthermia. However, pretreatment with repeated doses of ketamine aggravated methamphetamine-induced dopaminergic terminal loss as evidenced by a drastic decrease in the levels of dopamine, 3,4-dihydroxyphenylacetic acid, and dopamine transporter density as well as poor gait balance performance. In contrast, methamphetamine-induced serotonergic depletion was not altered by ketamine pretreatment. Likewise, the subsequent treatment with methamphetamine exacerbated the ketamine-induced glutamatergic damage as indicated by reduced levels of the vesicular glutamate transporter in hippocampus and striatum and poor memory performance in the Morris water maze. Finally, since activation of the D1 and AMPA/kainate receptors has been known to be involved in the release of glutamate and dopamine, we examined the effects of co-administration of SCH23390, a D1 antagonist, and CNQX, an AMPA/kainate antagonist. Intraventricular CNQX infusion abolished ketamine's potentiation of methamphetamine-induced dopamine neurotoxicity, while systemic SCH23390 mitigated methamphetamine's potentiation of ketamine-induced glutamatergic toxicity. We conclude that repeated doses of ketamine potentiate methamphetamine-induced dopamine neurotoxicity via AMPA/kainate activation and that conjunctive use of methamphetamine aggravates ketamine-induced glutamatergic neurotoxicity possibly via D1 receptor activation

  4. [Mutants of the yeast Saccharomyces cerevisiae characterized by enhanced induced mutagenesis. III. Effect of the him mutation on the effectiveness and specificity of UF-induced mutagenesis].

    Science.gov (United States)

    Ivanov, E L; Koval'tsova, S V; Korolev, V G

    1987-09-01

    We have studied the influence of him1-1, him2-1, him3-1 and himX mutations on induction frequency and specificity of UV-induced adenine-dependent mutations in the yeast Saccharomyces cerevisiae. Him mutations do not render haploid cells more sensitive to the lethal action of UV-light; however, in him strains adenine-dependent mutations (ade1, ade2) were induced more frequently (1.5--2-fold), as compared to the HIM strain. An analysis of the molecular nature of ade2 mutants revealed that him1-1, him2-1 and himX mutations increase specifically the yield of transitions (AT----GC and GC----AT), whereas in the him3-1 strain the yield of transversions was enhanced as well. We suggest him mutations analysed to affect specific repair pathway for mismatch correction.

  5. Enhancement of laser-induced breakdown spectroscopy (LIBS) Detection limit using a low-pressure and short-pulse laser-induced plasma process.

    Science.gov (United States)

    Wang, Zhen Zhen; Deguchi, Yoshihiro; Kuwahara, Masakazu; Yan, Jun Jie; Liu, Ji Ping

    2013-11-01

    Laser-induced breakdown spectroscopy (LIBS) technology is an appealing technique compared with many other types of elemental analysis because of the fast response, high sensitivity, real-time, and noncontact features. One of the challenging targets of LIBS is the enhancement of the detection limit. In this study, the detection limit of gas-phase LIBS analysis has been improved by controlling the pressure and laser pulse width. In order to verify this method, low-pressure gas plasma was induced using nanosecond and picosecond lasers. The method was applied to the detection of Hg. The emission intensity ratio of the Hg atom to NO (IHg/INO) was analyzed to evaluate the LIBS detection limit because the NO emission (interference signal) was formed during the plasma generation and cooling process of N2 and O2 in the air. It was demonstrated that the enhancement of IHg/INO arose by decreasing the pressure to a few kilopascals, and the IHg/INO of the picosecond breakdown was always much higher than that of the nanosecond breakdown at low buffer gas pressure. Enhancement of IHg/INO increased more than 10 times at 700 Pa using picosecond laser with 35 ps pulse width. The detection limit was enhanced to 0.03 ppm (parts per million). We also saw that the spectra from the center and edge parts of plasma showed different features. Comparing the central spectra with the edge spectra, IHg/INO of the edge spectra was higher than that of the central spectra using the picosecond laser breakdown process.

  6. Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to chemotherapy-induced cell death

    International Nuclear Information System (INIS)

    Porter, Holly A.; Carey, Gregory B.; Keegan, Achsah D.

    2012-01-01

    The adapters IRS1 and IRS2 link growth factor receptors to downstream signaling pathways that regulate proliferation and survival. Both suppress factor-withdrawal-induced apoptosis and have been implicated in cancer progression. However, recent studies suggest IRS1 and IRS2 mediate differential functions in cancer pathogenesis. IRS1 promoted breast cancer proliferation, while IRS2 promoted metastasis. The role of IRS1 and IRS2 in controlling cell responses to chemotherapy is unknown. To determine the role of IRS1 and IRS2 in the sensitivity of cells to chemotherapy, we treated 32D cells lacking or expressing IRS proteins with various concentrations of chemotherapeutic agents. We found that expression of IRS1, in contrast to IRS2, enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. When IRS2 was expressed with IRS1, the cells no longer showed enhanced sensitivity. Expression of IRS1 did not alter the expression of pro- and anti-apoptotic proteins; however, 32D-IRS1 cells expressed higher levels of Annexin A2. In 32D-IRS1 cells, IRS1 and Annexin A2 were both located in cytoplasmic and membrane fractions. We also found that IRS1 coprecipitated with Annexin A2, while IRS2 did not. Decreasing Annexin A2 levels reduced 32D-IRS1 cell sensitivity to chemotherapy. These results suggest IRS1 enhances sensitivity to chemotherapy in part through Annexin A2. -- Highlights: ► IRS1 enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. ► This sensitivity is abrogated by the expression of IRS2. ► Expressing IRS1 in 32D cells increased levels of Annexin A2. ► Both IRS1 and Annexin A2 were located in cytoplasmic and membrane fractions. ► Decreasing Annexin A2 in 32D-IRS1 cells abated their sensitivity to chemotherapy.

  7. Traditional Herbal Medicine, Rikkunshito, Induces HSP60 and Enhances Cytoprotection of Small Intestinal Mucosal Cells as a Nontoxic Chaperone Inducer

    Directory of Open Access Journals (Sweden)

    Kumiko Tamaki

    2012-01-01

    Full Text Available Increasing incidence of small intestinal ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDs has become a topic with recent advances of endoscopic technology. However, the pathogenesis and therapy are not fully understood. The aim of this study is to examine the effect of Rikkunshito (TJ-43, a traditional herbal medicine, on expression of HSP60 and cytoprotective ability in small intestinal cell line (IEC-6. Effect of TJ-43 on HSP60 expression in IEC-6 cells was evaluated by immunoblot analysis. The effect of TJ-43 on cytoprotective abilities of IEC-6 cells against hydrogen peroxide or indomethacin was studied by MTT assay, LDH-release assay, caspase-8 activity, and TUNEL. HSP60 was significantly induced by TJ-43. Cell necrosis and apoptosis were significantly suppressed in IEC-6 cells pretreated by TJ-43 with overexpression of HSP60. Our results suggested that HSP60 induced by TJ-43 might play an important role in protecting small intestinal epithelial cells from apoptosis and necrosis in vitro.

  8. Detection of parenchymal abnormalities in experimentally induced acute pyelonephritis in rabbits using contrast-enhanced ultrasonography, CT, and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jeong Ah; Kim, Bo Hyun; Kim, Seung Kwon; Seo, Jin Won [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Jong Sung [Laboratory Animal Research Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) in detecting acute pyelonephritis (APN) using the rabbit kidney model and compared it with CT and MRI. This study was approved by the Institutional Review Board. In a total of 20 New Zealand White rabbits, APN was induced experimentally. CEUS, CT, and MRI were performed on the first, third, and seventh postoperative days. After imaging studies, the subjects were sacrificed and the pathological diagnosis of APN was confirmed in each animal by a pathologist. Imaging studies were obtained in eight animals, including eight CEUS, four computed tomography (CT), and four magnetic resonance imaging (MRI) images. CEUS depicted diffuse renal enlargement (7), diffuse heterogeneous parenchymal enhancement (6), and focal areas of decreased parenchymal enhancement (6). These findings were well correlated with the CT and MRI findings in five cases in which these studies were available. CT and MRI showed diffuse renal enlargement, diffuse heterogeneous parenchymal enhancement, focal areas of decreased parenchymal enhancement, focal contour bulging, and the finding of perinephric spread of infection. In a rabbit model, CEUS could depict the parenchymal lesions of APN similar to CT or MRI; however, it was limited in depicting the perinephric extension of inflammation.

  9. Phonon-induced enhancements of the energy gap and critical current in superconducting aluminum

    International Nuclear Information System (INIS)

    Seligson, D.

    1983-05-01

    8 to 10 GHz phonons were generated by piezoelectric transduction of a microwave and by means of a quartz delay line, were allowed to enter the aluminum only after the microwaves had long since disappeared. The maximum enhancements detected were [deltaT/T/sub c/] = -0.07, for i/sub c/ and [deltaT/T/sub c/] = -0.03 for Δ. The power- and temperature-dependence (0.82 less than or equal to T/T/sub c/ less than or equal to 0.994) of the enhancements were compared with the prediction of a theory given by Eliashberg. The gap-enhancement was in good agreement with the theory only for low input lower. The critical current measurements are predicted to be in rough agreement with the Δ measurements but this was not observed. The magnitude of the critical current enhancements was typically more than twice the observed gap enhancements. The measured critical current enhancement was relatively independent of temperature whereas the gap enhancement decreased rapidly as the temperature was lowered

  10. Decrease of GSK3β phosphorylation in the rat nucleus accumbens core enhances cocaine-induced hyper-locomotor activity.

    Science.gov (United States)

    Kim, Wha Y; Jang, Ju K; Lee, Jung W; Jang, Hyunduk; Kim, Jeong-Hoon

    2013-06-01

    Glycogen synthase kinase 3β (GSK3β), which is abundantly present in the brain, is known to contribute to psychomotor stimulant-induced locomotor behaviors. However, most studies have been focused in showing that GSK3β is able to attenuate psychomotor stimulants-induced hyperactivity by increasing its phosphorylation levels in the nucleus accumbens (NAcc). So, here we examined in the opposite direction about the effects of decreased phosphorylation of GSK3β in the NAcc core on both basal and cocaine-induced locomotor activity by a bilateral microinjection into this site of an artificially synthesized peptide, S9 (0.5 or 5.0 μg/μL), which contains sequences around N-terminal serine 9 residue of GSK3β. We found that decreased levels of GSK3β phosphorylation in the NAcc core enhance cocaine-induced hyper-locomotor activity, while leaving basal locomotor activity unchanged. This is the first demonstration, to our knowledge, that the selective decrease of GSK3β phosphorylation levels in the NAcc core may contribute positively to cocaine-induced locomotor activity, while this is not sufficient for the generation of locomotor behavior by itself without cocaine. Taken together, these findings importantly suggest that GSK3β may need other molecular targets which are co-activated (or deactivated) by psychomotor stimulants like cocaine to contribute to generation of locomotor behaviors. © 2013 International Society for Neurochemistry.

  11. Interferon-induced transcription of a gene encoding a 15-kDA protein depends on an upstream enhancer element

    International Nuclear Information System (INIS)

    Reich, N.; Evans, B.; Levy, D.; Fahey, D.; Knight, E. Jr.; Darnell, J.E. Jr.

    1987-01-01

    A human gene encoding an interferon-induced 15-kDa protein has been isolated from a genomic library. The gene appears to be single-copy and is composed of two exons, the first of which contains the ATG translation initiation codon. In vitro nuclear run-on assays showed that the transcription rate of the gene is stimulated after interferon treatment. To analyze transcriptional regulatory sequences, the authors constructed recombinant plasmids for use in transient transfection assays of HeLa cells. Constructs containing 115 nucleotides 5' to the transcription initiation site were found to be fully inducible by interferon. Assays of deletion mutants identified a critical element for interferon induction located between -115 and -96, just upstream of the CCAAT box. Moreover, a DNA fragment including this region can confer interferon inducibility on a heterologous promoter (thymidine kinase) when cloned in either orientation upstream of the gene or downstream of the gene. These are properties characteristic of an enhancer element that is active only after treatment with interferon. This regulatory sequence may be shared by a group of interferon-induced genes, since a very similar sequence is present within the functional region near the RNA start site of another interferon-induced gene

  12. Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis

    International Nuclear Information System (INIS)

    Wu, C.-W.; Ping, Y.-H.; Yen, J.-C.; Chang, C.-Y.; Wang, S.-F.; Yeh, C.-L.; Chi, C.-W.; Lee, H.-C.

    2007-01-01

    Methamphetamine (METH) is an abused drug that may cause psychiatric and neurotoxic damage, including degeneration of monoaminergic terminals and apoptosis of non-monoaminergic cells in Brain. The cellular and molecular mechanisms underlying these METH-induced neurotoxic effects remain to be clarified. In this study, we performed a time course assessment to investigate the effects of METH on intracellular oxidative stress and mitochondrial alterations in a human dopaminergic neuroblastoma SH-SY5Y cell line. We characterized that METH induces a temporal sequence of several cellular events including, firstly, a decrease in mitochondrial membrane potential within 1 h of the METH treatment, secondly, an extensive decline in mitochondrial membrane potential and increase in the level of reactive oxygen species (ROS) after 8 h of the treatment, thirdly, an increase in mitochondrial mass after the drug treatment for 24 h, and finally, a decrease in mtDNA copy number and mitochondrial proteins per mitochondrion as well as the occurrence of apoptosis after 48 h of the treatment. Importantly, vitamin E attenuated the METH-induced increases in intracellular ROS level and mitochondrial mass, and prevented METH-induced cell death. Our observations suggest that enhanced oxidative stress and aberrant mitochondrial biogenesis may play critical roles in METH-induced neurotoxic effects

  13. Corrosion of zirconium alloys in nuclear reactors: A model for irradiation induced enhancement by local radiolysis in the porous oxide

    Energy Technology Data Exchange (ETDEWEB)

    Lemaignan, C; Salot, R [CEA/DRN/DTP, CENG-SECC, Grenoble (France)

    1997-02-01

    An analysis has been undertaken of the various cases of local enhancement of corrosion rate of zirconium alloys under irradiation. It is observed that in most cases a strong emission of energetic {beta}{sup -} is present leading to a local energy deposition rate higher than the core average. This suggests that the local transient radiolytic oxidizing species produced in the coolant by the {beta}{sup -} particles could contribute to corrosion enhancement, by increasing the local corrosion potential. This process is applicable to the local enhanced corrosion found in front of stainless steels structural parts, due to the contribution of Mn, and in front of Pt inserts or Cu-rich cruds. It explains also the irradiation corrosion enhancement of Cu-Zr alloys. Enhanced corrosion around neutron absorbing material is explained similarly by pair production from conversion of high energy capture photons in the cladding, leading to energetic electrons. The same process was found to be active with other highly ionizing species like {alpha} from Ni-rich alloys and fission products in homogeneous reactors. Due to the changes induced by the irradiation intensity on the concentration of the radiolytic species, the coolant chemistry, that controls the boundary conditions for oxide growth, has to be analyzed with respect to the local value of the energy deposition rate. An analysis has been undertaken which shows that, in a porous media, the water is exposed to a higher intensity than bulk water. This leads to a higher concentration of oxidizing radiolytic species at the root of the cracks of the porous oxide, and increases the corrosion rate under irradiation. This mechanism, deduced from the explanation proposed for localized irradiation enhanced corrosion, can be extended to the whole reactor core, where the general enhancement of Zr alloys corrosion under irradiation could be attributed to the general radiolysis in the porous zirconia. (author). 18 refs, 3 figs, 3 tabs.

  14. The nucleus of differentiated root plant cells: modifications induced by arbuscular mycorrhizal fungi

    Directory of Open Access Journals (Sweden)

    G Lingua

    2009-12-01

    Full Text Available The nuclei of plant cells show marked differences in chromatin organisation, related to their DNA content, which ranges from the type with large strands of condensed chromatin (reticulate or chromonematic nuclei to one with mostly decondensed chromatin (chromocentric or diffuse nuclei. A loosening of the chromatin structure generally occurs in actively metabolising cells, such as differentiating and secretory cells, in relation to their high transcriptional activity. Endoreduplication may occur, especially in plants with a small genome, which increases the availability of nuclear templates, the synthesis of DNA, and probably regulates gene expression. Here we describe structural and quantitative changes of the chromatin and their relationship with transcription that occur in differentiated cells following an increase of their metabolism. The nuclei of root cortical cells of three plants with different 2C DNA content (Allium porrum, Pisum sativum and Lycopersicon esculentm and their modifications induced by arbuscular mycorrhization, which strongly increase the metabolic activity of colonised cells, are taken as examples.

  15. In Vivo Evaluation of the Visual Pathway in Streptozotocin-Induced Diabetes by Diffusion Tensor MRI and Contrast Enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Swarupa Kancherla

    Full Text Available Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI. Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0.01 M citric acid, and a sham control group by intraperitoneal injection of citric acid only. One month later, diffusion tensor MRI (DTI was performed to examine the white matter integrity in the brain, followed by chromium-enhanced MRI of retinal integrity and manganese-enhanced MRI of anterograde manganese transport along the visual pathway. Prior to MRI experiments, the streptozotocin-induced diabetic rats showed significantly smaller weight gain and higher blood glucose level than the control rats. DTI revealed significantly lower fractional anisotropy and higher radial diffusivity in the prechiasmatic optic nerve of the diabetic rats compared to the control rats. No apparent difference was observed in the axial diffusivity of the optic nerve, the chromium enhancement in the retina, or the manganese enhancement in the lateral geniculate nucleus and superior colliculus between groups. Our results suggest that streptozotocin-induced diabetes leads to early injury in the optic nerve when no substantial change in retinal integrity or anterograde transport along the visual pathways was observed in MRI using contrast agent enhancement. DTI may be a useful tool for detecting and monitoring early pathophysiological changes in the visual system of experimental diabetes non-invasively.

  16. Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-κB signaling in cultured astrocytes

    International Nuclear Information System (INIS)

    Kakita, Hiroki; Aoyama, Mineyoshi; Hussein, Mohamed Hamed; Kato, Shin; Suzuki, Satoshi; Ito, Tetsuya; Togari, Hajime; Asai, Kiyofumi

    2009-01-01

    Recently, the number of reports of encephalitis/encephalopathy associated with influenza virus has increased. In addition, the use of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF), is associated with a significant increase in the mortality rate of influenza-associated encephalopathy. Activated astrocytes are a source of nitric oxide (NO), which is largely produced by inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore, we investigated whether DCF enhances nitric oxide production in astrocytes stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes with three cytokines, interleukin-1β, tumor necrosis factor-α and interferon-γ, and then treated the astrocytes with DCF or acetaminophen (N-acetyl-p-aminophenol: APAP). iNOS and NO production in astrocyte cultures were induced by proinflammatory cytokines. The addition of DCF augmented NO production, but the addition of APAP did not. NF-κB inhibitors SN50 and MG132 inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. Similarly, NF-κB p65 Stealth small interfering RNA suppressed iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. LDH activity and DAPI staining showed that DCF induces cell damage in cytokine-stimulated astrocytes. An iNOS inhibitor, L-NMMA, inhibited the cytokine- and DCF-induced cell damage. In conclusion, this study demonstrates that iNOS and NO are induced in astrocyte cultures by proinflammatory cytokines. Addition of DCF further augments NO production. This effect is mediated via NF-κB signaling and leads to cell damage. The enhancement of DCF on NO production may explain the significant increase in the mortality rate of influenza-associated encephalopathy in patients treated with DCF.

