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Sample records for induces significantly enhanced

  1. Significantly enhanced lung metastasis and reduced organ NK cell functions in diet-induced obese rats.

    Science.gov (United States)

    Spielmann, J; Hanke, J; Knauf, D; Ben-Eliyahu, S; Jacobs, R; Stangl, G I; Bähr, I; Kielstein, H

    2017-01-01

    Obesity was identified as a major risk factor for malignant diseases, but underlying mechanisms remain unclear. Natural killer (NK) cells, a pivotal aspect of innate immunity, are capable of identifying and killing virally infected and tumor cells. Previous studies have shown altered NK cell functions in obesity, and the current study aimed to investigate the relationship between altered NK cell functions and increased cancer risk in obesity. To induce obesity male F344-rats received a high-fat diet (34% fat) or a control diet (4% fat). Thereafter, syngeneic mammary adenocarcinoma cells (MADB106) or a vehicle were intravenously (i.v.) injected. 15 min after injection, half of each group of rats were killed, lungs removed and immunohistochemically stained. Numbers of NK cells, MADB106 cells and NK cell-tumor cell interactions were quantified. Twenty-one days after tumor-cell injection the other half group of rats was killed and lung metastases were counted and relative mRNA concentrations of different NK cell receptors were determined. After short-term MADB106-challenge, DIO fed animals showed significantly decreased NK cell numbers in the blood and NK cell-tumor cell interactions in the lung as compared to their control littermates. Twenty-one days after MADB106 injection, the lungs of the DIO fed rats showed significantly more lung metastases compared to control animals, accompanied by reduced relative mRNA concentrations of the activating NK cell receptor NKG2D. We conclude that induction of obesity in F344-rats leads to reduced lung NK cell function against tumor cells and results in significantly enhanced lung metastasis as compared to lean animals. It can be hypothesized that obesity-induced altered NK cell functions play an important role in cancer growth and metastasis.

  2. Significantly enhanced lung metastasis and reduced organ NK cell functions in diet-induced obese rats

    OpenAIRE

    Spielmann, J.; Hanke, J; Knauf, D.; Ben-Eliyahu, S.; Jacobs, R.; Stangl, G. I.; B?hr, I.; Kielstein, H.

    2017-01-01

    Background Obesity was identified as a major risk factor for malignant diseases, but underlying mechanisms remain unclear. Natural killer (NK) cells, a pivotal aspect of innate immunity, are capable of identifying and killing virally infected and tumor cells. Previous studies have shown altered NK cell functions in obesity, and the current study aimed to investigate the relationship between altered NK cell functions and increased cancer risk in obesity. Methods To induce obesity male F344-rat...

  3. Significant enhancement in energy density of polymer composites induced by dopamine-modified Ba0.6Sr0.4TiO3 nanofibers

    Science.gov (United States)

    Song, Yu; Shen, Yang; Hu, Penghao; Lin, Yuanhua; Li, Ming; Nan, C. W.

    2012-10-01

    Ba0.6Sr0.4TiO3 (BST) nanofibers prepared via electrospinning and modified by dopamine are used as dielectric fillers in polyvinylidene fluoride (PVDF)-based composites. With 4.4 vol. % of BST nanofibers, the extractable energy density of the BST/PVDF composites is more than doubled as compared with pure PVDF matrix. Such significant enhancement is attributed to the combined effect of both surface modification by dopamine and large aspect ratio of the BST nanofibers. Paraelectric or anti-ferroelectric fillers of large aspect ratio may serve as a general strategy for enhanced electric energy density in polymer composites.

  4. Significant enhancement of neutralino dark matter annihilation from electroweak bremsstrahlung.

    Science.gov (United States)

    Bringmann, Torsten; Calore, Francesca

    2014-02-21

    Indirect searches for the cosmological dark matter have become ever more competitive during the past years. Here, we report the first full calculation of leading electroweak corrections to the annihilation rate of supersymmetric neutralino dark matter. We find that these corrections can be huge, partially due to contributions that have been overlooked so far. Our results imply a significantly enhanced discovery potential of this well motivated dark matter candidate with current and upcoming cosmic ray experiments, in particular for gamma rays and models with somewhat small annihilation rates at the tree level.

  5. Green tea polyphenol induces significant cell death in human lung ...

    African Journals Online (AJOL)

    Green tea polyphenol induces significant cell death in ... The dose-dependent effects of EGCG on H1155 xenograft tumor growth, as well as ..... of mitochondrial ROS and changes in .... ATM phosphorylates histone H2AX in response to DNA.

  6. Enhancing the significance of gravitational wave bursts through signal classification

    Science.gov (United States)

    Vinciguerra, S.; Drago, M.; Prodi, G. A.; Klimenko, S.; Lazzaro, C.; Necula, V.; Salemi, F.; Tiwari, V.; Tringali, M. C.; Vedovato, G.

    2017-05-01

    The quest to observe gravitational waves challenges our ability to discriminate signals from detector noise. This issue is especially relevant for transient gravitational waves searches with a robust eyes wide open approach, the so called all-sky burst searches. Here we show how signal classification methods inspired by broad astrophysical characteristics can be implemented in all-sky burst searches preserving their generality. In our case study, we apply a multivariate analyses based on artificial neural networks to classify waves emitted in compact binary coalescences. We enhance by orders of magnitude the significance of signals belonging to this broad astrophysical class against the noise background. Alternatively, at a given level of mis-classification of noise events, we can detect about 1/4 more of the total signal population. We also show that a more general strategy of signal classification can actually be performed, by testing the ability of artificial neural networks in discriminating different signal classes. The possible impact on future observations by the LIGO-Virgo network of detectors is discussed by analysing recoloured noise from previous LIGO-Virgo data with coherent WaveBurst, one of the flagship pipelines dedicated to all-sky searches for transient gravitational waves.

  7. Induced seismicity associated with Enhanced Geothermal Systems

    Energy Technology Data Exchange (ETDEWEB)

    Majer, Ernest L. [Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 90-R1116, Berkeley, CA 94720 (United States); Baria, Roy [MIL-TECH UK Ltd., 62 Rosewood Way, West End, Woking, Surrey GU24 9PF (United Kingdom); Stark, Mitch [Calpine Corp., 10350 Socrates Mine Road, Middletown, CA 95461 (United States); Oates, Stephen [Shell International Exploration and Production, Kesslerpark 1, 2288-GS Rijswijk-ZH (Netherlands); Bommer, Julian [Civil and Environmental Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom); Smith, Bill [Northern California Power Agency, Middletown, P.O. Box 663, Middletown, CA 95461 (United States); Asanuma, Hiroshi [Graduate School of Environmental Studies, Tohoku University, 980-8579 Sendai (Japan)

    2007-06-15

    Enhanced Geothermal Systems (EGS) have the potential to make a significant contribution to the world energy inventory. One controversial issue associated with EGS, however, is the impact of induced seismicity or microseismicity, which has been the cause of delays and threatened cancellation of at least two EGS projects worldwide. Although microseismicity has in fact had few (or no) adverse physical effects on operations or on surrounding communities, there remains public concern over the amount and magnitude of the seismicity associated with current and future EGS operations. The primary objectives of this paper are to present an up-to-date review of what is already known about the seismicity induced during the creation and operation of EGS, and of the gaps in our knowledge that, once addressed, should lead to an improved understanding of the mechanisms generating the events. Several case histories also illustrate a number of technical and public acceptance issues. We conclude that EGS-induced seismicity need not pose a threat to the development of geothermal energy resources if site selection is carried out properly, community issues are handled adequately and operators understand the underlying mechanisms causing the events. Induced seismicity could indeed prove beneficial, in that it can be used to monitor the effectiveness of EGS operations and shed light on geothermal reservoir processes. (author)

  8. 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

  9. 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...

  10. Significant enhancement of formic acid oxidation using rhodium nanostructures.

    Science.gov (United States)

    Balan, Beena K; Sathe, Bhaskar R

    2012-12-01

    The electrocatalytic activity of as-synthesized shape selective Rh nanostructures has been demonstrated using cyclic voltammetry, revealing unique shape-dependant performance towards HCOOH oxidation. Interestingly, the enhancement factor (R) for different shapes of Rh with respect to that of commercial Rh towards formic acid oxidation ranges up to 20,000% for cubes as compared to 17,500% for pyramids and 11,000% for hexagons respectively. Mechanistic pathway for comparatively better sensitivity of cubes as compared to other shapes has been correlated with the results of X-ray diffraction.

  11. Mechanism and clinical significance of prostaglandin-induced iris pigmentation.

    Science.gov (United States)

    Stjernschantz, Johan W; Albert, Daniel M; Hu, Dan-Ning; Drago, Filippo; Wistrand, Per J

    2002-08-01

    The new glaucoma drugs latanoprost, isopropyl unoprostone, travoprost, and bimatoprost cause increased pigmentation of the iris in some patients. The purpose of the present article is to survey the available preclinical and clinical data on prostaglandin-induced iris pigmentation and to assess the phenomenon from a clinical perspective. Most of the data have been obtained with latanoprost, and it appears that there is a predisposition to latanoprost-induced iris pigmentation in individuals with hazel or heterochromic eye color. As latanoprost and travoprost are selective agonists for the prostaglandin F(2alpha) receptor, it is likely that the phenomenon is mediated by this receptor. Several studies indicate that latanoprost stimulates melanogenesis in iridial melanocytes, and transcription of the tyrosinase gene is upregulated. The safety aspects of latanoprost-induced iris pigmentation have been addressed in histopathologic studies, and no evidence of harmful consequences of the side effect has been found. Although a final assessment of the clinical significance of prostaglandin-induced iris pigmentation currently is impossible to make, it appears that the only clear-cut disadvantage is a potential heterochromia between the eyes in unilaterally treated patients because the heterochromia is likely to be permanent, or very slowly reversible.

  12. Significance and nature of bystander responses induced by various agents.

    Science.gov (United States)

    Verma, Neha; Tiku, Ashu Bhan

    2017-07-01

    Bystander effects in a biological system are the responses shown by non-targeted neighbouring cells/tissues/organisms. These responses are triggered by factors released from targeted cells when exposed to a stress inducing agent. The biological response to stress inducing agents is complex, owing to the diversity of mechanisms and pathways activated in directly targeted and bystander cells. These responses are highly variable and can be either beneficial or hazardous depending on the cell lines tested, dose of agent used, experimental end points and time course selected. Recently non-targeted cells have even been reported to rescue the directly exposed cells by releasing protective signals that might be induced by non-targeted bystander responses. The nature of bystander signal/s is not yet clear. However, there are evidences suggesting involvement of ROS, RNS, protein factors and even DNA molecules leading to the activation of a number of signaling pathways. These can act independently or in a cascade, to induce events leading to changes in gene expression patterns that could elicit detrimental or beneficial effects. Many review articles on radiation induced bystander responses have been published. However, to the best of our knowledge, a comprehensive review on bystander responses induced by other genotoxic chemicals and stress inducing agents has not been published so far. Therefore, the aim of the present review is to give an overview of the literature on different aspects of bystander responses: agents that induce these responses, factors that can modulate bystander responses and the mechanisms involved. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Clinical significance of nerve root enhancement in contrast-enhanced MR imaging of the postoperative lumbar spine

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yeon Soo; Lee, Eun Ja; Kang, Si Won; Choi, Eun Seok [The Catholic Univ. of Korea, Taejon (Korea, Republic of); Song, Chang June; Kim, Jong Chul [Chungnam National Univ. School of Medicine, Taejon (Korea, Republic of)

    2001-09-01

    To determine the significance of nerve root contrast enhancement in patients with residual or recurrent symptomatic postoperative lumbar spine. Eighty-eight patients with 116 postoperative lumbar disc lesions causing radiating back pain underwent enhanced MR imaging. Intradural nerve root enhancement was quantified by pixel measurement, and affected nerve roots were compared before and after contrast administration. Extradural nerve root enhancement was assessed visually, and nerve root enhancement and clinical symptoms were correlated. Associated lesions such as recurrent disc herniation, scar tissue, nerve root thickening and nerve root displacement were also evaluated. Of 26 cases (22.4%) involving intradural nerve root enhancement, 22 (84.6%) showed significant clinical symptoms (p=0.002). and of 59 (50.9%) demonstrating extradural enhancement, clinical symptoms showed significant correlation in 47 (79.7%) (p=0.001). Nerve root enhancement, including eleven cases where this was both intra-and extradural, showed highly significant association with clinical symptoms in 74 of the 116 cases (63.8%) (p=0.000). Among 33 cases (28.4%) of recurrent disc herniation, nerve root enhancement was observed in 28 (84.8%) and in 24 of these 28 (85.7%), significant correlation with clinical symptoms was observed (p=0.000). Where epidural fibrosis was present, correlation between nerve root enhancement and clinical symptoms was not significant (p>0.05). Nerve root thickening and displaced nerve root were, however, significantly associated with symptoms (87.2% and 88.6%, respectively). In patients with postoperative lumbar spine, the association between nerve root enhancement revealed by MRI and clinical symptoms was highly significant.

  14. Significance of inducible defense-related proteins in infected plants

    NARCIS (Netherlands)

    Loon, L.C. van; Rep, M.; Pieterse, C.M.J.

    2006-01-01

    Inducible defense-related proteins have been described in many plant species upon infection with oomycetes, fungi, bacteria, or viruses, or insect attack. Several types of proteins are common and have been classified into 17 families of pathogenesis-related proteins (PRs). Others have so far been fo

  15. Significance of inducible defense-related proteins in infected plants

    NARCIS (Netherlands)

    Loon, L.C. van; Rep, M.; Pieterse, C.M.J.

    2006-01-01

    Inducible defense-related proteins have been described in many plant species upon infection with oomycetes, fungi, bacteria, or viruses, or insect attack. Several types of proteins are common and have been classified into 17 families of pathogenesis-related proteins (PRs). Others have so far been

  16. Significance of inducible defense-related proteins in infected plants

    NARCIS (Netherlands)

    Loon, L.C. van; Rep, M.; Pieterse, C.M.J.

    2006-01-01

    Inducible defense-related proteins have been described in many plant species upon infection with oomycetes, fungi, bacteria, or viruses, or insect attack. Several types of proteins are common and have been classified into 17 families of pathogenesis-related proteins (PRs). Others have so far been fo

  17. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    Science.gov (United States)

    Jiang, Erkang; Wu, Lijun

    2009-04-01

    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).

  18. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    Institute of Scientific and Technical Information of China (English)

    JIANG Erkang; WU Lijun

    2009-01-01

    A bstract In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy a-particle irradiated and non-irradiated by- stander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensi- tive 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 a-particle radiation-induced damage in ir- radiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE).

  19. Weak magnetic field significantly enhances selenite removal kinetics by zero valent iron.

    Science.gov (United States)

    Liang, Liping; Sun, Wu; Guan, Xiaohong; Huang, Yuying; Choi, Wonyong; Bao, Hongliang; Li, Lina; Jiang, Zheng

    2014-02-01

    The effect of weak magnetic field (WMF) on Se(IV) removal by zero valent iron (ZVI) was investigated as functions of pH and initial Se(IV) concentrations. The presence of WMF significantly accelerated Se(IV) removal and extended the working pH range of ZVI from 4.0-6.0 to 4.0-7.2. The WMF induced greater enhancement in Se(IV) removal by ZVI at lower initial Se(IV) concentrations. The influence of WMF on Se(IV) removal by ZVI was associated with a more dramatic drop in ORP and a more rapid release of Fe(2+) compared to the case without WMF. SEM and XRD analysis revealed that WMF accelerated the corrosion of ZVI and the transformation of amorphous iron (hdyr)oxides to lepidocrocite. XANES analyses showed that WMF expedited the reduction of Se(IV) to Se(0) by ZVI at pH 6.0 when its initial concentration was ≤20.0 mg L(-1). Se(IV) dosed at 40.0 mg L(-1) was removed by ZVI via adsorption followed by reduction to Se(0) at pH 7.0 but via adsorption at 7.2 in the presence of WMF. Regardless of WMF, Se(IV) applied at 40.0 mg L(-1) was removed by reduction at pH 4.0-6.0. The WMF-induced improvement in Se(IV) removal by ZVI may be mainly attributable to the Lorentz force and magnetic field gradient force. Employing WMF to enhance Se(IV) removal by ZVI is a promising and environmental-friendly method since it does not need extra energy and costly reagents.

  20. The significance of the erosion-induced terrestrial carbonsink

    Energy Technology Data Exchange (ETDEWEB)

    Berhe, A.A.; Harte, J.; Harden, J.W.; Torn, M.S.

    2006-10-10

    Estimating carbon (C) balance in erosional and depositionallandscapes is complicated by the effects of soil redistribution on bothnet primary productivity (NPP) and decomposition. Recent studies arecontradictory as to whether soil erosion does or does not constitute a Csink. Here we clarify the conceptual basis for how erosion can constitutea C sink. Specifically, the criterion for an erosional C sink is thatdynamic replacement of eroded C, and reduced decomposition rates indepositional sites, must together more than compensate for erosionallosses. This criterion is in fact met in many erosional settings, andthus erosion and deposition can make a net positive contribution to Csequestration. We show that, in a cultivated Mississippi watershed and acoastal California watershed, the magnitude of the erosion-induced C sinkis likely to be on the order of 1 percent of NPP and 16 percent of erodedC. Although soil erosion has serious environmental impacts, the annualerosion-induced C sink offsets up to 10 percent of the global fossil fuelemissions of carbon dioxide for 2005.

  1. Unconventional scaling and significant enhancement of the spin Seebeck effect in multilayers

    Science.gov (United States)

    Ramos, R.; Kikkawa, T.; Aguirre, M. H.; Lucas, I.; Anadón, A.; Oyake, T.; Uchida, K.; Adachi, H.; Shiomi, J.; Algarabel, P. A.; Morellón, L.; Maekawa, S.; Saitoh, E.; Ibarra, M. R.

    2015-12-01

    Spin Seebeck effects (SSEs) have been investigated in highly crystalline magnetic multilayer [Fe3O4/Pt] n films. Voltage as well as power generated by the SSE were found to be significantly enhanced with increasing the number of layers n . This voltage enhancement defies the simple understanding of the SSE and suggests that spin current flowing between the magnetic layers in the thickness direction plays an important role in multilayer SSE systems and the observed voltage enhancement.

  2. Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke.

    Science.gov (United States)

    Azzopardi, David; Patel, Kharishma; Jaunky, Tomasz; Santopietro, Simone; Camacho, Oscar M; McAughey, John; Gaça, Marianna

    2016-07-01

    Electronic cigarettes (E-cigarettes) are a potential means of addressing the harm to public health caused by tobacco smoking by offering smokers a less harmful means of receiving nicotine. As e-cigarettes are a relatively new phenomenon, there are limited scientific data on the longer-term health effects of their use. This study describes a robust in vitro method for assessing the cytotoxic response of e-cigarette aerosols that can be effectively compared with conventional cigarette smoke. This was measured using the regulatory accepted Neutral Red Uptake assay modified for air-liquid interface (ALI) exposures. An exposure system, comprising a smoking machine, traditionally used for in vitro tobacco smoke exposure assessments, was adapted for use with e-cigarettes to expose human lung epithelial cells at the ALI. Dosimetric analysis methods using real-time quartz crystal microbalances for mass, and post-exposure chemical analysis for nicotine, were employed to detect/distinguish aerosol dilutions from a reference Kentucky 3R4F cigarette and two commercially available e-cigarettes (Vype eStick and ePen). ePen aerosol induced 97%, 94% and 70% less cytotoxicity than 3R4F cigarette smoke based on matched EC50 values at different dilutions (1:5 vs. 1:153 vol:vol), mass (52.1 vs. 3.1 μg/cm(2)) and nicotine (0.89 vs. 0.27 μg/cm(2)), respectively. Test doses where cigarette smoke and e-cigarette aerosol cytotoxicity were observed are comparable with calculated daily doses in consumers. Such experiments could form the basis of a larger package of work including chemical analyses, in vitro toxicology tests and clinical studies, to help assess the safety of current and next generation nicotine and tobacco products.

  3. Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke

    Science.gov (United States)

    Azzopardi, David; Patel, Kharishma; Jaunky, Tomasz; Santopietro, Simone; Camacho, Oscar M.; McAughey, John; Gaça, Marianna

    2016-01-01

    Abstract Electronic cigarettes (E-cigarettes) are a potential means of addressing the harm to public health caused by tobacco smoking by offering smokers a less harmful means of receiving nicotine. As e-cigarettes are a relatively new phenomenon, there are limited scientific data on the longer-term health effects of their use. This study describes a robust in vitro method for assessing the cytotoxic response of e-cigarette aerosols that can be effectively compared with conventional cigarette smoke. This was measured using the regulatory accepted Neutral Red Uptake assay modified for air–liquid interface (ALI) exposures. An exposure system, comprising a smoking machine, traditionally used for in vitro tobacco smoke exposure assessments, was adapted for use with e-cigarettes to expose human lung epithelial cells at the ALI. Dosimetric analysis methods using real-time quartz crystal microbalances for mass, and post-exposure chemical analysis for nicotine, were employed to detect/distinguish aerosol dilutions from a reference Kentucky 3R4F cigarette and two commercially available e-cigarettes (Vype eStick and ePen). ePen aerosol induced 97%, 94% and 70% less cytotoxicity than 3R4F cigarette smoke based on matched EC50 values at different dilutions (1:5 vs. 1:153 vol:vol), mass (52.1 vs. 3.1 μg/cm2) and nicotine (0.89 vs. 0.27 μg/cm2), respectively. Test doses where cigarette smoke and e-cigarette aerosol cytotoxicity were observed are comparable with calculated daily doses in consumers. Such experiments could form the basis of a larger package of work including chemical analyses, in vitro toxicology tests and clinical studies, to help assess the safety of current and next generation nicotine and tobacco products. PMID:27690199

  4. Significant anthropogenic-induced changes of climate classes since 1950.

    Science.gov (United States)

    Chan, Duo; Wu, Qigang

    2015-08-28

    Anthropogenic forcings have contributed to global and regional warming in the last few decades and likely affected terrestrial precipitation. Here we examine changes in major Köppen climate classes from gridded observed data and their uncertainties due to internal climate variability using control simulations from Coupled Model Intercomparison Project 5 (CMIP5). About 5.7% of the global total land area has shifted toward warmer and drier climate types from 1950-2010, and significant changes include expansion of arid and high-latitude continental climate zones, shrinkage in polar and midlatitude continental climates, poleward shifts in temperate, continental and polar climates, and increasing average elevation of tropical and polar climates. Using CMIP5 multi-model averaged historical simulations forced by observed anthropogenic and natural, or natural only, forcing components, we find that these changes of climate types since 1950 cannot be explained as natural variations but are driven by anthropogenic factors.

  5. Carbon-tuned bonding method significantly enhanced the hydrogen storage of BN-Li complexes.

    Science.gov (United States)

    Deng, Qing-ming; Zhao, Lina; Luo, You-hua; Zhang, Meng; Zhao, Li-xia; Zhao, Yuliang

    2011-11-01

    Through first-principles calculations, we found doping carbon atoms onto BN monolayers (BNC) could significantly strengthen the Li bond on this material. Unlike the weak bond strength between Li atoms and the pristine BN layer, it is observed that Li atoms are strongly hybridized and donate their electrons to the doped substrate, which is responsible for the enhanced binding energy. Li adsorbed on the BNC layer can serve as a high-capacity hydrogen storage medium, without forming clusters, which can be recycled at room temperature. Eight polarized H(2) molecules are attached to two Li atoms with an optimal binding energy of 0.16-0.28 eV/H(2), which results from the electrostatic interaction of the polarized charge of hydrogen molecules with the electric field induced by positive Li atoms. This practical carbon-tuned BN-Li complex can work as a very high-capacity hydrogen storage medium with a gravimetric density of hydrogen of 12.2 wt%, which is much higher than the gravimetric goal of 5.5 wt % hydrogen set by the U.S. Department of Energy for 2015.

  6. Contrast enhancement of the cochlear aqueduct in MR imaging: its frequency and clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, T.; Naganawa, S.; Fukatsu, H.; Sakurai, Y.; Ishigaki, T. [Department of Radiology, Nagoya University School of Medicine, 65 Tsurumai-cho, 466-8550, Shouwa-ku, Nagoya (Japan); Aoki, I.; Ninomiya, A. [Medical Systems Company, Toshiba Corporation, Nasu Operations, Otawara-shi, Tochigi (Japan); Nakashima, T. [Department of Otorhinolaryngology, Nagoya University School of Medicine, Shouwa-ku, Nagoya (Japan)

    2003-09-01

    There have been no previous reports on contrast enhancement of the cochlear aqueduct in magnetic resonance imaging. The purpose of the present study was to evaluate the frequency and significance of this finding. Thirty-one patients (15 men and 16 women; age range 18-81 years) with otologic symptoms (sudden sensorineural hearing loss, vertigo, or tinnitus) were examined using contrast-enhanced imaging on a 1.5-T MR scanner. The normal ear served as the control. Two radiologists evaluated contrast enhancement in the area of the cochlear aqueduct. Forty-eight of 62 ears (77.4%) showed contrast enhancement of the cochlear aqueduct, but no significant differences in the frequency of contrast enhancement were observed between patients with and patients without vertigo, tinnitus, sensorineural hearing loss, cerebellopontine angle tumors, or a high-riding jugular bulb. In addition, no gender- or age-related differences were noted. Contrast enhancement of the cochlear aqueduct was frequently observed, but the frequency of enhancement in symptomatic ears was not significantly higher than in control ears. The results of this study may prove helpful in avoiding unnecessary examinations and potential diagnostic confusion. (orig.)

  7. Significance of Gd-DTPA enhanced MRI in lumbar disc herniation

    Energy Technology Data Exchange (ETDEWEB)

    Hijikuro, Taiji; Nakai, Osamu; Shindo, Shigeo; Mizuno, Kouichi; Otani, Kazuyuki; Yamaura, Isakichi [Kudanzaka Hospital, Tokyo (Japan)

    2001-04-01

    To know the significance of enhanced MRI images for prediction of prognosis of lumbar disc herniation, the images of 202 patients were retrospectively compared in relation with their findings at surgery, histo-pathological ones, clinical process and morphology. After intravenous injection of soluble Gd, T1 and T2-weighted imaging had been done with Yokogawa SignaConta (0.5T). Surgery was conducted on 99 patients and conservative therapy, on 103. Patients were classified into 3 groups: those giving enhanced effect in and behind the herniation, and without the effect. The enhancement was observed in 62%. Bad prognosis was seen in 37% of patients without the enhancing effect and the enhanced MRI was concluded to be useful for prediction of prognosis. (K.H.)

  8. Changes and significance of IL-25 in chicken collagen II-induced experimental arthritis (CIA).

    Science.gov (United States)

    Kaiwen, Wang; Zhaoliang, Su; Yinxia, Zhao; Siamak, Sandoghchian Shotorbani; Zhijun, Jiao; Yuan, Xue; Heng, Yang; Dong, Zheng; Yanfang, Liu; Pei, Shen; Shengjun, Wang; Qixiang, Shao; Xinxiang, Huang; Liwei, Lu; Huaxi, Xu

    2012-08-01

    Rheumatoid arthritis (RA) is an autoimmune inflammatory disease. It is a systemic inflammatory disease, characterized by chronic, symmetrical, multi-articular synovial arthritis. IL-25 (IL-17E) is a member of the recently emerged cytokine family (IL-17s), which is expressed in Th2 cells and bone marrow-derived mast cells. Unlike the other members of this family, IL-25 is capable of inducing Th2-associated cytokines (IL-4, IL-5, and IL-13) and also promotes the release of some pro-immune factors (IL-6 and IL-8). IL-25 is also a pleiotropic factor, which constitutes a tissue-specific pathological injury and chronic inflammation. In this study, we used chicken collagen II-induced experimental arthritis (CIA) model in DBA/1 mice to investigate the relationship between IL-25 and other inflammatory factors, revealing the possible mechanism in CIA. Our results showed that the expression level of IL-25 was enhanced in the late stage of CIA, and IL-17 was increased in the early stage of the disease. It is well known that IL-17 has a crucial role in the development of RA pathogenesis, and IL-25 plays a significant role in humoral immune. For reasons given above, we suggested that the IL-25 inhibited IL-17 expression to some extent, while enhancing the production of IL-4. It was confirmed that IL-25 not only regulated the cellular immune, but also involved the humoral immune in rheumatoid arthritis.

  9. Continuous background light significantly increases flashing-light enhancement of photosynthesis and growth of microalgae.

    Science.gov (United States)

    Abu-Ghosh, Said; Fixler, Dror; Dubinsky, Zvy; Iluz, David

    2015-01-01

    Under specific conditions, flashing light enhances the photosynthesis rate in comparison to continuous illumination. Here we show that a combination of flashing light and continuous background light with the same integrated photon dose as continuous or flashing light alone can be used to significantly enhance photosynthesis and increase microalgae growth. To test this hypothesis, the green microalga Dunaliella salina was exposed to three different light regimes: continuous light, flashing light, and concomitant application of both. Algal growth was compared under three different integrated light quantities; low, intermediate, and moderately high. Under the combined light regime, there was a substantial increase in all algal growth parameters, with an enhanced photosynthesis rate, within 3days. Our strategy demonstrates a hitherto undescribed significant increase in photosynthesis and algal growth rates, which is beyond the increase by flashing light alone.

  10. Acoustic trauma-induced auditory cortex enhancement and tinnitus

    Institute of Scientific and Technical Information of China (English)

    Erin Laundrie; Wei Sun

    2014-01-01

    There is growing evidence suggests that noise-induced cochlear damage may lead to hyperexcitability in the central auditory system (CAS) which may give rise to tinnitus. However, the correlation between the onset of the neurophysiological changes in the CAS and the onset of tinnitus has not been well studied. To investigate this relationship, chronic electrodes were implanted into the auditory cortex (AC) and sound evoked activities were measured from awake rats before and after noise exposure. The auditory brainstem response (ABR) was used to assess the degree of noise-induced hearing loss. Tinnitus was evaluated by measuring gap-induced prepulse inhibition (gap-PPI). Rats were exposed monaurally to a high-intensity narrowband noise centered at 12 kHz at a level of 120 dB SPL for 1 h. After the noise exposure, all the rats developed either permanent (>2 weeks) or temporary (<3 days) hearing loss in the exposed ear(s). The AC amplitudes increased significantly 4 h after the noise exposure. Most of the exposed rats also showed decreased gap-PPI. The post-exposure AC enhancement showed a positive correlation with the amount of hearing loss. The onset of tinnitus-like behavior was happened after the onset of AC enhancement.