  17. 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

  18. 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

  19. Taxifolin enhances andrographolide-induced mitotic arrest and apoptosis in human prostate cancer cells via spindle assembly checkpoint activation.

    Directory of Open Access Journals (Sweden)

    Zhong Rong Zhang

    Full Text Available Andrographolide (Andro suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC, alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC.

  20. Taxifolin Enhances Andrographolide-Induced Mitotic Arrest and Apoptosis in Human Prostate Cancer Cells via Spindle Assembly Checkpoint Activation

    Science.gov (United States)

    Wong, Matthew Man-Kin; Chiu, Sung-Kay; Cheung, Hon-Yeung

    2013-01-01

    Andrographolide (Andro) suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi) has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose) polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC), alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC. PMID:23382917

  1. Effect of Thermal Annealing on Light-Induced Minority Carrier Lifetime Enhancement in Boron-Doped Czochralski Silicon

    International Nuclear Information System (INIS)

    Wang Hong-Zhe; Zheng Song-Sheng; Chen Chao

    2015-01-01

    The effect of thermal annealing on the light-induced effective minority carrier lifetime enhancement (LIE) phenomenon is investigated on the p-type Czochralski silicon (Cz-Si) wafer passivated by a phosphorus-doped silicon nitride (P-doped SiN_x) thin film. The experimental results show that low temperature annealing (below 300°C) can not only increase the effective minority carrier lifetime of P-doped SiN_x passivated boron-doped Cz-Si, but also improve the LIE phenomenon. The optimum annealing temperature is 180°C, and its corresponding effective minority carrier lifetime can be increased from initial 7.5 μs to maximum 57.7 μs by light soaking within 15 min after annealing. The analysis results of high-frequency dark capacitance-voltage characteristics reveal that the mechanism of the increase of effective minority carrier lifetime after low temperature annealing is due to the sharp enhancement of field effect passivation induced by the negative fixed charge density, while the mechanism of the LIE phenomenon after low temperature annealing is attributed to the enhancement of both field effect passivation and chemical passivation. (paper)

  2. Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to chemotherapy-induced cell death

    Science.gov (United States)

    Porter, Holly A.; Carey, Gregory B.; Keegan, Achsah D.

    2012-01-01

    The adaptors IRS1 and IRS2 link growth factor receptors to downstream signaling pathways that regulate proliferation and survival. Both suppress factor-withdrawal-induced apoptosis and have been implicated in cancer progression. However, recent studies suggest IRS1 and IRS2 mediate differential functions in cancer pathogenesis. IRS1 promoted breast cancer proliferation, while IRS2 promoted metastasis. The role of IRS1 and IRS2 in controlling cell responses to chemotherapy is unknown. To determine the role of IRS1 and IRS2 in the sensitivity of cells to chemotherapy, we treated 32D cells lacking or expressing IRS proteins with various concentrations of chemotherapeutic agents. We found that expression of IRS1, in contrast to IRS2, enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. When IRS2 was expressed with IRS1, the cells no longer showed enhanced sensitivity. Expression of IRS1 did not alter the expression of pro- and anti-apoptotic proteins; however, 32D-IRS1 cells expressed higher levels of Annexin A2. In 32D-IRS1 cells, IRS1 and Annexin A2 were both located in cytoplasmic and membrane fractions. We also found that IRS1 coprecipitated with Annexin A2, while IRS2 did not. Decreasing Annexin A2 levels reduced 32D-IRS1 cell sensitivity to chemotherapy. These results suggest IRS1 enhances sensitivity to chemotherapy in part through Annexin A2. PMID:22652453

  3. Signal enhancement of neutral He emission lines by fast electron bombardment of laser-induced He plasma

    Directory of Open Access Journals (Sweden)

    Hery Suyanto

    2016-08-01

    Full Text Available A time-resolved spectroscopic study is performed on the enhancement signals of He gas plasma emission using nanosecond (ns and picosecond (ps lasers in an orthogonal configuration. The ns laser is used for the He gas plasma generation and the ps laser is employed for the ejection of fast electrons from a metal target, which serves to excite subsequently the He atoms in the plasma. The study is focused on the most dominant He I 587.6 nm and He I 667.8 nm emission lines suggested to be responsible for the He-assisted excitation (HAE mechanism. The time-dependent intensity enhancements induced by the fast electrons generated with a series of delayed ps laser ablations are deduced from the intensity time profiles of both He emission lines. The results clearly lead to the conclusion that the metastable excited triplet He atoms are actually the species overwhelmingly produced during the recombination process in the ns laser-induced He gas plasma. These metastable He atoms are believed to serve as the major energy source for the delayed excitation of analyte atoms in ns laser-induced breakdown spectroscopy (LIBS using He ambient gas.

  4. Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Chun Yang

    2012-01-01

    Full Text Available Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST. Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

  5. Enhancement of acetylcholine-induced desensitization of guinea-pig ileal longitudinal muscle in Ca2+-free conditions.

    Science.gov (United States)

    Horio, S; Nagare, T; Moritoki, H

    1999-10-01

    1. To determine the role of cellular Ca2+ in desensitization, acetylcholine(ACh)-induced desensitization was studied under Ca2+-free condition in guinea-pig ileal longitudinal muscle. 2. Pretreatment of the tissue with 10(-4) M ACh (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses both to ACh and histamine. The desensitizing treatment performed in Ca2+-free solution enhanced desensitization of the responses to ACh and histamine significantly. 3. The desensitizing treatment with ACh caused suppression of the responses to high K+ (tonic component) and Bay K 8644. The desensitizing treatment performed in Ca2+-free solution potentiated the suppression of the responses to high K+ and Bay K 8644 significantly. 4. ACh-induced desensitization was enhanced significantly in the presence of a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine(H-7, 10(-4) M) to a similar extent as desensitization obtained under Ca2+-free condition, but not in the presence of a non-specific and less potent kinase inhibitor, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004, 10(-4) M). 5. These results suggested that voltage-gated Ca2+ channels were involved in ACh-induced desensitization and that intracellular Ca2+, which was increased during the stimulation with ACh, inhibited desensitization through the activation of protein kinase C. This kinase could have activated or protected Ca2+ channels during the desensitization process to reduce desensitization.

  6. Signal enhancement of neutral He emission lines by fast electron bombardment of laser-induced He plasma

    Energy Technology Data Exchange (ETDEWEB)

    Suyanto, Hery [Department of Physics, Faculty of Mathematics and Natural Sciences, Udayana University, Kampus Bukit Jimbaran, Denpasar 80361, Bali (Indonesia); Pardede, Marincan [Department of Electrical Engineering, University of Pelita Harapan, 1100 M.H. Thamrin Boulevard, Lippo Village, Tangerang 15811 (Indonesia); Hedwig, Rinda [Department of Computer Engineering, Bina Nusantara University, 9 K.H. Syahdan, Jakarta 14810 (Indonesia); Marpaung, Alion Mangasi [Department of Physics, Faculty of Mathematics and Natural Sciences, Jakarta State University, Rawamangun, Jakarta 12440 (Indonesia); Ramli, Muliadi [Department of Chemistry, Faculty of Mathematics and Natural Sciences, Syiah Kuala University, Darussalam, Banda Aceh 23111, NAD (Indonesia); Lie, Tjung Jie; Kurniawan, Koo Hendrik, E-mail: kurnia18@cbn.net.id [Research Center of Maju Makmur Mandiri Foundation, 40 Srengseng Raya, Kembangan, Jakarta Barat 11630 (Indonesia); Abdulmadjid, Syahrun Nur [Department of Physics, Faculty of Mathematics and Natural Sciences, Syiah Kuala University, Darussalam, Banda Aceh 23111, NAD (Indonesia); Tjia, May On [Research Center of Maju Makmur Mandiri Foundation, 40 Srengseng Raya, Kembangan, Jakarta Barat 11630 (Indonesia); Physics of Magnetism and Photonics Group, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, 10 Ganesha,Bandung 40132 (Indonesia); Kagawa, Kiichiro [Research Center of Maju Makmur Mandiri Foundation, 40 Srengseng Raya, Kembangan, Jakarta Barat 11630 (Indonesia); Fukui Science Education Academy, Takagi Chuo 2 chome, Fukui 910-0804 (Japan)

    2016-08-15

    A time-resolved spectroscopic study is performed on the enhancement signals of He gas plasma emission using nanosecond (ns) and picosecond (ps) lasers in an orthogonal configuration. The ns laser is used for the He gas plasma generation and the ps laser is employed for the ejection of fast electrons from a metal target, which serves to excite subsequently the He atoms in the plasma. The study is focused on the most dominant He I 587.6 nm and He I 667.8 nm emission lines suggested to be responsible for the He-assisted excitation (HAE) mechanism. The time-dependent intensity enhancements induced by the fast electrons generated with a series of delayed ps laser ablations are deduced from the intensity time profiles of both He emission lines. The results clearly lead to the conclusion that the metastable excited triplet He atoms are actually the species overwhelmingly produced during the recombination process in the ns laser-induced He gas plasma. These metastable He atoms are believed to serve as the major energy source for the delayed excitation of analyte atoms in ns laser-induced breakdown spectroscopy (LIBS) using He ambient gas.

  7. Acrolein enhances epigenetic modifications, FasL expression and hepatocyte toxicity induced by anti-HIV drug Zidovudine.

    Science.gov (United States)

    Ghare, Smita S; Donde, Hridgandh; Chen, Wei-Yang; Barker, David F; Gobejishvilli, Leila; McClain, Craig J; Barve, Shirish S; Joshi-Barve, Swati

    2016-09-01

    Zidovudine (AZT) remains the mainstay of antiretroviral therapy against HIV in resource-poor countries; however, its use is frequently associated with hepatotoxicity. Not all HIV patients on AZT develop hepatotoxicity, and the determining factors are unclear. Alcohol consumption and cigarette smoking are known risk factors for HIV hepatotoxicity, and both are significant sources of acrolein, a highly reactive and toxic aldehyde. This study examines the potential hepatotoxic interactions between acrolein and AZT. Our data demonstrate that acrolein markedly enhanced AZT-induced transcriptionally permissive histone modifications (H3K9Ac and H3K9Me3) allowing the recruitment of transcription factor NF-kB and RNA polymerase II at the FasL gene promoter, resulting in FasL upregulation and apoptosis in hepatocytes. Notably, the acrolein scavenger, hydralazine prevented these promoter-associated epigenetic changes and inhibited FasL upregulation and apoptosis induced by the combination of AZT and acrolein, as well as AZT alone. Our data strongly suggest that acrolein enhancement of promoter histone modifications and FasL upregulation are major pathogenic mechanisms driving AZT-induced hepatotoxicity. Moreover, these data also indicate the therapeutic potential of hydralazine in mitigating AZT hepatotoxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Local establishment of repetitive long-term potentiation-induced synaptic enhancement in cultured hippocampal slices with divided input pathways.

    Science.gov (United States)

    Oe, Yuki; Tominaga-Yoshino, Keiko; Ogura, Akihiko

    2011-09-01

    Long-term potentiation (LTP) in the rodent hippocampus is a popular model for synaptic plasticity, which is considered the cellular basis for brain memory. Because most LTP analysis involves acutely prepared brain slices, however, the longevity of single LTP has not been well documented. Using stable hippocampal slice cultures for long-term examination, we previously found that single LTP disappeared within 1 day. In contrast, repeated induction of LTP led to the development of a distinct type of plasticity that lasted for more than 3 weeks and was accompanied by the formation of new synapses. Naming this novel plastic phenomenon repetitive LTP-induced synaptic enhancement (RISE), we proposed it as a model for the cellular processes involved in long-term memory formation. However, because in those experiments LTP was induced pharmacologically in the whole slice, it is not known whether RISE has input-pathway specificity, an essential property for memory. In this study, we divided the input pathway of CA1 pyramidal neurons by a knife cut and induced LTP three times, the third by tetanic stimulation in one of the divided pathways to express RISE specifically. Voltage-sensitive dye imaging and Golgi-staining performed 2 weeks after the three LTP inductions revealed both enhanced synaptic strength and increased dendritic spine density confined to the tetanized region. These results demonstrate that RISE is a feasible cellular model for long-term memory. Copyright © 2011 Wiley-Liss, Inc.

  9. Chronic ethanol feeding promotes azoxymethane and dextran sulfate sodium-induced colonic tumorigenesis potentially by enhancing mucosal inflammation

    International Nuclear Information System (INIS)

    Shukla, Pradeep K.; Chaudhry, Kamaljit K.; Mir, Hina; Gangwar, Ruchika; Yadav, Nikki; Manda, Bhargavi; Meena, Avtar S.; Rao, RadhaKrishna

    2016-01-01

    Alcohol consumption is one of the major risk factors for colorectal cancer. However, the mechanism involved in this effect of alcohol is unknown. We evaluated the effect of chronic ethanol feeding on azoxymethane and dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in mouse colon. Inflammation in colonic mucosa was assessed at a precancerous stage by evaluating mucosal infiltration of neutrophils and macrophages, and analysis of cytokine and chemokine gene expression. Chronic ethanol feeding significantly increased the number and size of polyps in colon of AOM/DSS treated mice. Confocal microscopic and immunoblot analyses showed a significant elevation of phospho-Smad, VEGF and HIF1α in the colonic mucosa. RT-PCR analysis at a precancerous stage indicated that ethanol significantly increases the expression of cytokines IL-1α, IL-6 and TNFα, and the chemokines CCL5/RANTES, CXCL9/MIG and CXCL10/IP-10 in the colonic mucosa of AOM/DSS treated mice. Confocal microscopy showed that ethanol feeding induces a dramatic elevation of myeloperoxidase, Gr1 and CD68-positive cells in the colonic mucosa of AOM/DSS-treated mice. Ethanol feeding enhanced AOM/DSS-induced suppression of tight junction protein expression and elevated cell proliferation marker, Ki-67 in the colonic epithelium. This study demonstrates that chronic ethanol feeding promotes colonic tumorigenesis potentially by enhancing inflammation and elevation of proinflammatory cytokines and chemokines

  10. Curcuma aromatica Water Extract Attenuates Ethanol-Induced Gastritis via Enhancement of Antioxidant Status

    Directory of Open Access Journals (Sweden)

    Woo-Young Jeon

    2015-01-01

    Full Text Available Curcuma aromatica is an herbal medicine and traditionally used for the treatment of various diseases in Asia. We investigated the effects of C. aromatica water extract (CAW in the stomach of rats with ethanol-induced gastritis. Gastritis was induced in rats by intragastric administration of 5 mL/kg body weight of absolute ethanol. The CAW groups were given 250 or 500 mg of extract/kg 2 h before administration of ethanol, respectively. To determine the antioxidant effects of CAW, we determined the level of lipid peroxidation, the level of reduced glutathione (GSH, the activities of catalase, degree of inflammation, and mucus production in the stomach. CAW reduced ethanol-induced inflammation and loss of epithelial cells and increased the mucus production in the stomach. CAW reduced the increase in lipid peroxidation associated with ethanol-induced gastritis (250 and 500 mg/kg, p<0.01, resp. and increased mucosal GSH content (500 mg/kg, p<0.01 and the activity of catalase (250 and 500 mg/kg, p<0.01, resp.. CAW increased the production of prostaglandin E2. These findings suggest that CAW protects against ethanol-induced gastric mucosa injury by increasing antioxidant status. We suggest that CAW could be developed for the treatment of gastritis induced by alcohol.

  11. Loss of hypoxia-inducible factor 2 alpha in the lung alveolar epithelium of mice leads to enhanced eosinophilic inflammation in cobalt-induced lung injury.

    Science.gov (United States)

    Proper, Steven P; Saini, Yogesh; Greenwood, Krista K; Bramble, Lori A; Downing, Nathaniel J; Harkema, Jack R; Lapres, John J

    2014-02-01

    Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2α(Δ/Δ)) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2α(Δ/Δ) mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2α(Δ/Δ) and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung.

  12. Thioredoxin-albumin fusion protein prevents copper enhanced zinc-induced neurotoxicity via its antioxidative activity.

    Science.gov (United States)

    Tanaka, Ken-Ichiro; Shimoda, Mikako; Chuang, Victor T G; Nishida, Kento; Kawahara, Masahiro; Ishida, Tatsuhiro; Otagiri, Masaki; Maruyama, Toru; Ishima, Yu

    2018-01-15

    Zinc (Zn) is a co-factor for a vast number of enzymes, and functions as a regulator for immune mechanism and protein synthesis. However, excessive Zn release induced in pathological situations such as stroke or transient global ischemia is toxic. Previously, we demonstrated that the interaction of Zn and copper (Cu) is involved in the pathogenesis of Alzheimer's disease and vascular dementia. Furthermore, oxidative stress has been shown to play a significant role in the pathogenesis of various metal ions induced neuronal death. Thioredoxin-Albumin fusion (HSA-Trx) is a derivative of thioredoxin (Trx), an antioxidative protein, with improved plasma retention and stability of Trx. In this study, we examined the effect of HSA-Trx on Cu 2+ /Zn 2+ -induced neurotoxicity. Firstly, HSA-Trx was found to clearly suppress Cu 2+ /Zn 2+ -induced neuronal cell death in mouse hypothalamic neuronal cells (GT1-7 cells). Moreover, HSA-Trx markedly suppressed Cu 2+ /Zn 2+ -induced ROS production and the expression of oxidative stress related genes, such as heme oxygenase-1. In contrast, HSA-Trx did not affect the intracellular levels of both Cu 2+ and Zn 2+ after Cu 2+ /Zn 2+ treatment. Finally, HSA-Trx was found to significantly suppress endoplasmic reticulum (ER) stress response induced by Cu 2+ /Zn 2+ treatment in a dose dependent manner. These results suggest that HSA-Trx counteracted Cu 2+ /Zn 2+ -induced neurotoxicity by suppressing the production of ROS via interfering the related gene expressions, in addition to the highly possible radical scavenging activity of the fusion protein. Based on these findings, HSA-Trx has great potential as a promising therapeutic agent for the treatment of refractory neurological diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. A phagocytotic inducer from herbal constituent, pentagalloylglucose enhances lipoplex-mediated gene transfection in dendritic cells.

    Science.gov (United States)

    Kato, Shinichiro; Koizumi, Keiichi; Yamada, Miyuki; Inujima, Akiko; Takeno, Nobuhiro; Nakanishi, Tsuyoshi; Sakurai, Hiroaki; Nakagawa, Shinsaku; Saiki, Ikuo

    2010-01-01

    Antigen-presenting cells are key vehicles for delivering antigens in tumor immunotherapy, and the most potent of them are dendritic cells (DCs). Recent studies have demonstrated the usefulness of DCs genetically modified by lipofection in tumor immune therapy, although sufficient gene transduction into DCs is quite difficult. Here, we show that Paeoniae radix, herbal medicine, and the constituent, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), have an attractive function to enhance phagocytosis in murine dendritic cell lines, DC2.4 cells. In particular, PGG in combination with lipofectin (LPF) enhanced phagocytic activity. Furthermore, PGG enhanced lipofection efficacy in DC2.4 cells, but not in colorectal carcinoma cell lines, Colon26. In other words, PGG synergistically enhanced the effect of lipofectin-dependent phagocytosis on phagocytic cells. Hence, according to our data, PGG could be an effective aid in lipofection using dendritic cells. Furthermore, these findings provide an expectation that constituents from herbal plant enhance lipofection efficacy.

  14. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease.

    Science.gov (United States)

    Khurana, Surender; Loving, Crystal L; Manischewitz, Jody; King, Lisa R; Gauger, Phillip C; Henningson, Jamie; Vincent, Amy L; Golding, Hana

    2013-08-28

    Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.

  15. Selective Activation of M4 Muscarinic Acetylcholine Receptors Reverses MK-801-Induced Behavioral Impairments and Enhances Associative Learning in Rodents

    Science.gov (United States)

    2015-01-01

    Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central nervous system. Prior to this study, the M1 mAChR subtype was viewed as the primary candidate for these actions relative to the other mAChR subtypes. Here we describe the discovery of a novel M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic properties relative to other M4 PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801. VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant-induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both contextual and cue-mediated fear conditioning when administered alone in wild-type mice. These novel findings suggest that M4 PAMs may provide a strategy for addressing the more complex affective and cognitive disruptions associated with schizophrenia and other neuropsychiatric disorders. PMID:25137629

  16. Enhanced striatial 3H-spiroperidol binding induced by chronic haloperidol treatment inhibited by peptides administered during the withdrawal phase

    International Nuclear Information System (INIS)

    Bhargava, H.N.

    1984-01-01

    Chronic intragastric administration of haloperidol (1.5 mg/kg/day) for 21 days followed by a 3-day withdrawal period resulted in the development of enhanced locomotor activity response to apomorphine, and an increase in the number of binding sites for 3 H-spiroperidol in the striatal membranes of the rat brain. Subcutaneous administration of Pro-Leu-Gly-NH 2 or cyclo-(Leu-Gly) in doses of 2 mg/kg/day given for 3-days after termination of haloperidol treatment inhibited the enhanced response to apomorphine, as well as the increases in the number of 3 H-spiroperidol binding sites in the striatum. If indeed, the supersensitivity of striatal dopamine receptors is one of the mechanisms in the development of tardive dyskinesia symptoms, the present results suggest that the above peptides may be helpful in ameliorating some of the symptoms of tardive dyskinesia induced by neuroleptic drugs. 31 references, 3 figures

  17. The role of recombinant IL-12 in enhancing immune responses induced by hepatitis B vaccine in mice

    International Nuclear Information System (INIS)

    Lu Qun; Zhou Lixia; Zhao Yanrong; Miao Xiaoguang; Jin Jie; Ke Jinshan; Qin Xuliang; He Zheng

    2007-01-01

    Objective: To study the role played by recombinant IL-12 in enhancing the intensity and quality of the immune response to hepatitis B vaccine in mice, and investigate the possibility of adding recombinant IL-12 as adjuvants to hepatitis B therapeutic vaccine. Methods: Recombinant IL-12 was injected together with hepatitis B vaccine into mice and special anti-HBsAb in the mice and the cellular immune responses were examined. Results: Recombinant IL-12 can obviously enhance T lymphocyte multiplication activity, accelerate excretion of cytokines IFN-γ and IL-2, and increase the IgG2a antibody in mice. Conclusion: Recombinant IL-12 can remarkably strengthen the cellular immune responses induced by the hepatitis B vaccine, and modulate the immune responses toward Thl. (authors)

  18. Synthesis of surface oxygen-deficient BiPO{sub 4} nanocubes with enhanced visible light induced photocatalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Bingtao; Yin, Haoyong; Li, Tao; Gong, Jianying; Lv, Shumei; Nie, Qiulin, E-mail: yhy@hdu.edu.cn [College of Materials & Environmental Engineering, Hangzhou Dianzi University, Hangzhou (China)

    2017-05-15

    The visible light driven BiPO{sub 4} nanocubes with sufficient surface oxygen deficiency were fabricated by a hydrothermal process and subsequently ultrasonic assistant Fe reduction process. The products were characterized by XRD, DRS, XPS, SEM and TEM which showed that the BiPO{sub 4} had cuboid-like shape with a smooth surface and clear edges and the oxygen vacancies were successfully introduced on the surface of the BiPO{sub 4} nanocubes. The as prepared oxygen-deficient BiPO{sub 4} nanocubes showed greatly enhanced visible light induced photocatalytic activity in degradation of Rhodamine B. The enhanced photocatalytic performance and expanded visible light response of BiPO{sub 4} may be due to the introduction of surface oxygen vacancies which can generate the oxygen vacancies mid-gap states lower to the conduction band of BiPO{sub 4}. (author)

  19. Structural Origin of the Enhanced Glass-Forming Ability Induced by Microalloying Y in the ZrCuAl Alloy

    Directory of Open Access Journals (Sweden)

    Gu-Qing Guo

    2016-03-01

    Full Text Available In this work, the structural origin of the enhanced glass-forming ability induced by microalloying Y in a ZrCuAl multicomponent system is studied by performing synchrotron radiation experiments combined with simulations. It is revealed that the addition of Y leads to the optimization of local structures, including: (1 more Zr-centered and Y-centered icosahedral-like clusters occur in the microstructure; (2 the atomic packing efficiency inside clusters and the regularity of clusters are both enhanced. These structural optimizations help to stabilize the amorphous structure in the ZrCuAlY system, and lead to a high glass-forming ability (GFA. The present work provides an understanding of GFAs in multicomponent alloys and will shed light on the development of more metallic glasses with high GFAs.

  20. Two weeks of metformin treatment induces AMPK dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Treebak, Jonas Thue; Schjerling, Peter

    2014-01-01

    signaling. Methods: Oral doses of metformin or saline treatment were given muscle-specific kinase α2 dead AMPK mice (KD) and wild type (WT) littermates either once or chronically for 2 weeks. Soleus and Extensor Digitorum Longus (EDL) muscles were used for measurements of glucose transport and Western blot......Background: Metformin-induced activation of AMPK has been associated with enhanced glucose uptake in skeletal muscle but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent upon AMPK...... analyzes. Results: Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (45%, P...

  1. Enhancement of laser induced damage threshold of fused silica by acid etching combined with UV laser conditioning

    International Nuclear Information System (INIS)

    Chen Meng; Xiang Xia; Jiang Yong; Zu Xiaotao; Yuan Xiaodong; Zheng Wanguo; Wang Haijun; Li Xibin; Lu Haibing; Jiang Xiaodong; Wang Chengcheng

    2010-01-01

    Acid etching combined with UV laser conditioning is developed to enhance the laser induced damage threshold (LIDT) of fused silica. Firstly, the fused silica is etched for 1 ∼ 100 min with a buffered 1% HF solution. After acid etching, its transmittance, surface roughness and LIDT are measured. The results reveal that the fused silica has the highest LIDT and transmittance after etching for 10 min. Then UV laser (355 nm) conditioning is adopted to process the 10-min-etched fused silica. When the laser fluence is below 60% of fused silica's zero probability damage threshold, the LIDT increases gradually with the increase of laser conditioning fluence. However, the LIDT rapidly decreases to be lower than the threshold of the 10-min-etched fused silica when the conditioning fluence is up to 80% of the threshold. Proper acid etching and laser conditioning parameters will effectively enhance the laser damage resistance of fused silica. (authors)

  2. Turmeric active substance, curcumin, enhanced apomorphine-induced yawning in rats

    Directory of Open Access Journals (Sweden)

    Esmaeal Tamaddonfard

    2013-05-01

    Full Text Available Objective: Curcumin is a major constituent of turmeric and influences many functions of the brain. In the present study, we investigated the effect of curcumin on yawning induced by apomorphine in rats. Materials and Methods: Curcumin administered orallyfor 10 consecutive days. Yawning was induced by subcutaneous (s.c. injection of apomorphine (a dopamine receptor agonist and the number of yawns was recorded for a period of 30 min. Results: Apomorphine (0.05 and 0.1 mg/kg produced yawning. Haloperidol (a dopamine receptors antagonist at a dose of 0.05 mg/kg partially and at a dose of 0.2 mg/kg completely inhibited apomorphine-induced yawning. Curcumin alone produced no yawning, whereas at doses of 30 and 60 mg/kg, it increased yawning induced by 0.1 mg/kg of apomorphine. Curcumin at the high doses (30 and 60 mg/kg produced yawning when apomorphine (0.1 mg/kg action was partially blocked with 0.5 mg/kg of haloperidol. In the presence of complete blockade of apomorphine (0.1 mg/kg action with 0.2 mg/kg of haloperidol, curcumin did not produce yawning. Conclusion: The results showed that curcumin at high doses increased apomorphine-induced yawning. In the presence of partial, but not complete blockade of apomorphine action, curcumin produced yawning. Curcumin produced a dopamine-like effect on yawning.

  3. Stimulated Raman spectroscopy and nanoscopy of molecules using near field photon induced forces without resonant electronic enhancement gain

    Energy Technology Data Exchange (ETDEWEB)

    Tamma, Venkata Ananth [CaSTL Center, Department of Chemistry, University of California, Irvine, California 92697 (United States); Huang, Fei; Kumar Wickramasinghe, H., E-mail: hkwick@uci.edu [Department of Electrical Engineering and Computer Science, 142 Engineering Tower, University of California, Irvine, California 92697 (United States); Nowak, Derek [Molecular Vista, Inc., 6840 Via Del Oro, San Jose, California 95119 (United States)

    2016-06-06

    We report on stimulated Raman spectroscopy and nanoscopy of molecules, excited without resonant electronic enhancement gain, and recorded using near field photon induced forces. Photon-induced interaction forces between the sharp metal coated silicon tip of an Atomic Force Microscope (AFM) and a sample resulting from stimulated Raman excitation were detected. We controlled the tip to sample spacing using the higher order flexural eigenmodes of the AFM cantilever, enabling the tip to come very close to the sample. As a result, the detection sensitivity was increased compared with previous work on Raman force microscopy. Raman vibrational spectra of azobenzene thiol and l-phenylalanine were measured and found to agree well with published results. Near-field force detection eliminates the need for far-field optical spectrometer detection. Recorded images show spatial resolution far below the optical diffraction limit. Further optimization and use of ultrafast pulsed lasers could push the detection sensitivity towards the single molecule limit.

  4. Nanoparticle Enhanced Laser Induced Breakdown Spectroscopy: Effect of nanoparticles deposited on sample surface on laser ablation and plasma emission

    International Nuclear Information System (INIS)

    De Giacomo, A.; Gaudiuso, R.; Koral, C.; Dell'Aglio, M.; De Pascale, O.

    2014-01-01

    In this paper the use of metallic nanoparticles (NPs) for improving Laser Induced Breakdown Spectroscopy (LIBS) is discussed. In the case of conductors an emission signal enhancement up to 1–2 orders of magnitude was obtained depositing NPs on the sample surface by drying a micro-drop of colloidal solution. The basic mechanisms of Nanoparticle Enhanced LIBS (NELIBS) were studied and the main causes of this significantly large enhancement were found to be related to the effect of NPs on the laser ablation process, in terms of a faster and more efficient production of seed electrons with respect to conventional LIBS. The characteristics of NELIBS-produced plasma were investigated by emission spectroscopy and spectrally resolved images. In spite of similar plasma parameters, the NELIBS plasma was found to have larger emission volume and longer persistence than the LIBS one. A method to determine NP concentration and size was also proposed, which involved depositing NPs on non-interacting substrates, and proved the feasibility of LIBS as a fast detection tool for a preliminary characterization of NPs. - Highlights: • Effect of NPs on sample surface enables instantaneous field emission. • More efficient ablation • LIBS emission enhancement up to 1–2 orders of magnitude • Possibility of NP characterization in terms of concentration and size

  5. Large and homogeneous mass enhancement in the rattling-induced superconductor KOs2O6

    Science.gov (United States)

    Terashima, Taichi; Kurita, Nobuyuki; Kiswandhi, Andhika; Choi, Eun-Sang; Brooks, James S.; Sato, Kota; Yamaura, Jun-ichi; Hiroi, Zenji; Harima, Hisatomo; Uji, Shinya

    2012-05-01

    We have determined the Fermi surface in KOs2O6 (Tc=9.6 K and Bc2˜32 T) via de Haas-van Alphen (dHvA) oscillation measurements and a band structure calculation. We find effective masses up to 26(1)me (me is the free electron mass), which are unusually heavy for compounds where the mass enhancement is mostly due to electron-phonon interactions. Orbit-resolved mass enhancement parameters λdHvA are large but fairly homogeneous, concentrated in the range 5-8. We discuss origins of the large homogeneous mass enhancement in terms of rattling motion of the K ions.

  6. Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.

    Science.gov (United States)

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M; Xu, Lihong; Storm, Daniel R; Xia, Zhengui

    2015-05-20

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. Copyright © 2015 the authors 0270-6474/15/357833-17$15.00/0.

  7. Tumor-infiltrating lymphocyte activity is enhanced in tumors with low IL-10 production in HBV-induced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Shi, Yang; Song, Qingwei; Hu, Dianhe; Zhuang, Xiaohu; Yu, Shengcai

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers and can be induced by chronic HBV infection. The role of HBV-specific immune responses in mediating tumorigenesis and HCC prognosis is debated. The effect of intratumoral microenvironment on tumor-infiltrating lymphocytes (TILs) is also unclear. Here, we examined resected tumor tissue from 36 patients with HBV-induced HCC. We categorized study cohort based on ex vivo IL-10 secretion by tumor cells into high IL-10-secreting (Hi10) and low IL-10-secreting (Lo10) groups, and found that the Lo10 group was less sensitive to TLR ligand stimulation. TILs from the Lo10 group contained higher frequencies of HBV-specific IFN-g-producing cells and total IFN-g-producing cells, and possessed higher proliferative capacity. Moreover, the proliferative capacity of TILs from the Hi10 group was negatively correlated with IL-10 secretion from tumor cells. Together, our data demonstrated that low IL-10-producing capacity in HBV-induced HCC tumors is associated with enhanced TIL activity. - Highlights: • We examined intratumoral IL-10 production in HBV-induced HCC. • We grouped HCC tumors into Hi10 and Lo10 groups based on their IL-10 production. • Lo10 groups had better IFN-g response by TILs. • Lo10 groups had better TIL proliferative capacity. • Lo10 group tumor cells were refractory to TLR ligand stimulation

  8. Tumor-infiltrating lymphocyte activity is enhanced in tumors with low IL-10 production in HBV-induced hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yang, E-mail: yangshi_xz@126.com; Song, Qingwei; Hu, Dianhe; Zhuang, Xiaohu; Yu, Shengcai

    2015-05-22

    Hepatocellular carcinoma (HCC) is one of the most common cancers and can be induced by chronic HBV infection. The role of HBV-specific immune responses in mediating tumorigenesis and HCC prognosis is debated. The effect of intratumoral microenvironment on tumor-infiltrating lymphocytes (TILs) is also unclear. Here, we examined resected tumor tissue from 36 patients with HBV-induced HCC. We categorized study cohort based on ex vivo IL-10 secretion by tumor cells into high IL-10-secreting (Hi10) and low IL-10-secreting (Lo10) groups, and found that the Lo10 group was less sensitive to TLR ligand stimulation. TILs from the Lo10 group contained higher frequencies of HBV-specific IFN-g-producing cells and total IFN-g-producing cells, and possessed higher proliferative capacity. Moreover, the proliferative capacity of TILs from the Hi10 group was negatively correlated with IL-10 secretion from tumor cells. Together, our data demonstrated that low IL-10-producing capacity in HBV-induced HCC tumors is associated with enhanced TIL activity. - Highlights: • We examined intratumoral IL-10 production in HBV-induced HCC. • We grouped HCC tumors into Hi10 and Lo10 groups based on their IL-10 production. • Lo10 groups had better IFN-g response by TILs. • Lo10 groups had better TIL proliferative capacity. • Lo10 group tumor cells were refractory to TLR ligand stimulation.

  9. Cognitive-Enhancing Effect of Dianthus superbus var. Longicalycinus on Scopolamine-Induced Memory Impairment in Mice.

    Science.gov (United States)

    Weon, Jin Bae; Jung, Youn Sik; Ma, Choong Je

    2016-05-01

    Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer's disease.

  10. The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide.

    Science.gov (United States)

    Kurz, C; Ungerer, I; Lipka, U; Kirr, S; Schütt, T; Eckert, A; Leuner, K; Müller, W E

    2010-05-01

    beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress. We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Abeta-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Abeta and on neurite outgrowth in PC12 cells were investigated. Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Abeta(1-42). Similar protective effects against Abeta(1-42) were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Abeta load was markedly diminished in the brain of those animals after treatment with piracetam. Abeta production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Abeta-induced mitochondrial dysfunction and Abeta-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam. Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Abeta on brain function.

  11. Nec-1 Enhances Shikonin-Induced Apoptosis in Leukemia Cells by Inhibition of RIP-1 and ERK1/2

    Directory of Open Access Journals (Sweden)

    Hongming Pan

    2012-06-01

    Full Text Available Necrostatin-1 (Nec-1 inhibits necroptosis by allosterically inhibiting the kinase activity of receptor-interacting protein 1 (RIP1, which plays a critical role in necroptosis. RIP1 is a crucial adaptor kinase involved in the activation of NF-κB, production of reactive oxygen species (ROS and the phosphorylation of mitogen activated protein kinases (MAPKs. NF-κB, ROS and MAPKs all play important roles in apoptotic signaling. Nec-1 was regarded as having no effect on apoptosis. Here, we report that Nec-1 increased the rate of nuclear condensation and caspases activation induced by a low concentration of shikonin (SHK in HL60, K562 and primary leukemia cells. siRNA-mediated knockdown of RIP1 significantly enhanced shikonin-induced apoptosis in K562 and HL60 cells. Shikonin treatment alone could slightly inhibit the phosphorylation of ERK1/2 in leukemia cells, and the inhibitory effect on ERK1/2 was significantly augmented by Nec-1. We also found that Nec-1 could inhibit NF-κB p65 translocation to the nucleus at a later stage of SHK treatment. In conclusion, we found that Nec-1 can promote shikonin-induced apoptosis in leukemia cells. The mechanism by which Nec-1 sensitizes shikonin-induced apoptosis appears to be the inhibition of RIP1 kinase-dependent phosphorylation of ERK1/2. To our knowledge, this is the first study to document Nec-1 sensitizes cancer cells to apoptosis.

  12. Royal jelly protects against ultraviolet B-induced photoaging in human skin fibroblasts via enhancing collagen production.

    Science.gov (United States)

    Park, Hye Min; Hwang, Eunson; Lee, Kwang Gill; Han, Sang-Mi; Cho, Yunhi; Kim, Sun Yeou

    2011-09-01

    Royal jelly (RJ) is a honeybee product containing proteins, carbohydrates, fats, free amino acids, vitamins, and minerals. As its principal unsaturated fatty acid, RJ contains 10-hydroxy-2-decenoic acid (10-HDA), which may have antitumor and antibacterial activity and a capacity to stimulate collagen production. RJ has attracted interest in various parts of the world for its pharmacological properties. However, the effects of RJ on ultraviolet (UV)-induced photoaging of the skin have not been reported. In this study we measured the 10-HDA content of RJ by high-performance liquid chromatography and tested the effects of RJ on UVB-induced skin photoaging in normal human dermal fibroblasts. The effects of RJ and 10-HDA on UVB-induced photoaging were tested by measuring procollagen type I, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)-1 after UVB irradiation. The RJ contained about 0.211% 10-HDA. The UVB-irradiated human skin fibroblasts treated with RJ and 10-HDA had increased procollagen type I and TGF-β1 productions, but the level of MMP-1 was not changed. Thus RJ may potentially protect the skin from UVB-induced photoaging by enhancing collagen production.