  11. Enhanced oxidative stress is responsible for TRPV4-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Zhiwen Hong

    2016-10-01

    Full Text Available Transient receptor potential vanilloid 4 (TRPV4 has been reported to be responsible for neuronal injury in pathological conditions. Excessive oxidative stress can lead to neuronal damage, and activation of TRPV4 increases the production of reactive oxygen species and nitric oxide (NO in many types of cells. The present study explored whether TRPV4-induced neuronal injury is mediated through enhancing oxidative stress. We found that intracerebroventricular injection of the TRPV4 agonist GSK1016790A increased the content of methane dicarboxylic aldehyde (MDA and NO in the hippocampus, which was blocked by administration of the TRPV4 specific antagonist HC-067047. The activities of catalase (CAT and glutathione peroxidase (GSH-Px were decreased by GSK1016790A, whereas the activity of superoxide dismutase remained unchanged. Moreover, the protein level and activity of neuronal nitric oxide synthase (nNOS were increased by GSK1016790A, and the GSK1016790A-induced increase in NO content was blocked by an nNOS specific antagonist ARL-17477. The GSK1016790A-induced modulations of CAT, GSH-Px and nNOS activities and the protein level of nNOS were significantly inhibited by HC-067047. Finally, GSK1016790A-induced neuronal death and apoptosis in the hippocampal CA1 area were markedly attenuated by administration of a reactive oxygen species scavenger Trolox or ARL-17477. We conclude that activation of TRPV4 enhances oxidative stress by inhibiting CAT and GSH-Px and increasing nNOS, which is responsible, at least in part, for TRPV4-induced neurotoxicity.

  12. Significant light absorption enhancement in silicon thin film tandem solar cells with metallic nanoparticles.

    Science.gov (United States)

    Cai, Boyuan; Li, Xiangping; Zhang, Yinan; Jia, Baohua

    2016-05-13

    Enhancing the light absorption in microcrystalline silicon bottom cell of a silicon-based tandem solar cell for photocurrent matching holds the key to achieving the overall solar cell performance breakthroughs. Here, we present a concept for significantly improving the absorption of both subcells simultaneously by simply applying tailored metallic nanoparticles both on the top and at the rear surfaces of the solar cells. Significant light absorption enhancement as large as 56% has been achieved in the bottom subcells. More importantly the thickness of the microcrystalline layer can be reduced by 57% without compromising the optical performance of the tandem solar cell, providing a cost-effective strategy for high performance tandem solar cells.

  13. The Clinical Significance of Ependymal Enhancement at Presentation in Patients with Malignant Glioma

    Science.gov (United States)

    Kaidar-Person, Orit; Darawshe, Firas; Tzuk-Shina, Tzahala; Eran, Ayelet

    2015-01-01

    Introduction The current study evaluated the rate of ependymal enhancement and whether its presence influences survival of patients with malignant glioma (GBM). Methods A retrospective review of all patients who were treated in our institution from 2005 to 2011 was conducted. Data extracted from the medical records included age, date of diagnosis, co-morbidities, treatment regimen, and time of death. Magnetic resonance images (MRI) were evaluated for the presence of ependymal enhancement and its extent, and the correlation to survival was investigated. Results Between 2005 and 2011, 230 patients were treated for GBM. Eighty-nine patients were excluded from the study due to insufficient data, leaving 141 patients for analysis. Median age at diagnosis was 60 years. Sixty-seven (40.6%) patients had evidence of ependymal enhancement on MRI (group A), and 70 (42.4%) patients did not have evidence of enhancement. The assessment of ependymal enhancement was inconclusive due to mass effect and ventricular compression that precluded accurate assessment for 28 (17%) patients (group C). Median survival was 14 months for group A (range, 12–16 months), 15.9 months for group B (range, 14.28–17.65 months), and 11.7 months for group C (range, 6.47–16.92 months) (P>0.05). A multivariate analysis to predict survival indicated that male gender (P=0.039), hypertension (P=0.012), and biopsy only compared to complete gross tumor resection (P=0.001) were significant for poor survival. Conclusions Pretreatment ependymal enhancement on MRI was not found to be associated with poorer survival. These results might be due to better treatments options compared to prior reports. PMID:26886770

  14. The Clinical Significance of Ependymal Enhancement at Presentation in Patients with Malignant Glioma

    Directory of Open Access Journals (Sweden)

    Orit Kaidar-Person

    2015-10-01

    Full Text Available Introduction. The current study evaluated the rate of ependymal enhancement and whether its presence influences survival of patients with malignant glioma (GBM. Methods. A retrospective review of all patients who were treated in our institution from 2005 to 2011 was conducted. Data extracted from the medical records included age, date of diagnosis, co-morbidities, treatment regimen, and time of death. Magnetic resonance images (MRI were evaluated for the presence of ependymal enhancement and its extent, and the correlation to survival was investigated. Results. Between 2005 and 2011, 230 patients were treated for GBM. Eighty-nine patients were excluded from the study due to insufficient data, leaving 141 patients for analysis. Median age at diagnosis was 60 years. Sixty-seven (40.6% patients had evidence of ependymal enhancement on MRI (group A, and 70 (42.4% patients did not have evidence of enhancement. The assessment of ependymal enhancement was inconclusive due to mass effect and ventricular compression that precluded accurate assessment for 28 (17% patients (group C. Median survival was 14 months for group A (range, 12–16 months, 15.9 months for group B (range, 14.28–17.65 months, and 11.7 months for group C (range, 6.47–16.92 months (P>0.05. A multivariate analysis to predict survival indicated that male gender (P=0.039, hypertension (P=0.012, and biopsy only compared to complete gross tumor resection (P=0.001 were significant for poor survival. Conclusions. Pretreatment ependymal enhancement on MRI was not found to be associated with poorer survival. These results might be due to better treatments options compared to prior reports.

  15. Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Rong-Li Piao; David R Brigstock; Jie Zhu; Man-Li Zhang; Run-Ping Gao

    2012-01-01

    AIM:To determine the utility of connective tissue growth factor (CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus (HBV)-induced chronic liver diseases (CLD-B).METHODS:Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B (CHB) and 39 patients with HBVinduced active liver cirrhosis and 30 healthy individuals.Liver samples from 31 patients with CHB,8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor β-1 (TGF-β1) or CCN2 mRNA levels by in situ hybridization,and computer image analysis was performed to measure integrated optimal density (IOD) of CCN2 mRNA-positive cells in liver tissues.Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson's method.RESULTS:Serum CCN2 concentrations were,respectively,4.0-or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals (P < 0.01).There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues (r =0.87,P < 0.01).The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B (r =0.85,P < 0.01).Serum CCN2 was a reliable marker for the assessment of liver fibrosis,with areas under the receiver operating characteristic (ROC) curves (AUC) of 0.94 or 0.85 for,respectively,distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis.CONCLUSION:Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis.

  16. Significance of epiphyseal cartilage enhancement defects in pediatric osteomyelitis identified by MRI with surgical correlation

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, David P. [Vanderbilt University School of Medicine, Nashville, TN (United States); Hernanz-Schulman, Marta; Kan, J.H. [Vanderbilt Children' s Hospital, Department of Radiology and Radiological Sciences, Nashville, TN (United States); Martus, Jeffrey E.; Lovejoy, Steven A. [Vanderbilt Children' s Hospital, Division of Pediatric Orthopaedics, Nashville, TN (United States); Yu, Chang [Vanderbilt University, Department of Biostatistics, Nashville, TN (United States)

    2011-03-15

    Epiphyseal cartilage enhancement defects (ED) may occur in the setting of epiphyseal osteomyelitis (OM), and its significance is uncertain. The aim of this study is to evaluate the incidence and clinical impact of epiphyseal cartilage ED in pediatric epiphyseal OM. The 13 children involved in this retrospective review were younger than 6 years of age and diagnosed with OM. They underwent contrast-enhanced MRI and surgical exploration yielding 14 study epiphyses. Seventeen age-matched children without evidence of infection who underwent contrast-enhanced MRI in the same period yielded 28 control epiphyses. Images were reviewed for focal/global ED, correlated with cartilage abscesses and compared with surgical reports. Study and control ED were respectively present in 10/14 (71.4% - 6 global, 4 focal) and 6/28 (21.4% - 0 global, 6 focal), P = 0.0017. An analysis of ED patterns between study and control patients showed significant difference for global (P = 0.0006), but no difference for focal ED (P = 0.71). For the six study epiphyses with global ED, epiphyseal abscesses were present in two (33.3%). For the four study epiphyses with focal ED, epiphyseal abscesses were present in two (50%). For the controls, no abnormalities were found on follow-up of epiphyses with focal ED. ED are seen normally but more commonly in children with OM. ED should not be confused with epiphyseal abscesses. (orig.)

  17. Fingerprint: DWT, SVD Based Enhancement and Significant Contrast for Ridges and Valleys Using Fuzzy Measures

    CERN Document Server

    Bennet, D

    2011-01-01

    The performance of the Fingerprint recognition system will be more accurate with respect of enhancement for the fingerprint images. In this paper we develop a novel method for Fingerprint image contrast enhancement technique based on the discrete wavelet transform (DWT) and singular value decomposition (SVD) has been proposed. This technique is compared with conventional image equalization techniques such as standard general histogram equalization and local histogram equalization. An automatic histogram threshold approach based on a fuzziness measure is presented. Then, using an index of fuzziness, a similarity process is started to find the threshold point. A significant contrast between ridges and valleys of the best, medium and poor finger image features to extract from finger images and get maximum recognition rate using fuzzy measures. The experimental results show the recognition of superiority of the proposed method to get maximum performance up gradation to the implementation of this approach.

  18. Motivationally significant self-control: enhanced action withholding involves the right inferior frontal junction.

    Science.gov (United States)

    O'Connor, David A; Upton, Daniel J; Moore, Jennifer; Hester, Robert

    2015-01-01

    In everyday life, people use self-control to withhold actions. This ability is particularly important when the consequences of action withholding have an impact on the individual's well-being. Despite its importance, it is unclear as to how the neural nodes implicated in action withholding contribute to this real-world type of self-control. By modifying an action withholding paradigm, the go/no-go task, we examined how the brain exerts self-control during a scenario in which the implications of withholding an action are meaningful and motivationally significant. A successfully withheld response contributed to long-term monetary rewards, whereas failure to withhold a response incurred an immediate monetary punishment. Compared with neutral action withholding, participants significantly improved their performance when these contingencies were applied. Crucially, although the right IFG and pre-SMA were found to promote overall action withholding, the enhancement in behavioral performance relative to a neutral condition was only reflected by a physiological change in a region encompassing the right inferior frontal junction and precentral gyrus. We speculate that the ability to flexibly modulate attention to goal-relevant stimuli is crucial to enhanced, motivationally driven action withholding and that this ability is subserved by the right inferior frontal junction. These findings suggest that control-modulating factors, rather than action withholding processes per se, can be critical to improving motivationally significant action withholding outcomes.

  19. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes.

    Science.gov (United States)

    Thompson, Benjamin C; Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2014-07-01

    Cutaneous melanoma is a significant cause of morbidity and mortality. Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. Here, we report the effect of nicotinamide on DNA damage and repair in primary human melanocytes. Nicotinamide significantly enhanced the repair of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine) and cyclobutane pyrimidine dimers induced by UV exposure. It also enhanced the repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine induced by the culture conditions in unirradiated melanocytes. A significant increase in the percentage of melanocytes undergoing unscheduled but not scheduled DNA synthesis was observed, confirming that nicotinamide enhances DNA repair in human melanocytes. In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma.

  20. Hepatocellular carcinoma: clinical significance of signal heterogeneity in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, Nobuhiro; Nishie, Akihiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Moirta, Koichiro; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Fukuoka (Japan); Kubo, Yuichiro; Aishima, Shinichi [Kyushu University, Department of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka (Japan); Takayama, Yukihisa [Kyushu University, Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences, Fukuoka (Japan); Shirabe, Ken [Kyushu University, Department of Surgery and Science, Graduate School of Medical Sciences, Fukuoka (Japan)

    2015-01-15

    To clarify the relationship between the biological behaviour of hepatocellular carcinomas (HCCs) and their signal intensity in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging with a special focus on the signal heterogeneity. A total of 68 patients with 70 pathologically proven HCCs were enrolled. On the basis of the signal intensity in the hepatobiliary phase, the lesions were classified into three groups: group 1, homogeneous hypointensity (n = 44); group 2, heterogeneous hyperintensity (n = 20); and group 3, homogeneous hyperintensity (n = 6). The clinicopathological findings were compared among the three groups. The tumour size and the serum level of protein induced by vitamin K absence or antagonist-II (PIVKA-II) were significantly higher in group 2 compared to group 1 (p = 0.0155, p = 0.0215, respectively) and compared to group 3 (p = 0.0330, p = 0.0220, respectively). The organic anion transporting polypeptide 8 (OATP8) expression in group 2 and group 3 was significantly higher than in group 1 (p < 0.0001, p < 0.0001, respectively). Group 2 showed a significantly lower disease-free survival rate compared to group 1 (p = 0.0125), and group 2 was an independent prognostic factor for disease-free survival (p = 0.0308). HCCs in the hepatobiliary phase that are heterogeneously hyperintense on gadoxetic acid-enhanced MR imaging have more malignant potential than other types of HCCs. (orig.)

  1. Significance of terpenoids in induced indirect plant defence against herbivorous arthropods

    NARCIS (Netherlands)

    Mumm, R.; Posthumus, M.A.; Dicke, M.

    2008-01-01

    Many plants respond to herbivory by arthropods with an induced emission of volatiles such as green leaf volatiles and terpenoids. These herbivore-induced plant volatiles (HIPVs) can attract carnivores, for example, predators and parasitoids. We investigated the significance of terpenoids in attracti

  2. Activation-induced force enhancement in human adductor pollicis.

    Science.gov (United States)

    Oskouei, Ali E; Herzog, Walter

    2009-10-01

    It has been known for a long time that the steady-state isometric force after muscle stretch is bigger than the corresponding force obtained in a purely isometric contraction for electrically stimulated and maximal voluntary contractions (MVC). Recent studies using sub-maximal voluntary contractions showed that force enhancement only occurred in a sub-group of subjects suggesting that force enhancement for sub-maximal voluntary contractions has properties different from those of electrically-induced and maximal voluntary contractions. Specifically, force enhancement for sub-maximal voluntary contractions may contain an activation-dependent component that is independent of muscle stretching. To address this hypothesis, we tested for force enhancement using (i) sub-maximal electrically-induced contractions and stretch and (ii) using various activation levels preceding an isometric reference contraction at 30% of MVC (no stretch). All tests were performed on human adductor pollicis muscles. Force enhancement following stretching was found for all subjects (n=10) and all activation levels (10%, 30%, and 60% of MVC) for electrically-induced contractions. In contrast, force enhancement at 30% of MVC, preceded by 6s of 10%, 60%, and 100% of MVC was only found in a sub-set of the subjects and only for the 60% and 100% conditions. This result suggests that there is an activation-dependent force enhancement for some subjects for sub-maximal voluntary contractions. This activation-dependent force enhancement was always smaller than the stretch-induced force enhancement obtained at the corresponding activation levels. Active muscle stretching increased the force enhancement in all subjects, independent whether they showed activation dependence or not. It appears that post-activation potentiation, and the associated phosphorylation of the myosin light chains, might account for the stretch-independent force enhancement observed here.

  3. Changes and significance of coagulation function, hemodynamics and blood rheology in women with pregnancy induced hypertension

    Institute of Scientific and Technical Information of China (English)

    Bang-Zhi Zeng; Bo Zhang; Yu-Na Wang

    2016-01-01

    Objective:To observe the changes of coagulation function, hemodynamics and blood rheology in patients with pregnancy induced hypertension, and to explore its clinical significance. Methods: A total of 88 cases of women with pregnancy induced hypertension who were admitted in our hospital from July 2011 to February 2016 were selected as the research objects, at the same time, 90 normal pregnant women were selected as normal late pregnancy group. The coagulation parameters, hemodynamics, blood rheology indexes were detected in the two groups.Results:Before delivery, values of the PT and AT-Ⅲ in pregnancy induced hypertension group were significantly lower than those in the normal late pregnancy group, and the values of D-D and FIB were significantly higher than those in the normal late pregnancy group. After delivery, values of the PT and AT-Ⅲ in pregnancy induced hypertension group were significantly higher, and the FIB value was significantly lower, there were no significant differences between the two group. But the D-D value was still significantly higher than that in the normal late pregnancy group. The blood flow dynamics parameter in pregnancy induced hypertension group were significantly higher than that in the normal late pregnant group, the differences were statistically significant. The whole blood high and low shear viscosity, plasma viscosity, low shear reduction viscosity, hematocrit, erythrocyte deformation index, erythrocyte electrophoresis time and fibrinogen in pregnancy induced hypertension group were significantly higher than those in normal late pregnancy group.Conclusion:The blood indexes in patients with pregnancy induced hypertension showed a high coagulation state compared with the normal late pregnancy women. Timely detection of patients’ coagulation function, hemodynamics, and blood rheology indexes has important significance for the detection, auxiliary diagnosis and prevention of the disease.

  4. Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

    Science.gov (United States)

    Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

    2016-05-01

    Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications.

  5. Significantly improving trace thallium removal from surface waters during coagulation enhanced by nanosized manganese dioxide.

    Science.gov (United States)

    Huangfu, Xiaoliu; Ma, Chengxue; Ma, Jun; He, Qiang; Yang, Chun; Jiang, Jin; Wang, Yaan; Wu, Zhengsong

    2017-02-01

    Thallium (Tl) is an element of high toxicity and significant accumulation in human body. There is an urgent need for the development of appropriate strategies for trace Tl removal in drinking water treatment plants. In this study, the efficiency and mechanism of trace Tl (0.5 μg/L) removal by conventional coagulation enhanced by nanosized manganese dioxide (nMnO2) were explored in simulated water and two representative surface waters (a river water and a reservoir water obtained from Northeast China). Experimental results showed that nMnO2 significantly improve Tl(I) removal from selected waters. The removal efficiency was dramatically higher in the simulated water, demonstrating by less than 0.1 μg/L Tl residual. The enhancement of trace Tl removal in the surface waters decreased to a certain extent. Both adjusting water pH to alkaline condition and preoxidation of Tl(I) to Tl(III) benefit trace Tl removal from surface waters. Data also indicated that competitive cation of Ca(2+) decreased the efficiency of trace Tl removal, resulting from the reduction of Tl adsorption on nMnO2. Humic acid could largely low Tl removal efficiency during nMnO2 enhanced coagulation processes. Trace elemental Tl firstly adsorbed on nMnO2 and then removed accompanying with nMnO2 settling. The information obtained in the present study may provide a potential strategy for drinking water treatment plants threatened by trace Tl.

  6. Feeding enhances skeletal growth and energetic stores of an Atlantic coral under significantly elevated CO2

    Science.gov (United States)

    Drenkard, L.; Cohen, A. L.; McCorkle, D. C.; dePutron, S.; Zicht, A.

    2011-12-01

    Many corals living under the relatively acidic conditions of naturally high-CO2 reefs are calcifying as fast or faster than their conspecifics on naturally low CO2 reefs. These observations are inconsistent with most experimental work that shows a negative impact of ocean acidification on coral calcification. We investigated the link between coral nutritional (energetic) status and the calcification response to significantly elevated CO2. Juveniles of the Atlantic brooding coral, Favia fragum were reared for three weeks under fully crossed CO2 and feeding conditions: ambient (μar =1.6+-0.2) and high CO2 (μar =3.7+-0.3); fed and unfed. In most measured parameters, the effect of feeding is much stronger than the effect of CO2. Nutritionally enhanced (fed) corals, regardless of CO2 condition, have higher concentrations of total lipid and their skeletons are both significantly larger and more developmentally advanced than those of corals relying solely on autotrophy. In measurements of corallite weight, where the impact of CO2 is most apparent, no statistical difference is observed between unfed corals under ambient CO2 conditions and fed corals reared under 1600 ppm CO2. Our results suggest that coral energetic status, which can be enhanced by heterotrophic feeding but depleted by stressors such as bleaching, will play a key role in the coral response to ocean acidification and thus, in the resilience of reef ecosystems under climate change.

  7. Enhanced expression of resistin-like molecule beta in human colon cancer and its clinical significance.

    Science.gov (United States)

    Zheng, Li-Duan; Tong, Qiang-Song; Weng, Mi-Xia; He, Jun; Lv, Qing; Pu, Jia-Rui; Jiang, Guo-Song; Cai, Jia-Bin; Liu, Yuan; Hou, Xiao-Hua

    2009-02-01

    Previous studies have indicated that resistin-like molecule beta (RELM beta), an intestinal goblet cell-specific protein, is markedly increased in the intestinal tumors of min mice and over-expressed in a human colon cancer cell line. We hypothesized that RELM beta might be enhanced in human colon cancer. The aim of this study was to examine the clinical importance of RELM beta expression in colon cancer patients and to correlate its expression with various clinicopathological parameters, upstream regulatory molecule expression, tumor proliferative capacity, and patients' survival. Of the 80 colon cancer patients studied, 65 (81.25%) tested positive for RELM beta, mainly in the cytoplasm of colon mucosa. Contrasting sharply with the strongly RELM beta-positive tumors, normal colon mucous membrane was negative or weakly positive. RELM beta positivity in colon cancer was correlated with histological grade of differentiation and lymph node metastasis, but not with age, gender, tumor location and size, tumor infiltration, Dukes' stage, liver metastasis, and venous invasion. RELM beta expression was significantly correlated with the expression of transcription factor CDX-2 (P 0.05). The mean postoperative survival time (2.76 years) of RELM beta-positive patients was significantly longer than that (1.26 years) of RELM beta-negative patients (P = 0.032). These findings support evidence of the enhanced RELM beta expression in colon cancer patients and suggest that further investigation is warranted to explore the role of RELM beta in colon cancer.

  8. Tumour antigen targeted monoclonal antibodies incorporating a novel multimerisation domain significantly enhance antibody dependent cellular cytotoxicity against colon cancer.

    Science.gov (United States)

    Jain, Ajay; Poonia, Bhawna; So, Edward C; Vyzasatya, Ravi; Burch, Erin E; Olsen, Henrik S; Mérigeon, Emmanuel Y; Block, David S; Zhang, Xiaoyu; Schulze, Dan H; Hanna, Nader N; Twadell, William S; Yfantis, Harris G; Chan, Siaw L; Cai, Ling; Strome, Scott E

    2013-10-01

    Tumour antigen targeted antibodies (mAbs) can induce natural killer (NK) cells to kill tumours through antibody dependent cellular cytotoxicity (ADCC) upon engagement of NK cell expressed FcγRIIIa. FcγRIIIa polymorphisms partially dictate the potency of the ADCC response. The high affinity FcγRIIIa-158-valine (V) polymorphism is associated with more potent ADCC response than the low affinity FcγRIIIa-158-phenylalanine (F) polymorphism. Because approximately 45% of patients are homozygous for the FcγRIIIa-158-F polymorphism (FF genotype), their ability to mount ADCC is impaired. We investigated whether a novel mAb capable of binding multiple antigen specific targets and engaging multiple low affinity FcγRIIIa receptors could further enhance ADCC against colon cancer in vitro. Specifically, we generated a novel anti-epidermal growth factor receptor (EGFR) antibody (termed a stradobody) consisting of an unmodified Fab sequence and two Immunoglobulin G, subclass 1 (IgG1) Fc domains separated by an isoleucine zipper domain and the 12 amino-acid IgG2 hinge. The stradobody framework induced multimerisation and was associated with increased binding to the EGFR and FcγRIIIa. From a functional perspective, when compared to an unmodified anti-EGFR mAb with a sequence identical to cetuximab (a commercially available anti-EGFR mAb), stradobodies significantly enhanced ADCC. These effects were observed using both KRAS wild type HT29 and KRAS mutant SW480 colon cancer cells as targets, and by NK cells obtained from healthy donors and a cohort of patients with colon cancer. These data suggest that high avidity cross-linking of multiple tumour surface antigens and multiple NK cell associated FcγRIIIa molecules can enhance ADCC and partially overcome impaired ADCC by FF genotype individuals in vitro.

  9. COMPLEX HEAT TRANSFER ENHANCEMENT BY FLUID INDUCED VIBRATION

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A new method of heat transfer enhancement by fluid induced vibration was put forward, and its theoretical analysis and experimental study were performed. Though people always try to prophylaxis fluid induced vibration for regarding it as an accident, the utilization space of fluid induced vibration is still very large. The in-surface and out-surface vibrations which come from the fluid induce elastic tube bundles, can effectively increase the convective heat transfer coefficient, and also decrease the fouling resistance, then increase the heat transfer coefficient remarkably.

  10. ULTRASOUND INDUCED AND LASER ENHANCED COLD FUSION CHEMISTRY

    Institute of Scientific and Technical Information of China (English)

    T.V.Prevenslik

    1995-01-01

    The standard model of sonoluminescence suggests that the coulomb barrer to deuterium fusion may be overcome by high bubble gas temperatures caused by compression heating if the bubble diameter remains spherical during bubble collapse.However,in the more likely collapse geometry of a pancake shape,the temperature rise in the bubbles is negligible.But the collapsing pancake bubble is fund to significantly increase the frequency of the infrared energy available in the vibrational state of the water molecules at ambient temperature.For a collapse to liquied density,ultraviolet radiation at about 10eV is fund.Although the ultraviolet radiation is of a low intensity,higher intensities may be possible if the bubble collapse is enhanced by visible and infrared lases.Neither hot nor cold fusion is predicted in bubble collapse but the ultraviolet energy at about 10eV developed in the bubble is sufficient to provide the basis for a new field of chemistry called ultrasound induced and laser enhanced cold fusion chemistry.

  11. Locked Nucleic Acid Probes (LNA) for Enhanced Detection of Low-Level, Clinically Significant Mutations.

    Science.gov (United States)

    Nafa, Khedoudja; Hameed, Meera; Arcila, Marie E

    2016-01-01

    The detection of clinically significant somatic mutations present at low level in a tissue sample represents a challenge in any laboratory. While several high sensitivity methods are described, the incorporation of these new techniques in a clinical lab may be difficult if the technology is not readily available or requires major changes in the workflow of the laboratory. Techniques that are robust and easily adapted to existing laboratory protocols are highly advantageous. In this chapter we describe the use of locked nucleic acid (LNA) probes to modify existing polymerase chain reaction (PCR)-based protocols which can then be sequenced by Sanger sequencing. LNA probes are used to enhance the sensitivity of Sanger sequencing to mutation frequencies below 1 %. The method is robust and is easily incorporated for assessment of any sample with low tumor content or low mutant allele burden.

  12. Significant Broadband Photocurrent Enhancement by Au-CZTS Core-Shell Nanostructured Photocathodes.

    Science.gov (United States)

    Zhang, Xuemei; Wu, Xu; Centeno, Anthony; Ryan, Mary P; Alford, Neil M; Riley, D Jason; Xie, Fang

    2016-03-21

    Copper zinc tin sulfide (CZTS) is a promising material for harvesting solar energy due to its abundance and non-toxicity. However, its poor performance hinders their wide application. In this paper gold (Au) nanoparticles are successfully incorporated into CZTS to form Au@CZTS core-shell nanostructures. The photocathode of Au@CZTS nanostructures exhibits enhanced optical absorption characteristics and improved incident photon-to-current efficiency (IPCE) performance. It is demonstrated that using this photocathode there is a significant increase of the power conversion efficiency (PCE) of a photoelectrochemical solar cell of 100% compared to using a CZTS without Au core. More importantly, the PCE of Au@CZTS photocathode improved by 15.8% compared to standard platinum (Pt) counter electrode. The increased efficiency is attributed to plasmon resonance energy transfer (PRET) between the Au nanoparticle core and the CZTS shell at wavelengths shorter than the localized surface plasmon resonance (LSPR) peak of the Au and the semiconductor bandgap.

  13. Rebamipide and mosapride enhance pilocarpine-induced salivation

    Directory of Open Access Journals (Sweden)

    Kazuo Hike

    2009-08-01

    Full Text Available Background: During esophageal acid clearance, salivation plays an important role in defending the esophageal mucosa. Mosapride, an agent used in chronic, long-term therapy of gastro-esophageal reflux disease (GERD was regarded as mediating its efficacy through prokinetic properties. Rebamipide is also widely used as an anti-gastritis and anti-ulcer agent in GERD patients with chronic gastritis. The aim of this study is to investigate the effects of rebamipide, mosapride, and risperidone on the salivation induced by pilocarpine. Materials and Methods: The experiments were conducted on 4-week male SD rats (120-150g. The salivation was induced by intraperitoneally administrated pilocarpine and saliva was collected using preweighted small cotton balls inserted into the animal's mouth every 30 min for 180 min. Thirteen minutes before intraperitoneal administration of pilocarpine, rebamipide, mosapride, and risperidone were administered intraduodenally. Control rats were conducted by intraperitoneal administration of saline and intraduodenal administration of 0.5% methylcellulose solution. Rsults: The saliva weight at 0-30 min was significantly (p<0.01 increased after administration of pilocarpine, compared to control rats. An additional administration of mosapride and rebamipide increased the saliva weight at 0-30 min. The total volume of saliva for 150 min after administration of pilocarpine was the highest after preadministration of rebamipide, followed by mosapride, and risperidone. Conclusions: Increase in salivation produced by i.p. pilocarpine was enhanced by preadministration of rebamipide and mosapride.

  14. Actinomycin D-induced enhancement of ubiquinone biosynthesis in rat.

    Science.gov (United States)

    Gopalaswamy, U V; Aiyar, A S

    1976-07-01

    Administration of actinomycin D to fasted rats induces an enhancement of the labeling of hepatic ubiquinone by [2-14C] acetate both in vivo and in vitro. The incorporation of [2-14C] mevalonate into ubiquinone is also increased, although to a significantly lesser extent; this, however, presumably results from greater uptake of the labeled precursor by liver of drug-treated rats. The drug-administered animals show increased activity of liver microsomal mevalonate: NADP oxidoreductase, the rate-limiting enzyme in isoprenoid biogenesis. The incorporation of [u-14C] benzoic acid and CH3-[14C] methionine into ubiquinone in liver slices, however, reveals a decrease in actinomycin D administered rats. This appears to be due to a specific inhibition of the pathway leading to the benzoquinone moiety of ubiquinone and not to an increase in the pool-size of the precursors. The stimulatory effect of the drug on ubiquinone biosynthesis is also observable in cholesterol-fed rats. The actinomycin D-induced increase in ubiquinone biosynthesis is dependent on new protein synthesis since the effect is abolished by treating the animals with either cycloheximide or puromycin.