  13. RITA enhances chemosensivity of pre-B ALL cells to doxorubicin by inducing p53-dependent apoptosis.

    Science.gov (United States)

    Kazemi, Ahmad; Safa, Majid; Shahbazi, Atefeh

    2011-07-01

    The use of low-molecular-weight, non-peptidic molecules that disrupt the interaction between the p53 tumor suppressor and its negative regulator MDM2 has provided a promising alternative for the treatment of different types of cancer. Here, we used small-molecule reactivation of p53 and induction of tumor cell apoptosis (RITA) to sensitize leukemic NALM-6 cells to doxorubicin by upregulating p53 protein. RITA alone effectively inhibited NALM-6 cells viability in dose-dependent manner as measured by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay and induced apoptosis as evaluated by flow cytometry, whereas RITA in combination with doxorubicin enhanced NALM-6 cells to doxorubicin-sensitivity and promoted doxorubicin induced apoptosis. Levels of p53 protein and its proapoptotic target genes, quantified by western blot and real-time PCR respectively, showed that expression of p53 was significantly increased after RITA treatment. Using p53 inhibitors PFT-alpha and PFT-mu it was shown that p53-mediated apoptosis induced by RITA can be regulated by both p53-transcription-dependent and -independent pathways. Moreover, RITA-induced apoptosis was accompanied by the activation of caspase-3 and PARP cleavage. Therefore, exploiting synergistic effects between RITA and chemotherapeutics might be an effective clinical strategy for leukemia chemotherapy.

  14. Hyperthermia-enhanced TRAIL- and mapatumumab-induced apoptotic death is mediated through mitochondria in human colon cancer cells.

    Science.gov (United States)

    Song, Xinxin; Kim, Han-Cheon; Kim, Seog-Young; Basse, Per; Park, Bae-Hang; Lee, Byeong-Chel; Lee, Yong J

    2012-05-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world; death usually results from uncontrolled metastatic disease. Previously, we developed a novel strategy of TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) in combination with hyperthermia to treat hepatic colorectal metastases. However, previous studies suggest a potential hepatocyte cytotoxicity with TRAIL. Unlike TRAIL, anti-human TRAIL receptor antibody induces apoptosis without hepatocyte toxicity. In this study, we evaluated the anti-tumor efficacy of humanized anti-death receptor 4 (DR4) antibody mapatumumab (Mapa) by comparing it with TRAIL in combination with hyperthermia. TRAIL, which binds to both DR4 and death receptor 5 (DR5), was approximately tenfold more effective than Mapa in inducing apoptosis. However, hyperthermia enhances apoptosis induced by either agent. We observed that the synergistic effect was mediated through elevation of reactive oxygen species, c-Jun N-terminal kinase activation, Bax oligomerization, and translocalization to the mitochondria, loss of mitochondrial membrane potential, release of cytochrome c to cytosol, activation of caspases, and increase in poly(ADP-ribose) polymerase cleavage. We believe that the successful outcome of this study will support the application of Mapa in combination with hyperthermia to colorectal hepatic metastases. Copyright © 2011 Wiley Periodicals, Inc.

  15. Ionizing radiation-induced MEK and Erk activation does not enhance survival of irradiated human squamous carcinoma cells

    International Nuclear Information System (INIS)

    Bonner, James A.; Vroman, Benjamin T.; Christianson, Teresa J.H.; Karnitz, Larry M.

    1998-01-01

    Purpose: Ionizing radiation (IR) triggers several intracellular signaling cascades that have commonly been regarded as mitogenic, including the Raf-MEK-Erk kinase cascade. In addition to promoting proliferation, activated MEK and Erk may also prevent cell death induced by cytotoxic stimuli. Because Raf, MEK, and Erk are activated by IR in some tumor cell lines, this suggests that IR-induced activation of the kinase cascade may enhance the survival of irradiated cells. Methods and Materials: IR-induced activation of MEK and Erk was assessed in irradiated UM-SCC-6 cells, a human squamous carcinoma cell line. Activation of MEK and Erk was blocked with the pharmacological inhibitor of MEK activation, PD098059. Clonogenic survival was assessed in irradiated UM-SCC-6 cells that were pretreated with nothing or with the MEK inhibitor. Results: In UM-SCC-6 cells, IR doses as low as 2 Gy rapidly activated MEK and Erk. Pretreatment of the cells with the pharmacological inhibitor of MEK activation, PD098059, effectively blocked IR-induced activation of MEK and Erk. However, inhibition of the kinase cascade did not affect the clonogenic survival of irradiated cells in either early or delayed-plating experiments. Conclusion: Taken together, these results suggest that although MEK and Erk are rapidly activated by IR treatment, these protein kinases do not affect the clonogenic survival of irradiated UM-SCC6 cells

  16. Effects of the histamine H₃ receptor antagonist ABT-239 on cognition and nicotine-induced memory enhancement in mice.

    Science.gov (United States)

    Kruk, Marta; Miszkiel, Joanna; McCreary, Andrew C; Przegaliński, Edmund; Filip, Małgorzata; Biała, Grażyna

    2012-01-01

    The strong correlation between central histaminergic and cholinergic pathways on cognitive processes has been reported extensively. However, the role of histamine H(3) receptor mechanisms interacting with nicotinic mechanisms has not previously been extensively investigated. The current study was conducted to determine the interactions of nicotinic and histamine H(3) receptor systems with regard to learning and memory function using a modified elevated plus-maze test in mice. In this test, the latency for mice to move from the open arm to the enclosed arm (i.e., transfer latency) was used as an index of memory. We tested whether ABT-239 (4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl), an H(3) receptor antagonist/inverse agonist, had influence on two different stages of memory, i.e., memory acquisition and consolidation (administered prior to or immediately after the first trial, respectively) and whether ABT-239 influenced nicotine-induced memory enhancement. Our results revealed that the acute administration of nicotine (0.035 and 0.175 mg/kg), but not of ABT-239 (0.1-3 mg/kg) reduced transfer latency in the acquisition and consolidation phases. In combination studies, concomitant administration of either ABT-239 (1 and 3 mg/kg) and nicotine (0.035 mg/kg), or ABT-239 (0.1 mg/kg) and nicotine (0.0175 mg/kg) further increased nicotine-induced improvement in both memory acquisition and consolidation. The present data confirm an important role for H(3) receptors in regulating nicotine-induced mnemonic effects since inhibition of H(3) receptors augmented nicotine-induced memory enhancement in mice.

  17. Stress-induced enhancement of mouse amygdalar synaptic plasticity depends on glucocorticoid and ß-adrenergic activity.

    Directory of Open Access Journals (Sweden)

    Ratna Angela Sarabdjitsingh

    Full Text Available BACKGROUND: Glucocorticoid hormones, in interaction with noradrenaline, enable the consolidation of emotionally arousing and stressful experiences in rodents and humans. Such interaction is thought to occur at least partly in the basolateral nucleus of the amygdala (BLA which is crucially involved in emotional memory formation. Extensive evidence points to long-term synaptic potentiation (LTP as a mechanism contributing to memory formation. Here we determined in adolescent C57/Bl6 mice the effects of stress on LTP in the LA-BLA pathway and the specific roles of corticosteroid and β-adrenergic receptor activation in this process. PRINCIPAL FINDINGS: Exposure to 20 min of restraint stress (compared to control treatment prior to slice preparation enhanced subsequent LTP induction in vitro, without affecting baseline fEPSP responses. The role of glucocorticoid receptors, mineralocorticoid receptors and β2-adrenoceptors in the effects of stress was studied by treating mice with the antagonists mifepristone, spironolactone or propranolol respectively (or the corresponding vehicles prior to stress or control treatment. In undisturbed controls, mifepristone and propranolol administration in vivo did not influence LTP induced in vitro. By contrast, spironolactone caused a gradually attenuating form of LTP, both in unstressed and stressed mice. Mifepristone treatment prior to stress strongly reduced the ability to induce LTP in vitro. Propranolol normalized the stress-induced enhancement of LTP to control levels during the first 10 min after high frequency stimulation, after which synaptic responses further declined. CONCLUSIONS: Acute stress changes BLA electrical properties such that subsequent LTP induction is facilitated. Both β-adrenergic and glucocorticoid receptors are involved in the development of these changes. Mineralocorticoid receptors are important for the maintenance of LTP in the BLA, irrespective of stress-induced changes in the

  18. Deficiency of Smad7 enhances cardiac remodeling induced by angiotensin II infusion in a mouse model of hypertension.

    Directory of Open Access Journals (Sweden)

    Li Hua Wei

    Full Text Available Smad7 has been shown to negatively regulate fibrosis and inflammation, but its role in angiotensin II (Ang II-induced hypertensive cardiac remodeling remains unknown. Therefore, the present study investigated the role of Smad7 in hypertensive cardiopathy induced by angiotensin II infusion. Hypertensive cardiac disease was induced in Smad7 gene knockout (KO and wild-type (WT mice by subcutaneous infusion of Ang II (1.46 mg/kg/day for 28 days. Although equal levels of high blood pressure were developed in both Smad7 KO and WT mice, Smad7 KO mice developed more severe cardiac injury as demonstrated by impairing cardiac function including a significant increase in left ventricular (LV mass (P<0.01,reduction of LV ejection fraction(P<0.001 and fractional shortening(P<0.001. Real-time PCR, Western blot and immunohistochemistry detected that deletion of Smad7 significantly enhanced Ang II-induced cardiac fibrosis and inflammation, including upregulation of collagen I, α-SMA, interleukin-1β, TNF-α, and infiltration of CD3(+ T cells and F4/80(+ macrophages. Further studies revealed that enhanced activation of the Sp1-TGFβ/Smad3-NF-κB pathways and downregulation of miR-29 were mechanisms though which deletion of Smad7 promoted Ang II-mediated cardiac remodeling. In conclusions, Smad7 plays a protective role in AngII-mediated cardiac remodeling via mechanisms involving the Sp1-TGF-β/Smad3-NF.κB-miR-29 regulatory network.

  19. Enhancing inhibition-induced plasticity in tinnitus--spectral energy contrasts in tailor-made notched music matter.

    Directory of Open Access Journals (Sweden)

    Alwina Stein

    Full Text Available Chronic tinnitus seems to be caused by reduced inhibition among frequency selective neurons in the auditory cortex. One possibility to reduce tinnitus perception is to induce inhibition onto over-activated neurons representing the tinnitus frequency via tailor-made notched music (TMNM. Since lateral inhibition is modifiable by spectral energy contrasts, the question arises if the effects of inhibition-induced plasticity can be enhanced by introducing increased spectral energy contrasts (ISEC in TMNM. Eighteen participants suffering from chronic tonal tinnitus, pseudo randomly assigned to either a classical TMNM or an ISEC-TMNM group, listened to notched music for three hours on three consecutive days. The music was filtered for both groups by introducing a notch filter centered at the individual tinnitus frequency. For the ISEC-TMNM group a frequency bandwidth of 3/8 octaves on each side of the notch was amplified, additionally, by about 20 dB. Before and after each music exposure, participants rated their subjectively perceived tinnitus loudness on a visual analog scale. During the magnetoencephalographic recordings, participants were stimulated with either a reference tone of 500 Hz or a test tone with a carrier frequency representing the individual tinnitus pitch. Perceived tinnitus loudness was significantly reduced after TMNM exposure, though TMNM type did not influence the loudness ratings. Tinnitus related neural activity in the N1m time window and in the so called tinnitus network comprising temporal, parietal and frontal regions was reduced after TMNM exposure. The ISEC-TMNM group revealed even enhanced inhibition-induced plasticity in a temporal and a frontal cortical area. Overall, inhibition of tinnitus related neural activity could be strengthened in people affected with tinnitus by increasing spectral energy contrast in TMNM, confirming the concepts of inhibition-induced plasticity via TMNM and spectral energy contrasts.

  20. Ageing-induced enhancement of open porosity of mesoporous silica films studied by positron annihilation spectroscopy

    International Nuclear Information System (INIS)

    He Chunqing; Muramatsu, Makoto; Oshima, Nagayasu; Ohdaira, Toshiyuki; Kinomura, Atsushi; Suzuki, Ryoichi

    2006-01-01

    We show that ageing of the silica sol in a closed vessel enhanced the open porosity of calcined mesoporous silica film studied by positron. Positron annihilation lifetime spectroscopy (PALS) based on a pulsed slow positron beam was used to estimate the mesopore size. 2-dimensional PALS (2D-PALS) and ortho-positronium time-of-flight (Ps-TOF) were used to evaluate the open porosity, interconnectivity and tortuosity of mesopores in the silica films. Results revealed that little change in pore size but significant enhancement of open porosity and/or pore interconnectivity occurred in the silica film deposited after the precursor solution aged for a relative longer time

  1. Realistic-contact-induced enhancement of rectifying in carbon-nanotube/graphene-nanoribbon junctions

    International Nuclear Information System (INIS)

    Zhang, Xiang-Hua; Li, Xiao-Fei; Wang, Ling-Ling; Xu, Liang; Luo, Kai-Wu

    2014-01-01

    Carbon-nanotube/graphene-nanoribbon junctions were recently fabricated by the controllable etching of single-walled carbon-nanotubes [Wei et al., Nat. Commun. 4, 1374 (2013)] and their electronic transport properties were studied here. First principles results reveal that the transmission function of the junctions show a heavy dependence on the shape of contacts, but rectifying is an inherent property which is insensitive to the details of contacts. Interestingly, the rectifying ratio is largely enhanced in the junction with a realistic contact and the enhancement is insensitive to the details of contact structures. The stability of rectifying suggests a significant feasibility to manufacture realistic all-carbon rectifiers in nanoelectronics

  2. Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.

    Science.gov (United States)

    Su, W-Y; Cong, W-W; Shu, Y-J; Wang, D; Xu, G-H; Guo, C-H

    2013-07-08

    The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat.

  3. Improving contrast enhancement in magnetic resonance imaging using 5-aminolevulinic acid-induced protoporphyrin IX for high-grade gliomas.

    Science.gov (United States)

    Yamamoto, Junkoh; Kakeda, Shingo; Yoneda, Tetsuya; Ogura, Shun-Ichiro; Shimajiri, Shohei; Tanaka, Tohru; Korogi, Yukunori; Nishizawa, Shigeru

    2017-03-01

    Magnetic resonance imaging (MRI) with a gadolinium-based contrast agent is the gold standard for high-grade gliomas (HGGs). The compound 5-aminolevulinic acid (5-ALA) undergoes a high rate of cellular uptake, particularly in cancer cells. In addition, fluorescence-guided resection with 5-ALA is widely used for imaging HGGs. 5-ALA is water soluble, while protoporphyrin IX (PpIX) is water insoluble. It was speculated whether converting from 5-ALA to PpIX may relatively increase intracellular water content, and consequently, might enhance the T2 signal intensity in HGG. The aim of the present study was to assess whether 5-ALA-induced PpIX enhances the T2 signal intensity in patients with HGGs. A total of 4 patients who were candidates for HGG surgical treatment were prospectively analyzed with preoperative MRI. Patients received oral doses of 5-ALA (20 mg/kg) 3 h prior to anesthesia. At 2.5 h post-5-ALA administration, T2-weighted images (T2WIs) were obtained from all patients. Subsequently, tumors were evaluated via fluorescence using a modified operating microscope. Fluorescent tumor tissues were obtained to analyze the accumulation of 5-ALA-induced PpIX within the tumors, which was confirmed quantitatively by high-performance liquid chromatography (HPLC) analysis. The MRI T2 signal intensity within the tumors was evaluated prior to and following 5-ALA administration. Three glioblastoma multiformes (GBMs) and 1 anaplastic oligodendroglioma (AO) were included in the analysis. Intraoperatively, all GBMs exhibited strong fluorescence of 5-ALA-induced PpIX, whilst no fluorescence was observed in the AO sample. HPLC analysis indicated a higher accumulation of 5-ALA-induced PpIX in the GBM samples compared with the AO sample. In total, 48 regions of interest were identified within the tumors from T2-WIs. In the GBM group, the relative T2 signal intensity value within the tumors following 5-ALA administration was significantly increased compared with the T2 signal

  4. An AP-2 element acts synergistically with the cyclic AMP- and Phorbol ester-inducible enhancer of the human proenkephalin gene

    Energy Technology Data Exchange (ETDEWEB)

    Hyman, S.E.; Comb, M.; Pearlberg, J.; Goodman, H.M.

    1989-01-01

    An enhancer with two DNA elements, one containing the sequence CGTCA, is required for cyclic AMP-and phorbol ester-inducible transcription of the human proenkephalin gene. The authors report that an AP-2 element located adjacent to the enhancer acts synergistically with it to confer maximal response to cyclic AMP and phorbol esters.

  5. Optimized spacer layer thickness for plasmonic-induced enhancement of photocurrent in a-Si:H

    Energy Technology Data Exchange (ETDEWEB)

    Saleh, Z. M., E-mail: zaki.saleh@aauj.edu, E-mail: zakimsaleh@yahoo.com; Nasser, H.; Özkol, E.; Günöven, M.; Abak, K. [Middle East Technical University, Center for Solar Energy Research and Applications (GÜNAM) (Turkey); Canli, S. [Middle East Technical University, Central Laboratory (Turkey); Bek, A.; Turan, R. [Middle East Technical University, Center for Solar Energy Research and Applications (GÜNAM) (Turkey)

    2015-10-15

    Plasmonic interfaces consisting of silver nanoparticles of different sizes (50–100 nm) have been processed by the self-assembled dewetting technique and integrated to hydrogenated amorphous silicon (a-Si:H) using SiNx spacer layers to investigate the dependence of optical trapping enhancement on spacer layer thickness through the enhancements in photocurrent. Samples illuminated from the a-Si:H side exhibit a localized surface plasmon resonance (LSPR) that is red-shifted with the increasing particle size and broadened into the red with the increasing spacer layer thickness. The photocurrent measured in a-Si:H is not only consistent with the red-shift and broadening of the LSPR, but exhibits critical dependence on the spacer layer thickness also. The samples with plasmonic interfaces and a SiNx spacer layer exhibit appreciable enhancement of photocurrent compared with flat a-Si:H reference depending on the size of the Ag nanoparticle. Simulations conducted on one-dimensional square structures exhibit electric fields that are localized near the plasmonic structures but extend appreciably into the higher refractive index a-Si:H. These simulations produce a clear red-shift and broadening of extinction spectra for all spacer layer thicknesses and predict an enhancement in photocurrent in agreement with experimental results. The spectral dependence of photocurrent for six plasmonic interfaces with different Ag nanoparticle sizes and spacer layer thicknesses are correlated with the optical spectra and compared with the simulations to predict an optimal spacer layer thickness.

  6. Bubble induced flow field modulation for pool boiling enhancement over a tubular surface

    Science.gov (United States)

    Raghupathi, P. A.; Joshi, I. M.; Jaikumar, A.; Emery, T. S.; Kandlikar, S. G.

    2017-06-01

    We demonstrate the efficacy of using a strategically placed enhancement feature to modify the trajectory of bubbles nucleating on a horizontal tubular surface to increase both the critical heat flux (CHF) and the heat transfer coefficient (HTC). The CHF on a plain tube is shown to be triggered by a local dryout at the bottom of the tube due to vapor agglomeration. To mitigate this effect and delay CHF, the nucleating bubble trajectory is modified by incorporating a bubble diverter placed axially at the bottom of the tube. The nucleating bubble at the base of the diverter experiences a tangential evaporation momentum force (EMF) which causes the bubble to grow sideways away from the tube and avoid localized bubble patches that are responsible for CHF initiation. High speed imaging confirmed the lateral displacement of the bubbles away from the diverter closely matched with the theoretical predictions using EMF and buoyancy forces. Since the EMF is stronger at higher heat fluxes, bubble displacement increases with heat flux and results in the formation of separate liquid-vapor pathways wherein the liquid enters almost unobstructed at the bottom and the vapor bubble leaves sideways. Experimental results yielded CHF and HTC enhancements of ˜60% and ˜75%, respectively, with the diverter configuration when compared to a plain tube. This work can be used for guidance in developing enhancement strategies to effectively modulate the liquid-vapor flow around the heater surface at various locations to enhance HTC and CHF.

  7. Celecoxib-Induced Self-Assembly of Smart Albumin-Doxorubicin Conjugate for Enhanced Cancer Therapy.

    Science.gov (United States)

    Shi, Leilei; Xu, Li; Wu, Chenwei; Xue, Bai; Jin, Xin; Yang, Jiapei; Zhu, Xinyuan

    2018-03-14

    Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.

  8. Measurement Induced Enhancement of Squeezing in Nondegenerate Two-Photon Jaynes-Cummings Model

    International Nuclear Information System (INIS)

    Ye Saiyun

    2006-01-01

    Squeezing properties in the nondegenerate two-photon Jaynes-Cummings model are investigated. The effects of direct selective atomic measurement and the application of the classical field followed by atomic measurement are analyzed. Different values of the parameters of the classical field are taken into account. It is found that the field squeezing can be enhanced by measurement.

  9. A novel serine protease secreted by medicinal maggots enhances plasminogen activator-induced fibrinolysis

    DEFF Research Database (Denmark)

    van der Plas, Mariena J A; Andersen, Anders S; Nazir, Sheresma

    2014-01-01

    Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As haemostatic processes play an important role in wound healing, this study focused on the effects of maggot secretions on coagulation and fibrinolysis. The results showed that maggot secretions enhance plasmin...

  10. CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes

    NARCIS (Netherlands)

    Hasegawa, Yuki; Tang, Dave; Takahashi, Naoko; Hayashizaki, Yoshihide; Forrest, Alistair R R; Suzuki, Harukazu; Clevers, Hans

    2014-01-01

    Standard culture of human induced pluripotent stem cells (hiPSCs) requires basic Fibroblast Growth Factor (bFGF) to maintain the pluripotent state, whereas hiPSC more closely resemble epiblast stem cells than true naïve state ES which requires LIF to maintain pluripotency. Here we show that

  11. Inducible hydrogenase in cyanobacteria enhances N/sub 2/ fixation. [Nostoc, anabaena

    Energy Technology Data Exchange (ETDEWEB)

    Tel-Or, E.; Luijk, L.W.; Packer, L.

    1977-06-01

    Whether hydrogenase is activated or induced, we found no evidence for activation of either consumption or production of H/sub 2/ in aerobically-grown cultures but both of these activities increased 5--20-fold when cultures are grown under H/sub 2/ gas. On the other hand, hydrogenase-catalyzed consumption of H/sub 2/ is stimulated by light and/or light plus CO/sub 2/ in hydrogenase-induced cultures. Nitrogenase activity appears to be induced in cultures grown under H/sub 2/. Studies unambiguously establish that in H/sub 2/-induced cultures hydrogenase manifests a cooperativity with nitrogenase. In the presence of H/sub 2/ the activity of nitrogenase is stimulated 3--5-fold such that rates of about 3 ..mu..mol N/sub 2/ fixed/mg chlorophyll/h are obtained if the method of Peterson and Burris is used to convert acetylene reduction data to equivalents of /sup 15/N/sub 2/ fixation to ammonia.

  12. Green Tea Catechin Consumption Enhances Exercise-Induced Abdominal Fat Loss

    Science.gov (United States)

    Aim: This study evaluated the influence of a green tea catechin beverage on body composition and fat distribution in overweight and obese adults during exercised-induced weight loss. Methods: Participants (N=132) were randomly assigned to receive a 500 mL beverage containing approximately 625 mg of...

  13. Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation.

    Science.gov (United States)

    Shao, Genbao; Lai, Wensheng; Wan, Xiaolei; Xue, Jing; Wei, Ye; Jin, Jie; Zhang, Liuping; Lin, Qiong; Shao, Qixiang; Zou, Shengqiang

    2017-05-01

    Ovarian tumor is one of the most lethal gynecologic cancers, but differentiation therapy for this cancer is poorly characterized. Here, we show that thrichostatin A (TSA), the well known inhibitor of histone deacetylases (HDACs), can induce cell differentiation in HO8910 ovarian cancer cells. TSA-induced cell differentiation is characterized by typical morphological change, increased expression of the differentiation marker FOXA2, decreased expression of the pluripotency markers SOX2 and OCT4, suppressing cell proliferation, and cell cycle arrest in the G1 phase. TSA also induces an elevated expression of cell cycle inhibitory protein p21Cip1 along with a decrease in cell cycle regulatory protein cyclin D1. Significantly, blockage of epidermal growth factor receptor (EGFR) signaling pathway with specific inhibitors of this signaling cascade promotes the TSA-induced differentiation of HO8910 cells. These results imply that the EGFR cascade inhibitors in combination with TSA may represent a promising differentiation therapy strategy for ovarian cancer.

  14. Enhanced 15-HPETE production during oxidant stress induces apoptosis of endothelial cells.

    Science.gov (United States)

    Sordillo, Lorraine M; Weaver, James A; Cao, Yu-Zhang; Corl, Chris; Sylte, Matt J; Mullarky, Isis K

    2005-05-01

    Oxidant stress plays an important role in the etiology of vascular diseases by increasing rates of endothelial cell apoptosis, but few data exist on the mechanisms involved. Using a unique model of oxidative stress based on selenium deficiency (-Se), the effects of altered eicosanoid production on bovine aortic endothelial cells (BAEC) apoptosis was evaluated. Oxidant stress significantly increased the immediate oxygenation product of arachidonic acid metabolized by the 15-lipoxygenase pathway, 15-hydroxyperoxyeicosatetraenoic acid (15-HPETE). Treatment of -Se BAEC with TNFalpha/cyclohexamide (CHX) exhibited elevated levels of apoptosis, which was significantly reduced by the addition of a specific 15-lipoxygenase inhibitor PD146176. Furthermore, the addition of 15-HPETE to PD146176-treated BAEC, partially restored TNF/CHX-induced apoptosis. Increased exposure to 15-HPETE induced apoptosis, as determined by internucleosomal DNA fragmentation, chromatin condensation, caspase-3 activation, and caspase-9 activation, which suggests mitochondrial dysfunction. The expression of Bcl-2 protein also was decreased in -Se BAEC. Addition of a caspase-9 inhibitor (LEHD-fmk) completely blocked 15-HPETE-induced chromatin condensation in -Se BAEC, suggesting that 15-HPETE-induced apoptosis is caspase-9 dependent. Increased apoptosis of BAEC as a result of oxidant stress and subsequent production of 15-HPETE may play a critical role in a variety of inflammatory based diseases.

  15. Aggregation induced enhancement of linear and nonlinear optical emission from a hexaphenylene derivative

    NARCIS (Netherlands)

    Duan, Y.; Ju, C.G.; Yang, G.; Fron, E.; Coutino-Gonzalez, E.; Semin, S.V.; Fan, C.C.; Balok, R.S.; Cremers, J.; Tinnemans, P.T.; Feng, Y.Q.; Li, Y.L.; Hofkens, J.; Rowan, A.E.; Rasing, T.H.M.; Xu, J.L.

    2016-01-01

    The discovery of the phenomenon known as aggregation-induced emission (AIE) has opened the door to a variety of brilliant organic solid-state light-emitting materials. While AIE is well established in linear optics, the development of AIE luminogens (AIEgens) with highly efficient nonlinear optical

  16. Myths and facts on wastewater injection, hydraulic fracturing, enhanced oil recovery, and induced seismicity

    Science.gov (United States)

    Rubinstein, Justin L.; Mahani, Alireza Babaie

    2015-01-01

    The central United States has undergone a dramatic increase in seismicity over the past 6 years (Fig. 1), rising from an average of 24 M≥3 earthquakes per year in the years 1973–2008 to an average of 193 M≥3 earthquakes in 2009–2014, with 688 occurring in 2014 alone. Multiple damaging earthquakes have occurred during this increase including the 2011 M 5.6 Prague, Oklahoma, earthquake; the 2011 M 5.3 Trinidad, Colorado, earthquake; and the 2011M 4.7 Guy‐Greenbrier, Arkansas, earthquake. The increased seismicity is limited to a few areas and the evidence is mounting that the seismicity in many of these locations is induced by the deep injection of fluids from nearby oil and gas operations. Earthquakes that are caused by human activities are known as induced earthquakes. Most injection operations, though, do not appear to induce earthquakes. Although the message that these earthquakes are induced by fluid injection related to oil and gas production has been communicated clearly, there remains confusion in the popular press beyond this basic level of understanding.

  17. Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

    NARCIS (Netherlands)

    Vroman, Rozan; Kamermans, M.

    2015-01-01

    KEY POINTS: In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the

  18. Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

    NARCIS (Netherlands)

    Vroman, Rozan; Kamermans, Maarten

    2015-01-01

    In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the glutamate

  19. Hydrostatic pressure enhances mitomycin C induced apoptosis in urothelial carcinoma cells.

    Science.gov (United States)

    Chen, Shao-Kuan; Chung, Chih-Ang; Cheng, Yu-Che; Huang, Chi-Jung; Ruaan, Ruoh-Chyu; Chen, Wen-Yih; Li, Chuan; Tsao, Chia-Wen; Hu, Wei-Wen; Chien, Chih-Cheng

    2014-01-01

    Urothelial carcinoma (UC) of the bladder is the second most common cancer of the genitourinary system. Clinical UC treatment usually involves transurethral resection of the bladder tumor followed by adjuvant intravesical immunotherapy or chemotherapy to prevent recurrence. Intravesical chemotherapy induces fewer side effects than immunotherapy but is less effective at preventing tumor recurrence. Improvement to intravesical chemotherapy is, therefore, needed. Cellular effects of mitomycin C (MMC) and hydrostatic pressure on UC BFTC905 cells were assessed. The viability of the UC cells was determined using cellular proliferation assay. Changes in apoptotic function were evaluated by caspase 3/7 activities, expression of FasL, and loss of mitochondrial membrane potential. Reduced cell viability was associated with increasing hydrostatic pressure. Caspase 3/7 activities were increased following treatment of the UC cells with MMC or hydrostatic pressure. In combination with 10 kPa hydrostatic pressure, MMC treatment induced increasing FasL expression. The mitochondria of UC cells displayed increasingly impaired membrane potentials following a combined treatment with 10 μg/ml MMC and 10 kPa hydrostatic pressure. Both MMC and hydrostatic pressure can induce apoptosis in UC cells through an extrinsic pathway. Hydrostatic pressure specifically increases MMC-induced apoptosis and might minimize the side effects of the chemotherapy by reducing the concentration of the chemical agent. This study provides a new and alternative approach for treatment of patients with UC following transurethral resection of the bladder tumor. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. RSK2-induced stress tolerance enhances cell survival signals mediated by inhibition of GSK3β activity

    International Nuclear Information System (INIS)

    Lee, Cheol-Jung; Lee, Mee-Hyun; Lee, Ji-Young; Song, Ji Hong; Lee, Hye Suk; Cho, Yong-Yeon

    2013-01-01

    Highlights: •We demonstrated a novel function of RSK2 in stress tolerance. •RSK2 deficiency enhanced apoptosis by calcium stress. •RSK2-mediated GSK3β phosphorylation at serine 9 increased calcium-induced stress tolerance. •Calcium stress-induced apoptosis inhibited by adding back of RSK2 into RSK2 −/− MEFs. -- Abstract: Our previous studies demonstrated that RSK2 plays a key role in cell proliferation and transformation induced by tumor promoters such as epidermal growth factor (EGF) in mouse and human skin cells. However, no direct evidence has been found regarding the relationship of RSK2 and cell survival. In this study, we found that RSK2 interacted and phosphorylated GSK3β at Ser9. Notably, GSK3β phosphorylation at Ser9 was suppressed in RSK2 −/− MEFs compared with RSK2 +/+ MEFs by stimulation of EGF and calcium ionophore A23187, a cellular calcium stressor. In proliferation, we found that RSK2 deficiency suppressed cell proliferation compared with RSK2 +/+ MEFs. In contrast, GSK3β −/− MEFs induced the cell proliferation compared with GSK3β +/+ MEFs. Importantly, RSK2 −/− MEFs were induced severe cellular morphology change by A23187 and enhanced G1/G0 and sub-G1 accumulation of the cell cycle phase compared with RSK2 +/+ MEFs. The sub-G1 induction in RSK2 −/− MEFs by A23187 was correlated with increase of cytochrome c release, caspase-3 cleavage and apoptotic DNA fragmentation compared with RSK2 +/+ MEFs. Notably, return back of RSK2 into RSK2 −/− MEFs restored A23187-induced morphological change, and decreased apoptosis, apoptotic DNA fragmentation and caspase-3 induction compared with RSK2 −/− /mock MEFs. Taken together, our results demonstrated that RSK2 plays an important role in stress-tolerance and cell survival, resulting in cell proliferation and cancer development

  1. Enhanced Chondrocyte Proliferation in a Prototyped Culture System with Wave-Induced Agitation

    Directory of Open Access Journals (Sweden)

    Pilarek Maciej

    2017-06-01

    Full Text Available One of the actual challenges in tissue engineering applications is to efficiently produce as high of number of cells as it is only possible, in the shortest time. In static cultures, the production of animal cell biomass in integrated forms (i.e. aggregates, inoculated scaffolds is limited due to inefficient diffusion of culture medium components observed in such non-mixed culture systems, especially in the case of cell-inoculated fiber-based dense 3D scaffolds, inside which the intensification of mass transfer is particularly important. The applicability of a prototyped, small-scale, continuously wave-induced agitated system for intensification of anchorage-dependent CP5 chondrocytes proliferation outside and inside three-dimensional poly(lactic acid (PLA scaffolds has been discussed. Fibrous PLA-based constructs have been inoculated with CP5 cells and then maintained in two independent incubation systems: (i non-agitated conditions and (ii culture with wave-induced agitation. Significantly higher values of the volumetric glucose consumption rate have been noted for the system with the wave-induced agitation. The advantage of the presented wave-induced agitation culture system has been confirmed by lower activity of lactate dehydrogenase (LDH released from the cells in the samples of culture medium harvested from the agitated cultures, in contrast to rather high values of LDH activity measured for static conditions. Results of the proceeded experiments and their analysis clearly exhibited the feasibility of the culture system supported with continuously wave-induced agitation for robust proliferation of the CP5 chondrocytes on PLA-based structures. Aside from the practicability of the prototyped system, we believe that it could also be applied as a standard method offering advantages for all types of the daily routine laboratory-scale animal cell cultures utilizing various fiber-based biomaterials, with the use of only regular laboratory

  2. In situ transmission electron microscope studies of ion irradiation-induced and irradiation-enhanced phase changes

    International Nuclear Information System (INIS)

    Allen, C.W.

    1992-01-01

    Motivated at least initially by materials needs for nuclear reactor development, extensive irradiation effects studies employing transmission electron microscopes (TEM) have been performed for several decades, involving irradiation-induced and irradiation-enhanced microstructural changes, including phase transformations such as precipitation, dissolution, crystallization, amorphization, and order-disorder phenomena. From the introduction of commercial high voltage electron microscopes (HVEM) in the mid-1960s, studies of electron irradiation effects have constituted a major aspect of HVEM application in materials science. For irradiation effects studies two additional developments have had particularly significant impact; the development of TEM specimen holder sin which specimen temperature can be controlled in the range 10-2200 K and the interfacing of ion accelerators which allows in situ TEM studies of irradiation effects and the ion beam modification of materials within this broad temperature range. This paper treats several aspects of in situ studies of electron and ion beam-induced and enhanced phase changes and presents two case studies involving in situ experiments performed in an HVEM to illustrate the strategies of such an approach of the materials research of irradiation effects

  3. Kazinol Q from Broussonetia kazinoki Enhances Cell Death Induced by Cu(ll through Increased Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Hsue-Yin Hsu

    2011-04-01

    Full Text Available The ability of the flavan kazinol Q (KQ to induce DNA breakage in the presence of Cu(II was examined by agarose gel electrophoresis using supercoiled plasmid DNA. In KQ-mediated DNA breakage reaction, the involvement of reactive oxygen species (ROS, H2O2 and O2 - was established by the inhibition of DNA breakage by catalase and revealed DNA breakage by superoxide dismutase (SOD. The cell viability of gastric carcinoma SCM-1 cells treated with various concentrations of KQ was significantly decreased by cotreatment with Cu(II. Treatment of SCM-1 cells with 300 μM Cu(II enhanced the necrosis induced by 100 μM KQ. Treatment of SCM-1 cells with 100 mM KQ in the presence of 300 mM Cu(II increased the generation of H2O2. Taken together, the above finding suggested that KQ cotreatment with Cu(II produced increased amounts of H2O2, thus enhancing subsequent cell death due to necrosis.

  4. Enhancement and stabilization of plasma using collinear long-short double-pulse laser-induced breakdown spectroscopy

    Science.gov (United States)

    Cui, Minchao; Deguchi, Yoshihiro; Wang, Zhenzhen; Fujita, Yuki; Liu, Renwei; Shiou, Fang-Jung; Zhao, Shengdun

    2018-04-01

    A collinear long-short dual-pulse laser-induced breakdown spectroscopy (DP-LIBS) method was employed to enhance and stabilize the laser-induced plasma from steel sample. The long-pulse-width laser beam with the pulse width of 60 μs was generated by a Nd: YAG laser which was operated at FR (free running) mode. The comparative experiments were carried out between single pulse LIBS (SP-LIBS) and long-short DP-LIBS. The recorded results showed that the emission intensities and the temperature of plasma were enhanced by long-short DP-LIBS. The plasma images showed that the plasma was bigger and had a longer lifetime in long-short DP-LIBS situation. Through the calculation of time-resolved plasma temperature and intensity ratio, it can be concluded that the plasma was stabilized by the long-pulse-width laser beam. The long-short DP-LIBS method also generated the stable plasma condition from the samples with different initial temperatures, which overcame the difficulties of LIBS in the online measurement for steel production line.