  15. Does Enhanced External Counterpulsation (EECP Significantly Affect Myocardial Perfusion?: A Systematic Review & Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Qin

    Full Text Available Enhanced external counterpulsation (EECP is currently applied for treating coronary artery disease (CAD patients. However, the mechanism(s by which EECP ameliorates angina pectoris and long-term left ventricular function remain largely unknown. The aim of this study will be to assess whether EECP significantly affects myocardial perfusion in CAD patients through a systematic review and meta-analysis of the available literature.MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched for prospective studies on CAD patients that underwent EECP and reported myocardial perfusion data pre- and post-EECP. The impact of EECP was assessed based on the weighted mean difference (WMD in myocardial perfusion from pre-EECP to post-EECP. Statistical heterogeneity was assessed by the I2 index. Publication bias was assessed through visual inspection of the funnel plot as well as Begg's and Egger's testing.Standard EECP therapy (i.e., 35-36 one-hour sessions within a seven-week period significantly increased myocardial perfusion in CAD patients (pooled WMD: -0.19, 95% CI: -0.38 to 0.00, p = 0.049. A random effects analysis was applied on account of significant heterogeneity (I2 = 89.1%, p = 0.000. There was no evidence of significant publication bias (Begg's p = 0.091; Egger's p = 0.282.Standard EECP therapy significantly increases myocardial perfusion in CAD patients. This study's findings support the continued use of standard EECP therapy in CAD patients and provides one putative physiological mechanism to help explain the improvements in angina pectoris and long-term left ventricular function observed in CAD patients after EECP therapy.

  16. Behaviorally inhibited individuals demonstrate significantly enhanced conditioned response acquisition under non-optimal learning conditions.

    Science.gov (United States)

    Holloway, J L; Allen, M T; Myers, C E; Servatius, R J

    2014-03-15

    Behavioral inhibition (BI) is an anxiety vulnerability factor associated with hypervigilance to novel stimuli, threat, and ambiguous cues. The progression from anxiety risk to a clinical disorder is unknown, although the acquisition of defensive learning and avoidance may be a critical feature. As the expression of avoidance is also central to anxiety development, the present study examined avoidance acquisition as a function of inhibited temperament using classical eyeblink conditioning. Individuals were classified as behaviorally inhibited (BI) or non-inhibited (NI) based on combined scores from the Adult and Retrospective Measures of Behavioural Inhibition (AMBI and RMBI, respectively). Acquisition was assessed using delay, omission, or yoked conditioning schedules of reinforcement. Omission training was identical to delay, except that the emission of an eyeblink conditioned response (CR) resulted in omission of the unconditioned airpuff stimulus (US) on that trial. Each subject in the yoked group was matched on total BI score to a subject in the omission group, and received the same schedule of CS and US delivery, resulting in a partial reinforcement training schedule. Delay conditioning elicited significantly more CRs compared to the omission and yoked contingencies, the latter two of which did not differ from each other. Thus, acquisition of an avoidance response was not apparent. BI individuals demonstrated enhanced acquisition overall, while partial reinforcement training significantly distinguished between BI and NI groups. Enhanced learning in BI may be a function of an increased defensive learning capacity, or sensitivity to uncertainty. Further work examining the influence of BI on learning acquisition is important for understanding individual differences in disorder etiology in anxiety vulnerable cohorts.

  17. Significant enhancement of the charging efficiency in the cavities of ferroelectrets through gas exchange during charging

    Science.gov (United States)

    Qiu, Xunlin

    2016-11-01

    Ferroelectrets are non-polar polymer foams or polymer systems with internally charged cavities. They are charged through a series of dielectric barrier discharges (DBDs) that are caused by the electrical breakdown of the gas inside the cavities. Thus, the breakdown strength of the gas strongly influences the charging process of ferroelectrets. A gas with a lower breakdown strength has a lower threshold voltage, thus decreasing the onset voltage for DBD charging. However, a lower threshold voltage also leads to a lower value for the remanent polarization, as back discharges that are caused by the electric field of the internally deposited charges can take place already at lower charge levels. On this basis, a charging strategy is proposed where the DBDs start in a gas with a lower breakdown strength (in the present example, helium) and are completed at a higher breakdown strength (e.g., nitrogen or atmospheric air). Thus, the exchange of the gas in the cavities during charging can significantly enhance the charging efficiency, i.e., yield much higher piezoelectric coefficients in ferroelectrets at significantly lower charging voltages.

  18. Graphene Oxide Quantum Dots Covalently Functionalized PVDF Membrane with Significantly-Enhanced Bactericidal and Antibiofouling Performances

    Science.gov (United States)

    Zeng, Zhiping; Yu, Dingshan; He, Ziming; Liu, Jing; Xiao, Fang-Xing; Zhang, Yan; Wang, Rong; Bhattacharyya, Dibakar; Tan, Timothy Thatt Yang

    2016-02-01

    Covalent bonding of graphene oxide quantum dots (GOQDs) onto amino modified polyvinylidene fluoride (PVDF) membrane has generated a new type of nano-carbon functionalized membrane with significantly enhanced antibacterial and antibiofouling properties. A continuous filtration test using E. coli containing feedwater shows that the relative flux drop over GOQDs modified PVDF is 23%, which is significantly lower than those over pristine PVDF (86%) and GO-sheet modified PVDF (62%) after 10 h of filtration. The presence of GOQD coating layer effectively inactivates E. coli and S. aureus cells, and prevents the biofilm formation on the membrane surface, producing excellent antimicrobial activity and potentially antibiofouling capability, more superior than those of previously reported two-dimensional GO sheets and one-dimensional CNTs modified membranes. The distinctive antimicrobial and antibiofouling performances could be attributed to the unique structure and uniform dispersion of GOQDs, enabling the exposure of a larger fraction of active edges and facilitating the formation of oxidation stress. Furthermore, GOQDs modified membrane possesses satisfying long-term stability and durability due to the strong covalent interaction between PVDF and GOQDs. This study opens up a new synthetic avenue in the fabrication of efficient surface-functionalized polymer membranes for potential waste water treatment and biomolecules separation.

  19. Significantly enhanced hydrogen storage in metal-organic frameworks via spillover.

    Science.gov (United States)

    Li, Yingwei; Yang, Ralph T

    2006-01-25

    The utilization of hydrogen in fuel-cell powered vehicles is limited by the lack of a safe and effective system for hydrogen storage. At the present time, there is no viable storage technology capable of meeting the DOE targets. Porous metal-organic frameworks (MOFs) are novel and potential candidates for hydrogen storage. Until now it is still not possible to achieve any significant hydrogen storage capacity in MOFs at ambient temperature. Here, we report, for the first time, significant amounts of hydrogen storage in MOF-5 and IRMOF-8 at ambient temperature by using a very simple technique via hydrogen dissociation and spillover. Thus, hydrogen uptakes for MOF-5 and IRMOF-8 can be enhanced by a factor of 3.3 and 3.1, respectively (to nearly 2 wt % at 10 MPa and 298 K). Furthermore, the isotherms are totally reversible. These findings suggest that our technique is suitable for hydrogen storage in a variety of MOF materials because of their similar structures as MOF-5 and IRMOF-8.

  20. Significantly Enhanced Actuation Performance of IPMC by Surfactant-Assisted Processable MWCNT/Nafion Composite

    Institute of Scientific and Technical Information of China (English)

    Qingsong He; Min Yu; Dingshan Yu; Yan Ding; Zhendong Dai

    2013-01-01

    The performance of Ionic Polymer Metal Composite (IPMC) actuator was significantly enhanced by incorporating surfactant-assisted processable Multi-Walled Carbon Nanotubes (MWCNTs) into a Nation solution.Cationic surfactant Cetyl Trimethyl Ammonium Bromide (CTAB) was employed to disperse MWCNTs in the Nation matrix,forming a homogeneous and stable dispersion of nanotubes.The processing did not involve any strong acid treatment and thus effectively preserved the excellent electronic properties associated with MWCNT.The as-obtained MWCNT/Nafion-IPMC actuator was tested in terms of conductivity,bulk and surface morphology,blocking force and electric current.It was shown that the blocking force and the current of the new IPMC are 2.4 times and 1.67 times higher compared with a pure Nation-based IPMC.Moreover,the MWCNT/IPMC performance is much better than previously reported Nafion-IPMC doped by acid-treated MWCNT.Such significantly improved performance should be attributed to the improvement of electrical property associated with the addition of MWCNTs without acid treatment.

  1. [The latex agglutination with video digital registration: the enhancement of diagnostic significance of conventional technique].

    Science.gov (United States)

    Starovoĭtova, T A; Steriopolo, N A; Zaĭko, V V; Vengerov, Iu Iu

    2012-02-01

    The rapid semiquantitative latex-tests, because of their analytic characteristics and convenient application, became widespread in the practice of laboratory diagnostics. Though, in spite of high sensitivity and specificity, their diagnostic effectiveness is lower that it could be mainly because of the impossibility to document the results of latex agglutinative re4actions and to manage the objective quality control. The application of systems of video digital registration permits to enhance the clinical significance of these analyses. By means of scanner systems (control and program complex "Expert Lab") the image of analytic objects is received with the results of latex agglutination reaction. The application of program techniques (the programs "Expert Lab - Agglutination" and "Expert Lab - Agglutination - Micros") in data processing permits to get the precise qualitative characteristics of active reactions, to ensure the automatic interpretation of results and gives an opportunity to proceed with the internal laboratory quality control. The saving of analytic object image in computer memory after termination of reaction favors the formation of data base, the implementation of retrospective evaluation of obtained results, additional consultations in dubious cases, including on-line. The application of complex "Expert Lab" permitted to develop the miniaturizes matrix systems permitting to decrease the withdrawal of latex reagents, to increase the productivity of analytical stage of operation preserving all analytical characteristics of method.

  2. Affective significance enhances covert attention: roles of anxiety and word familiarity.

    Science.gov (United States)

    Calvo, Manuel G; Eysenck, Michael W

    2008-11-01

    To investigate the processing of emotional words by covert attention, threat-related, positive, and neutral word primes were presented parafoveally (2.2 degrees away from fixation) for 150 ms, under gaze-contingent foveal masking, to prevent eye fixations. The primes were followed by a probe word in a lexical-decision task. In Experiment 1, results showed a parafoveal threat-anxiety superiority: Parafoveal prime threat words facilitated responses to probe threat words for high-anxiety individuals, in comparison with neutral and positive words, and relative to low-anxiety individuals. This reveals an advantage in threat processing by covert attention, without differences in overt attention. However, anxiety was also associated with greater familiarity with threat words, and the parafoveal priming effects were significantly reduced when familiarity was covaried out. To further examine the role of word knowledge, in Experiment 2, vocabulary and word familiarity were equated for low- and high-anxiety groups. In these conditions, the parafoveal threat-anxiety advantage disappeared. This suggests that the enhanced covert-attention effect depends on familiarity with words.

  3. The impact of significant others in motivational enhancement therapy: findings from project MATCH.

    Science.gov (United States)

    Manuel, Jennifer K; Houck, Jon M; Moyers, Theresa B

    2012-05-01

    Social network support for abstinence has been associated with improved treatment outcomes among samples of individuals with alcohol use disorders. As a result, research studies have focused on the inclusion of significant others (SOs) in the treatment process. Nonetheless, little is known about 1) the specific influence SOs may have on clients during treatment sessions or 2) whether SO within-session behaviors have any relationship to client post-treatment drinking. In the current study, Motivational Enhancement Therapy sessions in which a SO was present were coded using a behavioral coding system designed to measure SO and client within-session language. Relationships were observed between SO and client within-session language. Furthermore, some specific SO categories of language predicted post-treatment client drinking. This study is the first systematic evaluation of SO contributions in substance abuse treatment sessions. Future research examining SO language in the treatment of alcohol use disorders might allow clinicians to avoid contributions from SOs that are associated with poorer drinking outcomes.

  4. 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...

  5. Focused R&D For Electrochromic Smart Windowsa: Significant Performance and Yield Enhancements

    Energy Technology Data Exchange (ETDEWEB)

    Mark Burdis; Neil Sbar

    2003-01-31

    There is a need to improve the energy efficiency of building envelopes as they are the primary factor governing the heating, cooling, lighting and ventilation requirements of buildings--influencing 53% of building energy use. In particular, windows contribute significantly to the overall energy performance of building envelopes, thus there is a need to develop advanced energy efficient window and glazing systems. Electrochromic (EC) windows represent the next generation of advanced glazing technology that will (1) reduce the energy consumed in buildings, (2) improve the overall comfort of the building occupants, and (3) improve the thermal performance of the building envelope. ''Switchable'' EC windows provide, on demand, dynamic control of visible light, solar heat gain, and glare without blocking the view. As exterior light levels change, the window's performance can be electronically adjusted to suit conditions. A schematic illustrating how SageGlass{reg_sign} electrochromic windows work is shown in Figure I.1. SageGlass{reg_sign} EC glazings offer the potential to save cooling and lighting costs, with the added benefit of improving thermal and visual comfort. Control over solar heat gain will also result in the use of smaller HVAC equipment. If a step change in the energy efficiency and performance of buildings is to be achieved, there is a clear need to bring EC technology to the marketplace. This project addresses accelerating the widespread introduction of EC windows in buildings and thus maximizing total energy savings in the U.S. and worldwide. We report on R&D activities to improve the optical performance needed to broadly penetrate the full range of architectural markets. Also, processing enhancements have been implemented to reduce manufacturing costs. Finally, tests are being conducted to demonstrate the durability of the EC device and the dual pane insulating glass unit (IGU) to be at least equal to that of conventional

  6. Thyroid Nodules Detected by Contrast-Enhanced Magnetic Resonance Angiography: Prevalence and Clinical Significance.

    Science.gov (United States)

    Lim, Hyun Kyung; Park, Sung Tae; Ha, Hongil; Choi, Seo-youn

    2016-01-01

    Incidental thyroid lesions are frequently found on contrast-enhanced magnetic resonance (CE-MR) angiography. The purpose of this study is to determine the prevalence of thyroid incidentalomas detected by CE-MR angiography and to evaluate their clinical significance by correlation with ultrasound (US) and cytopathological results. We retrospectively reviewed 3,299 consecutive CE-MR angiography examinations performed at our institution between January 2010 and March 2013. Two radiologists evaluated the CE-MR angiography imaging in consensus regarding the presence, location, and vascularity of thyroid incidentaloma. We correlated these findings with follow-up US and cytopathologic results. The prevalence of thyroid incidentalomas detected by CE-MR angiography was 4.6% (152/3,299 patients). CE-MR angiography showed hypervascularity in 86.8% (145/167), isovascularity in 8.4% (14/167), and hypovascularity in 4.8% (8/167) of thyroid nodules compared to vascularity of thyroid parenchyma. Among the patients with thyroid incidentaloma, 34 patients (22.4%) were followed by US examination, and all 36 nodules on CE-MR angiography were detected on follow-up US. Of these nodules, 9 (25%) nodules were classified as probably benign, 26 (72.2%) as indeterminate, and 1 (2.8%) as suspicious malignant nodule. Among the 16 nodules with available cytopathologic results, 12 nodules were benign, 2 nodules were follicular neoplasm, and 2 nodules showed non-diagnostic results. Incidental thyroid nodules were found in 4.6% of CE-MR angiography examinations. Because the high incidence of indeterminate US feature among thyroid incidentaloma, when a thyroid incidentaloma is detected on CE-MR angiography, further evaluation with US should be performed.

  7. Thyroid Nodules Detected by Contrast-Enhanced Magnetic Resonance Angiography: Prevalence and Clinical Significance.

    Directory of Open Access Journals (Sweden)

    Hyun Kyung Lim

    Full Text Available Incidental thyroid lesions are frequently found on contrast-enhanced magnetic resonance (CE-MR angiography. The purpose of this study is to determine the prevalence of thyroid incidentalomas detected by CE-MR angiography and to evaluate their clinical significance by correlation with ultrasound (US and cytopathological results.We retrospectively reviewed 3,299 consecutive CE-MR angiography examinations performed at our institution between January 2010 and March 2013. Two radiologists evaluated the CE-MR angiography imaging in consensus regarding the presence, location, and vascularity of thyroid incidentaloma. We correlated these findings with follow-up US and cytopathologic results.The prevalence of thyroid incidentalomas detected by CE-MR angiography was 4.6% (152/3,299 patients. CE-MR angiography showed hypervascularity in 86.8% (145/167, isovascularity in 8.4% (14/167, and hypovascularity in 4.8% (8/167 of thyroid nodules compared to vascularity of thyroid parenchyma. Among the patients with thyroid incidentaloma, 34 patients (22.4% were followed by US examination, and all 36 nodules on CE-MR angiography were detected on follow-up US. Of these nodules, 9 (25% nodules were classified as probably benign, 26 (72.2% as indeterminate, and 1 (2.8% as suspicious malignant nodule. Among the 16 nodules with available cytopathologic results, 12 nodules were benign, 2 nodules were follicular neoplasm, and 2 nodules showed non-diagnostic results.Incidental thyroid nodules were found in 4.6% of CE-MR angiography examinations. Because the high incidence of indeterminate US feature among thyroid incidentaloma, when a thyroid incidentaloma is detected on CE-MR angiography, further evaluation with US should be performed.

  8. Electrophoretic particle guidance significantly enhances olfactory drug delivery: a feasibility study.

    Directory of Open Access Journals (Sweden)

    Jinxiang Xi

    Full Text Available BACKGROUND: Intranasal olfactory drug delivery provides a non-invasive method that bypasses the Blood-Brain-Barrier and directly delivers medication to the brain and spinal cord. However, a device designed specifically for olfactory delivery has not yet been found. METHODS: In this study, a new delivery method was proposed that utilized electrophoretic forces to guide drug particles to the olfactory region. The feasibility of this method was numerically evaluated in both idealized 2-D and anatomically accurate 3-D nose models. The influence of nasal airflow, electrode strength, and drug release position were also studied on the olfactory delivery efficiency. FINDINGS: Results showed that by applying electrophoretic forces, the dosage to the olfactory region was significantly enhanced. In both 2-D and 3-D cases, electrophoretic-guided delivery achieved olfactory dosages nearly two orders of magnitude higher than that without electrophoretic forces. Furthermore, releasing drugs into the upper half of the nostril (i.e., partial release led to olfactory dosages two times higher than releasing drugs over the entire area of the nostril. By combining the advantages of pointed drug release and appropriate electrophoretic guidance, olfactory dosages of more than 90% were observed as compared to the extremely low olfactory dosage (<1% with conventional inhaler devices. CONCLUSION: Results of this study have important implications in developing personalized olfactory delivery protocols for the treatment of neurological disorders. Moreover, a high sensitivity of olfactory dosage was observed in relation to different pointed release positions, indicating the importance of precise particle guidance for effective olfactory delivery.

  9. 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.

  10. 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.

  11. Enhancement of DNA vaccine-induced immune responses by a 72-bp element from SV40 enhancer

    Institute of Scientific and Technical Information of China (English)

    LI Hai-shan; XU Jian-qing; HONG Kun-xue; SHAO Yi-ming; LIU Yong; LI Ding-feng; ZHANG Ran-ran; TANG Hai-li; ZHANG Yu-wei; HUANG Wei; LIU Ying; PENG Hong

    2007-01-01

    Background Although DNA vaccine is considered as the next generation of vaccine, most DNA vaccine candidates are still suffering from the relatively weak immunogenicity despite the increased dosage of plasmid DNA administered. In order to enhance the immune responses elicited by a codon-optimized HIV gag DNA vaccine, a modified plasmid vector pDRVI1.0 and a booster immunization with replicating Tiantan vaccinia (RTV) strain expressing the same gene were employed.Methods Vector pDRVI1.0 was constructed through inserting the 72-bp element from the SV40 enhancer, which was reported promoting nuclear transport of plasmid DNA, to the upstream of cytomegalovirus enhancer/promoter region of the plasmid vector pVR1012. Gene expression levels from expression plasmids based on pDRVI1.0 and pVR1012 were tested. Humoral and cellular immune responses induced by DNA vaccine alone or DNA prime-RTV boost regimen were determined in mice.Results It was shown that the 72-bp element significantly enhanced the gene expression level in non-dividing cells.gag-specific humoral and cellular immune responses induced by DNA vaccination were both significantly improved, while the Th1/Th2 balance was not obviously affected by the 72-bp element. RTV boosting further significantly enhanced DNA vaccine-primed antibody and T cell responses in a Th1-biased manner.Conclusions The 72-bp SV40 enhancer element should be included in the DNA vaccine vector and RTV strain is a very efficient live vector for boosting immunization.

  12. Suramin induces and enhances apoptosis in a model of hyperoxia-induced oligodendrocyte injury.

    Science.gov (United States)

    Stark, Simone; Schuller, Alexandra; Sifringer, Marco; Gerstner, Bettina; Brehmer, Felix; Weber, Sven; Altmann, Rodica; Obladen, Michael; Buhrer, Christoph; Felderhoff-Mueser, Ursula

    2008-01-01

    Recent evidence suggests oxygen as a powerful trigger for cell death in the immature white matter, leading to periventricular leukomalacia (PVL) as a cause of adverse neurological outcome in survivors of preterm birth. This oligodendrocyte (OL) death is associated with oxidative stress, upregulation of apoptotic signaling factors (i.e., Fas, caspase-3) and decreased amounts of neurotrophins. In search of neuroprotective strategies we investigated whether the polysulfonated urea derivative suramin, recently identified as a potent inhibitor of Fas signaling, affords neuroprotection in an in vitro model of hyperoxia-induced injury to immature oligodendrocytes. Immature OLs (OLN-93) were subjected to 80% hyperoxia (48 h) in the presence or absence of suramin (0, 30, 60, 120 microM). Cell death was assessed by flow cytometry (Annexin V, caspase-3 activity assay) and immunohistochemistry for activated caspase-3. Immunoblotting for the death receptor Fas, cleaved caspase-8 and the phosphorylated isoform of the serine-threonin kinase Akt (pAkt) was performed. Suramin lead to OL apoptosis and potentiated hyperoxia-induced injury in a dose-dependent manner. Immunoblotting revealed increased Fas and caspase-8 expression by suramin treatment. This effect was significantly enhanced when suramin was combined with hyperoxia. Furthermore, pAkt levels decreased following suramin exposure, indicating interference with neurotrophin-dependent growth factor signaling. These data indicate that suramin causes apoptotic cell death and aggravates hyperoxia-induced cell death in immature OLs. Its mechanism of action includes an increase of previously described hyperoxia-induced expression of pro-apoptotic factors and deprivation of growth factor dependent signaling components.

  13. High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome.

    Science.gov (United States)

    Lai, Hao; Jia, Xiao; Yu, Qiuxiao; Zhang, Chenglu; Qiao, Jie; Guan, Youfei; Kang, Jihong

    2014-11-01

    Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS.

  14. Persistent adrenal enhancement may be the earliest CT sign of significant hypovolaemic shock

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, S.C.W.; Lee, R.; Tung, H.K.S.; Chan, F.L

    2003-04-01

    AIM: To report two cases of intense and persistent adrenal enhancement on computed tomography (CT) examinations of the abdomen. MATERIALS AND METHODS: Two patients presented with septic shock, one due to pyogenic liver abscess and the other strangulated obturator hernia with gangrenous bowel. Both patients were resuscitated with fluid before undergoing unenhanced and enhanced CT. RESULTS: In both patients intravascular volume was not reduced as evident by normal calibre of the aorta and inferior vena cava. One patient had abnormal enhancement pattern in the liver and kidneys, suggesting hypoperfusion. The other patient had normal enhancement pattern of the other abdominal viscera. Both patient subsequently died with multi-organ failure. CONCLUSION: We propose that adrenal enhancement may be a sign of hyperperfusion in early stage of shock due to the crucial role of the adrenal glands in this clinical situation. This may not persist with further circulatory compromise due to vasoconstriction. If confirmed, its recognition has potential value of identifying a therapeutic window before irreversible shock set in.

  15. Investigations into mild electric foot shock stress-induced cognitive enhancement: possible role of angiotensin neuropeptides.

    Science.gov (United States)

    Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

    2013-09-01

    This study was designed to investigate the role of angiotensin neuropeptides in mild electric foot shock stress-induced cognitive enhancement in mice. Mild stress was induced by applying mild electric foot shocks of 0.15 mA intensity for 0.5 s. The stress-induced alteration in cognition was assessed using a Morris water maze test. The animals were subjected to mild electric foot shocks 5 min before we recorded escape latency time (ELT), an index of learning, during the first 4 days of a 5-day trial in the Morris water maze. The time spent in target quadrant (TSTQ), an index of retrieval, was noted on the fifth day without prior administration of electric foot shock. The angiotensin-converting enzyme inhibitor lisinopril (5, 10 and 20 mg/kg), and telmisartan (1, 2 and 5 mg/kg), an angiotensin II receptor blocker, were employed to assess the role of angiotensin neuropeptides. The application of mild electric shocks significantly decreased ELT and increased TSTQ, indicating enhancement in stress-induced learning and memory. However, administration of lisinopril and telmisartan significantly attenuated the stress-induced decrease in ELT and increase in TSTQ. It may be concluded that mild electric foot shock-induced stress triggers the release of angiotensin neuropeptides that may be responsible for memory enhancement.

  16. Glioma Cell Invasion is Significantly Enhanced in Composite Hydrogel Matrices Composed of Chondroitin 4- and 4,6-Sulfated Glycosaminoglycans.

    Science.gov (United States)

    Logun, Meghan T; Bisel, Nicole S; Tanasse, Emily A; Zhao, Wujun; Gunasekera, Bhagya; Mao, Leidong; Karumbaiah, Lohitash

    2016-01-01

    Glioblastoma multiforme (GBM) is the most aggressive form of astrocytoma accounting for a majority of primary malignant brain tumors in the United States. Chondroitin sulfate proteoglycans (CSPGs) and their glycosaminoglycan (GAG) side chains are key constituents of the brain extracellular matrix (ECM) implicated in promoting tumor invasion. However, the mechanisms by which sulfated CS-GAGs promote brain tumor invasion are currently unknown. We hypothesize that glioma cell invasion is triggered by the altered sulfation of CS-GAGs in the tumor extracellular environment, and that this is potentially mediated by independent mechanisms involving CXCL12/CXCR4 and LAR signaling respectively. This was tested in vitro by encapsulating the human glioma cell line U87MG-EGFP into monosulfated (4-sulfated; CS-A), composite (4 and 4,6-sulfated; CS-A/E), unsulfated hyaluronic acid (HA), and unsulfated agarose (AG; polysaccharide) hydrogels within microfluidics-based choice assays. Our results demonstrated the enhanced preferential cell invasion into composite hydrogels, when compared to other hydrogel matrices (p<0.05). Haptotaxis assays demonstrated the significantly (p<0.05) faster migration of U87MG-EGFP cells in CXCL12 containing CS-GAG hydrogels when compared to other hydrogel matrices containing the same chemokine concentration. This is likely due to the significantly (p<0.05) greater affinity of composite CS-GAGs to CXCL12 over other hydrogel matrices. Results from qRT-PCR assays further demonstrated the significant (p<0.05) upregulation of the chemokine receptor CXCR4, and the CSPG receptor LAR in glioma cells within CS-GAG hydrogels compared to control hydrogels. Western blot analysis of cell lysates derived from glioma cells encapsulated in different hydrogel matrices further corroborate qRT-PCR results, and indicate the presence of a potential variant of LAR that is selectively expressed only in glioma cells encapsulated in CS-GAG hydrogels. These results suggest that

  17. Enhanced surface plasmon polariton propagation induced by active dielectrics

    OpenAIRE

    Athanasopoulos, C.; Mattheakis, M.; Tsironis, G. P.

    2013-01-01

    We present numerical simulations for the propagation of surface plasmon polaritons in a dielectric-metal-dielectric waveguide using COMSOL multiphysics software. We show that the use of an active dielectric with gain that compensates metal absorption losses enhances substantially plasmon propagation. Furthermore, the introduction of the active material induces, for a specific gain value, a root in the imaginary part of the propagation constant leading to infinite propagation of the surface pl...

  18. The significance of the activity of dissolved oxygen, and other gases, enhanced by high hydrostatic pressure.

    Science.gov (United States)

    Ludwig, Horst; Macdonald, Alister G

    2005-04-01

    The partial pressure of oxygen and other gases dissolved in water and subjected to high hydrostatic pressure is increased. Although this was established many years ago it remains a problematical phenomenon. The review deals with some of the underlying theoretical difficulties and discusses the kinetic and environmental implications of the pressure-enhanced partial pressures.

  19. Prognostic significance of contrast-enhanced CT attenuation value in extrahepatic cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Asayama, Yoshiki [Kyushu University, Department of Advanced Imaging and Interventional Radiology, Graduate School of Medical Sciences, Fukuoka (Japan); Nishie, Akihiro; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Honda, Hiroshi [Kyushu University, Departments of Clinical Radiology, Fukuoka (Japan); Ohtsuka, Takao [Kyushu University, Departments of Surgery and Oncology, Fukuoka (Japan); Yoshizumi, Tomoharu [Kyushu University, Departments of Surgery and Sciences, Fukuoka (Japan); Aishima, Shinichi [Saga University, Pathology and Microbiology, Faculty of Medicine, Saga (Japan); Kyushu University, Departments of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka (Japan); Oda, Yoshinao [Kyushu University, Departments of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka (Japan)

    2017-06-15

    To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT - attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT - attenuation value at unenhanced CT)] x 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. (orig.)

  20. Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells.

    Science.gov (United States)

    Park, Jae Hyeon; Lee, Jeong Eun; Lee, Soo-Jin; Park, Soo Jin; Park, Kyung Hun; Jeong, Mihye; Koh, Hyun Chul

    2013-10-23

    Oxidative stress created by environmental toxicants activates several signaling pathways. Autophagy is one of the first lines of defense against oxidative stress damage. The autophagy pathway can be induced and up-regulated in response to intracellular reactive oxygen species (ROS). Recently, we reported that fipronil (FPN)-induced mitochondria-dependent apoptosis is mediated through ROS in human neuroblastoma SH-SY5Y cells. In this study, we explored the role of autophagy to prevent FPN neurotoxicity. We investigated the modulation of FPN-induced apoptosis according to autophagy regulation. FPN activated caspase-9 and caspase-3, and induced nuclear fragmentation and condensation, all of which indicate that FPN-induced cell death was due to apoptosis. In addition, we observed FPN-induced autophagic cell death by monitoring the expression of LC3-II and Beclin-1. Exposure to FPN in SH-SY5Y cells led to the production of ROS. Treatment with N-acetyl-cysteine (NAC) effectively blocked both apoptosis and autophagy. Interestingly, pretreatment with rapamycin, an autophagy inducer, significantly enhanced the viability of FPN-exposed cells; the enhancement of cell viability was partially due to alleviation of FPN-induced apoptosis via a decrease in levels of cleaved caspase-3. However, pretreatment with 3-methyladenine (3MA) a specific inhibitor for autophagy, remarkably strengthened FPN toxicity and further induced activation of caspase-3 in these cells. Our studies suggest that FPN-induced cytotoxicity is modified by autophagy regulation and that rapamycin is neuroprotective against FPN-induced apoptosis through enhancing autophagy.