  5. Light-induced retinal injury enhanced neurotrophins secretion and neurotrophic effect of mesenchymal stem cells in vitro

    Directory of Open Access Journals (Sweden)

    Wei Xu

    2013-04-01

    Full Text Available PURPOSE: To investigate neurotrophins expression and neurotrophic effect change in mesenchymal stem cells (MSCs under different types of stimulation. METHODS: Rats were exposed in 10,000 lux white light to develop light-induced retinal injury. Supernatants of homogenized retina (SHR, either from normal or light-injured retina, were used to stimulate MSCs. Quantitative real time for polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA were conducted for analysis the expression change in basic fibroblast growth factor (bFGF, brain-derived neurotrophic factor (BDNF and ciliary neurotrophic factor (CNTF in MSCs after stimulation. Conditioned medium from SHR-stimulated MSCs and control MSCs were collected for evaluation their effect on retinal explants. RESULTS: Supernatants of homogenized retina from light-injured rats significantly promoted neurotrophins secretion from MSCs (p<0.01. Conditioned medium from mesenchymal stem cells stimulated by light-injured SHR significantly reduced DNA fragmentation (p<0.01, up-regulated bcl-2 (p<0.01 and down-regulated bax (p<0.01 in retinal explants, displaying enhanced protective effect. CONCLUSIONS: Light-induced retinal injury is able to enhance neurotrophins secretion from mesenchymal stem cells and promote the neurotrophic effect of mesenchymal stem cells.

  6. Inhibition of histone deacetylases 1 and 6 enhances cytarabine-induced apoptosis in pediatric acute myeloid leukemia cells.

    Science.gov (United States)

    Xu, Xuelian; Xie, Chengzhi; Edwards, Holly; Zhou, Hui; Buck, Steven A; Ge, Yubin

    2011-02-16

    Pediatric acute myeloid leukemia (AML) remains a challenging disease to treat even with intensified cytarabine-based chemotherapy. Histone deacetylases (HDACs) have been reported to be promising therapeutic targets for treating AML. However, HDAC family members that are involved in chemotherapy sensitivities remain unknown. In this study, we sought to identify members of the HDAC family that are involved in cytarabine sensitivities, and to select the optimal HDACI that is most efficacious when combined with cytarabine for treating children with AML. Expression profiles of classes I, II, and IV HDACs in 4 pediatric AML cell lines were determined by Western blotting. Inhibition of class I HDACs by different HDACIs was measured post immnunoprecipitation. Individual down-regulation of HDACs in pediatric AML cells was performed with lentiviral shRNA. The effects of cytarabine and HDACIs on apoptosis were determined by flow cytometry analysis. Treatments with structurally diverse HDACIs and HDAC shRNA knockdown experiments revealed that down-regulation of both HDACs 1 and 6 is critical in enhancing cytarabine-induced apoptosis in pediatric AML, at least partly mediated by Bim. However, down-regulation of HDAC2 may negatively impact cytarabine sensitivities in the disease. At clinically achievable concentrations, HDACIs that simultaneously inhibited both HDACs 1 and 6 showed the best anti-leukemic activities and significantly enhanced cytarabine-induced apoptosis. Our results further confirm that HDACs are bona fide therapeutic targets for treating pediatric AML and suggest that pan-HDACIs may be more beneficial than isoform-specific drugs.

  7. Enhancing performance of a motor imagery based brain-computer interface by incorporating electrical stimulation-induced SSSEP

    Science.gov (United States)

    Yi, Weibo; Qiu, Shuang; Wang, Kun; Qi, Hongzhi; Zhao, Xin; He, Feng; Zhou, Peng; Yang, Jiajia; Ming, Dong

    2017-04-01

    Objective. We proposed a novel simultaneous hybrid brain-computer interface (BCI) by incorporating electrical stimulation into a motor imagery (MI) based BCI system. The goal of this study was to enhance the overall performance of an MI-based BCI. In addition, the brain oscillatory pattern in the hybrid task was also investigated. Approach. 64-channel electroencephalographic (EEG) data were recorded during MI, selective attention (SA) and hybrid tasks in fourteen healthy subjects. In the hybrid task, subjects performed MI with electrical stimulation which was applied to bilateral median nerve on wrists simultaneously. Main results. The hybrid task clearly presented additional steady-state somatosensory evoked potential (SSSEP) induced by electrical stimulation with MI-induced event-related desynchronization (ERD). By combining ERD and SSSEP features, the performance in the hybrid task was significantly better than in both MI and SA tasks, achieving a ~14% improvement in total relative to the MI task alone and reaching ~89% in mean classification accuracy. On the contrary, there was no significant enhancement obtained in performance while separate ERD feature was utilized in the hybrid task. In terms of the hybrid task, the performance using combined feature was significantly better than using separate ERD or SSSEP feature. Significance. The results in this work validate the feasibility of our proposed approach to form a novel MI-SSSEP hybrid BCI outperforming a conventional MI-based BCI through combing MI with electrical stimulation.

  8. Arsenic-induced nutrient uptake in As-hyperaccumulator Pteris vittata and their potential role to enhance plant growth.

    Science.gov (United States)

    Liu, Xue; Feng, Hua-Yuan; Fu, Jing-Wei; Chen, Yanshan; Liu, Yungen; Ma, Lena Q

    2018-05-01

    It is known that arsenic (As) promotes growth of As-hyperaccumulator Pteris vittata (PV), however, the associated mechanisms are unclear. Here we examined As-induced nutrient uptake in P. vittata and their potential role to enhance plant growth in sterile agar by excluding microbial effects. As-hyperaccumulator P. multifida (PM) and non-hyperaccumulator P. ensiformis (PE) belonging to the Pteris genus were used as comparisons. The results showed that, after 40 d of growth, As induced biomass increase in hyperaccumulators PV and PM by 5.2-9.4 fold whereas it caused 63% decline in PE. The data suggested that As played a beneficial role in promoting hyperaccumulator growth. In addition, hyperaccumulators PV and PM accumulated 7.5-13, 1.4-3.6, and 1.8-4.4 fold more As, Fe, and P than the non-hyperaccumulator PE. In addition, nutrient contents such as K and Zn were also increased while Ca, Mg, and Mn decreased or unaffected under As treatment. This study demonstrated that As promoted growth in hyperaccumulators and enhanced Fe, P, K, and Zn uptake. Different plant growth responses to As among hyperaccumulators PV and PM and non-hyperaccumulator PE may help to better understand why hyperaccumulators grow better under As-stress. Published by Elsevier Ltd.

  9. Biotin enhances ATP synthesis in pancreatic islets of the rat, resulting in reinforcement of glucose-induced insulin secretion.

    Science.gov (United States)

    Sone, Hideyuki; Sasaki, Yuka; Komai, Michio; Toyomizu, Masaaki; Kagawa, Yasuo; Furukawa, Yuji

    2004-02-13

    Previous studies showed that biotin enhanced glucose-induced insulin secretion. Changes in the cytosolic ATP/ADP ratio in the pancreatic islets participate in the regulation of insulin secretion by glucose. In the present study we investigated whether biotin regulates the cytosolic ATP/ADP ratio in glucose-stimulated islets. When islets were stimulated with glucose plus biotin, the ATP/ADP ratio increased to approximately 160% of the ATP/ADP ratio in islets stimulated with glucose alone. The rate of glucose oxidation, assessed by CO(2) production, was also about 2-fold higher in islets treated with biotin. These increasing effects of biotin were proportional to the effects seen in insulin secretion. There are no previous reports of vitamins, such as biotin, directly affecting ATP synthesis. Our data indicate that biotin enhances ATP synthesis in islets following the increased rate of substrate oxidation in mitochondria and that, as a consequence of these events, glucose-induced insulin release is reinforced by biotin.

  10. Do Anesthetic Techniques Influence the Threshold for Glomerular Capillary Hemorrhage Induced in Rats by Contrast-Enhanced Diagnostic Ultrasound?

    Science.gov (United States)

    Miller, Douglas L; Lu, Xiaofang; Fabiilli, Mario; Dou, Chunyan

    2016-02-01

    Glomerular capillary hemorrhage can be induced by ultrasonic cavitation during contrast-enhanced diagnostic ultrasound (US) exposure, an important nonthermal US bioeffect. Recent studies of pulmonary US exposure have shown that thresholds for another nonthermal bioeffect of US, pulmonary capillary hemorrhage, is strongly influenced by whether xylazine is included in the specific anesthetic technique. The objective of this study was to determine the influence of xylazine on contrast-enhanced diagnostic US-induced glomerular capillary hemorrhage. In this study, anesthesia with ketamine only was compared to ketamine plus xylazine for induction of glomerular capillary hemorrhage in rats by 1.6-MHz intermittent diagnostic US with a microsphere contrast agent (similar to Definity; Lantheus Medical Imaging, Inc, North Billerica, MA). Glomerular capillary hemorrhage was measured as a percentage of glomeruli with hemorrhage found in histologic sections for groups of rats scanned at different peak rarefactional pressure amplitudes. There was a significant difference between the magnitude of the glomerular capillary hemorrhage between the anesthetics at 2.3 MPa, with 45.6% hemorrhage for ketamine only, increasing to 63.2% hemorrhage for ketamine plus xylazine (P Ultrasound in Medicine.

  11. Enhancement of antigen-induced eosinophilic inflammation in the airways of mast-cell deficient mice by diesel exhaust particles

    International Nuclear Information System (INIS)

    Ichinose, Takamichi; Takano, Hirohisa; Miyabara, Yuichi; Sadakaneo, Kaori; Sagai, Masaru; Shibamoto, Takayuki

    2002-01-01

    The present study was conducted to clarify the involvement of mast cells in the exacerbating effect of diesel exhaust particles (DEP) toward allergic airway inflammation and airway hyperresponsiveness (AHR). Airway inflammation by the infiltration of cosinophils with goblet cell proliferation and AHR, as well as by the production of antigen-specific IgG1 and IgE, in plasma were examined using mast cell-deficient mice (W/W v ) and normal mice (W/W + ). Both groups of mice received ovalbumin (OVA) or OVA+DEP intratracheally. The eosinophilic airway inflammation and goblet cell proliferation promoted by OVA were significantly greater in W/W + than in W/W v . A similar result was observed in AHR, but was not significant among both groups of mice. DEP enhanced OVA induced-allergic airway inflammation, goblet cell proliferation, and development of AHR in W/W v , but not in W/W + . DEP decreased production of antigen-specific IgG1 and IgE in both groups of mice. Mast cells were observed in the submucosal layer of the main bronchus in W/W v . The number of mast cells was significantly decreased by OVA treatment. The results indicate that mast cells are not necessary to enhance airway damage and development of AHR in W/W v by DEP. However, mast cells may be required for the OVA-induced cosinophilic inflammation, airway damage with goblet cell proliferation, and AHR in W/W +

  12. MicroRNA-661 Enhances TRAIL or STS Induced Osteosarcoma Cell Apoptosis by Modulating the Expression of Cytochrome c1

    Directory of Open Access Journals (Sweden)

    Lin Fan

    2017-04-01

    Full Text Available Aim: Osteosarcoma (OS is an aggressive bone malignancy that affects rapidly growing bones and is associated with a poor prognosis. Our previous study showed that cytochrome c1 (CYC1, a subunit of the cytochrome bc1 complex (complex III of the mitochondrial electron chain, is overexpressed in human OS tissues and cell lines and its silencing induces apoptosis in vitro and inhibits tumor growth in vivo. Here, we investigated the mechanism underlying the modulation of CYC1 expression in OS and its role in the resistance of OS to apoptosis. Methods: qRT-PCR, luciferase reporter assay, western blotting, fow cytometry, and animal experiments were performed in this study. Results: MicroRNA (miR-661 was identified as a downregulated miRNA in OS tissues and cells and shown to directly target CYC1. Ectopically expressed miR-661 inhibited OS cell growth, promoted apoptosis, and reduced the activity of mitochondrial complex III. miR-661 overexpression enhanced TRAIL or STS induced apoptosis and promoted the release of cytochrome c into the cytosol, which induced caspase-9 activation, and these effects were abolished by a caspase-3 inhibitor. Overexpression of CYC1 rescued the effects of miR-661 on sensitizing OS cells to TRAIL or STS induced apoptosis, indicating that the antitumor effect of miR-661 is mediated by the downregulation of CYC1. In vivo, miR-661 overexpression sensitized tumors to TRAIL or STS induced apoptosis in a xenograft mouse model, and these effects were attenuated by co-expression of CYC1. Conclusion: Taken together, our results indicate that miR-661 plays a tumor suppressor role in OS mediated by the downregulation of CYC1, suggesting a potential mechanism underlying cell death resistance in OS.

  13. Dewetting-Induced Photoluminescent Enhancement of Poly(lauryl methacrylate)/Quantum Dot Thin Films.

    Science.gov (United States)

    Geldmeier, Jeffrey; Rile, Lexy; Yoon, Young Jun; Jung, Jaehan; Lin, Zhiqun; Tsukruk, Vladimir V

    2017-12-19

    A new method for enhancing photoluminescence from quantum dot (QD)/polymer nanocomposite films is proposed. Poly(lauryl methacrylate) (PLMA) thin films containing embedded QDs are intentionally allowed to undergo dewetting on substrates by exposure to a nonsolvent vapor. After controlled dewetting, films exhibited typical dewetting morphologies with increased amounts of scattering that served to outcouple photoluminescence from the film and reduce internal light propagation within the film. Up to a 5-fold enhancement of the film emission was achieved depending on material factors such as the initial film thickness and QD concentration within the film. An increase in initial film thickness was shown to increase the dewetted maximum feature size and its characteristic length until a critical thickness was reached where dewetting became inhibited. A unique light exposure-based photopatterning method is also presented for the creation of high contrast emissive patterns as guided by spatially controlled dewetting.

  14. Enhanced ionic liquid mobility induced by confinement in 1D CNT membranes

    Science.gov (United States)

    Berrod, Q.; Ferdeghini, F.; Judeinstein, P.; Genevaz, N.; Ramos, R.; Fournier, A.; Dijon, J.; Ollivier, J.; Rols, S.; Yu, D.; Mole, R. A.; Zanotti, J.-M.

    2016-04-01

    Water confined within carbon nanotubes (CNT) exhibits tremendous enhanced transport properties. Here, we extend this result to ionic liquids (IL) confined in vertically aligned CNT membranes. Under confinement, the IL self-diffusion coefficient is increased by a factor 3 compared to its bulk reference. This could lead to high power battery separators.Water confined within carbon nanotubes (CNT) exhibits tremendous enhanced transport properties. Here, we extend this result to ionic liquids (IL) confined in vertically aligned CNT membranes. Under confinement, the IL self-diffusion coefficient is increased by a factor 3 compared to its bulk reference. This could lead to high power battery separators. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01445c

  15. Preparation and physical properties of enhanced radiation induced crosslinking of ethylene-vinyl alcohol copolymer (EVOH)

    International Nuclear Information System (INIS)

    Deng Pengyang; Liu Meihua; Zhang Wanxi; Sun Jiazhen

    2007-01-01

    Preparation and physical properties of ethylene-vinyl alcohol copolymer (EVOH) crosslinked by enhanced radiation have been studied through various methods. It was found that the most effective agent for irradiation-crosslinking was triallyl isocyanurate (TAIC) among four kinds of polyfunctional monomers. Gel content (65.6%) was formed for EVOH-44 (content of ethylene is 44 mol%) at 200 kGy with 5% TAIC, but for EVOH-32 (content of ethylene is 32 mol%), only 37.4% gel content was formed under the same conditions. This result showed that the more the content of ethylene units comprised in EVOH, the easier the chemical bonds could be formed between different molecular chains. Tensile strength and elastic modulus increased after crosslinking at high test temperature and elongation at break decreased at the same time. Hygroscopicity of EVOH showed noticeable decrease after enhancement radiation-crosslinking

  16. Preheat-induced signal enhancement in the infrared stimulated luminescence of young and bleached sediment samples

    International Nuclear Information System (INIS)

    Richardson, C.A.

    2000-01-01

    Natural and laboratory bleached surface and young samples of potassium feldspar sand separates and polymineral silt had their infrared stimulated luminescence (IRSL) signal measured before and after preheating at 220 deg. C for 10 min or 160 deg. C for 16 h. For both preheats, the laboratory bleached sand samples underwent a signal enhancement which was stable with laboratory storage. The youngest samples also showed natural signal enhancement. The silt sample showed no recuperation of bleached signal on preheating, but some in the natural signal. A range of filtered bleaches was applied to one surface sand sample. Signal levels before and after preheating were reduced by filtering out the UV from the bleaching spectrum. The unfiltered bleach, however, most closely reproduced the behaviour of the natural sample

  17. Electron-beam-induced acoustic-wave enhancement of gaseous combustion

    International Nuclear Information System (INIS)

    Bidwell, S.W.; Bosch, R.A.; Gilgenbach, R.M.

    1989-01-01

    The combustion rate of premixed gases in a closed vessel was increased by injecting a high-current electron beam into the gas mixture within about 20 ms of spark ignition. This effect was observed with the fuels ethylene, methane, ethane, propane, and n-butane. Experimental results provide strong evidence that e-beam excitation of the fundamental longitudinal-acoustic mode of the cylindrical chamber is the mechanism of combustion enhancement. An observable combustion enhancement required that the amplitude of the fluid velocity oscillation in this acoustic mode be greater than or approximately equal to the flame propagation speed and was associated with a wrinkled or cellular flame structure with dimensions on the order of 1/2 cm. These results are in good agreement with values for the threshold acoustic velocity amplitude and dimension of cellular structure predicted for a periodically accelerated flame

  18. Enhancement of molecular NMR signal induced by polarization transfer from laser-polarized 129Xe

    International Nuclear Information System (INIS)

    Sun Xianping

    2001-01-01

    There is a large non-equilibrium nuclear polarization and a longer relaxation time in the laser-polarized 129 Xe produced by means of optical pumping and spin exchange. The characteristics of the laser-polarized 129 Xe permit the transfer of the polarization to enhance the atomic nuclear spin in liquid, solid and surface of solid molecules. Therefore, the sensitivity in nuclear magnetic resonance measurements for the molecules is enhanced and applications in the investigations of materials and surface sciences are expanded. The progress in the investigations of materials and surface sciences are expanded. The progress in the investigations of the polarization transfer between laser-polarized 129 Xe and the atomic nuclei in the molecules, the relative physics and the measurement of some parameters are introduced

  19. Theory and simulations of radiation friction induced enhancement of laser-driven longitudinal fields

    Science.gov (United States)

    Gelfer, E. G.; Fedotov, A. M.; Weber, S.

    2018-06-01

    We consider the generation of a quasistatic longitudinal electric field by intense laser pulses propagating in a transparent plasma with radiation friction (RF) taken into account. For both circular and linear polarization of the driving pulse we develop a 1D analytical model of the process, which is valid in a wide range of laser and plasma parameters. We define the parameter region where RF results in an essential enhancement of the longitudinal field. The amplitude and the period of the generated longitudinal wave are estimated and optimized. Our theoretical predictions are confirmed by 1D and 2D PIC simulations. We also demonstrate numerically that RF should substantially enhance the longitudinal field generated in a plasma by a 10 PW laser such as ELI Beamlines.