  1. Microtubule dynamics control HGF-induced lung endothelial barrier enhancement.

    Directory of Open Access Journals (Sweden)

    Xinyong Tian

    Full Text Available Microtubules (MT play a vital role in many cellular functions, but their role in peripheral actin cytoskeletal dynamics which is essential for control of endothelial barrier and monolayer integrity is less understood. We have previously described the enhancement of lung endothelial cell (EC barrier by hepatocyte growth factor (HGF which was associated with Rac1-mediated remodeling of actin cytoskeleton. This study investigated involvement of MT-dependent mechanisms in the HGF-induced enhancement of EC barrier. HGF-induced Rac1 activation was accompanied by phosphorylation of stathmin, a regulator of MT dynamics. HGF also stimulated MT peripheral growth monitored by time lapse imaging and tracking analysis of EB-1-decorated MT growing tips, and increased the pool of acetylated tubulin. These effects were abolished by EC pretreatment with HGF receptor inhibitor, downregulation of Rac1 pathway, or by expression of a stathmin-S63A phosphorylation deficient mutant. Expression of stathmin-S63A abolished the HGF protective effects against thrombin-induced activation of RhoA cascade, permeability increase, and EC barrier dysfunction. These results demonstrate a novel MT-dependent mechanism of HGF-induced EC barrier regulation via Rac1/PAK1/stathmin-dependent control of MT dynamics.

  2. Enhanced Thermoelectric Performance of Nanostructured Bi2Te3 through Significant Phonon Scattering.

    Science.gov (United States)

    Yang, Lei; Chen, Zhi-Gang; Hong, Min; Han, Guang; Zou, Jin

    2015-10-28

    N-type Bi2Te3 nanostructures were synthesized using a solvothermal method and in turn sintered using sparking plasma sintering. The sintered n-type Bi2Te3 pellets reserved nanosized grains and showed an ultralow lattice thermal conductivity (∼0.2 W m(-1) K(-1)), which benefits from high-density small-angle grain boundaries accommodated by dislocations. Such a high phonon scattering leads an enhanced ZT of 0.88 at 400 K. This study provides an efficient method to enhance thermoelectric performance of thermoelectric nanomaterials through nanostructure engineering, making the as-prepared n-type nanostructured Bi2Te3 as a promising candidate for room-temperature thermoelectric power generation and Peltier cooling.

  3. Observation of Significant Quantum Efficiency Enhancement from a Polarized Photocathode with Distributed Bragg Reflector

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shukui [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Poelker, Matthew [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Stutzman, Marcy L. [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Chen, Yiqiao [SVT Associates, Inc., Eden Prairie, MN (United States); Moy, Aaron [SVT Associates, Inc., Eden Prairie, MN (United States)

    2015-09-01

    Polarized photocathodes with higher Quantum efficiency (QE) would help to reduce the technological challenge associated with producing polarized beams at milliampere levels, because less laser light would be required, which simplifies photocathode cooling requirements. And for a given amount of available laser power, higher QE would extend the photogun operating lifetime. The distributed Bragg reflector (DBR) concept was proposed to enhance the QE of strained-superlattice photocathodes by increasing the absorption of the incident photons using a Fabry-Perot cavity formed between the front surface of the photocathode and the substrate that includes a DBR, without compromising electron polarization. Here we present recent results showing QE enhancement of a GaAs/GaAsP strained-superlattice photocathode made with a DBR structure. Typically, a GaAs/GaAsP strained-superlattice photocathode without DBR provides a QE of 1%, at a laser wavelength corresponding to peak polarization. In comparison, the GaAs/GaAsP strained-superlattice photocathodes with DBR exhibited an enhancement of over 2 when the incident laser wavelength was tuned to meet the resonant condition for the Fabry-Perot resonator.

  4. Change and significance of nuclear factor-κB in adriamycin induced cardiomyopathy in rats

    Institute of Scientific and Technical Information of China (English)

    LI Hong-li; LIU Bin; ZHOU Ling-wang; YU Wei-han

    2005-01-01

    Background This study aimed at investigating the change and significance of nuclear factor-κB (NF-κB) in cardiomyopathy induced by adriamycin (ADR) in rats.Methods Sixty male Wistar rats were randomly divided into three groups: control, ADR and ADR+pyrrolidine dithiocarbamate (PDTC) groups. After 30-day experiment, myocardial histopathological observation was performed. Location and distribution of NF-κB p50 was examined by immunohistochemical assay. Expression of NF-κB p50 protein was examined by immunobolt assay. Electrophoretic Mobility Shift Assay examined activity of NF-κB; Myocardium p53 gene expression was examined by RT-PCR analysis. Results The myocardial lesions of rats were less pronounced in ADR +PDTC group than in ADR group. Compared with control group, there were many myocardium nucleuses, which expressed NF-κB p50 and distribute under epicardium. Expression of NF-κB p50 protein in nucleus increased significantly in ADR group. The NF-κB binding activity increased significantly in ADR group. Myocardium expressions of p53 mRNA increased in ADR group. Conclusions The NF-κB binding activity increased significantly in cardiomyopathy induced by ADR in rats. Moreover, NF-κB plays an important role in causing degeneration of myocardial tissue and regulating expression of related-apoptosis genes.

  5. Identifying potentially induced seismicity and assessing statistical significance in Oklahoma and California

    CERN Document Server

    McClure, Mark; Chiu, Kitkwan; Ranganath, Rajesh

    2016-01-01

    In this study, we develop a statistical method for identifying induced seismicity from large datasets and apply the method to decades of wastewater disposal and seismicity data in California and Oklahoma. The method is robust against a variety of potential pitfalls. The study regions are divided into gridblocks. We use a longitudinal study design, seeking associations between seismicity and wastewater injection along time-series within each gridblock. The longitudinal design helps control for non-random application of wastewater injection. We define a statistical model that is flexible enough to describe the seismicity observations, which have temporal correlation and high kurtosis. In each gridblock, we find the maximum likelihood estimate for a model parameter that relates induced seismicity hazard to total volume of wastewater injected each year. To assess significance, we compute likelihood ratio test statistics in each gridblock and each state, California and Oklahoma. Resampling is used to empirically d...

  6. 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

  7. Chronic stress induced disturbances in Laminin: a significant contributor to modulating microglial pro-inflammatory tone?

    Science.gov (United States)

    Pietrogrande, Giovanni; Mabotuwana, Nishani; Zhao, Zidan; Mahmoud, Abdolhoseini; Johnson, Sarah J; Nilsson, Michael; Walker, Frederick R

    2017-09-21

    Over the last decade, evidence supporting a link between microglia enhanced neuro-inflammatory signalling and mood disturbance has continued to build. One issue that has not been well addressed yet are the factors that drive microglia to enter into a higher pro-inflammatory state. The current study addressed the potential role of the extracellular matrix protein Laminin. C57BL6 adult mice were either exposed to chronic stress or handled for 6 consecutive weeks. Changes in Laminin, microglial morphology and pro-inflammatory cytokine expression were examined in tissue obtained from mice exposed to a chronic restraint stress procedure. These in-vivo investigations were complemented by an extensive set of in-vitro experiments utilising both a primary microglia and BV2 cell line to examine how Laminin influenced microglial pro-inflammatory tone. Chronic stress was associated with enhanced the expression of Laminin, microglial de-ramification and pro-inflammatory cytokine signalling. We further identified that microglia when cultured in the presence of Laminin produced and released significantly greater levels of pro-inflammatory cytokines; took longer to return to baseline following stimulation and exhibited enhanced phagocytic activity. These results suggest that chronic restraint stress is capable of modulating Laminin within the CNS, an effect that has implications for understanding environmental mediated disturbances of microglial function. Copyright © 2017. Published by Elsevier Inc.

  8. Enhanced transpiration rate in the high pigment 1 tomato mutant and its physiological significance.

    Science.gov (United States)

    Carvalho, R F; Aidar, S T; Azevedo, R A; Dodd, I C; Peres, L E P

    2011-05-01

    Tomato high pigment (hp) mutants represent an interesting horticultural resource due to their enhanced accumulation of carotenoids, flavonoids and vitamin C. Since hp mutants are known for their exaggerated light responses, the molecules accumulated are likely to be antioxidants, recruited to deal with light and others stresses. Further phenotypes displayed by hp mutations are reduced growth and an apparent disturbance in water loss. Here, we examined the impact of the hp1 mutation and its near isogenic line cv Micro-Tom (MT) on stomatal conductance (gs), transpiration (E), CO(2) assimilation (A) and water use efficiency (WUE). Detached hp1 leaves lost water more rapidly than control leaves, but this behaviour was reversed by exogenous abscisic acid (ABA), indicating the ability of hp1 to respond to this hormone. Although attached hp1 leaves had enhanced gs, E and A compared to control leaves, genotypic differences were lost when water was withheld. Both instantaneous leaf-level WUE and long-term whole plant WUE did not differ between hp1 and MT. Our results indicate a link between exaggerated light response and water loss in hp1, which has important implications for the use of this mutant in both basic and horticultural research.

  9. Significant enhancement of ${\\rm H_2}$ formation in disk galaxies under strong ram pressure

    CERN Document Server

    Henderson, Benjamin

    2016-01-01

    We show, for the first time, that ${\\rm H_2}$ formation on dust grains can be enhanced in disk galaxies under strong ram-pressure (RP). We numerically investigate how the time evolution, of ${\\rm H}$ {\\sc i} and ${\\rm H_2}$ components in disk galaxies orbiting a group/cluster of galaxies, can be influenced by hydrodynamical interaction between the gaseous components of the galaxies and the hot intra-cluster medium (ICM). We find that compression of ${\\rm H}$ {\\sc i} caused by RP increases ${\\rm H_2}$ formation in disk galaxies, before RP rapidly strips ${\\rm H}$ {\\sc i}, cutting off the fuel supply and causing a drop in ${\\rm H_2}$ density. We also find that the level of this ${\\rm H_2}$ formation enhancement in a disk galaxy under RP depends on the mass of its host cluster dark matter (DM) halo, initial positions and velocities of the disk galaxy, and disk inclination angle with respect to the orbital plane. We demonstrate that dust growth is a key factor in the evolution of the ${\\rm H}$ {\\sc i} and ${\\rm H...

  10. Quercetin induces autophagy via FOXO1-dependent pathways and autophagy suppression enhances quercetin-induced apoptosis in PASMCs in hypoxia.

    Science.gov (United States)

    He, Yuanzhou; Cao, Xiaopei; Guo, Pujian; Li, Xiaochen; Shang, Huihui; Liu, Jin; Xie, Min; Xu, Yongjian; Liu, Xiansheng

    2017-02-01

    Quercetin, an important dietary flavonoid has been demonstrated to potentially reverse or even prevent pulmonary arterial hypertension (PAH) progression. However, the effects of quercetin on apoptosis and autophagy in pulmonary arterial smooth muscle cells (PASMCs) have not yet been clearly elucidated. The current study found that quercetin significantly induce the apoptotic and autophagic capacities of PASMCs in vitro and in vivo in hypoxia. In addition, we found that quercetin increases FOXO1 (a major mediator in autophagy regulation) expression and transcriptional activity. Moreover, FOXO1 knockdown by siRNAs inhibited the phosphorylation of mTOR and 4E-BPI, which is downstream of P70-S6K, and markedly blocked quercetin-induced autophagy. We also observed that FOXO1-mediated autophagy was achieved via SESN3 not Rictor upregulation and after mTOR suppression. Furthermore, Treatment with autophagy-specific inhibitors could markedly enhance quercetin-induced apoptosis in PASMCs under hypoxia. Finally, quercetin in combination with autophagy inhibition treatment could enhance the therapeutic effects of quercetin in hypoxia-associated PAH in vivo. Taken together, quercetin could enhance hypoxia-induced autophagy through the FOXO1-SENS3-mTOR pathway in PASMCs. Combining quercetin and autophagy inhibitors may be a novel therapeutic strategy for treating hypoxia-associated PAH. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Curcumin significantly enhances dual PI3K/Akt and mTOR inhibitor NVP-BEZ235-induced apoptosis in human renal carcinoma Caki cells through down-regulation of p53-dependent Bcl-2 expression and inhibition of Mcl-1 protein stability.

    Directory of Open Access Journals (Sweden)

    Bo Ram Seo

    Full Text Available The PI3K/Akt and mTOR signaling pathways are important for cell survival and growth, and they are highly activated in cancer cells compared with normal cells. Therefore, these signaling pathways are targets for inducing cancer cell death. The dual PI3K/Akt and mTOR inhibitor NVP-BEZ235 completely inhibited both signaling pathways. However, NVP-BEZ235 had no effect on cell death in human renal carcinoma Caki cells. We tested whether combined treatment with natural compounds and NVP-BEZ235 could induce cell death. Among several chemopreventive agents, curcumin, a natural biologically active compound that is extracted from the rhizomes of Curcuma species, markedly induced apoptosis in NVP-BEZ235-treated cells. Co-treatment with curcumin and NVP-BEZ235 led to the down-regulation of Mcl-1 protein expression but not mRNA expression. Ectopic expression of Mcl-1 completely inhibited curcumin plus NVP-NEZ235-induced apoptosis. Furthermore, the down-regulation of Bcl-2 was involved in curcumin plus NVP-BEZ235-induced apoptosis. Curcumin or NVP-BEZ235 alone did not change Bcl-2 mRNA or protein expression, but co-treatment reduced Bcl-2 mRNA and protein expression. Combined treatment with NVP-BEZ235 and curcumin reduced Bcl-2 expression in wild-type p53 HCT116 human colon carcinoma cells but not p53-null HCT116 cells. Moreover, Bcl-2 expression was completely reversed by treatment with pifithrin-α, a p53-specific inhibitor. Ectopic expression of Bcl-2 also inhibited apoptosis in NVP-BE235 plus curcumin-treated cells. In contrast, NVP-BEZ235 combined with curcumin did not have a synergistic effect on normal human skin fibroblasts and normal human mesangial cells. Taken together, combined treatment with NVP-BEZ235 and curcumin induces apoptosis through p53-dependent Bcl-2 mRNA down-regulation at the transcriptional level and Mcl-1 protein down-regulation at the post-transcriptional level.

  12. Gut symbiont enhances insecticide resistance in a significant pest, the oriental fruit fly Bactrocera dorsalis (Hendel).

    Science.gov (United States)

    Cheng, Daifeng; Guo, Zijun; Riegler, Markus; Xi, Zhiyong; Liang, Guangwen; Xu, Yijuan

    2017-02-01

    Symbiotic bacteria affect insect physiology and ecology. They may also mediate insecticide resistance within their hosts and thereby impact pest and vector control practices. Here, we document a novel mechanism of insecticide resistance in which a gut symbiont of the tephritid pest fruit fly Bactrocera dorsalis enhances resistance to the organophosphate insecticide trichlorphon. We demonstrated that the gut symbiont Citrobacter sp. (CF-BD) plays a key role in the degradation of trichlorphon. Based on a comparative genomics analysis with other Citrobacter species, phosphatase hydrolase genes were identified in CF-BD. These CF-BD genes had higher expression when trichlorphon was present. Bactrocera dorsalis inoculated with isolated CF-BD obtained higher trichlorphon resistance, while antibiotic-treated flies were less resistant confirming the key role of CF-BD in insecticide resistance. Our findings suggest that symbiont-mediated insecticide resistance can readily develop in B. dorsalis and may represent a more widely relevant insecticide resistance mechanism than previously recognized.

  13. Significantly enhanced base activation of peroxymonosulfate by polyphosphates: Kinetics and mechanism.

    Science.gov (United States)

    Lou, Xiaoyi; Fang, Changling; Geng, Zhuning; Jin, Yuming; Xiao, Dongxue; Wang, Zhaohui; Liu, Jianshe; Guo, Yaoguang

    2017-04-01

    Base activation of peroxydisulfate (PDS) is a common process aiming for water treatment, but requires high doses of PDS and strongly basic solutions. Peroxymonosulfate (PMS), another peroxygen of sulfurate derived from PDS, may also be activated by a less basic solution. However, enhancing the base-PMS reactivity is still challenging. Here it is reported that pyrophosphate (PA) and tripolyphosphate (PB) can efficiently enhance PMS activation under weakly alkaline conditions (pH 9.5) via the formation of superoxide anion radical (O2(•-)) and singlet oxygen ((1)O2). The rate constant of Acid Orange 7 (AO7) degradation in PA/PMS system (kPA/PMS) was nearly 4.4-15.9 fold higher than that in PMS/base system (kPMS/base) without any polyphosphates. Increases in PA (or PB) concentration, PMS dose and pH favored the rapid dye degradation. Gas chromatograph-mass spectrometer (GC-MS) data confirmed AO7 and 2,4,6-trichlorophenol (2,4,6-TCP) were decomposed to a series of organic intermediates. The radical quenching and probe oxidation experiments indicate the degradation of organic compounds in the PA/PMS and PB/PMS processes was not reliant on sulfate radical (SO4(•-)) and hydroxyl radical (OH) species but on O2(-) and (1)O2 reactive species. Comparison experiments show that the polyphosphate/PMS process was much more favorable than PDS/base process. The present work provides a novel way to activate PMS for contaminant removal using industrial polyphosphate wastewaters. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Plasma-induced polymerization for enhancing paper hydrophobicity.

    Science.gov (United States)

    Song, Zhaoping; Tang, Jiebin; Li, Junrong; Xiao, Huining

    2013-01-30

    Hydrophobic modification of cellulose fibers was conducted via plasma-induced polymerization in an attempt to graft the hydrophobic polymer chains on paper surface, this increasing the hydrophobicity of paper. Two hydrophobic monomers, butyl acrylate (BA) and 2-ethylhexyl acrylate (2-EHA), were grafted on cellulose fibers, induced by atmospheric cold plasma. Various influencing factors associated with the plasma-induced grafting were investigated. Contact-angle measurement, Fourier Transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM) were used to ascertain the occurrence of the grafting and characterized the changes of the cellulose fiber after modification. The results showed that the hydrophobicity of the modified paper sheet was improved significantly after the plasma-induced grafting. The water contact angle on the paper surface reached up to 130°. The morphological differences between modified and unmodified samples were also revealed by SEM observation. The resulting paper is promising as a green-based packaging material.

  15. Lactobacillus plantarum TN627 significantly reduces complications of alloxan-induced diabetes in rats.

    Science.gov (United States)

    Bejar, Wacim; Hamden, Khaled; Ben Salah, Riadh; Chouayekh, Hichem

    2013-12-01

    This study aimed to assess the potential of the probiotic strain Lactobacillus plantarum TN627 for preventing alloxan-induced diabetes in rats. The oral administration of this probiotic was noted to significantly improve the immunological parameters, protect the pancreatic tissues, and reduce the pancreatic and plasmatic α-amylase activities and level of plasma glucose in the treated as compared to the control group of rats. Furthermore, this probiotic treatment was observed to markedly reduce pancreatic and plasmatic lipase activities and serum triglyceride and LDL-cholesterol rates and to increase the level of HDL-Cholesterol. It also exerted efficient protective effects on the liver and kidney functions evidenced by significant decreases in serum aspartate transaminase, alanine transaminase, lactate dehydrogenase, and gamma-glutamyl transpeptidase activities, as well as creatinine and urea contents. Taken together, the findings indicate that L. plantarum TN627 exhibits attractive in vivo antidiabetic effects that may be helpful in preventing diabetic complications in adult rats.

  16. Sulforaphane-induced transcription of thioredoxin reductase in lens: possible significance against cataract formation

    Directory of Open Access Journals (Sweden)

    Varma SD

    2013-10-01

    Full Text Available Shambhu D Varma, Krish Chandrasekaran, Svitlana Kovtun Department of Ophthalmology and Visual Sciences, University of Maryland, Baltimore, MD, USA Purpose: Sulforaphane is a phytochemically derived organic isothiocyanate 1-isothiocyanato-4-methylsulfinyl-butane present naturally in crucifers, including broccoli and cauliflower. Biochemically, it has been reported to induce the transcription of several antioxidant enzymes. Since such enzymes have been implicated in preventing cataract formation triggered by the intraocular generation of oxy-radical species, the purpose of this investigation was to examine whether it could induce the formation of antioxidant enzymes in the eye lens. Thioredoxin reductase (TrxR was used as the target of such induction. Methods: Mice lenses were cultured for an overnight period of 17 hours in medium 199 fortified with 10% fetal calf serum. Incubation was conducted in the absence and presence of sulforaphane (5 µM. Subsequently, the lenses were homogenized in phosphate-buffered saline (PBS, followed by centrifugation. TrxR activity was determined in the supernatant by measuring the nicotinamide adenine dinucleotide phosphate (reduced (NADPH-dependent reduction of 5,5´-dithiobis-2-nitrobenzoic acid (DTNB. Non-specific reduction of DTNB was corrected for by conducting parallel determinations in the presence of aurothiomalate. The reduction of DTNB was followed spectrophotometrically at 410 nm. Results: The activity of TrxR in the lenses incubated with sulforaphane was found to be elevated to 18 times of that observed in lenses incubated without sulforaphane. It was also noticeably higher in the lenses incubated without sulforaphane than in the un-incubated fresh lenses. However, this increase was much lower than that observed for lenses incubated with sulforaphane. Conclusion: Sulforaphane has been found to enhance TrxR activity in the mouse lens in culture. In view of the protective effect of the antioxidant enzymes

  17. Enhancing the analytical performance of laser-induced breakdown spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Cremers, D.A.; Chinni, R.C.; Pichahchy, A.E.; Thornquist, H.K.

    1998-12-31

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The objective of this work is to enhance the analytical capabilities of laser-induced breakdown spectroscopy (LIBS). LIBS is a method of elemental analysis in which powerful laser pulses are focused on a sample to form a microplasma. LIBS is perhaps the most versatile elemental analysis method, applicable to a variety of different real-world analysis problems. Therefore, it is important to enhance the capabilities of the method as much as possible. Accomplishments include: (1) demonstration of signal enhancements of 5--30 times from soils and metals using a double pulse method; (2) development of a model of the observed enhancement obtained using double pulses; (3) demonstration that the analytical performance achievable using low laser-pulse energies (10 and 25 mJ) can match that achievable using an energy of 100 mJ; and (4) demonstration that time-gated detection is not necessary with LIBS.

  18. Enhanced nonlinear susceptibility via double-double electromagnetically induced transparency

    Science.gov (United States)

    Alotaibi, Hessa M. M.; Sanders, Barry C.

    2016-11-01

    We investigate the nonlinear optical susceptibility of an alkali-metal atom with tripod electronic configuration responsible for generating cross-phase modulation and self-phase modulation under the condition of double-double electromagnetically induced transparency. Our investigation demonstrates an enhancement in the nonlinear optical susceptibility of an alkali-metal atom by a factor of 1000 in the region of the second transparency window. This enhancement is in comparison with the atom's susceptibility in the first transparency window for the same parameters under the same conditions. Nonlinear-absorption enhancement arises by canceling Raman-gain generation, which arises when the probe and signal fields have equal intensities. At the center of the second transparency window, we obtain the condition required to attain a nonvanishing nonlinear optical susceptibility. In the bare-state picture, the coupling field must be off resonant from a bare-to-bare-state transition, while working in the semiclassical dressed picture required the signal field to be tuned off resonantly with a bare-to-dressed-state transition. The relation that governs the values of coupling- and signal-field detuning are also obtained. Our scheme exhibits the fact that the second transparency window has advantages over the first transparency window with respect to obtaining an enhanced Kerr effect, and our calculation includes simulation of both low-temperature and Doppler-broadened regimes.

  19. Strain induced ionic conductivity enhancement in epitaxial Ce0.9Gd0.1O22d

    DEFF Research Database (Denmark)

    Kant, K. Mohan; Esposito, Vincenzo; Pryds, Nini

    2012-01-01

    Strained epitaxial Ce0.9Gd0.1O2d (CGO) thin films are deposited on MgO(001) substrates with SrTiO3 (STO) buffer layers. The strain in CGO epitaxial thin films is induced and controlled by varying the thickness of STO buffer layers. The induced strain is found to significantly enhance the in...

  20. Evidence of convective heat transfer enhancement induced by spinodal decomposition.

    Science.gov (United States)

    Poesio, P; Lezzi, A M; Beretta, G P

    2007-06-01

    Spinodal decomposition can be driven by either diffusion or self-induced convection; the importance of convection relative to diffusion depends on the Péclet number, defined as the ratio between convective and diffusive mass fluxes. Diffusion is the dominating mechanism of phase segregation when the Péclet number is small - i.e., when viscosity and diffusivity are large - or when the domain characteristic size is small. For low-viscosity mixtures, convection is the dominating process and the segregation is very rapid as it takes a few seconds compared to the hours needed in the case of pure diffusion. In such cases, strong convective motion of the phase segregating domains is generated even in small-size systems and is almost independent of the temperature difference as long as it is below the transition value. We study experimentally the enhancement of heat transfer in a 1-mm -thick cell. A water-acetonitrile-toulene mixture is quenched into a two-phase region so as to induce convection-driven spinodal decomposition. The heat transfer rate is measured and compared to that obtained in the absence of convective motion. A substantial reduction in the cooling time obtains in the case of spinodal decomposition. The heat transfer enhancement induced by this self-induced, disordered but effectively convective effect may be exploited in the cooling or heating of small-scale systems whereby forced convection cannot be achieved because of the small sizes involved. A scaling analysis of the data based on the diffuse interface H model for a symmetric mixture near the equilibrium point yields very encouraging agreement and insights.

  1. Roxarsone and its metabolites in chicken manure significantly enhance the uptake of As species by vegetables.

    Science.gov (United States)

    Huang, Lianxi; Yao, Lixian; He, Zhaohuan; Zhou, Changmin; Li, Guoliang; Yang, Baomei; Deng, Xiancai

    2014-04-01

    Roxarsone is an organoarsenic feed additive which can be finally degraded to other higher toxic metabolites after excreted by animal. In this work, the uptake of As species by vegetables treated with chicken manure bearing roxarsone and its metabolites was investigated. It was showed that more than 96% of roxarsone added in chicken feed was degraded and converted to arsenite, monomethylarsonic acid, dimethylarsinic acid, arsenate, 4-hydroxyphenylarsonic acid and other unknown As species. Arsenite and arsenate could be found in roots of vegetables but only arsenite transported up to shoots. Chicken manure bearing roxarsone and its metabolites increased 33-175% of arsenite and 28% ∼ seven times of arsenate in vegetable roots, 68-175% of arsenite in edible vegetable shoots. Arsenite, the most toxic As form, was the major extractable As species in vegetables accounted for 79-98%. The results reflected that toxic element As could be absorbed by vegetables via the way: roxarsone in feed → animal → animal manure → soil → crop and the uptake of As species would be enhanced by using chicken manure bearing roxarsone and its metabolites as organic fertilizer.

  2. The significant adhesion enhancement of Ag–polytetrafluoroethylene antibacterial coatings by using of molecular bridge

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Ruijie, E-mail: guoruijie@tyut.edu.cn [Key Laboratory of Interface Science and Engineering in Advanced Materials (Taiyuan University of Technology), Ministry of Education, Taiyuan, 030024 (China); Yin, Guangda; Sha, Xiaojuan [Key Laboratory of Interface Science and Engineering in Advanced Materials (Taiyuan University of Technology), Ministry of Education, Taiyuan, 030024 (China); Zhao, Qi [Division of Mechanical Engineering and Mechatronics, University of Dundee, Dundee, DD1 4HN (United Kingdom); Wei, Liqiao; Wang, Huifang [Key Laboratory of Interface Science and Engineering in Advanced Materials (Taiyuan University of Technology), Ministry of Education, Taiyuan, 030024 (China)

    2015-06-30

    Highlights: • The more effective coupling agent is employed to modify surface. • S–Ag displays more intensive bond strength than that of N–Ag. • The coatings possess the highest level of adhesion. - Abstract: Weak adhesion between the metal-based antibacterial coatings and polymer substrates limits their clinical applications; surface modification is an effective way to solve this intrinsic problem. In this study, UV irradiation was employed to activate the inert silicon rubber substrates, and the grafting of coupling agent (3-mercaptopropyl) trimethoxy silane into the UV-irradiated substrates generated reactive surface containing −SH groups. During electroless plating S which has lone pair electrons anchored Ag{sup +} and produced antibacterial coatings with improved adhesion. The grafting of (3-mercaptopropyl) trimethoxy silane into silicon rubber was verified by X-ray photoelectron spectroscopy (XPS). The adhesion was tested by American Society of Testing Materials (ASTM D 3359-02). Surface elements content and distribution were observed and analyzed by X-ray energy disperse spectroscopy (EDS). The antibacterial performance was characterized by inhibition halo test and shake flash method. The results showed that the as-prepared composite Ag–polytetrafluoroethylene coatings possessed remarkably enhanced adhesion and superior antibacterial activity.

  3. p53 acetylation enhances Taxol-induced apoptosis in human cancer cells.

    Science.gov (United States)

    Kim, Jae Hyeong; Yoon, Eun-Kyung; Chung, Hye-Jin; Park, Seong-Yeol; Hong, Kyeong-Man; Lee, Chang-Hun; Lee, Yeon-Su; Choi, Kyungho; Yang, Young; Kim, Kyungtae; Kim, In-Hoo

    2013-01-01

    Microtubule inhibitors (MTIs) such as Taxol have been used for treating various malignant tumors. Although MTIs have been known to induce cell death through mitotic arrest, other mechanisms can operate in MTI-induced cell death. Especially, the role of p53 in this process has been controversial for a long time. Here we investigated the function of p53 in Taxol-induced apoptosis using p53 wild type and p53 null cancer cell lines. p53 was upregulated upon Taxol treatment in p53 wild type cells and deletion of p53 diminished Taxol-induced apoptosis. p53 target proteins including MDM2, p21, BAX, and β-isoform of PUMA were also upregulated by Taxol in p53 wild type cells. Conversely, when the wild type p53 was re-introduced into two different p53 null cancer cell lines, Taxol-induced apoptosis was enhanced. Among post-translational modifications that affect p53 stability and function, p53 acetylation, rather than phosphorylation, increased significantly in Taxol-treated cells. When acetylation was enhanced by anti-Sirt1 siRNA or an HDAC inhibitor, Taxol-induced apoptosis was enhanced, which was not observed in p53 null cells. When an acetylation-defective mutant of p53 was re-introduced to p53 null cells, apoptosis was partially reduced compared to the re-introduction of the wild type p53. Thus, p53 plays a pro-apoptotic role in Taxol-induced apoptosis and acetylation of p53 contributes to this pro-apoptotic function in response to Taxol in several human cancer cell lines, suggesting that enhancing acetylation of p53 could have potential implication for increasing the sensitivity of cancer cells to Taxol.