  20. Nanostructure induced changes in lifetime and enhanced second-harmonic response of organic-plasmonic hybrids

    Energy Technology Data Exchange (ETDEWEB)

    Leißner, Till [NanoSYD, Mads Clausen Institute, University of Southern Denmark, Alsion 2, 6400 Sønderborg (Denmark); Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense (Denmark); Kostiučenko, Oksana; Rubahn, Horst-Günter; Fiutowski, Jacek, E-mail: fiutowski@mci.sdu.dk [NanoSYD, Mads Clausen Institute, University of Southern Denmark, Alsion 2, 6400 Sønderborg (Denmark); Brewer, Jonathan R. [Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense (Denmark)

    2015-12-21

    In this letter we show that the optical response of organic nanofibers, grown from functionalized para-quaterphenylene molecules, can be controlled by forming organic-plasmonic hybrid systems. The interaction between nanofibers and supporting regular arrays of nanostructures leads to a strongly enhanced second harmonic response. At the same time, the fluorescence lifetime of the nanofibers is reduced from 0.32 ns for unstructured gold films to 0.22 ns for gold nanosquare arrays, demonstrating efficient organic–plasmonic interaction. To study the origin of these effects, we applied two-photon laser scanning microscopy and fluorescence lifetime imaging microscopy. These findings provide an effective approach for plasmon-enhanced second-harmonic generation at the nanoscale, which is attractive for nanophotonic circuitry.

  1. SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture.

    Science.gov (United States)

    Arhoma, A; Chantry, A D; Haywood-Small, S L; Cross, N A

    2017-11-15

    Multiple Myeloma (MM) is currently incurable despite many novel therapies. Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a potential anti-tumour agent although effects as a single agent are limited. In this study, we investigated whether the Histone Deacetylase (HDAC) inhibitor SAHA can enhance TRAIL-induced apoptosis and target TRAIL resistance in both suspension culture, and 3D cell culture as a model of disseminated MM lesions that form in bone. The effects of SAHA and/or TRAIL in 6 Multiple Myeloma cell lines were assessed in both suspension cultures and in an Alginate-based 3D cell culture model. The effect of SAHA and/or TRAIL was assessed on apoptosis by assessment of nuclear morphology using Hoechst 33342/Propidium Iodide staining. Viable cell number was assessed by CellTiter-Glo luminescence assay, Caspase-8 and -9 activities were measured by Caspase-Glo™ assay kit. TRAIL-resistant cells were generated by culture of RPMI 8226 and NCI-H929 by acute exposure to TRAIL followed by selection of TRAIL-resistant cells. TRAIL significantly induced apoptosis in a dose-dependent manner in OPM-2, RPMI 8226, NCI-H929, U266, JJN-3 MM cell lines and ADC-1 plasma cell leukaemia cells. SAHA amplified TRAIL responses in all lines except OPM-2, and enhanced TRAIL responses were both via Caspase-8 and -9. SAHA treatment induced growth inhibition that further increased in the combination treatment with TRAIL in MM cells. The co-treatment of TRAIL and SAHA reduced viable cell numbers all cell lines. TRAIL responses were further potentiated by SAHA in 3D cell culture in NCI-H929, RPMI 8226 and U266 at lower TRAIL + SAHA doses than in suspension culture. However TRAIL responses in cells that had been selected for TRAIL resistance were not further enhanced by SAHA treatment. SAHA is a potent sensitizer of TRAIL responses in both TRAIL sensitive and resistant cell lines, in both suspension and 3D culture, however SAHA did not sensitise TRAIL-sensitive cell

  2. Enhanced Arabidopsis disease resistance against Botrytis cinerea induced by sulfur dioxide.

    Science.gov (United States)

    Xue, Meizhao; Yi, Huilan

    2018-01-01

    Sulfur dioxide (SO 2 ) is a common air pollutant that has complex impacts on plants. The effect of prior exposure to 30mgm -3 SO 2 on defence against Botrytis cinerea (B. cinerea) in Arabidopsis thaliana and the possible mechanisms of action were investigated. The results indicated that pre-exposure to 30mgm -3 SO 2 resulted in significantly enhanced resistance to B. cinerea infection. SO 2 pre-treatment significantly enhanced the activities of defence-related enzymes including phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), β-1,3-glucanase (BGL) and chitinase (CHI). Transcripts of the defence-related genes PAL, PPO, PR2, and PR3, encoding PAL, PPO, BGL and CHI, respectively, were markedly elevated in Arabidopsis plants pre-exposed to SO 2 and subsequently inoculated with B. cinerea (SO 2 + treatment group) compared with those that were only treated with SO 2 (SO 2 ) or inoculated with B. cinerea (CK+). Moreover, SO 2 pre-exposure also led to significant increases in the expression levels of MIR393, MIR160 and MIR167 in Arabidopsis. Meanwhile, the expression of known targets involved in the auxin signalling pathway, was negatively correlated with their corresponding miRNAs. Additionally, the transcript levels of the primary auxin-response genes GH3-like, BDL/IAA12, and AXR3/IAA17 were markedly repressed. Our findings indicate that 30mgm -3 SO 2 pre-exposure enhances disease resistance against B. cinerea in Arabidopsis by priming defence responses through enhancement of defence-related gene expression and enzyme activity, and miRNA-mediated suppression of the auxin signalling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The exercise-induced biochemical milieu enhances collagen content and tensile strength of engineered ligaments.

    Science.gov (United States)

    West, Daniel W D; Lee-Barthel, Ann; McIntyre, Todd; Shamim, Baubak; Lee, Cassandra A; Baar, Keith

    2015-10-15

    Exercise stimulates a dramatic change in the concentration of circulating hormones, such as growth hormone (GH), but the biological functions of this response are unclear. Pharmacological GH administration stimulates collagen synthesis; however, whether the post-exercise systemic milieu has a similar action is unknown. We aimed to determine whether the collagen content and tensile strength of tissue-engineered ligaments is enhanced by serum obtained post-exercise. Primary cells from a human anterior cruciate ligament (ACL) were used to engineer ligament constructs in vitro. Blood obtained from 12 healthy young men 15 min after resistance exercise contained GH concentrations that were ∼7-fold greater than resting serum (P Ligament constructs were treated for 7 days with medium supplemented with serum obtained at rest (RestTx) or 15 min post-exercise (ExTx), before tensile testing and collagen content analysis. Compared with RestTx, ExTx enhanced collagen content (+19%; 181 ± 33 vs. 215 ± 40 μg per construct P = 0.001) and ligament mechanical properties - maximal tensile load (+17%, P = 0.03 vs. RestTx) and ultimate tensile strength (+10%, P = 0.15 vs. RestTx). In a separate set of engineered ligaments, recombinant IGF-1, but not GH, enhanced collagen content and mechanics. Bioassays in 2D culture revealed that acute treatment with post-exercise serum activated mTORC1 and ERK1/2. In conclusion, the post-exercise biochemical milieu, but not recombinant GH, enhances collagen content and tensile strength of engineered ligaments, in association with mTORC1 and ERK1/2 activation. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  4. A mechanistic understanding of processing additive-induced efficiency enhancement in bulk heterojunction organic solar cells

    KAUST Repository

    Schmidt, Kristin

    2013-10-31

    The addition of processing additives is a widely used approach to increase power conversion efficiencies for many organic solar cells. We present how additives change the polymer conformation in the casting solution leading to a more intermixed phase-segregated network structure of the active layer which in turn results in a 5-fold enhancement in efficiency. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Enhanced Ig production by human peripheral lymphocytes induced by aggregated C1q

    NARCIS (Netherlands)

    Daha, M. R.; Klar, N.; Hoekzema, R.; van Es, L. A.

    1990-01-01

    Because B cells express receptors for C1q, we have investigated the role of C1q in the stimulation of B cells. When B cells were cultured in the presence of C1q that had been frozen, T cells, and suboptimal concentrations of PWM, there was a dose-dependent enhancement of IgM, IgG, and IgA by the B

  6. From nanochannel-induced proton conduction enhancement to a nanochannel-based fuel cell.

    Science.gov (United States)

    Liu, Shaorong; Pu, Qiaosheng; Gao, Lin; Korzeniewski, Carol; Matzke, Carolyn

    2005-07-01

    The apparent proton conductivity inside a nanochannel can be enhanced by orders of magnitude due to the electric double layer overlap. A nanochannel filled with an acidic solution is thus a micro super proton conductor, and an array of such nanochannels forms an excellent proton conductive membrane. Taking advantage of this effect, a new class of proton exchange membrane is developed for micro fuel cell applications.

  7. Nimotuzumab enhances temozolomide?induced growth suppression of glioma cells expressing mutant EGFR in vivo

    OpenAIRE

    Nitta, Yusuke; Shimizu, Saki; Shishido?Hara, Yukiko; Suzuki, Kaori; Shiokawa, Yoshiaki; Nagane, Motoo

    2016-01-01

    Abstract A mutant form of epidermal growth factor receptor (EGFR), EGFRvIII, is common in glioblastoma (GBM) and confers enhanced tumorigenic activity and drug resistance. Nimotuzumab, an anti?EGFR antibody, has shown preclinical and clinical activity to GBM, but its specific activity against EGFRvIII has not been fully investigated. Human glioma U87MG or LNZ308 cells overexpressing either wild?type (wt) EGFR or EGFRvIII were treated with nimotuzumab, temozolomide, or both. Expression and pho...

  8. Magnetic-Field Induced Enhancement in the Fluorescence Yield Spectrum of Doubly Excited States in Helium

    International Nuclear Information System (INIS)

    Stroem, Magnus; Saathe, Conny; Agaaker, Marcus; Soederstroem, Johan; Rubensson, Jan-Erik; Stranges, Stefano; Richter, Robert; Alagia, Michele; Gorczyca, T. W.; Robicheaux, F.

    2006-01-01

    An influence of static magnetic fields on the fluorescence yield spectrum of He in the vicinity of the N=2 thresholds has been observed. The experimental results are in excellent agreement with predictions based on multichannel quantum defect theory, and it is demonstrated that the Rydberg electron l mixing due to the diamagnetic interaction is essential for the description of the observed fluorescence yield intensity enhancement

  9. Polyamine deprivation-induced enhanced uptake of methylglyoxal bis(guanylhydrazone) by tumor cells.

    Science.gov (United States)

    Seppänen, P; Alhonen-Hongisto, L; Jänne, J

    1981-05-05

    1. Putrescine and spermidine depletion produced by alpha-difluoromethylornithine, an irreversible inhibitor or ornithine decarboxylase (EC 4.1.1.17), resulted in a strikingly enhanced cellular uptake of methylglyoxal bis(guanylhydrazone) in cultured Ehrlich ascites carcinoma cells and human lymphocytic leukemia cells. 2. A prior priming of the cells with difluoromethylornithine followed by a short exposure of the cells to methylglyoxal bis(guanylhydrazone) rapidly established intracellular concentrations of the latter drug approaching 10 mM. 3. The enhanced transport of methylglyoxal bis(guanylhydrazone) into the tumor cells apparently required metabolic energy as the uptake of extracellular drug rapidly ceased and intracellular methylglyoxal bis(guanylhydrazone) was excreted into the medium when the glycolysis of the tumor cells was inhibited by iodoacetate. 4. A sequential treatment of cultured tumor cells with difluoromethylornithine until established polyamine depletion followed by an addition of low concentrations of methylglyoxal bis(guanylhydrazone) produced an antiproliferative action not achieved with either of the drugs alone. 5. A similar treatment schedule, i.e a priming of mice inoculated with Ehrlich ascites cells with difluoromethylornithine for a few days, likewise enhanced the uptake of methylglyoxal bis(guanylhydrazone) by the carcinoma cells, but only marginally increased the drug concentration in the liver and small intestine of the animals.

  10. Resonant optical tunneling-induced enhancement of the photonic spin Hall effect

    Science.gov (United States)

    Jiang, Xing; Wang, Qingkai; Guo, Jun; Zhang, Jin; Chen, Shuqing; Dai, Xiaoyu; Xiang, Yuanjiang

    2018-04-01

    Due to the quantum analogy with optics, the resonant optical tunneling effect (ROTE) has been proposed to investigate both the fundamental physics and the practical applications of optical switches and liquid refractive index sensors. In this paper, the ROTE is used to enhance the spin Hall effect (SHE) of transmitted light. It is demonstrated that sandwiching a layer of a high-refractive-index medium (boron nitride crystal) between two low-refractive-index layers (silica) can effectively enhance the photonic SHE due to the increased refractive index gradient and an enhanced evanescent field near the interface between silica and boron nitride. A maximum transverse shift of the horizontal polarization state in the ROTE structure of about 22.25 µm has been obtained, which is at least three orders of magnitude greater than the transverse shift in the frustrated total internal reflection structure. Moreover, the SHE can be manipulated by controlling the component materials and the thickness of the ROTE structure. These findings open the possibility for future applications of photonic SHE in precision metrology and spin-based photonics.

  11. Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth.

    Science.gov (United States)

    Hornberger, Troy A; McLoughlin, Thomas J; Leszczynski, Jori K; Armstrong, Dustin D; Jameson, Ruth R; Bowen, Phyllis E; Hwang, Eun-Sun; Hou, Honglin; Moustafa, Mohamed E; Carlson, Bradley A; Hatfield, Dolph L; Diamond, Alan M; Esser, Karyn A

    2003-10-01

    Dietary intake of selenium has been implicated in a wide range of health issues, including aging, heart disease and cancer. Selenium deficiency, which can reduce selenoprotein levels, has been associated with several striated muscle pathologies. To investigate the role of selenoproteins in skeletal muscle biology, we used a transgenic mouse (referred to as i6A-) that has reduced levels of selenoproteins due to the introduction and expression of a dominantly acting mutant form of selenocysteine transfer RNA (tRNA[Ser]Sec). As a consequence, each organ contains reduced levels of most selenoproteins, yet these mice are normal with regard to fertility, overall health, behavior and blood chemistries. In the present study, although skeletal muscles from i6A- mice were phenotypically indistinguishable from those of wild-type mice, plantaris muscles were approximately 50% heavier after synergist ablation, a model of exercise overload. Like muscle in wild-type mice, the enhanced growth in the i6A- mice was completely blocked by inhibition of the mammalian target of rapamycin (mTOR) pathway. Muscles of transgenic mice exhibited increased site-specific phosphorylation on both Akt and p70 ribosomal S6 kinase (p70S6k) (P accounting for the enhanced response to synergist ablation. Thus, a single genetic alteration resulted in enhanced skeletal muscle adaptation after exercise, and this is likely through subtle changes in the resting phosphorylation state of growth-related kinases.

  12. Phonon-induced enhancements of the energy gap and critical current in superconducting aluminum

    International Nuclear Information System (INIS)

    Seligson, D.

    1983-01-01

    The enhancement of the energy gap, Δ, and critical current, i/sub c/, in superconducting aluminum thin films were under the influence of 8 to 10 GHz phonons. The phonons were generated by piezoelectric transduction of a 1 kW microwave pulse of about 1 μsec duration. By means of a quartz delay line, the phonons were allowed to enter the aluminum only after the microwaves had long since disappeared. The critical current was measured in long narrow Al strips, in which the current flow is 1-dimensional and well described by Ginsburg-Landau theory. To measure Δ the Al film was used as one electrode in a superconductor-insulator-superconductor tunnel junction whose current-voltage characteristic gave Δ directly. For the measurements of i/sub c/, the total critical current was measured in the presence of the phonon perturbation. For the measurements of Δ the change of Δ away from its equilibrium value was measured. In both cases the first measurements of enhancement of these macroscopic variables under phonon irradiation is reported. The gap-enhancement was found to be in good agreement with theory, but only for relatively and surprisingly low input power. The critical current measurements are predicted to be in rough agreement with the Δ measurements but this was not observed

  13. Cordyceps sinensis health supplement enhances recovery from taxol-induced leukopenia.

    Science.gov (United States)

    Liu, Wei-Chung; Chuang, Wei-Ling; Tsai, Min-Lung; Hong, Ji-Hong; McBride, William H; Chiang, Chi-Shiun

    2008-04-01

    This study aimed to evaluate the ability of the health food supplement Cordyceps sinensis (CS) to ameliorate suppressive effects of chemotherapy on bone marrow function as a model for cancer treatment. Mice were treated with Taxol (17 mg/kg body wt) one day before oral administration of a hot-water extract of CS (50 mg/kg daily) that was given daily for 3 weeks. White blood cell counts in peripheral blood of mice receiving Taxol were at 50% of normal levels on day 28 but had recovered completely in mice treated with CS. In vitro assays showed that CS enhanced the colony-forming ability of both granulocyte macrophage colony forming unit (GM-CFU) and osteogenic cells from bone marrow preparations and promoted the differentiation of bone marrow mesenchymal stromal cells into adipocytes, alkaline phosphatase-positive osteoblasts, and bone tissue. This result could be attributed to enhanced expression of Cbfa1 (core binding factor a) and BMP-2 (bone morphogenetic protein) with concurrent suppression of ODF (osteoclast differentiation factor/RANK [receptor activator of NF-kappaB]) ligand. In summary, CS enhances recovery of mice from leukopenia caused by Taxol treatment. It appears to do so by protecting both hematopoietic progenitor cells directly and the bone marrow stem cell niche through its effects on osteoblast differentiation.

  14. Impurity enrichment and radiative enhancement using induced SOL flow in DIII-D

    International Nuclear Information System (INIS)

    Wade, M.R.; West, W.P.; Wood, R.D.

    1998-07-01

    Experiments on DIII-D have demonstrated the efficacy of using induced scrap-off-layer (SOL) flow to preferentially enrich impurities in the divertor plasma. This SOL floe is produced through simultaneous deuterium gas injection at the midplane and divertor exhaust. Using this SOL flow, an improvement in enrichment (defined as the ratio of impurity fraction in the divertor to that in the plasma core) has been observed for all impurities in trace-level experiments (i.e., impurity level is non-perturbative), with the degree of improvement increasing with impurity atomic number. In the case of argon, exhaust gas enrichment using modest SOL flow is as high as 17. Using this induced SOL flow technique and argon injection, radiative plasmas have been produced that combine high radiation losses (P rad /P input > 70%), low core fuel dilution (Z eff E > 1.0 τ E,ITER93H )

  15. Enhanced non-disjunction and recombination as consequences of γ-induced deficiencies in Petunia hybrida

    International Nuclear Information System (INIS)

    Cornu, A.; Maizonnier, D.

    1979-01-01

    Non-disjunction events, spontaneous or induced, are rather frequent in plants. In Petunia, no significant effect of γ-radiations was detected. However, the study of some monogametic mutants characterized by a terminal deletion showed that, at the level of the chromosome pair involved by this deletion, both the frequency of specific trisomics and the recombination fractions between 4 marker loci were considerably increased in the progeny of the mutants as compared with that of the control. These features, i.e. deletion-induced non-disjunction and recombination, may be considered as indirect effects of radiations. Generalization to other species may be of importance in the fields of mammalian genetics and plant breeding. (Auth.)

  16. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-05

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights

  17. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase

    OpenAIRE

    Rajfer, R. A.; Kilic, A.; Neviaser, A. S.; Schulte, L. M.; Hlaing, S. M.; Landeros, J.; Ferrini, M. G.; Ebramzadeh, E.; Park, S-H.

    2017-01-01

    Objectives We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Materials and Methods Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression na...

  18. Neural mechanisms of reactivation-induced updating that enhance and distort memory

    OpenAIRE

    St. Jacques, Peggy L.; Olm, Christopher; Schacter, Daniel L.

    2013-01-01

    We remember a considerable number of personal experiences because we are frequently reminded of them, a process known as memory reactivation. Although memory reactivation helps to stabilize and update memories, reactivation may also introduce distortions if novel information becomes incorporated with memory. Here we used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms mediating reactivation-induced updating in memory for events experienced during a museum tou...