  4. Metformin enhances TRAIL-induced apoptosis by Mcl-1 degradation via Mule in colorectal cancer cells

    Science.gov (United States)

    Kim, Jung Lim; Kim, Bo Ram; Na, Yoo Jin; Jo, Min Jee; Jeong, Yoon A.; Lee, Suk-Young; Lee, Sun Il; Lee, Yong Yook; Oh, Sang Cheul

    2016-01-01

    Metformin is an anti-diabetic drug with a promising anti-cancer potential. In this study, we show that subtoxic doses of metformin effectively sensitize human colorectal cancer (CRC) cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), which induces apoptosis. Metformin alone did not induce apoptosis, but significantly potentiated TRAIL-induced apoptosis in CRC cells. CRC cells treated with metformin and TRAIL showed activation of the intrinsic and extrinsic pathways of caspase activation. We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL. Further experiments revealed that metformin did not affect mRNA levels, but increased proteasomal degradation and protein stability of Mcl-1. Knockdown of Mule triggered a significant decrease of Mcl-1 polyubiquitination. Metformin caused the dissociation of Noxa from Mcl-1, which allowed the binding of the BH3-containing ubiquitin ligase Mule followed by Mcl-1ubiquitination and degradation. The metformin-induced degradation of Mcl-1 required E3 ligase Mule, which is responsible for the polyubiquitination of Mcl-1. Our study is the first report indicating that metformin enhances TRAIL-induced apoptosis through Noxa and favors the interaction between Mcl-1 and Mule, which consequently affects Mcl-1 ubiquitination. PMID:27517746

  5. Significantly enhanced pregnancy rates per cycle through cryopreservation and thaw of pronuclear stage oocytes.

    Science.gov (United States)

    Veeck, L L; Amundson, C H; Brothman, L J; DeScisciolo, C; Maloney, M K; Muasher, S J; Jones, H W

    1993-06-01

    To examine the results of a 5-year trial using cryopreservation to limit multiple pregnancy and optimize overall pregnancy per cycle. Retrospective clinical evaluation of pregnancy rates (PRs) per cycle after freezing pronuclear stage human oocytes. Tertiary care academic center. Six hundred seventeen patients treated in 776 IVF-ET cycles from January 1987 to December 1991 (less oocyte donation cycles). Pregnancy rate per cycle after transfer of pre-embryos developed from thawed pronuclear stage oocytes. Three thousand seven hundred thirty-one oocytes were frozen. Of these, 2,039 were thawed. One thousand three hundred seventy-seven survived thawing (68%), and 1,370 were transferred after passing through syngamy to at least the first cleavage (68%). Of patients with thawing, 359 of 401 (90%) (449 of 505 cycles [89%]) received intrauterine transfer. One hundred thirty-three separate clinical pregnancies were established from 128 different cycles (128/449; 29%); 5 cycles had two thaws, each of which resulted in pregnancy. This PR is less than the overall fresh PR observed in patients who had excess pronucleate oocytes frozen (279/776; 36%) but is remarkably similar when adjusted for the number of pre-embryos transferred per cycle. The age of the patient at the time of cryopreservation and the number of quality of pre-embryos ultimately available for transfer were important factors in the establishment of pregnancy. The mode of ovarian stimulation and duration of cryostorage did not prove meaningful. Cryopreserved pronucleate oocytes that survive freezing, thawing, and progress through syngamy demonstrate a similar potential for implantation and pregnancy when compared with fresh conceptuses, the cumulative effect of which is an enhanced total PR per cycle.

  6. FOCUSED R&D FOR ELECTROCHROMIC SMART WINDOWS: SIGNIFICANT PERFORMANCE AND YIELD ENHANCEMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Marcus Milling

    2004-09-23

    Developments made under this program will play a key role in underpinning the technology for producing EC devices. It is anticipated that the work begun during this period will continue to improve materials properties, and drive yields up and costs down, increase durability and make manufacture simpler and more cost effective. It is hoped that this will contribute to a successful and profitable industry, which will help reduce energy consumption and improve comfort for building occupants worldwide. The first major task involved improvements to the materials used in the process. The improvements made as a result of the work done during this project have contributed to the enhanced performance, including dynamic range, uniformity and electrical characteristics. Another major objective of the project was to develop technology to improve yield, reduce cost, and facilitate manufacturing of EC products. Improvements directly attributable to the work carried out as part of this project and seen in the overall EC device performance, have been accompanied by an improvement in the repeatability and consistency of the production process. Innovative test facilities for characterizing devices in a timely and well-defined manner have been developed. The equipment has been designed in such a way as to make scaling-up to accommodate higher throughput necessary for manufacturing relatively straightforward. Finally, the third major goal was to assure the durability of the EC product, both by developments aimed at improving the product performance, as well as development of novel procedures to test the durability of this new product. Both aspects have been demonstrated, both by carrying out a number of different durability tests, both in-house and by independent third-party testers, and also developing several novel durability tests.

  7. Significance of bacterial flora in abdominal irradiation-induced inhibition of lung metastases

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, T.; Ando, K.; Koike, S.

    1988-06-01

    We have previously reported that abdominal irradiation prior to i.v. injection of syngeneic tumor cells reduced metastases in lung. Our report described an investigation of the significance of intestinal organisms in the radiation effect. We found that eliminating intestinal organisms with antibiotics totally abolished the radiation effect. Monoassociation of germ-free mice revealed that the radiation effect was observable only for Enterobacter cloacae, never for Streptococcus faecium, Bifidobacterium adlesentis, or Escherichia coli. After abdominal irradiation of regular mice, E. cloacae multiplied in cecal contents, adhered to mucous membranes, invaded the cecal wall, and translocated to mesenteric lymph nodes. Intravenous administration of E. cloacae in place of abdominal irradiation inhibited metastases. E. cloacae-monoassociated mice developed fewer metastases than germ-free mice, and the reduction was further enhanced by abdominal irradiation. We concluded that abdominal irradiation caused the invasion of E. cloacae from the mucous membrane of the intestine and inhibited formation of lung metastases.

  8. High-Fat Diet-Induced Obesity Enhances Allograft Rejection.

    Science.gov (United States)

    Molinero, Luciana L; Yin, Dengping; Lei, Yuk Man; Chen, Luqiu; Wang, Ying; Chong, Anita S; Alegre, Maria-Luisa

    2016-05-01

    Obesity promotes a state of low-grade inflammation that exacerbates chronic inflammatory diseases, such as asthma and inflammatory bowel disease. In transplantation, the survival of organs transplanted into obese patients is reduced compared with allografts in lean recipients. However, whether this is due to increased alloimmunity remains to be addressed conclusively. We used a mouse model of high-fat diet (HFD)-induced obesity and assessed immune responses to allogeneic stimulation in vitro, allogeneic splenocyte immunization in vivo, and allogeneic heart transplantation. Our results indicate that HFD altered the composition and phenotype of splenic antigen-presenting cells that led to their enhanced capacity to stimulate T cells. Immunization with allogeneic splenocytes in vivo resulted in increased alloreactivity, as determined by IFNγ production. Moreover, cardiac allograft rejection in HFD mice was modestly accelerated compared to aged-matched control animals fed a low-fat diet, correlating with enhanced alloreactive T cell function. Our results highlight the increased alloresponse triggered by HFD-induced obesity and its negative impact on transplant outcome.

  9. Evaluating research for clinical significance: using critically appraised topics to enhance evidence-based neuropsychology.

    Science.gov (United States)

    Bowden, Stephen C; Harrison, Elise J; Loring, David W

    2014-01-01

    Meehl's (1973, Psychodiagnosis: Selected papers. Minneapolis: University of Minnesota Press) distinction between statistical and clinical significance holds special relevance for evidence-based neuropsychological practice. Meehl argued that despite attaining statistical significance, many published findings have limited practical value since they do not inform clinical care. In the context of an ever expanding clinical research literature, accessible methods to evaluate clinical impact are needed. The method of Critically Appraised Topics (Straus, Richardson, Glasziou, & Haynes, 2011, Evidence-based medicine: How to practice and teach EBM (4th ed.). Edinburgh: Elsevier Churchill-Livingstone) was developed to provide clinicians with a "toolkit" to facilitate implementation of evidence-based practice. We illustrate the Critically Appraised Topics method using a dementia screening example. We argue that the skills practiced through critical appraisal provide clinicians with methods to: (1) evaluate the clinical relevance of new or unfamiliar research findings with a focus on patient benefit, (2) help focus of research quality, and (3) incorporate evaluation of clinical impact into educational and professional development activities.

  10. Self-cloning significantly enhances the production of catalase in Bacillus subtilis WSHDZ-01.

    Science.gov (United States)

    Xu, Sha; Guo, Yaqiong; Du, Guocheng; Zhou, Jingwen; Chen, Jian

    2014-08-01

    The katA gene that encodes catalase (CAT) in Bacillus subtilis WSHDZ-01 was overexpressed in B. subtilis WB600 and B. subtilis WSHDZ-01. The CAT yield in both transformed strains was significantly improved compared to that in the wild-type WSHDZ-01 in shake flask culture. When cultured in a 3-L stirred tank reactor (STR), the recombinant CAT activity in B. subtilis WSHDZ-01 could be improved by 419 %, reaching up to 39,117 U/mL and was 8,149.4 U/mg dry cell weight, which is the highest activity reported in Bacillus sp. However, the recombinant CAT in B. subtilis WB600 cultured in a 3-L STR was not significantly improved by any of the common means for process optimization, and the highest CAT activity was 3,673.5 U/mg dry cell weight. The results suggest that self-cloning of the complete expression cassette in the original strain is a reasonable strategy to improve the yield of wild-type enzymes.

  11. Mitochondrial oxidative stress significantly influences atherogenic risk and cytokine-induced oxidant production.

    Science.gov (United States)

    Harrison, Corey M; Pompilius, Melissa; Pinkerton, Kent E; Ballinger, Scott W

    2011-05-01

    Oxidative stress associated with cardiovascular disease (CVD) risk factors contributes to disease development. However, less is known whether specific subcellular components play a role in disease susceptibility. In this regard, it has been previously reported that vascular mitochondrial damage and dysfunction are associated with atherosclerosis. However, no studies have determined whether altered mitochondrial oxidant production directly influences atherogenic susceptibility and response in primary cells to atherogenic factors such as tumor necrosis factor-α (TNF-α). We undertook this study to determine whether increased mitochondrial oxidant production affects atherosclerotic lesion development associated with CVD risk factor exposure and endothelial cell response to TNF-α. We assessed atherosclerotic lesion formation, oxidant stress, and mitochondrial DNA damage in male apolipoprotein E (apoE)-null mice with normal and decreased levels of mitochondrial superoxide dismutase-2 (SOD2; apoE(-/-) and apoE(-/-), SOD2(+/-), respectively) exposed to environmental tobacco smoke or filtered air. Atherogenesis, oxidative stress, and mitochondrial damage were significantly higher in apoE(-/-), SOD2(+/-) mice than in apoE(-/-) controls. Furthermore, experiments with small interfering RNA in endothelial cells revealed that decreased SOD2 activity increased TNF-α-mediated cellular oxidant levels compared with controls. Endogenous mitochondrial oxidative stress is an important CVD risk factor that can modulate atherogenesis and cytokine-induced endothelial cell oxidant generation. Consequently, CVD risk factors that induce mitochondrial damage alter cellular response to endogenous atherogenic factors, increasing disease susceptibility.

  12. Changes and significance of SIRT3 expression in cellular senescence induced by high glucose

    Directory of Open Access Journals (Sweden)

    Bin ZHANG

    2011-09-01

    Full Text Available Objective To investigate the role of the silent information regulator 3(SIRT3 in the decrepitude process of human diploid fibroblasts(WI-38 induced by high glucose.Methods The WI-38 cells [population doublings(PDs,20-32] were cultured in media containing different concentrations of glucose as follows: low glucose(3.34mmol/L,LG,normal glucose(5.56mmol/L,NG,and high glucose(25mmol/L,HG.The protein expression levels of p21,p27,catalase,MnSOD,and SIRT3 were evaluated through Western blot.The double-label immunofluorescence assay was used to detect the location and expression of SIRT3,MnSOD,and senescence-associated heterochromatin foci(SAHF in the WI-38 cells.The ROS level was determined with fluorescent probe.Results The results from the Western blot showed that the protein expression of SIRT3,catalase,and MnSOD decreased significantly in the HG group compared with the LG and NG groups(P 0.05.SIRT3 and MnSOD were highly expressed in the cytoplasm.The ROS levels in the HG group were elevated compared with those in the LG and NG groups.Conclusion SIRT3 may play an important role in cellular senescence induced by high glucose in human diploid fibroblasts.

  13. Sequential changes of hypoxia- inducible factor 1 alpha in experimental spinal cord injury and its significance

    Institute of Scientific and Technical Information of China (English)

    鞠延; 贺民; 毛伯镛

    2002-01-01

    Objective: To study the sequential changes of HIF-1α(hypoxia-inducible factor 1 alpha) in experimental spinalcord injury in rats and to analyze its potential effects inSCI.Methods: A static compression model of SCI wasemployed in this study. Expressions of HIF-1α weremeasured with immunohistochemical staining, while flowcytometry was used to determine the apoptotic ratio andbcl-2 expressions.Results: HIF-1α began to increase 1 day after injury,and reached the peak at 3-7 days. Two weeks later, itdeclined significantly. The sequential changes of HIF-1αcoincided well with the alterations of apoptotic ratio andcontents of bel-2.Conclusions: HIF-1α possibly participates in thesecondary ischemic and hypoxic procedures after spinalcord injury, and may mediate the traumatic apoptosis.Further understanding of HIF-1α may provide newtherapeutic regimens for SCI.

  14. Significance of Shrinkage Induced Clamping Pressure in Fiber-Matrix Bonding in Cementitious Composite Materials

    DEFF Research Database (Denmark)

    Stang, Henrik

    1996-01-01

    The present paper accesses the significance of shrinkage inducedclamping pressure in fiber/matrix bonding mechanisms incementitious composite materials. The paper contains a description of an experimental setup whichallows mbox{measurement} of the clamping pressure which develops on anelastic...... acting on any elastic inhomogeneityembedded in the same cementitious matrix material. Fiber-shaped inhomogeneities are of special interest in cementitious composite material systems andresults are presented for the development of clamping pressure on three typical fiber types in two typical cementpastes...... used in high performance cementitious composite materials.Assuming a Coulomb type of friction on the fiber/matrix interface andusing typical values for the frictional coefficient it is shownthat the shrinkage induced clamping pressure could be one of the mostimportant factors determining the frictional...

  15. Significant performance enhancement in continuous wave terahertz photomixers based on fractal structures

    Science.gov (United States)

    Jafari, H.; Heidarzadeh, H.; Rostami, A.; Rostami, G.; Dolatyari, M.

    2017-01-01

    A photoconductive fractal antenna significantly improves the performance of photomixing-based continuous wave (CW) terahertz (THz) systems. An analysis has been carried out for the generation of CW-THz radiation by photomixer photoconductive antenna technique. To increase the active area for generation and hence the THz radiation power we used interdigitated electrodes that are coupled with a fractal tree antenna. In this paper, both semiconductor and electromagnetic problems are considered. Here, photomixer devices with Thue-Morse fractal tree antennas in two configurations (narrow and wide) are discussed. This new approach gives better performance, especially in the increasing of THz output power of photomixer devices, when compared with the conventional structures. In addition, applying the interdigitated electrodes improved THz photocurrent, considerably. It produces THz radiation power several times higher than the photomixers with simple gap.

  16. Nanodiamonds on tetrahedral amorphous carbon significantly enhance dopamine detection and cell viability.

    Science.gov (United States)

    Peltola, Emilia; Wester, Niklas; Holt, Katherine B; Johansson, Leena-Sisko; Koskinen, Jari; Myllymäki, Vesa; Laurila, Tomi

    2017-02-15

    We hypothesize that by using integrated carbon nanostructures on tetrahedral amorphous carbon (ta-C), it is possible to take the performance and characteristics of these bioelectrodes to a completely new level. The integrated carbon electrodes were realized by combining nanodiamonds (NDs) with ta-C thin films coated on Ti-coated Si-substrates. NDs were functionalized with mixture of carboxyl and amine groups NDandante or amine NDamine, carboxyl NDvox or hydroxyl groups NDH and drop-casted or spray-coated onto substrate. By utilizing these novel structures we show that (i) the detection limit for dopamine can be improved by two orders of magnitude [from 10µM to 50nM] in comparison to ta-C thin film electrodes and (ii) the coating method significantly affects electrochemical properties of NDs and (iii) the ND coatings selectively promote cell viability. NDandante and NDH showed most promising electrochemical properties. The viability of human mesenchymal stem cells and osteoblastic SaOS-2 cells was increased on all ND surfaces, whereas the viability of mouse neural stem cells and rat neuroblastic cells was improved on NDandante and NDH and reduced on NDamine and NDvox. The viability of C6 cells remained unchanged, indicating that these surfaces will not cause excess gliosis. In summary, we demonstrated here that by using functionalized NDs on ta-C thin films we can significantly improve sensitivity towards dopamine as well as selectively promote cell viability. Thus, these novel carbon nanostructures provide an interesting concept for development of various in vivo targeted sensor solutions.

  17. Mutation of Escherichia coli cytosine deaminase significantly enhances molecular chemotherapy of human glioma.

    Science.gov (United States)

    Kaliberov, S A; Market, J M; Gillespie, G Y; Krendelchtchikova, V; Della Manna, D; Sellers, J C; Kaliberova, L N; Black, M E; Buchsbaum, D J

    2007-07-01

    Combined treatment using adenoviral (Ad)-directed enzyme/prodrug therapy and radiation therapy has the potential to become a powerful method of cancer therapy. We have developed an Ad vector encoding a mutant bacterial cytosine deaminase (bCD) gene (AdbCD-D314A), which has a higher affinity for cytosine than wild-type bCD (bCDwt). The purpose of this study was to evaluate cytotoxicity in vitro and therapeutic efficacy in vivo of the combination of AdbCD-D314A with the prodrug 5-fluorocytosine (5-FC) and ionizing radiation against human glioma. The present study demonstrates that AdbCD-D314A infection resulted in increased 5-FC-mediated cell killing, compared with AdbCDwt. Furthermore, a significant increase in cytotoxicity following AdbCD-D314A and radiation treatment of glioma cells in vitro was demonstrated as compared to AdbCDwt. Animal studies showed significant inhibition of subcutaneous or intracranial tumor growth of D54MG glioma xenografts by the combination of AdbCD-D314A/5-FC with ionizing radiation as compared with either agent alone, and with AdbCDwt/5-FC plus radiation. The results suggest that the combination of AdbCD-D314A/5-FC with radiation produces markedly increased cytotoxic effects in cancer cells in vitro and in vivo. These data indicate that combined treatment with this novel mutant enzyme/prodrug therapy and radiotherapy provides a promising approach for cancer therapy.

  18. Enhanced Peculiar Velocities in Brane-Induced Gravity

    CERN Document Server

    Wyman, Mark

    2010-01-01

    The mounting evidence for anomalously large peculiar velocities in our Universe presents a challenge for the LCDM paradigm. The recent estimates of the large scale bulk flow by Watkins et al. are inconsistent at the nearly 3 sigma level with LCDM predictions. Meanwhile, Lee and Komatsu have recently estimated that the occurrence of high-velocity merging systems such as the Bullet Cluster (1E0657-57) is unlikely at a 6.5-5.8 sigma level, with an estimated probability between 3.3x10^{-11} and 3.6x10^{-9} in LCDM cosmology. We show that these anomalies are alleviated in a broad class of infrared-modifed gravity theories, called brane-induced gravity, in which gravity becomes higher-dimensional at ultra large distances. These theories include additional scalar forces that enhance gravitational attraction and therefore speed up structure formation at late times and on sufficiently large scales. The peculiar velocities are enhanced by 24-34% compared to standard gravity, with the maximal enhancement nearly consiste...

  19. 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.

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

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    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

  1. Schisandrin B prevents doxorubicin-induced chronic cardiotoxicity and enhances its anticancer activity in vivo.

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    Yang Xu

    Full Text Available BACKGROUND: To mitigate the cardiotoxicity of anthracycline antibiotics without compromising their anticancer activities is still an issue to be solved. We previously demonstrated that schisandrin B (Sch B could protect against doxorubicin (Dox-induced acute cardiotoxicity via enhancing cardiomyocytic glutathione redox cycling that could attenuate oxidative stress generated from Dox. In this study, we attempted to prove if Sch B could also protect against Dox-induced chronic cardiotoxicity, a more clinically relevant issue, without compromising its anticancer activity. METHODOLOGY: Rat was given intragastrically either vehicle or Sch B (50 mg/kg two hours prior to i.p. Dox (2.5 mg/kg weekly over a 5-week period with a cumulative dose of Dox 12.5 mg/kg. At the 6th and 12th week after last dosing, rats were subjected to cardiac function measurement, and left ventricles were processed for histological and ultrastructural examination. Dox anticancer activity enhanced by Sch B was evaluated by growth inhibition of 4T1, a breast cancer cell line, and S180, a sarcoma cell line, in vitro and in vivo. PRINCIPAL FINDINGS: Pretreatment with Sch B significantly attenuated Dox-induced loss of cardiac function and damage of cardiomyocytic structure. Sch B substantially enhanced Dox cytotoxicities toward S180 in vitro and in vivo in mice, and increased Dox cytotoxcity against 4T1 in vitro. Although we did not observe this enhancement against the implanted 4T1 primary tumor, the spontaneous metastasis to lung was significantly reduced in combined treatment group than Dox alone group. CONCLUSION: Sch B is capable of protecting Dox-induced chronic cardiotoxicity and enhancing its anticancer activity. To the best of our knowledge, Sch B is the only molecule ever proved to function as a cardioprotective agent as well as a chemotherapeutic sensitizer, which is potentially applicable for cancer treatment.

  2. TRIB3 downregulation enhances doxorubicin-induced cytotoxicity in gastric cancer cells.

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    Wu, I-Jung; Lin, Rong-Jaan; Wang, Hsin-Chiao; Yuan, Tein-Ming; Chuang, Show-Mei

    2017-05-15

    TRIB3, which is a pseudokinase known to regulate multiple pro-survival pathways, appears to be a potential therapeutic target for the treatment of human tumors. However, its precise role in cancer is controversial, as TRIB3 protein levels have been associated with both good and poor prognosis in cancer patients. Here, we investigated the significance of TRIB3 expression in the survival of gastric cancer cells exposed to anticancer drugs. We found that the tested anticancer drug, doxorubicin, induced cytotoxicity by decreasing TRIB3 transcription, which was followed by apoptotic cell death. Moreover, TRIB3 siRNA knockdown appeared to enhance doxorubicin-induced apoptosis in gastric cancer cells, concurrently with altering the expression of downstream apoptotic factors. Conversely, overexpression of TRIB3 significantly protected cells against doxorubicin-induced apoptosis. Our results indicate that downregulation of TRIB3 appears to promote cell death and enhance doxorubicin-induced apoptosis, supporting the anti-apoptotic role of TRIB3. The inductions of three classes of MAPKs failed to affect doxorubicin-mediated TRIB3 downregulation, while TRIB3 overexpression did not affect doxorubicin-induced MAPK activation. In sum, our findings indicate that TRIB3 plays an anti-apoptotic role in doxorubicin-treated gastric cancer cell lines, perhaps indicating that the status of TRIB3 expression in response to anticancer drugs, such as doxorubicin, irinotecan or oxaliplatin, may reflect the efficiency for cancer therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Yohimbine enhances protection of berberine against LPS-induced mouse lethality through multiple mechanisms.

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    Hui Li

    Full Text Available Sepsis remains a major cause of mortality in intensive care units, better therapies are urgently needed. Gram-negative bacterial lipopolysaccharide (LPS is an important trigger of sepsis. We have demonstrated that berberine (Ber protects against lethality induced by LPS, which is enhanced by yohimbine (Y pretreatment, and Ber combined with Y also improves survival in septic mice. However, the precise mechanisms by which Y enhances protection of Ber against LPS-induced lethality remain unclear. The present study confirmed that simultaneously administered Y also enhanced protection of Ber against LPS-induced lethality. Ber or/and Y attenuated liver injury, but not renal injury in LPS-challenged mice. Ber or/and Y all inhibited LPS-stimulated IκBα, JNK and ERK phosphorylation, NF-κB activation as well as TNF-α production. Ber also increased IL-10 production in LPS-challenged mice, which was enhanced by Y. Furthermore, Ber or/and Y all suppressed LPS-induced IRF3, TyK2 and STAT1 phosphorylation, as well as IFN-β and IP-10 mRNA expression in spleen of mice at 1 h after LPS challenge. Especially, Y enhanced the inhibitory effect of Ber on LPS-induced IP-10 mRNA expression. In vitro experiments further demonstrated that Y significantly enhanced the inhibitory effect of Ber on TNF-α production in LPS-treated peritoneal macrophages, Ber combined with Y promoted LPS-induced IL-10 production and LPS-stimulated IκBα, JNK, ERK and IRF3 phosphorylation and NF-κB activation were also suppressed by Ber or/and Y pretreatment in peritoneal macrophages. Taken together, these results demonstrate that Y enhances the protection of Ber against LPS-induced lethality in mice via attenuating liver injury, upregulating IL-10 production and suppressing IκBα, JNK, ERK and IRF3 phosphorylation. Ber combined with Y may be an effective immunomodulator agent for the prevention of sepsis.

  4. Significant Enhancement of Mechanical and Thermal Properties of Thermoplastic Polyester Elastomer by Polymer Blending and Nanoinclusion

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    Manwar Hussain

    2016-01-01

    Full Text Available Thermoplastic elastomer composites and nanocomposites were fabricated via melt processing technique by blending thermoplastic elastomer (TPEE with poly(butylene terephthalate (PBT thermoplastic and also by adding small amount of organo modified nanoclay and/or polytetrafluoroethylene (PTFE. We study the effect of polymer blending on the mechanical and thermal properties of TPEE blends with and without nanoparticle additions. Significant improvement was observed by blending only TPEE and virgin PBT polymers. With a small amount (0.5 wt.% of nanoclay or PTFE particles added to the TPEE composite, there was further improvement in both the mechanical and thermal properties. To study mechanical properties, flexural strength (FS, flexural modulus (FM, tensile strength (TS, and tensile elongation (TE were all investigated. Thermogravimetric analysis (TGA and differential scanning calorimetry (DSC were used to analyze the thermal properties, including the heat distortion temperature (HDT, of the composites. Scanning electron microscopy (SEM was used to observe the polymer fracture surface morphology. The dispersion of the clay and PTFE nanoparticles was confirmed by transmission electron microscopy (TEM analysis. This material is proposed for use as a baffle plate in the automotive industry, where both high HDT and high modulus are essential.

  5. Expression and significance of PTEN, hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying-An Jiang; Li-Fang Fan; Chong-Qing Jiang; You-Yuan Zhang; He-Sheng Luo; Zhi-Jiao Tang; Dong Xia; Ming Wang

    2003-01-01

    AIM: To investigate the expression and significance of PTEN,hypoxia-inducible factor-1 alpha (HIF-1α), and targeting gene VEGF during colorectal carciogenesis.METHODS: Total 71 cases colorectal neoplasms (9 cases of colorectal adenoma and 62 colorectal adenocarcinoma)were formalin fixed and paraffin-embedded, and all specimens were evaluated for PTEN mRNA, HIF-1α mRNA and VEGF protein expression. PTEN mRNA, HIF-1α mRNA were detected by in situ hybridization. VEGF protein was identified by citrate-microwave SP immunohistochemical method.RESULTS: There were significant differences in PTEN, HIF1α and VEGF expression between colorectal adenomas and colorectal adenocarcinoma (P<0.05). The level of PTEN expression decreased as the pathologic stage increased.Conversely, HIF-1α and VEGF expression increased with the Dukes stage as follows: stage A (0.1029±0.0457:0.1207± 0.0436), stage B (0.1656±0.0329: 0.1572±0.0514),and stage C+D (0.2335±0.0748: 0.2219±0.0803). For PTEN expression, there was a significant difference among Dukes stage A, B, and C+D, and the level of PTEN expression was found to be significant higher in Dukes stage A or B than that of Dukes stage C or D. For HIF-1α expression,there was a significant difference between Dukes stage A and B, and the level of HIF-1α expression was found to be significantly higher in Dukes stage C+D than that of Dukes stage A or B. The VEGF expression had similar results as HIF-1α expression. In colorectal adenocarcinoma,decreased levels of PTEN were significantly associated with increased expression of HIF-1α mRNA (r=-0.36, P<0.05)and VEGF protein (r=-0.48, P<0.05) respectively. The levels of HIF-1 were positively correlated with VEGF expression (r=0.71, P<0.01).CONCLUSION: Loss of PTEN expression and increased levels of HIF-1α and VEGF may play an important role in carcinogenesis and progression of colorectal adenocarcinoma.

  6. The incidence of clinically significant contrast-induced nephropathy following non-emergent coronary angiography.

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    Weisbord, Steven D; Hartwig, Kathryn C; Sonel, Ali F; Fine, Michael J; Palevsky, Paul

    2008-06-01

    The primary aim of this study was to assess the incidence of clinically significant contrast-induced nephropathy (CIN) among patients undergoing non-emergent coronary angiography. Although retrospective analyses have emphasized the association of CIN with adverse patient outcomes, the actual incidence of clinically significant CIN following non-emergent coronary angiography is not clear. We prospectively identified patients with baseline estimated glomerular filtration rates (eGFR) or = 25% and > or = 0.5 mg/dl. We tracked the need for dialysis, hospitalization related to kidney injury, and 30-day mortality to examine the association of CIN with these outcomes. We enrolled 181 patients with a median eGFR of 52 ml/min/1.73 m(2). Of the 165 patients (91%) with post-procedure Scr data, the incidence of CIN was 6.1-8.5%. One patient required dialysis (0.55%) and one (0.55%) died within 30 days. Although 38 patients required hospital admission, CIN was not associated with the need for hospitalization. Patients with an increase in Scr > or = 25% demonstrated a trend toward increased risk for 30-day mortality (P = 0.09), whereas those with increments in Scr > or = 0.5 mg/dl had a marginally higher risk for dialysis (P = 0.06) and 30-day mortality (P = 0.06), although these associations failed to meet the level of statistical significance. Biochemically defined CIN occurs in a small, but notable proportion of patients undergoing non-emergent coronary angiography. However, clinically significant CIN is very uncommon. 2008 Wiley-Liss, Inc.

  7. A Significant Enhancement of Cluster Formation of Krypton and Xenon Gases

    Institute of Scientific and Technical Information of China (English)

    LIU Bingchen

    2001-01-01

    @@ Clusters of rare gases have currently become a kind of widely used targets in the study of high-intensity laser interaction with matter[1,2]. However, a good understanding of the cluster media is vital if results from laser-cluster interaction experiments are to be interpreted correctly. During the course of investigation of the time history of a cluster jet generated in supersonic expansion of rare gases into vaccum through a supersonic conical nozzle (26 mm long, opening angle 5°) by time resolving Rayleigh scattering measurements in which a 532 nm 0.3 mJ laser beam was used, we find that the general trend of argon clusters is similar to that reported by R.A. Smith et al.[3]. However, the picture for Krypton and Xenon gases is completely different. A two-peak structure of the scattered light intensity, instead of a single-peak one, has been revealed. It is interesting to note that the second peak is much more stronger than the first one. As an example, Fig.1 shows the time history of Xen clusters produced at a gas backing pressure P0=3 atm. In the Figure, the peak intensity of the second peak is surprisingly 62 times higher than the first one, indicating that the average cluster size c in the latter case is increased about 62 times under the assumption that during the expansion process all the atoms in the gas condensate into clusters. The result, which is believed to be related to a double gas ejection via the pulsed valve′s two adjacent openings, is of significant importance since this effect would be promising for applications in which very large size clusters are required while a relatively modest vacuum maintains. Meanwhile, this finding may provide us with the opportunity of a further understanding into the nucleation mechanism of expanding gases in a nozzle.