  19. Emphysema induced by elastase enhances acute inflammatory pulmonary response to intraperitoneal LPS in rats.

    Science.gov (United States)

    da Fonseca, Lídia Maria Carneiro; Reboredo, Maycon Moura; Lucinda, Leda Marília Fonseca; Fazza, Thaís Fernanda; Rabelo, Maria Aparecida Esteves; Fonseca, Adenilson Souza; de Paoli, Flavia; Pinheiro, Bruno Valle

    2016-12-01

    Abnormalities in lungs caused by emphysema might alter their response to sepsis and the occurrence of acute lung injury (ALI). This study compared the extension of ALI in response to intraperitoneal lipopolysaccharide (LPS) injection in Wistar rats with and without emphysema induced by elastase. Adult male Wistar rats were randomized into four groups: control, emphysema without sepsis, normal lung with sepsis and emphysema with sepsis. Sepsis was induced, and 24 h later the rats were euthanised. The following analysis was performed: blood gas measurements, bronchoalveolar lavage (BAL), lung permeability and histology. Animals that received LPS showed significant increase in a lung injury scoring system, inflammatory cells in bronchoalveolar lavage (BAL) and IL-6, TNF-α and CXCL2 mRNA expression in lung tissue. Animals with emphysema and sepsis showed increased alveolocapillary membrane permeability, demonstrated by higher BAL/serum albumin ratio. In conclusion, the presence of emphysema induced by elastase increases the inflammatory response in the lungs to a systemic stimulus, represented in this model by the intraperitoneal injection of LPS. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  20. Elevated sodium chloride concentrations enhance the bystander effects induced by low dose alpha-particle irradiation

    International Nuclear Information System (INIS)

    Han Wei; Zhu Lingyan; Jiang Erkang; Wang Jun; Chen Shaopeng; Bao Linzhi; Zhao Ye; Xu An; Yu Zengliang; Wu Lijun

    2007-01-01

    Previous studies have shown that high NaCl can be genotoxic, either alone or combined with irradiation. However, little is known about the relationship between environmental NaCl at elevated conditions and radiation-induced bystander effects (RIBE). RIBE, which has been considered as non-targeted bystander responses, has been demonstrated to occur widely in various cell lines. In the present study, RIBE under the elevated NaCl culture condition was assessed in AG 1522 cells by both the induction of γ-H2AX, a reliable marker of DNA double-strand break (DSB) for the early process ( G -methyl-L-arginine, an inhibitor of nitric oxide synthase, the induced fraction of foci-positive cells was effectively inhibited both in 0.2 cGy α-particle irradiated and adjacent non-irradiated regions under either normal or elevated NaCl conditions. These results suggested that the cultures with elevated NaCl medium magnified the damage effects induced by the low dose α-particle irradiation and nitric oxide generated by irradiation was also very important in this process

  1. Hole-induced d"0 ferromagnetism enhanced by Na-doping in GaN

    International Nuclear Information System (INIS)

    Zhang, Yong; Li, Feng

    2017-01-01

    The d"0 ferromagnetism in wurtzite GaN is investigated by the first-principle calculations. It is found that spontaneous magnetization occurs if sufficient holes are injected in GaN. Both Ga vacancy and Na doping can introduce holes into GaN. However, Ga vacancy has a high formation energy, and is thus unlikely to occur in a significant concentration. In contrast, Na doping has relatively low formation energy. Under N-rich growth condition, Na doping with a sufficient concentration can be achieved, which can induce half-metallic ferromagnetism in GaN. Moreover, the estimated Curie temperature of Na-doped GaN is well above the room temperature. - Highlights: • Hole-induced ferromagnetism in GaN is confirmed. • Both Ga Vacancy and Na-doping can introduce hole into GaN. • The concentration of Ga vacancy is too low to induce detectable ferromagnetism. • Na-doped GaN is a possible ferromagnet with a high curie-temperature.

  2. Maternal immunity enhances Mycoplasma hyopneumoniae vaccination induced cell-mediated immune responses in piglets.

    Science.gov (United States)

    Bandrick, Meggan; Theis, Kara; Molitor, Thomas W

    2014-06-05

    Passively acquired maternal derived immunity (MDI) is a double-edged sword. Maternal derived antibody-mediated immunity (AMI) and cell-mediated immunity (CMI) are critical immediate defenses for the neonate; however, MDI may interfere with the induction of active immunity in the neonate, i.e. passive interference. The effect of antigen-specific MDI on vaccine-induced AMI and CMI responses to Mycoplasma hyopneumoniae (M. hyopneumoniae) was assessed in neonatal piglets. To determine whether CMI and AMI responses could be induced in piglets with MDI, piglets with high and low levels of maternal M. hyopneumoniae-specific immunity were vaccinated against M. hyopneumoniae at 7 d of age. Piglet M. hyopneumoniae-specific antibody, lymphoproliferation, and delayed type hypersensitivity (DTH) responses were measured 7 d and 14 d post vaccination. Piglets with M. hyopneumoniae-specific MDI failed to show vaccine-induced AMI responses; there was no rise in M. hyopneumoniae antibody levels following vaccination of piglets in the presence of M. hyopneumoniae-specific MDI. However, piglets with M. hyopneumoniae-specific MDI had primary (antigen-specific lymphoproliferation) and secondary (DTH) M. hyopneumoniae-specific CMI responses following vaccination. In this study neonatal M. hyopneumoniae-specific CMI was not subject to passive interference by MDI. Further, it appears that both maternal derived and endogenous CMI contribute to M. hyopneumoniae-specific CMI responses in piglets vaccinated in the face of MDI.

  3. Angiotensin II-induced hypertension increases plasma membrane Na pump activity by enhancing Na entry in rat thick ascending limbs.

    Science.gov (United States)

    Gonzalez-Vicente, Agustin; Garvin, Jeffrey L

    2013-11-01

    Thick ascending limbs (TAL) reabsorb 30% of the filtered NaCl load. Na enters the cells via apical Na-K-2Cl cotransporters and Na/H exchangers and exits via basolateral Na pumps. Chronic angiotensin II (ANG II) infusion increases net TAL Na transport and Na apical entry; however, little is known about its effects on the basolateral Na pump. We hypothesized that in rat TALs Na pump activity is enhanced by ANG II-infusion, a model of ANG II-induced hypertension. Rats were infused with 200 ng·kg(-1)·min(-1) ANG II or vehicle for 7 days, and TAL suspensions were obtained. We studied plasma membrane Na pump activity by measuring changes in 1) intracellular Na (Nai) induced by ouabain; and 2) ouabain-sensitive oxygen consumption (QO2). We found that the ouabain-sensitive rise in Nai in TALs from ANG II-infused rats was 12.8 ± 0.4 arbitrary fluorescent units (AFU)·mg(-1)·min(-1) compared with only 9.9 ± 1.1 AFU·mg(-1)·min(-1) in controls (P Na pump expression, the number of Na pumps in the plasma membrane, or the affinity for Na. When furosemide (1.1 mg·kg(-1)·day(-1)) was coinfused with ANG II, no increase in plasma membrane Na pump activity was observed. We concluded that in ANG II-induced hypertension Na pump activity is increased in the plasma membrane of TALs and that this increase is caused by the chronically enhanced Na entry occurring in this model.

  4. Transgenerational inheritance of modified DNA methylation patterns and enhanced tolerance induced by heavy metal stress in rice (Oryza sativa L.).

    Science.gov (United States)

    Ou, Xiufang; Zhang, Yunhong; Xu, Chunming; Lin, Xiuyun; Zang, Qi; Zhuang, Tingting; Jiang, Lili; von Wettstein, Diter; Liu, Bao

    2012-01-01

    DNA methylation is sensitive and responsive to stressful environmental conditions. Nonetheless, the extent to which condition-induced somatic methylation modifications can impose transgenerational effects remains to be fully understood. Even less is known about the biological relevance of the induced epigenetic changes for potentially altered well-being of the organismal progenies regarding adaptation to the specific condition their progenitors experienced. We analyzed DNA methylation pattern by gel-blotting at genomic loci representing transposable elements and protein-coding genes in leaf-tissue of heavy metal-treated rice (Oryza sativa) plants (S0), and its three successive organismal generations. We assessed expression of putative genes involved in establishing and/or maintaining DNA methylation patterns by reverse transcription (RT)-PCR. We measured growth of the stressed plants and their unstressed progenies vs. the control plants. We found (1) relative to control, DNA methylation patterns were modified in leaf-tissue of the immediately treated plants, and the modifications were exclusively confined to CHG hypomethylation; (2) the CHG-demethylated states were heritable via both maternal and paternal germline, albeit often accompanying further hypomethylation; (3) altered expression of genes encoding for DNA methyltransferases, DNA glycosylase and SWI/SNF chromatin remodeling factor (DDM1) were induced by the stress; (4) progenies of the stressed plants exhibited enhanced tolerance to the same stress their progenitor experienced, and this transgenerational inheritance of the effect of condition accompanying heritability of modified methylation patterns. Our findings suggest that stressful environmental condition can produce transgenerational epigenetic modifications. Progenies of stressed plants may develop enhanced adaptability to the condition, and this acquired trait is inheritable and accord with transmission of the epigenetic modifications. We suggest

  5. Endoplasmic reticulum targeting sequence enhances HBV-specific cytotoxic T lymphocytes induced by a CTL epitope-based DNA vaccine

    International Nuclear Information System (INIS)

    Xu Wei; Chu Yiwei; Zhang Ruihua; Xu Huanbin; Wang Ying; Xiong Sidong

    2005-01-01

    CD8 + T cells play a critical role in protective immunity against Hepatitis B Virus (HBV). Epitope-based DNA vaccines expressing HBV-dominant CTL epitopes can be used as candidate vaccines capable of inducing cytotoxic T Lymphocytes (CTL) responses. A plasmid DNA encoding a CTL epitope of HBV core antigen, HBc 18-27 , was constructed. Intramuscular immunization of C57BL/6 mice with this DNA vaccine resulted in successful induction of HBV-specific CTL responses. In order to promote transportation of the peptide into endoplasmic reticulum (ER) to bind to MHC class I molecules for optimal class I antigen presentation, an ER targeting sequence (ERTS) was fused with the C 18-27 encoding gene. ERTS fusion significantly enhanced specific CD8 + T cell responses in terms of CTL cytolysis as well as IFN-γ secretion. This enhancement was correlated with promoted epitope presentation on target cell surface. We report here an enhanced immunogenicity of an epitope-based DNA vaccine using an ER targeting signal sequence, which has significant implications for future design of therapeutic HBV vaccine

  6. Doxorubicin induces ZAKα overexpression with a subsequent enhancement of apoptosis and attenuation of survivability in human osteosarcoma cells.

    Science.gov (United States)

    Fu, Chien-Yao; Tseng, Yan-Shen; Chen, Ming-Cheng; Hsu, Hsi-Hsien; Yang, Jaw-Ji; Tu, Chuan-Chou; Lin, Yueh-Min; Viswanadha, Vijaya Padma; Kuo, Wei-Wen; Huang, Chih-Yang

    2018-02-01

    Human osteosarcoma (OS) is a malignant cancer of the bone. It exhibits a characteristic malignant osteoblastic transformation and produces a diseased osteoid. A previous study demonstrated that doxorubicin (DOX) chemotherapy decreases human OS cell proliferation and might enhance the relative RNA expression of ZAK. However, the impact of ZAKα overexpression on the OS cell proliferation that is inhibited by DOX and the molecular mechanism underlying this effect are not yet known. ZAK is a protein kinase of the MAPKKK family and functions to promote apoptosis. In our study, we found that ZAKα overexpression induced an apoptotic effect in human OS cells. Treatment of human OS cells with DOX enhanced ZAKα expression and decreased cancer cell viability while increasing apoptosis of human OS cells. In the meantime, suppression of ZAKα expression using shRNA and inhibitor D1771 both suppressed the DOX therapeutic effect. These findings reveal a novel molecular mechanism underlying the DOX effect on human OS cells. Taken together, our findings demonstrate that ZAKα enhances the apoptotic effect and decreases cell viability in DOX-treated human OS cells. © 2017 Wiley Periodicals, Inc.

  7. AMRI-59 has a role of radiosensitizer via enhancement of γ-ionizing radiation-induced apoptotic cell death

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Wan Gi; Cho, Jeong Hyun; Kim, Ju Yeon; Hwang, Sang Gu; Um, Hong Duck; Park, Jong Kuk [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    Recent in vitro studies have suggested that may increase the invasiveness of some cancer cells (e.g., glioma, hepatocellular carcinoma, and pancreatic cancer cells) by stimulating several intracellular signaling pathways and in vivo studies have found that radiotherapy of primary tumor sites may promote metastasis. Thus, in addition to having therapeutic effects, IR might promote the malignant traits of surviving cancer cells. The existing efforts to develop radiosensitizing agents have focused on overcoming radioresistance and reducing damage to normal tissues. Recently, concepts of personalized- or precision medicine are developed due to advancement of mega data technique, which provide new targets to develop new anti-cancer drugs. In this study, we sought to identify the radiosensitizer effect of AMRI-59 in vitro and in vivo., which is recently developed specific inhibitor of peroxiredoxin (Prx) I. AMRI-59 enhanced radiation-induced cell death and its mean calculated dose enhancement ratio was 1.26. We also found combination of AMRI-59 and IR In a xenograft assay, the combined PHCM and radiation group showed 14.3 days of growth delay versus the control in terms of tumor growth. The enhancement factor of this combined treatment was determined to be 2.03.

  8. S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.

    Science.gov (United States)

    Bektik, Emre; Dennis, Adrienne; Pawlowski, Gary; Zhou, Chen; Maleski, Danielle; Takahashi, Satoru; Laurita, Kenneth R; Deschênes, Isabelle; Fu, Ji-Dong

    2018-05-04

    Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of 5-ethynyl-20-deoxyuridine (EdU)⁺/α-myosin heavy chain (αMHC)-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP low cells. However, S-phase synchronization did not enhance the reprogramming with a polycistronic-viral vector, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

  9. Enhancement of plasmon-induced charge separation efficiency by coupling silver nanocubes with a thin gold film

    Science.gov (United States)

    Akiyoshi, Kazutaka; Saito, Koichiro; Tatsuma, Tetsu

    2016-10-01

    Plasmon-induced charge separation (PICS), in which an energetic electron is injected from a plasmonic nanoparticle (NP) to a semiconductor on contact, is often inhibited by a protecting agent adsorbed on the NP. We addressed this issue for an Ag nanocube-TiO2 system by coating it with a thin Au layer or by inserting the Au layer between the nanocubes (NCs) and TiO2. Both of the electrodes exhibit much higher photocurrents due to PICS than the electrodes without the Au film or the Ag NCs. These photocurrent enhancements can be explained in terms of PICS with accelerated electron transfer, in which electron injection from the Ag NCs or Ag@Au core-shell NCs to TiO2 is promoted by the Au film, or PICS enhanced by a nanoantenna effect, in which the electron injection from the Au film to TiO2 is enhanced by optical near field generated by the Ag NC.

  10. Elevated sodium chloride concentrations enhance the bystander effects induced by low dose alpha-particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Han Wei; Zhu Lingyan; Jiang Erkang; Wang Jun; Chen Shaopeng; Bao Linzhi; Zhao Ye; Xu An; Yu Zengliang [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Wu Lijun [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China)], E-mail: ljw@ipp.ac.cn

    2007-11-01

    Previous studies have shown that high NaCl can be genotoxic, either alone or combined with irradiation. However, little is known about the relationship between environmental NaCl at elevated conditions and radiation-induced bystander effects (RIBE). RIBE, which has been considered as non-targeted bystander responses, has been demonstrated to occur widely in various cell lines. In the present study, RIBE under the elevated NaCl culture condition was assessed in AG 1522 cells by both the induction of {gamma}-H2AX, a reliable marker of DNA double-strand break (DSB) for the early process (<1 h post irradiation), and the generation of micronuclei (MN), a sensitive marker for relative long process of RIBE. Our results showed that in the absence of irradiation, NaCl at elevated concentration such as 8.0, 9.0 and 10.0 g/L did not significantly increase the frequency of {gamma}-H2AX foci-positive cells and the number of foci per positive cell comparing with that NaCl at a normal concentration (6.8 g/L). However, with 0.2 cGy {alpha}-particle irradiation, the induced fraction of {gamma}-H2AX foci-positive cells and the number of induced {gamma}-H2AX foci per positive cell were significantly increased in both irradiated and adjacent non-irradiated regions. Similarly, the induction of MN by 0.2 cGy {alpha}-particle irradiation also increased with the elevated NaCl concentrations. With N{sup G}-methyl-L-arginine, an inhibitor of nitric oxide synthase, the induced fraction of foci-positive cells was effectively inhibited both in 0.2 cGy {alpha}-particle irradiated and adjacent non-irradiated regions under either normal or elevated NaCl conditions. These results suggested that the cultures with elevated NaCl medium magnified the damage effects induced by the low dose {alpha}-particle irradiation and nitric oxide generated by irradiation was also very important in this process.

  11. High LET Radiation Can Enhance TGF(Beta) Induced EMT and Cross-Talk with ATM Pathways

    Science.gov (United States)

    Wang, Minli; Hada, Megumi; Huff, Janice; Pluth, Janice M.; Anderson, Janniffer; ONeill, Peter; Cucinotta, Francis A.

    2010-01-01

    The TGF(Beta) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation in mammary epithelial cells. We investigated possible interactions between the TGF(Beta) and ATM pathways following simulated space radiation using hTERT immortalized human esophageal epithelial cells (EPC-hTERT), mink lung epithelial cells (Mv1lu), and several human fibroblast cell lines. TGF(Beta) is a key modulator of the Epithelial-Mesenchymal Transition (EMT), important in cancer progression and metastasis. The implication of EMT by radiation also has several lines of developing evidence, however is poorly understood. The identification of TGF(Beta) induced EMT can be shown in changes to morphology, related gene over expression or down regulation, which can be detected by RT-PCR, and immunostaining and western blotting. In this study, we have observed morphologic and molecular alternations consistent with EMT after Mv1lu cells were treated with TGF(Beta) High LET radiation enhanced TGF(Beta) mediated EMT with a dose as low as 0.1Gy. In order to consider the TGF(Beta) interaction with ATM we used a potent ATM inhibitor Ku55933 and investigated gene expression changes and Smad signaling kinetics. Ku559933 was observed to reverse TGF(Beta) induced EMT, while this was not observed in dual treated cells (radiation+TGF(Beta)). In EPC-hTERT cells, TGF(Beta) alone was not able to induce EMT after 3 days of application. A combined treatment with high LET, however, significantly caused the alteration of EMT markers. To study the function of p53 in the process of EMT, we knocked down P53 through RNA interference. Morphology changes associated with EMT were observed in epithelial cells with silenced p53. Our study indicates: high LET radiation can enhance TGF(Beta) induced EMT; while ATM is triggering the process of TGF(Beta)-induced EMT, p53 might be an essential repressor for EMT phenotypes.

  12. Plant phenology, growth and nutritive quality of Briza maxima: Responses induced by enhanced ozone atmospheric levels and nitrogen enrichment

    International Nuclear Information System (INIS)

    Sanz, J.; Bermejo, V.; Muntifering, R.; Gonzalez-Fernandez, I.; Gimeno, B.S.; Elvira, S.; Alonso, R.

    2011-01-01

    An assessment of the effects of tropospheric ozone (O 3 ) levels and substrate nitrogen (N) supplementation, singly and in combination, on phe