  8. A Significant Increase of RNAi Efficiency in Human Cells by the CMV Enhancer with a tRNAlys Promoter

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    Ma Weiwei

    2009-01-01

    Full Text Available RNA interference (RNAi is the process of mRNA degradation induced by double-stranded RNA in a sequence-specific manner. Different types of promoters, such as U6, H1, tRNA, and CMV, have been used to control the inhibitory effect of RNAi expression vectors. In the present study, we constructed two shRNA expression vectors, respectively, controlled by tRNAlys and CMV enhancer-tRNAlys promoters. Compared to the vectors with tRNAlys or U6 promoter, the vector with a CMV enhancer-tRNAlys promoter silenced pokemon more efficiently on both the mRNA and the protein levels. Meanwhile, the silencing of pokemon inhibited the proliferation of MCF7 cells, but the induction of apoptosis of MCF7 cells was not observed. We conclude that the CMV enhancer-tRNAlys promoter may be a powerful tool in driving intracellular expression of shRNA which can efficiently silence targeted gene.

  9. Expression and significance of GIT1 in hippocampus of lithium-pilocarpine-induced epileptic rats

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    Li-hua ZHENG

    2015-07-01

    Full Text Available Objective  To investigate the expression changes of G-protein-coupled receptor kinase-interacting protein 1 (GIT1 in lithium-pilocarpine-induced epileptic rat model and explore its role in the genesis and development of epilepsy.  Methods  The lithium-pilocarpine-induced model of status epilepticus (SE was established in 42 specific pathogen free (SPF male adult Wistar rats, and those rats were randomly divided into control group and 6 epilepsy groups (1, 3, 7, 14, 30, 60 d after SE. The expression of GIT1 mRNA was detected by fluroescent quantitative polymerase chain reaction (PCR, while the expression of GIT1 protein was examined by Western blotting and immunohistochemistry was applied to test the expression of CA1 region, dentate gyrus and parahippocampal cortex in rat hippocampus at different time points.  Results  GIT1 mRNA level rised in acute phase on 1st and 3rd day after SE (P = 0.012, 0.002, then increased continously in latency on 7th and 14th day (P = 0.003, 0.001, and reached the peak in chronic phase on 30th and 60th day (P = 0.000, for all. GIT1 protein expression rised in acute phase and increased continously in chronic phase, but there was no significant difference compared with control group (P > 0.05, for all. Then, it reached the peak in chronic phase (P = 0.000, for all. Until the 30th day, the GIT1 expression of CA1 region, dentate gyrus and parahippocampal cortex in the hippocampus of rats in 6 epilepsy groups was significantly higher than that of control group (P = 0.000, for all.  Conclusions  The up-regulated expression of GIT1 in the hippocampus of epileptic rat was probably involved in the formation process of chronic epilepsy by regulating cytoskeleton dynamic regrouping to influence excitatory neural networks. DOI: 10.3969/j.issn.1672-6731.2015.06.011

  10. Disorder-induced Purcell enhancement in nanoparticle chains

    CERN Document Server

    Petrov, Mihail I

    2014-01-01

    In this paper we report on numerical study of plasmonic nanoparticle chains with long-range dipole-dipole interaction. We have shown that introduction of positional disorder gives a peak in the density of resonant states (DOS) at the frequency of individual nanoparticle resonance. This peak is referred to Dyson singularity in one-dimensional disordered structures [Dyson F., 1953] and, according to our calculations, governs the spectral properties of local DOS. This provides disorder-induced Purcell enhancement that can found its applications in random lasers and for SERS spectroscopy. We stress that this effect relates not only to plasmonic nanoparticles but to an arbitrary chain of nanoparticles or atoms with resonant polarizabilities.

  11. Enhanced bradycardia induced by beta-adrenoceptor antagonists in rats pretreated with isoniazid.

    Science.gov (United States)

    Vidrio, H; Sánchez-Salvatori, M A; Medina, M

    1998-12-01

    High doses of isoniazid increase hypotension induced by vasodilators and change the accompanying reflex tachycardia to bradycardia, an interaction attributed to decreased synthesis of brain gamma-aminobutyric acid (GABA). In the present study, the possible enhancement by isoniazid of bradycardia induced by beta-adrenoceptor antagonists was determined in rats anaesthetised with chloralose-urethane. Isoniazid significantly increased bradycardia after propranolol, pindolol, labetalol and atenolol, as well as after clonidine, but not after hexamethonium or carbachol. Enhancement was not observed in rats pretreated with methylatropine or previously vagotomised. These results are compatible with interference by isoniazid with GABAergic inhibition of cardiac parasympathetic tone. Such interference could be exerted centrally, possibly at the nucleus ambiguus, or peripherally at the sinus node.

  12. Simplified, Enhanced Protein Purification Using an Inducible, Autoprocessing Enzyme Tag

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    Shen, Aimee; Lupardus, Patrick J.; Morell, Montse; Ponder, Elizabeth L.; Sadaghiani, A. Masoud; Garcia, K. Christopher; Bogyo, Matthew

    2009-01-01

    We introduce a new method for purifying recombinant proteins expressed in bacteria using a highly specific, inducible, self-cleaving protease tag. This tag is comprised of the Vibrio cholerae MARTX toxin cysteine protease domain (CPD), an autoprocessing enzyme that cleaves exclusively after a leucine residue within the target protein-CPD junction. Importantly, V. cholerae CPD is specifically activated by inositol hexakisphosphate (InsP6), a eukaryotic-specific small molecule that is absent from the bacterial cytosol. As a result, when His6-tagged CPD is fused to the C-terminus of target proteins and expressed in Escherichia coli, the full-length fusion protein can be purified from bacterial lysates using metal ion affinity chromatography. Subsequent addition of InsP6 to the immobilized fusion protein induces CPD-mediated cleavage at the target protein-CPD junction, releasing untagged target protein into the supernatant. This method condenses affinity chromatography and fusion tag cleavage into a single step, obviating the need for exogenous protease addition to remove the fusion tag(s) and increasing the efficiency of tag separation. Furthermore, in addition to being timesaving, versatile, and inexpensive, our results indicate that the CPD purification system can enhance the expression, integrity, and solubility of intractable proteins from diverse organisms. PMID:19956581

  13. Simplified, enhanced protein purification using an inducible, autoprocessing enzyme tag.

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    Aimee Shen

    Full Text Available We introduce a new method for purifying recombinant proteins expressed in bacteria using a highly specific, inducible, self-cleaving protease tag. This tag is comprised of the Vibrio cholerae MARTX toxin cysteine protease domain (CPD, an autoprocessing enzyme that cleaves exclusively after a leucine residue within the target protein-CPD junction. Importantly, V. cholerae CPD is specifically activated by inositol hexakisphosphate (InsP(6, a eukaryotic-specific small molecule that is absent from the bacterial cytosol. As a result, when His(6-tagged CPD is fused to the C-terminus of target proteins and expressed in Escherichia coli, the full-length fusion protein can be purified from bacterial lysates using metal ion affinity chromatography. Subsequent addition of InsP(6 to the immobilized fusion protein induces CPD-mediated cleavage at the target protein-CPD junction, releasing untagged target protein into the supernatant. This method condenses affinity chromatography and fusion tag cleavage into a single step, obviating the need for exogenous protease addition to remove the fusion tag(s and increasing the efficiency of tag separation. Furthermore, in addition to being timesaving, versatile, and inexpensive, our results indicate that the CPD purification system can enhance the expression, integrity, and solubility of intractable proteins from diverse organisms.

  14. Survivin S81A Enhanced TRAIL's Activity in Inducing Apoptosis

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    Ferry Sandra

    2010-12-01

    Full Text Available BACKGROUND: Survivin is rarely expressed in normal healthy adult tissues, however, it is upregulated in the majority of cancers. Survivin, which belongs to IAPs family, has been widely reported to protect cells from apoptosis by inhibiting caspases pathway. Survivin’s mitotic activity is modulated by many kinases, and its phosphor status can also influence its ability to inhibit apoptosis. There are several important survivin’s phosphorylation sites, such as S20 and T34. We have continued our investigation on other potential survivin’s phosphorylation sites that could be important site for regulating survivin’s cyto-protection. METHODS: By assuming that S81 could be a potential target to modify activity of survivin, wild-type survivin (Survivin, antisense survivin (Survivin-AS, mutated-survivin Thr34Ala (Survivin-T34A and mutated-survivin Ser81Ala (Survivin-S81A were constructed and inserted into pMSCV-IRES-GFP vector with cytomegalovirus (CMV promoter. Each retroviral product was produced in BOSC23 cells. LY294002 pretreatment and TRAIL treatment along with infection of retroviral products were performed in murine fibrosarcoma L929 cells. For analysis, flow cytometric apoptosis assay and western blot were performed. RESULTS: In our present study, survivin for providing cytoprotection was regulated by PI3K. The results showed that LY294002, an inhibitor of PI3K, effectively suppressed survivin-modulated cytoprotection in a TRAIL-induced apoptotic model. In addition, mutated survivin S81A showed marked suppression on survivin’s cytoprotection. Along with that, TRAIL’s apoptotic activity was enhanced for inducing apoptosis. CONCLUSIONS: We suggested that survivin could inhibit apoptosis through PI3K and S81A could be another potential target in order to inhibit Survivin-modulated cytoprotection as well as to sensitize efficacy of TRAIL or other related apoptotic inducers. KEYWORDS: apoptosis, survivin, TRAIL, S81A, L929, LY294002.

  15. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

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    Ewelina Szliszka

    2009-12-01

    Full Text Available Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer.

  16. Significant Enhancement of the Adhesion between Metal Films and Polymer Substrates by UV-Ozone Surface Modification in Nanoscale.

    Science.gov (United States)

    Liu, Junshan; He, Licheng; Wang, Liang; Man, Yuncheng; Huang, Luyi; Xu, Zheng; Ge, Dan; Li, Jingmin; Liu, Chong; Wang, Liding

    2016-11-09

    Polymer metallization is extensively used in a variety of micro- and nanosystem technologies. However, the deposited metal film exhibits poor adhesion to polymer substrates, which may cause difficulties in many applications. In this work, ultraviolet (UV)-ozone surface modification is for the first time put forward to enhance the adhesion between metal films and polymer substrates. The adhesion of sputtered Cu films on UV-ozone modified poly(methyl methacrylate) (PMMA) substrates is enhanced by a factor of 6, and that of Au films is improved by a factor of 10. Moreover, metal films on the modified PMMA substrates can withstand a long-time liquid immersion. To understand the mechanism for the adhesion enhancement, the surface modification is studied with contact angle measurements, attenuated total reflection Fourier-transform infrared spectrometry (ATR-FTIR) and atomic force microscopy (AFM). Detailed characterization results indicate that the significant adhesion enhancement is attributed to the increases of both the surface wettability by generating some polar functional groups and the roughness of the surface in nanoscale. To demonstrate this novel polymer metallization method, a 6-in. PMMA chip with arrays of three-electrode electrochemical microsensors is designed and fabricated, and the microsensor exhibits excellent reproducibility, uniformity, and long-term stability.

  17. Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

    Science.gov (United States)

    Millière, Raphaël

    2017-01-01

    There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED)”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On

  18. Depletion of Paraspeckle Protein 1 Enhances Methyl Methanesulfonate-Induced Apoptosis through Mitotic Catastrophe.

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    Xiangjing Gao

    Full Text Available Previously, we have shown that paraspeckle protein 1 (PSPC1, a protein component of paraspeckles that was involved in cisplatin-induced DNA damage response (DDR, probably functions at the G1/S checkpoint. In the current study, we further examined the role of PSPC1 in another DNA-damaging agent, methyl methanesulfonate (MMS-induced DDR, in particular, focusing on MMS-induced apoptosis in HeLa cells. First, it was found that MMS treatment induced the expression of PSPC1. While MMS treatment alone can induce apoptosis, depletion of PSPC1 expression using siRNA significantly increased the level of apoptosis following MMS exposure. In contrast, overexpressing PSPC1 decreased the number of apoptotic cells. Interestingly, morphological observation revealed that many of the MMS-treated PSPC1-knockdown cells contained two or more nuclei, indicating the occurrence of mitotic catastrophe. Cell cycle analysis further showed that depletion of PSPC1 caused more cells entering the G2/M phase, a prerequisite of mitosis catastrophe. On the other hand, over-expressing PSPC1 led to more cells accumulating in the G1/S phase. Taken together, these observations suggest an important role for PSPC1 in MMS-induced DDR, and in particular, depletion of PSPC1 can enhance MMS-induced apoptosis through mitotic catastrophe.

  19. Significance of erosion-induced carbon fluxes in the carbon balance of a Mediterranean catchment

    Science.gov (United States)

    Nadeu, Elisabet; de Vente, Joris; Boix-Fayos, Carolina

    2014-05-01

    Large uncertainties surround our knowledge of the processes through which carbon (C) sequestration takes place in terrestrial ecosystems. Nevertheless, terrestrial ecosystems could be capturing up to one fourth of the CO2 that is emitted annually to the atmosphere from the burning of fossil fuels and land use changes. Soils are the third largest C reservoir in the C cycle, storing around 1500 Gt of C. Over the last decades, geomorphologists and soil scientists have claimed the role of soil erosion within the C cycle and its potential contribution to the terrestrial C sink. In order to assess the impact of soil erosion on the C cycle, however, an understanding and quantification of the impact of soil erosion on soil C stocks is needed. This implies quantifying lateral and vertical C fluxes associated to detachment, transport and deposition of soil and sediment at different spatial scales. As an example, we present a C budget for a mountainous catchment in south-eastern Spain for a 28 year study period during which the catchment underwent significant land use changes and hydrological correction works (i.e. check-dam construction and reforestations). We quantified lateral C fluxes induced by soil erosion processes and closed a soil/sediment C budget by combining field measurements and numerical modeling. In addition, correlation analysis was conducted between catchment properties (topographic, land use, lithology) and measured C deposition rates to understand the controlling factors on C yield (export) and C concentration in sediments. The results showed that the highest C yields (associated to high sediment yields) were found in subcatchments dominated by soft lithologies and high drainage densities. On the other hand, C concentration in deposited sediments was higher in areas dominated by forest cover, and presented high variability in those parts of the catchment with smoother slopes. Overall, we estimated that around 4000 Mg of C were mobilized from the catchment

  20. Protease-mediated enhancement of lymphocyte-induced angiogenesis in X-ray irradiated mice

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    Kaminski, M.J.; Majewski, S.; Kaminska, G.; Bem, W.; Szmurlo, A. (Akademia Medyczna, Warsaw (Poland). Zaklad Histologii i Embriologii)

    1983-02-01

    Angiogenesis was induced in mice by intradermal injection of semi-syngeneic splenocytes, and after three days the number of newly formed blood vessels at the injection site was counted. When recipients were total-body irradiated with 700 R 2 hours before the lymphocyte injection, the angiogenesis was significantly higher than in non-irradiated mice. The angiogenesis enhancement was of a systemic (not local) character as revealed in experiments with shielding of irradiated animals. This enhancement was not due to X-ray dependent immunosuppression, as shown in experiments with non-irradiated, pharmacologically immunosuppressed mice. Decreased angiogenesis was observed in irradiated mice after treatment with cortisone acetate, aprotinin, and EACA. The results suggest that proteases might be involved in mediating the angiogenesis enhancement after X-irradiation.

  1. Significance of nitric oxide on the pathogenesis of steroid-induced femoral head necrosis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@Steroid-induced femoral head necrosis is claimed to be an ischemic femoral head disease. But there is no discussion on the role of nitric oxide (NO) in the idiopathic disease. The concentration of NO indirectly in serum with steroid induced avascular necrosis of femoral head (ANFH) and in controls are studied in this article.

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

    Science.gov (United States)

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

    2015-08-15

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

  3. Glutamine enhances glucose-induced mesangial cell proliferation.

    Science.gov (United States)

    Lagranha, Claudia J; Doi, Sonia Q; Pithon-Curi, Tania C; Curi, Rui; Sellitti, Donald F

    2008-05-01

    The proliferation of mesangial cells (MC) in the presence of glutamine (0-20 mM) was determined in both low (5 mM) and high (25 mM) glucose-containing medium. Glutamine in a high glucose (HG) environment increased cell proliferation in a dose-dependent manner. Inhibition of glutamine:fructose 6-phosphate amidotransferase (GFAT) and of phosphodiesterase significantly reduced glutamine-induced proliferation. Supraphysiologic levels of glutamine increase MC proliferation in a HG milieu via GFAT and cAMP-dependent pathways, suggesting that glutamine could pose a risk for diabetic nephropathy.

  4. Risperidone significantly inhibits interferon-gamma-induced microglial activation in vitro.

    Science.gov (United States)

    Kato, Takahiro; Monji, Akira; Hashioka, Sadayuki; Kanba, Shigenobu

    2007-05-01

    Microglia has recently been regarded to be a mediator of neuroinflammation via the release of proinflammatory cytokines, nitric oxide (NO) and reactive oxygen species (ROS) in the central nervous system (CNS). Microglia has thus been reported to play an important role in the pathology of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The pathological mechanisms of schizophrenia remain unclear while some recent neuroimaging studies suggest even schizophrenia may be a kind of neurodegenerative disease. Risperidone has been reported to decrease the reduction of MRI volume during the clinical course of schizophrenia. Many recent studies have demonstrated that immunological mechanisms via such as interferon (IFN)-gamma and cytokines might be relevant to the pathophysiology of schizophrenia. In the present study, we thus investigated the effects of risperidone on the generation of nitric oxide, inducible NO synthase (iNOS) expression and inflammatory cytokines: interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha by IFN-gamma-activated microglia by using Griess assay, Western blotting and ELISA, respectively. In comparison with haloperidol, risperidone significantly inhibited the production of NO and proinflammatory cytokines by activated microglia. The iNOS levels of risperidone-treated cells were much lower than those of the haloperidol-treated cells. Antipsychotics, especially risperidone may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia.

  5. Mixed martial arts induces significant fatigue and muscle damage up to 24 hours post-combat.

    Science.gov (United States)

    Ghoul, Nihel; Tabben, Montassar; Miarka, Bianca; Tourny, Claire; Chamari, Karim; Coquart, Jeremy

    2017-06-22

    This study investigates the physiological/physical responses to a simulated mixed martial arts (MMA) competition over 24 hr. Twelve fighters performed a simulated MMA competition, consisting of three 5-min MMA matches. Physiological/physical data were assessed before (Trest), directly after round 1 (Trd1), round 2 (Trd2) and round 3 (Trd3), and then 30-min (Trecovery30min) and/or 24-hr (Trecovery24h) post-competition. Heart rate (HR), rating of perceived exertion (RPE) and blood lactate concentration ([La]) were assessed at Trest, Trd1, Trd2 and Trd3. Biological data were collected at Trest, Trd3, Trecovery30min and Trecovery24h. Physical tests were performed at Trest, Trecovery30min and Trecovery24h. HR, RPE and [La] were high during competition. Leukocytes, hemoglobin, total protein and glycemia were increased at Trd3 compared with all other time points (p<0.05). Cortisol was increased at Trd3 compared with Trest and Trecovery24h (p<0.05). Testosterone was higher at Trd3 and Trecovery30min than Trest (p<0.001). Higher values of uric acid were noted during recovery periods (p<0.001). Lactate dehydrogenase was lower at Trest compared with Trd3, Trecovery30min and Trecovery24h (p<0.05). Countermovement jump was higher at Trest than Trecovery30min (p=0.020). Consequently, MMA is a high-intensity intermittent combat sport that induces significant fatigue and muscle damage, both of which are still present 24-hr post-competition.

  6. A helicopter flight does not induce significant changes in systemic biomarker profiles.

    Science.gov (United States)

    Kåsin, Jan Ivar; Kjekshus, John; Aukrust, Pål; Mollnes, Tom Eirik; Wagstaff, Anthony

    2009-01-01

    Whole-body vibration and noise are inherent characteristics of helicopter operations. The helicopter pilot is affected by vibration from both low-frequency noise and mechanical vibration sources. The way this energy is transmitted to different tissues and organs depends on intensity, frequency and resonance phenomena within the body. Whole-body vibration is known to affect the muscular and skeletal system in the lower part of the spine, but less is known about the response at the cellular level to this stimulation. In some studies, chronic pathological changes have been described in different types of tissue in people exposed to low-frequency noise and vibration. The aim of the present study was to investigate possible cellular reactions to acute exposure to low-frequency noise and vibration in a helicopter. Thirteen healthy males aged 38 (18-69) years were subjected to a 3.5 h helicopter flight in a Westland Sea King Rescue helicopter. Blood tests taken before and after the flight were analysed for more than 40 parameters, including acute phase reactants, markers of leucocyte and platelet activation, complement and hemostasis markers, as well as a broad panel of cytokines, chemokines, growth factors and cell adhesion molecules. The subjects served as their own controls. With the exception of an increase in vascular cell adhesion molecule-1 (VCAM-1) during the flight, no statistically significant changes in the biomarkers were found after controlling for diurnal variation in the control blood tests, which were observed independently of the helicopter flight. In conclusion, one helicopter flight does not induce measurable changes in systemic biomarkers.

  7. Significance of CpG methylation for solar UV-induced mutagenesis and carcinogenesis in skin.

    Science.gov (United States)

    Ikehata, Hironobu; Ono, Tetsuya

    2007-01-01

    Mutations detected in the p53 gene in human nonmelanoma skin cancers show a highly UV-specific mutation pattern, a dominance of C --> T base substitutions at dipyrimidine sites plus frequent CC --> TT tandem substitutions, indicating a major involvement of solar UV in the skin carcinogenesis. These mutations also have another important characteristic of frequent occurrences at CpG dinucleotide sites, some of which actually show prominent hotspots in the p53 gene. Although mammalian solar UV-induced mutation spectra were studied intensively in the aprt gene using rodent cultured cells and the UV-specific mutation pattern was confirmed, the second characteristic of the p53 mutations in human skin cancers had not been reproduced. However, studies with transgenic mouse systems developed thereafter for mutation research, which harbor methyl CpG-abundant transgenes as mutation markers, yielded complete reproductions of the situation of the human skin cancer mutations in terms of both the UV-specific pattern and the frequent occurrence at CpG sites. In this review, we evaluate the significance of the CpG methylation for solar UV mutagenesis in the mammalian genome, which would lead to skin carcinogenesis. We propose that the UV-specific mutations at methylated CpG sites, C --> T transitions at methyl CpG-associated dipyrimidine sites, are a solar UV-specific mutation signature, and have estimated the wavelength range effective for the solar-UV-specific mutation as 310-340 nm. We also recommend the use of methyl CpG-enriched sequences as mutational targets for studies on solar-UV genotoxicity for human, rather than conventional mammalian mutational marker genes such as the aprt and hprt genes.

  8. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells.

    Science.gov (United States)

    Breit, Andreas; Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

    2016-07-01

    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction.

  9. uv induced enhancement of recombination among lambda bacteriophages: relation with replication of irradiated DNA

    Energy Technology Data Exchange (ETDEWEB)

    Cordone, L.; Sperandeo-Mineo, R.M.; Mannino, S.

    1975-07-01

    Experimental results are reported showing the dependence of the uv induced enhancement of recombinants on the presence of the functional O gene product. This fact is tentatively interpreted as a replication dependence of the uv induced recombination.

  10. Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression.

    Directory of Open Access Journals (Sweden)

    Lakshmi T Sunkara

    Full Text Available Host defense peptides (HDPs constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. In this study, we tested the hypothesis that exogenous administration of butyrate, a major type of short-chain fatty acids derived from bacterial fermentation of undigested dietary fiber, is capable of inducing HDPs and enhancing disease resistance in chickens. We have found that butyrate is a potent inducer of several, but not all, chicken HDPs in HD11 macrophages as well as in primary monocytes, bone marrow cells, and jejuna and cecal explants. In addition, butyrate treatment enhanced the antibacterial activity of chicken monocytes against Salmonella enteritidis, with a minimum impact on inflammatory cytokine production, phagocytosis, and oxidative burst capacities of the cells. Furthermore, feed supplementation with 0.1% butyrate led to a significant increase in HDP gene expression in the intestinal tract of chickens. More importantly, such a feeding strategy resulted in a nearly 10-fold reduction in the bacterial titer in the cecum following experimental infections with S. enteritidis. Collectively, the results indicated that butyrate-induced synthesis of endogenous HDPs is a phylogenetically conserved mechanism of innate host defense shared by mammals and aves, and that dietary supplementation of butyrate has potential for further development as a convenient antibiotic-alternative strategy to enhance host innate immunity and disease resistance.

  11. Complete Au@ZnO core-shell nanoparticles with enhanced plasmonic absorption enabling significantly improved photocatalysis.

    Science.gov (United States)

    Sun, Yiqiang; Sun, Yugang; Zhang, Tao; Chen, Guozhu; Zhang, Fengshou; Liu, Dilong; Cai, Weiping; Li, Yue; Yang, Xianfeng; Li, Cuncheng

    2016-05-19

    Nanostructured ZnO exhibits high chemical stability and unique optical properties, representing a promising candidate among photocatalysts in the field of environmental remediation and solar energy conversion. However, ZnO only absorbs the UV light, which accounts for less than 5% of total solar irradiation, significantly limiting its applications. In this article, we report a facile and efficient approach to overcome the poor wettability between ZnO and Au by carefully modulating the surface charge density on Au nanoparticles (NPs), enabling rapid synthesis of Au@ZnO core-shell NPs at room temperature. The resulting Au@ZnO core-shell NPs exhibit a significantly enhanced plasmonic absorption in the visible range due to the Au NP cores. They also show a significantly improved photocatalytic performance in comparison with their single-component counterparts, i.e., the Au NPs and ZnO NPs. Moreover, the high catalytic activity of the as-synthesized Au@ZnO core-shell NPs can be maintained even after many cycles of photocatalytic reaction. Our results shed light on the fact that the Au@ZnO core-shell NPs represent a promising class of candidates for applications in plasmonics, surface-enhanced spectroscopy, light harvest devices, solar energy conversion, and degradation of organic pollutants.

  12. Perforin enhances the granulysin-induced lysis of Listeria innocua in human dendritic cells

    Directory of Open Access Journals (Sweden)

    Wagner Carsten A

    2007-08-01

    Full Text Available Abstract Background Cytotoxic T lymphocytes (CTL and natural killer (NK cells play an essential role in the host defence against intracellular pathogens such as Listeria, and Mycobacteria. The key mediator of bacteria-directed cytotoxicity is granulysin, a 9 kDa protein stored in cytolytic granules together with perforin and granzymes. Granulysin binds to cell membranes and is subsequently taken up via a lipid raft-associated mechanism. In dendritic cells (DC granulysin is further transferred via early endosomes to L. innocua-containing phagosomes were bacteriolysis is induced. In the present study we analysed the role of perforin in granulysin-induced intracellular bacteriolysis in DC. Results We found granulysin-induced lysis of intracellular Listeria significantly increased when perforin was simultaneously present. In pulse-chase experiments enhanced bacteriolysis was observed when perforin was added up to 25 minutes after loading the cells with granulysin demonstrating no ultimate need for simultaneous uptake of granulysin and perforin. The perforin concentration sufficient to enhance granulysin-induced intracellular bacteriolysis did not cause permanent membrane pores in Listeria-challenged DC as shown by dye exclusion test and LDH release. This was in contrast to non challenged DC that were more susceptible to perforin lysis. For Listeria-challenged DC, there was clear evidence for an Ca2+ influx in response to sublytic perforin demonstrating a short-lived change in the plasma membrane permeability. Perforin treatment did not affect granulysin binding, initial uptake or intracellular trafficking to early endosomes. However, enhanced colocalization of granulysin with listerial DNA in presence of perforin was found by confocal laser scanning microscopy. Conclusion The results provide evidence that perforin increases granulysin-mediated killing of intracellular Listeria by enhanced phagosome-endosome fusion triggered by a transient Ca2+ flux.

  13. A hydrogen peroxide-generating agent, 6-formylpterin, enhances heat-induced apoptosis.

    Science.gov (United States)

    Wada, S; Cui, Z-G; Kondo, T; Zhao, Q-L; Ogawa, R; Shoji, M; Arai, T; Makino, K; Furuta, I

    2005-05-01

    The enhancement of heat-induced apoptosis by 6-formylpterin, an intra-cellular generator of hydrogen peroxide (H2O2), was examined in human myelomonocytic lymphoma U937 cells. The cells were treated with either 6-formylpterin alone at a nontoxic concentration of 300 microM (37 degrees C), heat shock (44 degrees C per 20 min) alone or a combination of the two, then incubated at 37 degrees C for 6 h. Assessments of apoptosis, mitochondrial membrane potential and caspase-3 activation were performed by flow cytometry. Moreover, caspase-8 activation and changes in the intra-cellular Ca2+ concentration ([Ca2+]i) were examined. Bax, Bcl-2, Bcl-XL, Bid, cytochrome c and PKCd were detected by Western blotting. The induction of heat-induced apoptosis evaluated by morphological observation and DNA fragmentation were promoted by the addition of 6-formylpterin. Mitochondrial membrane potential was decreased and the activation of caspase-3 and -8 was enhanced in the cells treated with the combination. A decreased-expression of Bid was noted, although no significant changes in Bax, Bcl-2 and Bcl-XL expression were observed after the combined treatment. Furthermore, both the release of cytochrome c from mitochondria to cytosol and the translocation of PKCd from cytosol to mitochondria, which were induced by heat shock, were enhanced by the addition of 6-formylpterin. The number of cells with a higher [Ca2+]i was also increased by the addition of 6-formylpterin. These findings suggest that the increase in [Ca2+]i, the activation of the mitochondria-caspase dependent pathway and the translocation of PKCd to mitochondria play principal roles in the enhancement of heat-induced apoptosis by 6-FP.

  14. Fluid-enabled significant enhancement and active tuning of magnetic resonances in free-standing plasmonic metamaterials.

    Science.gov (United States)

    Leong, Eunice Sok Ping; Liu, Yan Jun; Deng, Jie; Fong, Yih Ting; Zhang, Nan; Wu, Si Ji; Teng, Jing Hua

    2014-10-07

    We report significantly enhanced magnetic resonance by fluid infiltration in a free-standing metamaterial that consists of metal-dielectric-metal films on an ultrathin Si3N4 membrane patterned with etched through nanohole arrays. When different fluids are drop-casted on the structure, the magnetic resonance has high sensitivities of 282 nm per RIU in peak shift and 12% per RIU in peak intensity change, whereas the electric resonance has nearly no changes. This work shows a promising way of using fluids to actively tune the magnetic resonance of metamaterial structures by combining with micro/nano-fluidic technologies.

  15. Evaluating clinically significant change in mother and child functioning: comparison of traditional and enhanced behavioral parent training.

    Science.gov (United States)

    Rajwan, Estrella; Chacko, Anil; Wymbs, Brian T; Wymbs, Frances A

    2014-11-01

    The Strategies to Enhance Positive Parenting (STEPP) program, an enhanced behavioral parent training (BPT) intervention, was developed to improve engagement in and outcomes following treatment for single-mother families of school-age youth with attention-deficit/hyperactivity disorder (ADHD). A previous randomized clinical trial of the STEPP program demonstrated that the intervention resulted in statistically significant improvements at the group-level in child oppositional behavior, various areas of child impairment, parental stress, and parenting behavior, relative to a wait-list control condition and a traditional BPT group. Despite benefits at the group-level, little is known about outcomes at the individual-level of enhanced BPT relative to traditional BPT for various child- and parent-level outcomes. The current study compares the extent to which traditional BPT and the STEPP program result in reliable change and recovery across various child- and parent-level outcomes in a sample of 80, 5-12 year old youth with ADHD (70 % male). Analyses demonstrated the benefit of participating in either BPT treatment; and participation in the STEPP program compared to traditional BPT was associated with only minimal incremental clinical benefit. Results, as well as clinical and research implications for assessment and treatment of high-risk families of youth with ADHD enrolled in BPT are discussed.

  16. Zero Valent Iron Significantly Enhances Methane Production from Waste Activated Sludge by Improving Biochemical Methane Potential Rather Than Hydrolysis Rate

    Science.gov (United States)

    Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

    2015-02-01

    Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system.

  17. Zero valent iron significantly enhances methane production from waste activated sludge by improving biochemical methane potential rather than hydrolysis rate.

    Science.gov (United States)

    Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

    2015-02-05

    Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system.

  18. Dexamethasone-Induced Oxidative Stress Enhances Myeloma Cell Radiosensitization While Sparing Normal Bone Marrow Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Soumen Bera

    2010-12-01

    Full Text Available Dexamethasone (Dex and radiation therapy are established modalities in multiple myeloma. In this study, we propose a novel combination of Dex plus radiation that shows superior clonogenic cell killing and apoptosis of myeloma cells and selectively eliminates myeloma cells when cocultured with bone marrow stromal cells (BMSCs. Dex was found to inhibit the release of interleukin-6 from irradiated BMSCs, which is an established myeloma cell proproliferative cytokine. In 5TGM1 model, the combination of Dex with skeletal targeted radiotherapy (153-Sm-EDTMP prolonged median survival time and inhibited radiation-induced myelosuppression. A two-cycle treatment of Dex plus 153-Sm-EDTMP was well tolerated and further improved median survival time. Mechanistically, Dex increased superoxide and hydrogen peroxide production and augmented radiation-induced oxidative stress and cell death of myeloma cells. In contrast, Dex inhibited radiation-induced increase in pro-oxidant levels and enhanced the clonogenic survival in normal hematopoietic stem and progenitor cells. Treatment with either N-acetylcysteine or the combination of polyethylene glycol (PEG-conjugated copper, zinc-superoxide dismutase, and PEG-catalase significantly protected myeloma cells from Dex-induced clonogenic death. Overall, these results demonstrate that Dex in combination with radiotherapy enhances the killing of myeloma cells while protecting normal bone marrow hematopoiesis through a mechanism that involves selective increases in oxidative stress.

  19. 'Bois noir' phytoplasma induces significant reprogramming of the leaf transcriptome in the field grown grapevine

    Directory of Open Access Journals (Sweden)

    Dermastia Marina

    2009-10-01

    Full Text Available Abstract Background Phytoplasmas are bacteria without cell walls from the class Mollicutes. They are obligate intracellular plant pathogens which cause diseases in hundreds of economically important plants including the grapevine (Vitis vinifera. Knowledge of their biology and the mechanisms of their interactions with hosts is largely unknown because they are uncultivable and experimentally inaccessible in their hosts. We detail here the global transcriptional profiling in grapevine responses to phytoplasmas. The gene expression patterns were followed in leaf midribs of grapevine cv. 'Chardonnay' naturally infected with a phytoplasma from the stolbur group 16SrXII-A, which is associated with the grapevine yellows disease 'Bois noir'. Results We established an on field experimental system in a productive vineyard that allowed application of molecular tools in a plant natural environment. Global transcription profiles of infected samples were compared with the healthy ones using microarray datasets and metabolic pathway analysis software (MapMan. The two-year-long experiment revealed that plant genes involved in primary and secondary metabolic pathways were changed in response to infection and that these changes might support phytoplasma nutrition. A hypothesis that phytoplasmas interact with the plant carbohydrate metabolism was proven and some possibilities how the products of this pathway might be utilized by phytoplasmas are discussed. In addition, several photosynthetic genes were largely down-regulated in infected plants, whereas defense genes from the metabolic pathway leading to formation of flavonoids and some PR proteins were significantly induced. Few other genes involved in defense-signaling were differentially expressed in healthy and infected plants. A set of 17 selected genes from several differentially expressed pathways was additionally analyzed with quantitative real-time PCR and confirmed to be suitable for a reliable

  20. Development of enhanced piezoelectric energy harvester induced by human motion.

    Science.gov (United States)

    Minami, Y; Nakamachi, E

    2012-01-01

    In this study, a high frequency piezoelectric energy harvester converted from the human low vibrated motion energy was newly developed. This hybrid energy harvester consists of the unimorph piezoelectric cantilever and a couple of permanent magnets. One magnet was attached at the end of cantilever, and the counterpart magnet was set at the end of the pendulum. The mechanical energy provided through the human walking motion, which is a typical ubiquitous presence of vibration, is converted to the electric energy via the piezoelectric cantilever vibration system. At first, we studied the energy convert mechanism and the performance of our energy harvester, where the resonance free vibration of unimorph cantilever with one permanent magnet under a rather high frequency was induced by the artificial low frequency vibration. The counterpart magnet attached on the pendulum. Next, we equipped the counterpart permanent magnet pendulum, which was fluctuated under a very low frequency by the human walking, and the piezoelectric cantilever, which had the permanent magnet at the end. The low-to-high frequency convert "hybrid system" can be characterized as an enhanced energy harvest one. We examined and obtained maximum values of voltage and power in this system, as 1.2V and 1.2 µW. Those results show the possibility to apply for the energy harvester in the portable and implantable Bio-MEMS devices.

  1. Significant differences in genotoxicity induced by retrovirus integration in human T cells and induced pluripotent stem cells.

    Science.gov (United States)

    Zheng, Weiyan; Wang, Yingjia; Chang, Tammy; Huang, He; Yee, Jiing-Kuan

    2013-04-25

    Retrovirus is frequently used in the genetic modification of mammalian cells and the establishment of induced pluripotent stem cells (iPSCs) via cell reprogramming. Vector-induced genotoxicity could induce profound effect on the physiology and function of these stem cells and their differentiated progeny. We analyzed retrovirus-induced genotoxicity in somatic cell Jurkat and two iPSC lines. In Jurkat cells, retrovirus frequently activated host gene expression and gene activation was not dependent on the distance between the integration site and the transcription start site of the host gene. In contrast, retrovirus frequently down-regulated host gene expression in iPSCs, possibly due to the action of chromatin silencing that spreads from the provirus to the nearby host gene promoter. Our data raises the issue that some of the phenotypic variability observed among iPSC clones derived from the same parental cell line may be caused by retrovirus-induced gene expression changes rather than by the reprogramming process itself. It also underscores the importance of characterizing retrovirus integration and carrying out risk assessment of iPSCs before they can be applied in basic research and clinics.

  2. Significant internal quantum efficiency enhancement of GaN/AlGaN multiple quantum wells emitting at ~350 nm via step quantum well structure design

    KAUST Repository

    Wu, Feng

    2017-05-03

    Significant internal quantum efficiency (IQE) enhancement of GaN/AlGaN multiple quantum wells (MQWs) emitting at similar to 350 nm was achieved via a step quantum well (QW) structure design. The MQW structures were grown on AlGaN/AlN/sapphire templates by metal-organic chemical vapor deposition (MOCVD). High resolution x-ray diffraction (HR-XRD) and scanning transmission electron microscopy (STEM) were performed, showing sharp interface of the MQWs. Weak beam dark field imaging was conducted, indicating a similar dislocation density of the investigated MQWs samples. The IQE of GaN/AlGaN MQWs was estimated by temperature dependent photoluminescence (TDPL). An IQE enhancement of about two times was observed for the GaN/AlGaN step QW structure, compared with conventional QW structure. Based on the theoretical calculation, this IQE enhancement was attributed to the suppressed polarization-induced field, and thus the improved electron-hole wave-function overlap in the step QW.

  3. Significant internal quantum efficiency enhancement of GaN/AlGaN multiple quantum wells emitting at ~350 nm via step quantum well structure design

    Science.gov (United States)

    Wu, Feng; Sun, Haiding; AJia, Idris A.; Roqan, Iman S.; Zhang, Daliang; Dai, Jiangnan; Chen, Changqing; Feng, Zhe Chuan; Li, Xiaohang

    2017-06-01

    Significant internal quantum efficiency (IQE) enhancement of GaN/AlGaN multiple quantum wells (MQWs) emitting at ~350 nm was achieved via a step quantum well (QW) structure design. The MQW structures were grown on AlGaN/AlN/sapphire templates by metal-organic chemical vapor deposition (MOCVD). High resolution x-ray diffraction (HR-XRD) and scanning transmission electron microscopy (STEM) were performed, showing sharp interface of the MQWs. Weak beam dark field imaging was conducted, indicating a similar dislocation density of the investigated MQWs samples. The IQE of GaN/AlGaN MQWs was estimated by temperature dependent photoluminescence (TDPL). An IQE enhancement of about two times was observed for the GaN/AlGaN step QW structure, compared with conventional QW structure. Based on the theoretical calculation, this IQE enhancement was attributed to the suppressed polarization-induced field, and thus the improved electron-hole wave-function overlap in the step QW.

  4. Amplification of an MFS Transporter Encoding Gene penT Significantly Stimulates Penicillin Production and Enhances the Sensitivity of Penicillium chrysogenum to Phenylacetic Acid

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Xinxin Xu; Gang Liu

    2012-01-01

    Penicillin is historically important as the first discovered drug against bacterial infections in human.Although the penicillin biosynthetic pathway and regulatory mechanism have been well studied in Penicillium chrysogenum,the compartnentation and molecular transport of penicillin or its precursors are still poorly understood.In search of the genomic database,more than 830 open reading frames (ORFs) were found to encode transmembrane proteins of P.chrysogenum.In order to investigate their roles on penicillin production,one of them (penT) was selected and cloned.The deduced protein of penT belongs to the major facilitator superfamily (MFS) and contains 12transmembrane spanning domains (TMS).During fermentation,the transcription of penT was greatly induced by penicillin precursors phenylacetic acid (PAA) and phenoxyacetic acid (POA).Knock-down of penT resulted in significant decrease of penicillin production,while over-expression of penT under the promoter of trpC enhanced the penicillin production.Introduction of an additional penT in the wild-type strain of P.chrysogenum doubled the penicillin production and enhanced the sensitivity of P.chrysogenum to the penicillin precursors PAA or POA.These results indicate that penT stimulates penicillin production probably through enhancing the translocation of penicillin precursors across fungal cellular membrane.

  5. Amplification of an MFS transporter encoding gene penT significantly stimulates penicillin production and enhances the sensitivity of Penicillium chrysogenum to phenylacetic acid.

    Science.gov (United States)

    Yang, Jing; Xu, Xinxin; Liu, Gang

    2012-11-20

    Penicillin is historically important as the first discovered drug against bacterial infections in human. Although the penicillin biosynthetic pathway and regulatory mechanism have been well studied in Penicillium chrysogenum, the compartmentation and molecular transport of penicillin or its precursors are still poorly understood. In search of the genomic database, more than 830 open reading frames (ORFs) were found to encode transmembrane proteins of P. chrysogenum. In order to investigate their roles on penicillin production, one of them (penT) was selected and cloned. The deduced protein of penT belongs to the major facilitator superfamily (MFS) and contains 12 transmembrane spanning domains (TMS). During fermentation, the transcription of penT was greatly induced by penicillin precursors phenylacetic acid (PAA) and phenoxyacetic acid (POA). Knock-down of penT resulted in significant decrease of penicillin production, while over-expression of penT under the promoter of trpC enhanced the penicillin production. Introduction of an additional penT in the wild-type strain of P. chrysogenum doubled the penicillin production and enhanced the sensitivity of P. chrysogenum to the penicillin precursors PAA or POA. These results indicate that penT stimulates penicillin production probably through enhancing the translocation of penicillin precursors across fungal cellular membrane.

  6. ZnO nanowire/reduced graphene oxide nanocomposites for significantly enhanced photocatalytic degradation of Rhodamine 6G

    Science.gov (United States)

    Zhang, Chao; Zhang, Jing; Su, Yanjie; Xu, Minghan; Yang, Zhi; Zhang, Yafei

    2014-02-01

    We have demonstrated a facile and low-cost approach to synthesize ZnO nanowire (NW)/reduced graphene oxide (RGO) nanocomposites, in which ZnO NWs and graphene oxide (GO) were produced in large scale separately and then hybridized into ZnO NW/RGO nanocomposites by mechanical mixing and low-temperature thermal reduction. Rhodamine 6G (Rh6G) was used as a model dye to evaluate the photocatalytic properties of ZnO NW/RGO nanocomposites. The obtained nanocomposites show significantly enhanced photocatalytic performance, which took only 10 min to decompose over 98% Rh6G. Finally the mechanism of the great enhancement about photocatalytic activity of ZnO NW/RGO nanocomposites is studied. It is mainly attributed to that RGO nanosheets can transfer the electrons of ZnO NWs excited by ultraviolet (UV) irradiation, increase electron migration efficiency, and then longer the lifetime of the holes in ZnO NWs. The high charge separation efficiency of photo-generated electron-hole pairs directly leads to the lower recombination rate of ZnO NW/RGO nanocomposites, makes more effective electrons and holes to participate the radical reactions with Rh6G, thus significantly improving the photocatalytic properties. The high degradation efficiency makes the ZnO NW/RGO nanocomposites promising candidates in the application of environmental pollutant and wastewater treatment.

  7. The significance of T cells, B cells, antibodies and macrophages against encephalomyocarditis (EMC)-D virus-induced diabetes in mice.

    Science.gov (United States)

    Kounoue, Etsushi; Izumi, Ken-ichi; Ogawa, Shuichiro; Kondo, Shiori; Katsuta, Hitoshi; Akashi, Tomoyuki; Niho, Yoshiyuki; Harada, Mine; Tamiya, Sadafumi; Kurisaki, Hironori; Nagafuchi, Seiho

    2008-01-01

    In order to clarify the significance of protective mechanisms against encephalomyocarditis (EMC) virus-induced diabetes in mice, we studied the relative importance of T cells, B cells, antibodies and macrophages in the prevention of virus-induced diabetes. Neither T cell-deficient athymic nude mice nor B cell-deficient microMT/microMT mice showed an enhanced clinical course of EMC-D virus-induced diabetes, indicating that neither T cells nor B cells played a major role in the protection against EMC-D-virus-induced diabetes. Transfer of a large amount of antiserum to EMC-D-virus-infected mice protected the development of diabetes only when transferred within 36 h of infection, the timing of which was earlier than that for the production of natural neutralizing antibodied. Since pretreatment of mice with the macrophage-activating immunopotentiator Corynebacterium parvum (CP) completely prevented the development of diabetes, we studied the clinical outcome of EMC-D-virus-infected mice pretreated with CP. Mice treated with CP showed reduced proliferation of EMC-D virus in the affected organs, including the pancreas, while the levels of development of neutralizing antibody and serum interferon were not enhanced compared with the controls. Finally, we studied the macrophages derived from mice pretreated with CP and found that they inhibited the growth of EMC-D virus in vitro more than those derived from non-treated and thioglycolate-treated mice. Taken together, it can be suggested that neither T cells nor B cells, which have to do with adaptive immunity, play a significant role in the pathogenesis of EMC-D-virus-induced diabetes, while innate immunity, which is dependent on activated macrophages, contributes to in vivo resistance against EMC-D-virus-induced diabetes.

  8. 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

  9. [Exercise-induced atrioventricular block. Significance of the ischemic component. Report of 4 new cases].

    Science.gov (United States)

    Rumoroso, J R; Montes Orbe, P M; Cembellín, J C; Pérez-García, P; González-Liébana, J; Gómez-Varela, S; Bodegas, A; Barrenetxea, J I

    1997-04-01

    We report four new cases of exercise-induced atrio-ventricular block (appearing during treadmill exercise testing). The mechanism was ischemia in two patients and the conduction disturbance disappeared after coronary artery bypass grafting. The literature on this matter is reviewed. Also the etiology, the natural history and management are discussed in these cases.

  10. Compression-induced HIF-1 enhances thrombosis and PAI-1 expression in mouse skin.

    Science.gov (United States)

    Kaneko, Maki; Minematsu, Takeo; Yoshida, Mikako; Nishijima, Yoshimi; Noguchi, Hiroshi; Ohta, Yasunori; Nakagami, Gojiro; Mori, Taketoshi; Sanada, Hiromi

    2015-09-01

    Pressure ulcers result from tissue hypoxia caused by external forces. Thrombosis due to external forces is considered important, and hypoxia inducible factor-1 (HIF-1) is a master regulator of pressure ulcer development. To date, however, their causal relationship has not been determined. This study therefore investigated the mutual relationship between thrombosis and HIF-1 activation in compressed mouse skin, based on a hypothesis that HIF-1 regulation by plasminogen activator inhibitor-1 (PAI-1) enhances thrombosis. Compression of mouse skin significantly increased the numbers of thrombi and HIF-1α-positive cells compared with control skin. A thrombosis inhibitor significantly reduced the numbers of HIF-1α-positive cells and an HIF-1 inhibitor significantly inhibited thrombosis in compressed skin tissue, suggesting a mutual relationship between thrombosis and HIF-1 activation. Compression of mouse skin also enhanced the level of Pai-1 messenger RNA expression, but this increase was significantly reduced by treatment with an HIF-1 inhibitor, whereas a thrombosis inhibitor had no effect. These results suggested the involvement of PAI-1 in HIF-1-enhanced thrombosis and that an additional factor participates in regulating Pai-1 expression in compressed skin. These findings may suggest new strategies in pressure ulcer management.

  11. Current-induced enhancement of DNA bubble creation

    Science.gov (United States)

    Gu, Lei; Fu, Hua-Hua

    2016-05-01

    Current-induced heating of short double-stranded DNA chains is studied within a two-probe transport setup by using the Langevin approach. The electrons are modeled by a tight-binding Hamiltonian. The DNA atomic motion is described by the Peyrard-Bishop-Dauxois atomic potential, coupled with electrons through the Holstein interaction. The solvent environment is accounted for as a classical heat bath. Voltage biases of 0.1˜ 0.5 {{V}} can effectively break the base pairs and lead to the melting transition, which can be detected from the resulting significant reduction of the conductance. When the bias increases, the opening of base pairs near the leads with higher chemical potential is suppressed and bubble (localized separation of the double strand) formation becomes asymmetric. Our results suggest that the voltage bias can excite the base pairs, hence increases the chemical activity of DNA.

  12. Complete Au@ZnO core-shell nanoparticles with enhanced plasmonic absorption enabling significantly improved photocatalysis

    Science.gov (United States)

    Sun, Yiqiang; Sun, Yugang; Zhang, Tao; Chen, Guozhu; Zhang, Fengshou; Liu, Dilong; Cai, Weiping; Li, Yue; Yang, Xianfeng; Li, Cuncheng

    2016-05-01

    Nanostructured ZnO exhibits high chemical stability and unique optical properties, representing a promising candidate among photocatalysts in the field of environmental remediation and solar energy conversion. However, ZnO only absorbs the UV light, which accounts for less than 5% of total solar irradiation, significantly limiting its applications. In this article, we report a facile and efficient approach to overcome the poor wettability between ZnO and Au by carefully modulating the surface charge density on Au nanoparticles (NPs), enabling rapid synthesis of Au@ZnO core-shell NPs at room temperature. The resulting Au@ZnO core-shell NPs exhibit a significantly enhanced plasmonic absorption in the visible range due to the Au NP cores. They also show a significantly improved photocatalytic performance in comparison with their single-component counterparts, i.e., the Au NPs and ZnO NPs. Moreover, the high catalytic activity of the as-synthesized Au@ZnO core-shell NPs can be maintained even after many cycles of photocatalytic reaction. Our results shed light on the fact that the Au@ZnO core-shell NPs represent a promising class of candidates for applications in plasmonics, surface-enhanced spectroscopy, light harvest devices, solar energy conversion, and degradation of organic pollutants.Nanostructured ZnO exhibits high chemical stability and unique optical properties, representing a promising candidate among photocatalysts in the field of environmental remediation and solar energy conversion. However, ZnO only absorbs the UV light, which accounts for less than 5% of total solar irradiation, significantly limiting its applications. In this article, we report a facile and efficient approach to overcome the poor wettability between ZnO and Au by carefully modulating the surface charge density on Au nanoparticles (NPs), enabling rapid synthesis of Au@ZnO core-shell NPs at room temperature. The resulting Au@ZnO core-shell NPs exhibit a significantly enhanced plasmonic

  13. Round window membrane intracochlear drug delivery enhanced by induced advection.

    Science.gov (United States)

    Borkholder, David A; Zhu, Xiaoxia; Frisina, Robert D

    2014-01-28

    Delivery of therapeutic compounds to the inner ear via absorption through the round window membrane (RWM) has advantages over direct intracochlear infusions; specifically, minimizing impact upon functional hearing measures. However, previous reports show that significant basal-to-apical concentration gradients occur, with the potential to impact treatment efficacy. Here we present a new approach to inner ear drug delivery with induced advection aiding distribution of compounds throughout the inner ear in the murine cochlea. Polyimide microtubing was placed near the RWM niche through a bullaostomy into the middle ear cavity allowing directed delivery of compounds to the RWM. We hypothesized that a posterior semicircular canalostomy would induce apical flow from the patent cochlear aqueduct to the canalostomy due to influx of cerebral spinal fluid. To test this hypothesis, young adult CBA/CaJ mice were divided into two groups: bullaostomy approach only (BA) and bullaostomy+canalostomy (B+C). Cochlear function was evaluated by distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) thresholds during and after middle ear infusion of salicylate in artificial perilymph (AP), applied near the RWM. The mice recovered for 1week, and were re-tested. The results demonstrate there was no significant impact on auditory function utilizing the RWM surgical procedure with or without the canalostomy, and DPOAE thresholds were elevated reversibly during the salicylate infusion. Comparing the threshold shifts for both methods, the B+C approach had more of a physiological effect than the BA approach, including at lower frequencies representing more apical cochlear locations. Unlike mouse cochleostomies, there was no deleterious auditory functional impact after 1week recovery from surgery. The B+C approach had more drug efficacy at lower frequencies, underscoring potential benefits for more precise control of delivery of inner ear therapeutic compounds.

  14. Locomotion Induces Stimulus-Specific Response Enhancement in Adult Visual Cortex.

    Science.gov (United States)

    Kaneko, Megumi; Fu, Yu; Stryker, Michael P

    2017-03-29

    The responses of neurons in the visual cortex (V1) of adult mammals have long been thought to be stable over long periods. Here, we investigated whether repeated exposure to specific stimuli would enhance V1 visual responses in mice using intrinsic signal imaging through the intact skull and two-photon imaging of calcium signals in single neurons. Mice ran on Styrofoam balls floating on air while viewing one of three different, high-contrast visual stimuli. V1 responses to the stimuli that were viewed by the animal were specifically enhanced, while responses to other stimuli were unaffected. Similar exposure in stationary mice or in mice in which NMDA receptors were partially blocked did not significantly enhance responses. These findings indicate that stimulus-specific plasticity in the adult visual cortex depends on concurrent locomotion, presumably as a result of the high-gain state of the visual cortex induced by locomotion.SIGNIFICANCE STATEMENT We report a rapid and persistent increase in visual cortical responses to visual stimuli presented during locomotion in intact mice. We first used a method that is completely noninvasive to image intrinsic signals through the intact skull. We then measured the same effects on single neurons using two-photon calcium imaging and found that the increase in response to a particular stimulus produced by locomotion depends on how well the neuron is initially driven by the stimulus. To our knowledge, this is the first time such enhancement has been described in single neurons or using noninvasive measurements.

  15. Significant reduction of endemic MRSA acquisition and infection in cardiothoracic patients by means of an enhanced targeted infection control programme.

    Science.gov (United States)

    Schelenz, S; Tucker, D; Georgeu, C; Daly, S; Hill, M; Roxburgh, J; French, G L

    2005-06-01

    Due to increasing methicillin-resistant Staphylococcus aureus (MRSA) infection in cardiothoracic patients at St Thomas' Hospital, an enhanced infection control programme was introduced in September 2000. It was based on UK national guidelines on the control of MRSA and targeted additional identified risk factors for surgical site infection (SSI). It included recognition of the problem by senior staff and their taking responsibility for it; intensive support, education and advice from the infection control team; improved ward and theatre hygiene; pre-admission, admission and weekly MRSA screening; isolation and clearance treatment; nursing care pathways for MRSA colonized patients; and teicoplanin plus gentamicin surgical prophylaxis. The effectiveness of the programme was assessed by retrospective analysis of computerized patient data for the 16 months before and after the introduction of the programme. There was no significant change in the number of operations or the proportion of patients admitted with MRSA, although nine patients were cleared of carriage before admission. However, there were significant falls in the proportion of patients acquiring MRSA on the ward [38/1036 to 14/921, P=0.003, RR 2.4 (95%CI 1.32-4.42)] and in the rate of bloodstream MRSA infections [12/1075 to 2/956, P=0.014, RR 5.34 (95%CI 1.20-23.78)]. Sternal and leg wound infections both halved (from 28/1075 to 13/956 and 16/1075 to 7/956, respectively) but this did not reach statistical significance. These results demonstrate that an enhanced, targeted infection control programme based on the UK national guidelines, SSI prevention guidelines and local risk assessment can reduce the incidence of nosocomial MRSA acquisition and invasive infection in cardiothoracic patients in the face of continuing endemic risk.

  16. Significance of peripheral afferent input to the alpha-motoneurone pool for enhancement of tremor during an isometric fatiguing contraction.

    Science.gov (United States)

    Cresswell, A G; Löscher, W N

    2000-05-01

    The objective of this study was to investigate the contribution of peripheral afferent input to the enhancement of isometric tremor during a sustained submaximal isometric contraction. It was hypothesised that during muscle fatigue, when excitatory drive is high, peripheral afferent input may augment oscillations in the stretch reflex arc and result in bursting motor-unit activity and increased tremor. Nine healthy subjects maintained isometric plantar flexions at 30% of their maximum voluntary contraction until the limit of endurance, under three test conditions. Two paradigms were used to reduce afferent input to the triceps surae alpha-motoneurone pool: (1) continued vibration of the Achilles tendon, and (2) ischaemic partial block of the tibial nerve. These were compared to a control experiment, in which there was no intervention. By recording H-reflexes from the gastrocnemius and soleus muscles, it was possible to assess the effectiveness of reducing the afferent input. When H-reflex suppression had stabilised, the fatiguing contraction was commenced and tremor was computed from the continuously recorded torque signal. Superimposed maximum twitches were elicited as indirect measures of excitatory drive. The increase in tremor root mean square throughout the fatiguing contraction was significantly less for both the vibration and ischaemic conditions. Furthermore, tremor mean power frequency decreased significantly with endurance time in the control experiment, while no significant change was seen in the other two experimental conditions. It is concluded that the enhancement of isometric tremor seen during a fatiguing submaximal isometric contraction is facilitated by peripheral afferent input to the alpha-motoneurone pool.

  17. Modeling Microgravity Induced Fluid Redistribution Autoregulatory and Hydrostatic Enhancements

    Science.gov (United States)

    Myers, J. G.; Werner, C.; Nelson, E. S.; Feola, A.; Raykin, J.; Samuels, B.; Ethier, C. R.

    2017-01-01

    Space flight induces a marked cephalad (headward) redistribution of blood and interstitial fluid potentially resulting in a loss of venous tone and reduction in heart muscle efficiency upon introduction into the microgravity environment. Using various types of computational models, we are investigating how this fluid redistribution may induce intracranial pressure changes, relevant to reported reductions in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome. Methods: We utilize a lumped parameter cardiovascular system (CVS) model, augmented by compartments comprising the cerebral spinal fluid (CSF) space, as the primary tool to describe how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. Models of ocular fluid pressures and biomechanics then accept the output of the above model as boundary condition input to allow more detailed, local analysis (see IWS Abstract by Ethier et al.). Recently, we enhanced the capabilities our previously reported CVS model through the implementation of robust autoregulatory mechanisms and a more fundamental approach to the implementation of hydrostatic mechanisms. Modifying the approach of Blanco et al., we implemented auto-regulation in a quasi-static manner, as an averaged effect across the span of one heartbeat. This approach reduced the higher frequency perturbations from the regulatory mechanism and was intended to allow longer simulation times (days) than models that implement within-beat regulatory mechanisms (minutes). A more fundamental approach to hydrostatics was implemented by a quasi-1D approach, in which compartment descriptions include compartment length, orientation and relative position, allowed for modeling of body orientation, relative body positioning and, in the future, alternative gravity environments. At this time the inclusion of hydrostatic mechanisms supplies additional capabilities to train and validate the CVS model

  18. Inhibition of hypoxia-inducible carbonic anhydrase-IX enhances hexokinase Ⅱ inhibitor-induced hepatocellular carcinoma cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Su-jong YU; Hyo-suk LEE; Jung-hwan YOON; Jeong-hoon LEE; Sun-jung MYUNG; Eun-sun JANG; Min-sun KWAK; Eun-ju CHO; Ja-june JANG; Yoon-jun KIM

    2011-01-01

    Aim: The hypoxic condition within large or infiltrative hypovascular tumors produces intracellular acidification, which could activate many signaling pathways and augment cancer cell growth and invasion. Carbonic anhydrase-Ⅸ (CA-Ⅸ) is an enzyme lowering pH. This study is to examine whether hypoxia induces CA-Ⅸ in hepatocellular carcinoma (HCC) cells, and to evaluate its clinical implication in HCC patients.Methods: Human HCC cell lines (Huh-7 and HepG2 cells) were used, and cell growth was assessed using MTS assay. CA-IX expression and apoptotic/kinase signaling were evaluated using immunoblotting. The cells were transfected with CA-Ⅸ-specific siRNA, or treated with its inhibitor 4-(2-aminoethyl) benzenesulfonamide (CAI#1), and/or the hexokinase Ⅱ inhibitor, 3-bromopyruvate (3-BP). A clinic pathological analysis of 69 patients who underwent an HCC resection was performed using a tissue array.Results: Incubation of HCC cells under hypoxia (1% 02, 5% C02, 94% N2) for 36 h significantly increased CA-IX expression level. CAI#1(400 μmol/L) or CA-IX siRNA (100 μmol/L) did not influence HCC cell growth and induce apoptosis. However, CAI#1 or CA-IX siRNA at these concentrations enhanced the apoptosis induced by 3-BP (100 μmol/L). This enhancement was attributed to increased ER stress and JNK activation, as compared with 3-BP alone. Furthermore, a clinic pathological analysis of 69 HCC patients revealed that tumor CA-Ⅸ intensity was inversely related to E-cadherin intensity.Conclusion: Inhibition of hypoxia-induced CA-Ⅸ enhances hexokinase Ⅱ inhibitor-induced HCC apoptosis. Furthermore, CA-IX expres sion profiles may have prognostic implications in HCC patients. Thus, the inhibition of CA-Ⅸ, in combination with a hexokinase Ⅱ inhibitor, may be therapeutically useful in patients with HCCs that are aggressively growing in a hypoxic environment.

  19. Damage of vascular endothelial barrier induced by explosive blast and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Wang; Jing Chen

    2016-01-01

    In recent years,injuries induced by explosive blast have got more and more attention owing to weapon development and frequent terrorist activities.Tear.bleeding and edema of tissues and organs are the main manifestations of blast shock wave damage.Vascular endothelial barrier is the main defense of tissues and organs' integrity.This article aims to discuss possible mechanisms of endothelial barrier damage induced by explosive blast and main manifestations of blood brain barrier,blood-air barrier,and intestinal vascular barrier impairments.In addition,the main regulatory factors of vascular permeability are also summarized so as to provide theoretical basis for prevention and cure of vascular endothelial barrier damage resulting from explosive blast.

  20. GAS6 enhances repair following cuprizone-induced demyelination.

    Directory of Open Access Journals (Sweden)

    Vladislav Tsiperson

    Full Text Available Growth arrest-specific protein 6 (gas6 activities are mediated through the Tyro3, Axl, and Mer family of receptor tyrosine kinases. Gas6 is expressed and secreted by a wide variety of cell types, including cells of the central nervous system (CNS. In this study, we tested the hypothesis that administration of recombinant human Gas6 (rhGas6 protein into the CNS improves recovery following cuprizone withdrawal. After a 4-week cuprizone diet, cuprizone was removed and PBS or rhGas6 (400 ng/ml, 4 µg/ml and 40 µg/ml was delivered by osmotic mini-pump into the corpus callosum of C57Bl6 mice for 14 days. Nine of 11 (82% PBS-treated mice had abundant lipid-associated debris in the corpus callosum by Oil-Red-O staining while only 4 of 19 (21% mice treated with rhGas6 had low Oil-Red-O positive droplets. In rhGas6-treated mice, SMI32-positive axonal spheroids and APP-positive deposits were reduced in number relative to PBS-treated mice. Compared to PBS, rhGas6 enhanced remyelination as revealed by MBP immunostaining and electron microscopy. The rhGas6-treated mice had more oligodendrocytes expressing Olig1 in the cytoplasm, indicative of oligodendrocyte progenitor cell maturation. Relative to PBS-treated mice, rhGas6-treated mice had fewer activated microglia in the corpus callosum by Iba1 immunostaining. The data show that rhGas6 treatment resulted in more efficient repair following cuprizone-induced injury.

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

    Energy Technology Data Exchange (ETDEWEB)

    Eggleston, D. L. [Occidental College, Physics Department, Los Angeles, California 90041 (United States)

    2014-07-15

    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{sub 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{sub 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{sub r}/ω{sub 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.

  2. Significant enhancement of energy barriers in dinuclear dysprosium single-molecule magnets through electron-withdrawing effects.

    Science.gov (United States)

    Habib, Fatemah; Brunet, Gabriel; Vieru, Veacheslav; Korobkov, Ilia; Chibotaru, Liviu F; Murugesu, Muralee

    2013-09-11

    The effect of electron-withdrawing ligands on the energy barriers of Single-Molecule Magnets (SMMs) is investigated. By introducing highly electron-withdrawing atoms on targeted ligands, the energy barrier was significantly enhanced. The structural and magnetic properties of five novel SMMs based on a dinuclear {Dy2} phenoxo-bridged motif are explored and compared with a previously studied {Dy2} SMM (1). All complexes share the formula [Dy2(valdien)2(L)2]·solvent, where H2valdien = N1,N3-bis(3-methoxysalicylidene) diethylenetriamine, the terminal ligand L = NO3(-) (1), CH3COO(-) (2), ClCH2COO(-) (3), Cl2CHCOO(-) (4), CH3COCHCOCH3(-) (5), CF3COCHCOCF3(-) (6), and solvent = 0.5 MeOH (4), 2 CH2Cl2 (5). Systematic increase of the barrier was observed for all complexes with the most drastic increase seen in 6 when the acac ligand of 5 was fluorinated resulting in a 7-fold enhancement of the anisotropic barrier. Ab initio calculations reveal more axial g tensors as well as higher energy first excited Kramers doublets in 4 and 6 leading to higher energy barriers for those complexes.

  3. Defect-induced enhanced photocatalytic activities of reduced α-Fe2O3 nanoblades

    Science.gov (United States)

    Feng, Honglei; Wang, Yiqian; Wang, Chao; Diao, Feiyu; Zhu, Wenhui; Mu, Peng; Yuan, Lu; Zhou, Guangwen; Rosei, Federico

    2016-07-01

    Bicrystalline α-Fe2O3 nanoblades (NBs) synthesized by thermal oxidation of iron foils were reduced in vacuum, to study the effect of reduction treatment on microstructural changes and photocatalytic properties. After the vacuum reduction, most bicrystalline α-Fe2O3 NBs transform into single-layered NBs, which contain more defects such as oxygen vacancies, perfect dislocations and dense pores. By comparing the photodegradation capability of non-reduced and reduced α-Fe2O3 NBs over model dye rhodamine B (RhB) in the presence of hydrogen peroxide, we find that vacuum-reduction induced microstructural defects can significantly enhance the photocatalytic efficiency. Even after 10 cycles, the reduced α-Fe2O3 NBs still show a very high photocatalytic activity. Our results demonstrate that defect engineering is a powerful tool to enhance the photocatalytic performance of nanomaterials.

  4. Rosiglitazone enhances fluorouracil-induced apoptosis of HT-29 cells by activating peroxisome proliferator-activated receptor γ

    Institute of Scientific and Technical Information of China (English)

    Yan-Qin Zhang; Xiao-Qing Tang; Li Sun; Lin Dong; Yong Qin; Hua-Qing Liu; Hong Xia; Jian-Guo Cao

    2007-01-01

    AIM: To examine whether and how rosiglitazone enhances apoptosis induced by fluorouracil in human colon cancer (HT-29) cells.METHODS: Human colon cancer HT-29 cells were cultured in vitro and treated with fluorouracil and/or rosiglitazone. Proliferation and growth of HT-29 cells were evaluated by MTT assay and trypan blue exclusion methods, respectively. The apoptosis of HT-29 cells was determined by acridine orange/ethidium bromide staining and flow cytometry using PI fluorescence staining. The expressions of peroxisome proliferator-activated receptor y (PPARy), Bcl-2 and Bax in HT-29 cells were analyzed by Western blot.RESULTS: Although rosiglitazone at the concentration below 30 umol/L for 72 h exerted almost no inhibitory effect on proliferation and growth of HT-29 cells, it could significantly enhance fluorouracil-induced HT-29 cell proliferation and growth inhibition. Furthermore, 10 umol/L rosilitazone did not induce apoptosis of HT-29 cells but dramatically enhanced fluorouracil-induced apoptosis of HT-29 cells. However, rosiglitazone did not improve apoptosis induced by fluorouracil in HT-29 cells pretreated with GW9662, a PPARy antagonist. Meanwhile, the expression of Bax and PPARy was up-regulated, while the expression of Bcl-2 was down regulated in HT-29 cells treated with rosiglitazone in a time-dependent manner. However, the effect of rosiglitazone on Bcl-2 and Bax was blocked or diminished in the presence of GW9662.CONCLUSION: Rosiglitazone enhances fluorouracil-induced apoptosis of HT-29 cells by activating PPARγ.

  5. Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms

    Institute of Scientific and Technical Information of China (English)

    Ying-jia ZHONG; Yong QIN; Lin-chuan; LIAO Xia WANG; Fang SHI; Xue-lian ZHENG; Qiong WANG; Lan YANG; Hong SUN; Fan HE; Lin ZHANG; Yong LIN

    2011-01-01

    To investigate the anticancer effect of crocetin,a major ingredient in saffron,and its underlying mechanisms.Methods:Cervical cancer cell line HeLa,non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristine.Cell proliferation was examined using MTT assay.Cell cycle distribution and sub-G1 fraction were analyzed using flow cytometric analysis after propidium iodide staining.Apoptosis was detected using the Annexin V-FITC Apoptosis Detection Kit with flow cytometry.Cell death was measured based on the release of lactate dehydrogenase (LDH).The expression levels of p53 and p21wAF1/Cip1 as well as caspase activation were examined using Western blot analysis.Results:Treatment of the 3 types of cancer cells with crocetin (60-240 μmol/L) for 48 h significantly inhibited their proliferation in a concentration-dependent manner.Crocetin (240 μmol/L) significantly induced cell cycle arrest through p53-dependent and -independent mechanisms accompanied with p21WAF1/Cip1 induction.Crocetin (120-240 μmoVL) caused cytotoxicity in the 3 types of cancer cells by enhancing apoptosis in a time-dependent manner.In the 3 types of cancer cells,crocetin (60 μmol/L) significantly enhanced the cytotoxicity induced by vincristine (1 μmol/L).Furthermore,this synergistic effect was also detected in the vincristine-resistant breast cancer cell line MCF-7/VCR.Conclusion:Ccrocetin is a potential anticancer agent,which may be used as a chemotherapeutic drug or as a chemosensitizer for vin-cristine.

  6. Curcumin Enhances the Radiosensitivity of U87 Cells by Inducing DUSP-2 Up-Regulation

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    Yu Qian

    2015-03-01

    Full Text Available Objective: Glioblastoma multiforme (GBM, an aggressive primary brain tumor, is radioresistant and recurs despite aggressive surgery, chemotherapy, and radiotherapy. Curcumin as a potential radiosensitizer has received extensive attention in cancer treatment. To explore an effectiveness of this radiosensitizer for GBM treatment, we evaluated the radiosensitizing effect of curcumin and investigated its potential molecular mechanisms in the human glioma cell line U87. Methods: The cytotoxic effects of curcumin on U87 cells were evaluated using the Cell Counting Kit-8 assay, and the radiosensitivity of U87 cells treated with curcumin was accessed by colony information assay. The effects of curcumin on cell proliferation and cell cycle regulation were determined using the 5-ethynyl-2-deoxyuridine incorporation assay and flow cytometry, respectively. Western blotting was applied to determine the effects of curcumin on protein expression of dual-specificity phosphatase-2 (DUSP-2, extracellular signal-regulated kinase (ERK, and c-Jun N-terminal kinase (JNK as well as phosphorylated ERK and JNK. Results: Curcumin significantly inhibited the proliferation of U87 cells in a dose-and time-dependent manner. Curcumin treatment at the concentrations of 5 µM and 10 M could significantly reduce the clonogenic activity and enhance the radiosensitivity of U87 cells with sensitive enhancement ratios (SERs of 1.71 and 4.65, respectively. Curcumin resulted in G2/M cell cycle arrest in U87 cells, which were radiosensitive. Pre-treatment of U87-MG cells with 5 µM curcumin enhanced radiation-induced cell proliferation inhibition and apoptosis. Furthermore, we observed that curcumin increased DUSP-2 protein expression and decreased the phosphorylation of ERK and JNK. Conclusion: Our results suggest that low-dose curcumin may enhance the radiosensitivity of human glioma U87 cells in vitro by inducing G2/M cell cycle arrest through up-regulation of DUSP-2 expression and

  7. Significance of matrix metalloproteinases in norepinephrine-induced remodelling of rat hearts.

    Science.gov (United States)

    Briest, Wilfried; Hölzl, Alexander; Rassler, Beate; Deten, Alexander; Baba, Hideo A; Zimmer, Heinz-Gerd

    2003-02-01

    Norepinephrine (NE) induced hypertrophy and remodelling of the extracellular matrix (ECM) in the left ventricle (LV) of the rat heart with resulting fibrosis. However, there was no increased collagen deposition in the right ventricle (RV). To test the hypothesis that lack of RV fibrosis is the result of elevated cleavage of collagens we inhibited the activity of matrix metalloproteinases (MMP) by doxycycline (Doxy) and then measured function and collagen metabolism in the RV as compared to the LV. Female Sprague-Dawley rats were treated with 30 mg/kg per day doxycycline alone or in combination with i.v. infusion of NE (0.1 mg/kg per h). The activity of MMP-2 was increased both in the LV and RV after 3 days of NE infusion and reduced after concomitant doxycycline treatment which also caused inhibition when given alone. After 14 days of NE infusion in combination with doxycycline there was an additional increase in the NE-induced elevation of collagen accumulation in the LV (interstitial collagen fraction: NE-Doxy 1.797%, PDoxy: 36.4 mmHg) and RV dP/dt(max) (NE: 5500 mmHg/s, PDoxy: 2550 mmHg/s). Also in the NE-stimulated LV, the doxycycline-induced collagen accumulation was associated with reduced LV dP/dt(max) (NE-Doxy: 13169 mmHg/s; NE: 18849 mmHg/s, P<0.05). MMP inhibition leads to myocardial stiffness with negative functional consequences for the RV and LV in NE-treated rat hearts.

  8. EXPERIMENTAL STUDY OF ENHANCED HEAT TRANSFER BY FLOW-INDUCED VIBRATION OF ELASTIC TUBE BUNDLES

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new concept of heat transfer enhancement by flow-induced vibration was put forward, and a novel heat transfer element called elastic tube bundles was designed. The experimental investigation was performed on its characteristics of flow-induced virbration in out-tube or in-tube flow. Under the conditions of fixed heat flux and steam-water heat transfer, the regularity of heat transfer enhancement by flow-induced vibration was examined.

  9. The gap junction blocker carbenoxolone enhances propofol and sevoflurane-induced loss of consciousness

    Institute of Scientific and Technical Information of China (English)

    Zhigang Liu; Yongfang Liu; Bo Zhao; Li Du; Zhongyuan Xia; Xiangdong Chen; Tao Luo

    2012-01-01

    General anesthetics induce loss of consciousness by inhibiting ascending arousal pathways, and they interfere with gap junction electrical coupling.The present study aimed to determine whether inhibition of gap junction-mediated signaling could influence general anesthetic-induced loss of consciousness.The general anesthetics sevoflurane and propofol were used.Intracerebroventricular administration of carbenoxolone, a gap junction blocker, significantly decreased the time to loss of the righting reflex (P < 0.05), but prolonged the time to recovery of the reflex (P < 0.05).Moreover, intracerebroventricular administration of carbenoxolone increased the sensitivity to sevoflurane, with a leftward shift of the loss of righting reflex dose-response curve, and decreased the 50% effective concentration of sevoflurane.These results suggest that the gap junction blocker carbenoxolone enhances propofol and sevoflurane-mediated general anesthesia.

  10. The baculovirus uses a captured host phosphatase to induce enhanced locomotory activity in host caterpillars.

    Directory of Open Access Journals (Sweden)

    Susumu Katsuma

    Full Text Available The baculovirus is a classic example of a parasite that alters the behavior or physiology of its host so that progeny transmission is maximized. Baculoviruses do this by inducing enhanced locomotory activity (ELA that causes the host caterpillars to climb to the upper foliage of plants. We previously reported that this behavior is not induced in silkworms that are infected with a mutant baculovirus lacking its protein tyrosine phosphatase (ptp gene, a gene likely captured from an ancestral host. Here we show that the product of the ptp gene, PTP, associates with baculovirus ORF1629 as a virion structural protein, but surprisingly phosphatase activity associated with PTP was not required for the induction of ELA. Interestingly, the ptp knockout baculovirus showed significantly reduced infectivity of larval brain tissues. Collectively, we show that the modern baculovirus uses the host-derived phosphatase to establish adequate infection for ELA as a virion-associated structural protein rather than as an enzyme.

  11. [Etiological analysis and significance of anterior knee pain induced by gluteal muscles contracture].

    Science.gov (United States)

    Zhao, Gang; Liu, Yu-jie; Wang, Jun-liang; Qi, Wei; Qu, Feng; Yuan, Bang-tuo; Wang, Jiang-tao; Shen, Xue-zhen; Liu, Yang; Zhu, Juan-li

    2014-12-01

    To explore causes of gluteal muscle contracture induced anterior knee pain and curative effect of arthroscopic release. From March 2002 to August 2013,36 patients with gluteal muscle contracture induced anterior knee pain were treated, including 15 males, 21 females, aged from 9 to 40 years old with an average (18.7±7.2) years old; the courses of diseases ranged from 4 to 30 years. The clinical manifestations involved limited to symmelia, positive Ober sign, buttocks touch contracture belts, knee and patella slide to lateral when doing squat activities. All patients were performed gluteal muscle contracture release under arthroscopic. Postoperative complications were observed, Kujala scoring before and after operation was used for compare curative effect. All patients were followed up with an average of 29 months. The incision were healed well, and no complications were occurred. Postoperative Kujala score were improved more than preoperative. Gluteal muscle contracture release could alleviate hypertension of lateral patella, and palys an important role in preventing patellofemoral arthritis.

  12. Significance of chymase-dependent matrix metalloproteinase-9 activation on indomethacin-induced small intestinal damages in rats.

    Science.gov (United States)

    Kakimoto, Kazuki; Takai, Shinji; Murano, Mitsuyuki; Ishida, Kumi; Yoda, Yukiko; Inoue, Takuya; Jin, Denan; Umegaki, Eiji; Higuchi, Kazuhide

    2010-02-01

    The side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) include gastrointestinal damage not only in the stomach but also in the small intestine. Chymase converts promatrix metalloproteinase-9 to matrix metalloproteinase (MMP)-9, which plays an important role in NSAID-induced gastric damage, but it has been unclear whether chymase-dependent MMP-9 activation is involved in the NSAID-induced small intestinal damage. To clarify the involvement of chymase-dependent MMP-9 activation on NSAID-induced small intestinal damage, the effect of a chymase inhibitor, 2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl] thiazole-4-carboxylic acid (TY-51469), on indomethacin-induced small intestinal damage in rats was evaluated. Until 6 h after oral administration of indomethacin in rats, intestinal MMP-9 activity was unchanged compared with normal rats, but significant increases in MMP-9 activity were observed 12 and 24 h after indomethacin administration. Significant increases in the small intestinal damage score were also observed 12 and 24 h after indomethacin administration. In the extract from the small intestine 24 h after indomethacin administration, the MMP-9 activation was significantly attenuated by TY-51469. Intraperitoneal injection of TY-51469 (10 mg/kg) 3 h before indomethacin administration significantly attenuated the MMP-9 activity in the small intestine compared with placebo treatment. Myeloperoxidase activity, which indicates accumulation of neutrophils, was significantly increased in the small intestine in the placebo-treated rats, but its activity was significantly attenuated by TY-51469 treatment. The area of small intestinal damage was also significantly ameliorated by TY-51469 treatment. These findings suggest that chymase-dependent MMP-9 activation has a significant role in indomethacin-induced small intestinal damage in rats.

  13. TNF-related apoptosis-inducing ligand deficiency enhances survival in murine colon ascendens stent peritonitis

    Directory of Open Access Journals (Sweden)

    Beyer K

    2016-06-01

    Full Text Available Katharina Beyer,1 Laura Stollhof,1 Christian Poetschke,2 Wolfram von Bernstorff,1 Lars Ivo Partecke,1 Stephan Diedrich,1 Stefan Maier,1 Barbara M Bröker,2 Claus-Dieter Heidecke1 1Department of General, Visceral, Thoracic, and Vascular Surgery, 2Institute of Immunology, University of Greifswald, Greifswald, GermanyBackground: Apart from inducing apoptosis in tumor cells, tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL influences inflammatory reactions. Murine colon ascendens stent peritonitis (CASP represents a model of diffuse peritonitis. Recently, it has been demonstrated that administration of exogenous TRAIL not only induces apoptosis in neutrophils but also enhances survival in this model. The aim of this study was to examine the impact of genetic TRAIL deficiency on the course of CASP.Methods: Peritonitis was induced in 6- to 8-week-old female TRAIL−/− mice as well as in wild-type mice. The sepsis severity score and survival of mice were monitored. Bacterial loads in blood as well as in the lymphoid organs were examined. Additionally, the number of apoptotic cells within the lymphoid organs was determined.Results: As early as 8 hours postinduction of CASP, TRAIL−/− mice were significantly more affected by sepsis than wild-type mice, as measured by the sepsis severity score. However, during the further course of sepsis, TRAIL deficiency led to significantly decreased sepsis severity scores, resulting in an enhanced overall survival in TRAIL−/− mice. The better survival of TRAIL−/− mice was accompanied by a decreased bacterial load within the blood. In marked contrast, the number of apoptotic cells within the lymphoid organs was highly increased in TRAIL−/− mice 20 hours after induction of CASP.Conclusion: Hence, exogenous and endogenous TRAIL is protective during the early phase of sepsis, while endogenous TRAIL appears to be detrimental in the later course of this disease.Keywords: CASP, mice

  14. Clinical significance of mammillary body enhancement in Wernicke encephalopathy: report of 2 cases and review of the literature.

    Science.gov (United States)

    Konno, Yoshihiro; Kanoto, Masafumi; Hosoya, Takaaki; Toyoguchi, Yuki; Kawanami, Toru; Kato, Takeo

    2014-01-01

    In 2 cases of Wernicke encephalopathy in which the initial symptom was double vision, the only abnormal finding on magnetic resonance (MR) imaging was abnormal enhancement of the mammillary bodies. The mammillary bodies are the region most vulnerable to abnormal enhancement. Because MR imaging with contrast enhancement can detect such abnormal enhancement at an early stage, it should be performed more often in patients with oculomotor disorders to avoid underdiagnosis of Wernicke encephalopathy.

  15. Genetic deletion of the P2Y2 receptor offers significant resistance to development of lithium-induced polyuria accompanied by alterations in PGE2 signaling.

    Science.gov (United States)

    Zhang, Yue; Pop, Ioana L; Carlson, Noel G; Kishore, Bellamkonda K

    2012-01-01

    Lithium (Li)-induced polyuria is due to resistance of the medullary collecting duct (mCD) to the action of arginine vasopressin (AVP), apparently mediated by increased production of PGE(2). We previously reported that the P2Y(2) receptor (P2Y(2)-R) antagonizes the action of AVP on the mCD and may play a role in Li-induced polyuria by enhancing the production of PGE(2) in mCD. Hence, we hypothesized that genetic deletion of P2Y(2)-R should ameliorate Li-induced polyuria. Wild-type (WT) or P2Y(2)-R knockout (KO) mice were fed normal or Li-added diets for 14 days and euthanized. Li-induced polyuria, and decreases in urine osmolality and AQP2 protein abundance in the renal medulla, were significantly less compared with WT mice despite the lack of differences in Li intake or terminal serum or inner medullary tissue Li levels. Li-induced increased urinary excretion of PGE(2) was not affected in KO mice. However, prostanoid EP(3) receptor (EP3-R) protein abundance in the renal medulla of KO mice was markedly lower vs. WT mice, irrespective of the dietary regimen. The protein abundances of other EP-Rs were not altered across the groups irrespective of the dietary regimen. Ex vivo stimulation of mCD with PGE(2) generated significantly more cAMP in Li-fed KO mice (130%) vs. Li-fed WT mice (100%). Taken together, these data suggest 1) genetic deletion of P2Y(2)-R offers significant resistance to the development of Li-induced polyuria; and 2) this resistance is apparently due to altered PGE(2) signaling mediated by a marked decrease in EP3-R protein abundance in the medulla, thus attenuating the EP3-mediated decrease in cAMP levels in mCD.

  16. ESP-102, a standardized combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, significantly improved scopolamine-induced memory impairment in mice.

    Science.gov (United States)

    Kang, So Young; Lee, Ki Yong; Koo, Kyung Ah; Yoon, Jeong Seon; Lim, Song Won; Kim, Young Choong; Sung, Sang Hyun

    2005-02-25

    We assessed the effects of oral treatments of ESP-102, a standardized combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, on learning and memory deficit. The cognition-enhancing effect of ESP-102 was investigated in scopolamine-induced (1 mg/kg body weight, s.c.) amnesic mice with both passive avoidance and Morris water maze performance tests. Acute oral treatment (single administration prior to scopolamine treatment) of mice with ESP-102 (doses in the range of 10 to 100 mg/kg body weight) significantly reduced scopolamine-induced memory deficits in the passive avoidance performance test. Another noteworthy result included the fact that prolonged oral daily treatments of mice with much lower amounts of ESP-102 (1 and 10 mg/kg body weight) for ten days reversed scopolamine-induced memory deficits. In the Morris water maze performance test, both acute and prolonged oral treatments with ESP-102 (single administration of 100 mg/kg body weight or prolonged daily administration of 1 and 10 mg/kg body weight for ten days, respectively, significantly ameliorated scopolamine-induced memory deficits as indicated by the formation of long-term and/or short-term spatial memory. In addition, we investigated the effects of ESP-102 on neurotoxicity induced by amyloid-beta peptide (Abeta25-35) or glutamate in primary cultured cortical neurons of rats. Pretreatment of cultures with ESP-102 (0.001, 0.01 and 0.1 mug/ml) significantly protected neurons from neurotoxicity induced by either glutamate or Abeta25-35. These results suggest that ESP-102 may have some protective characteristics against neuronal cell death and cognitive impairments often observed in Alzheimer's disease, stroke, ischemic injury and other neurodegenerative diseases.

  17. Enhancement of solubility and dissolution rate of poorly water soluble raloxifene using microwave induced fusion method

    Directory of Open Access Journals (Sweden)

    Payal Hasmukhlal Patil

    2013-09-01

    Full Text Available The objective of the present work was to enhance the solubility and dissolution rate of the drug raloxifene HCl (RLX, which is poorly soluble in water. The solubility of RLX was observed to increase with increasing concentration of hydroxypropyl methylcellulose (HPMC E5 LV. The optimized ratio for preparing a solid dispersion (SD of RLX with HPMC E5 LV using the microwave-induced fusion method was 1:5 w/w. Microwave energy was used to prepare SDs. HPMC E5 LV was used as a hydrophilic carrier to enhance the solubility and dissolution rate of RLX. After microwave treatment, the drug and hydrophilic polymer are fused together, and the drug is converted from the crystalline form into an amorphous form. This was confirmed through scanning electron microscopy (SEM, differential scanning calorimetry (DSC and powder X-ray diffraction (PXRD studies. These results suggested that the microwave method is a simple and efficient method of preparing SDs. The solubility and dissolution rate of the SDs were increased significantly compared with pure RLX due to the surfactant and wetting properties of HPMC E5 LV and the formation of molecular dispersions of the drug in HPMC E5 LV. It was concluded that the solubility and dissolution rate of RLX are increased significantly when an SD of the drug is prepared using the microwave-induced fusion method.

  18. Significance of Sulphur nutrition against metal induced oxidative stress in plants

    Directory of Open Access Journals (Sweden)

    Mohd Mazid

    2011-09-01

    Full Text Available Sulphur (S is available to plants as sulphate (SO42- in the soil to the roots and as gaseous SO2 in the atmosphere to the shoots. Of all the macronutrient, S is perhaps the nutrient which has attracted the most attention in soil science and plant nutrition due to its potential defensive characteristics to pests, good nutritive potentiality to crops and its relative immobility in the soil-plant system. This review highlights the mechanisms of uptake and translocation of S from soil and its transport in xylem and phloem tissues of plants. Moreover, it also throws new insights, have led us to revisit the hypothesis of S chelation in reference to oxidative stress induced by heavy metals sequestration.

  19. Diet-Induced Obesity Enhances TRPV1-Mediated Neurovascular Reactions in the Dura Mater.

    Science.gov (United States)

    Marics, Balázs; Peitl, Barna; Pázmándi, Kitti; Bácsi, Attila; Németh, József; Oszlács, Orsolya; Jancsó, Gábor; Dux, Mária

    2017-03-01

    Exploring the pathophysiological changes in transient receptor potential vanilloid 1 (TRPV1) receptor of the trigeminovascular system in high-fat, high-sucrose (HFHS) diet-induced obesity of experimental animals. Clinical and experimental observations suggest a link between obesity and migraine. Accumulating evidence indicates that metabolic and immunological alterations associated with obesity may potentially modulate trigeminovascular functions. A possible target for obesity-induced pathophysiological changes is the TRPV1/capsaicin receptor which is implicated in the pathomechanism of headaches in a complex way. Male Sprague-Dawley rats were fed a regular (n = 25) or HFHS diet (n = 26) for 20 weeks. At the end of the dietary period, body weight of the animals was normally distributed in both groups and it was significantly higher in animals on HFHS diet. Therefore, experimental groups were regarded as control and HFHS diet-induced obese groups. Capsaicin-induced changes in meningeal blood flow and release of calcitonin gene-related peptide (CGRP) from dural trigeminal afferents were measured in control and obese rats. The distribution of TRPV1- and CGRP-immunoreactive meningeal sensory nerves was also compared in whole mount preparations of the dura mater. Metabolic parameters of the animals were assessed by examining glucose and insulin homeostasis as well as plasma cytokine concentrations. HFHS diet was accompanied by reduced food consumption and greater fluid and energy intakes in addition to increased body weight of the animals. HFHS diet increased fasting blood glucose and insulin concentrations as well as levels of circulating proinflammatory cytokines interleukin-1β and interleukin-6. In obese animals, dural application of the archetypal TRPV1 agonist capsaicin resulted in significantly augmented vasodilatory and vasoconstrictor responses as compared to controls. Diet-induced obesity was also associated with enhanced basal and capsaicin-induced

  20. 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

    2015-01-05

    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.

  1. 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

  2. Enhancement of Absorption by Micro-Mixing induced by Villi Motion

    Science.gov (United States)

    Wang, Yanxing; Brasseur, James; Banco, Gino

    2009-11-01

    Motions of surface villi create microscale flows that can couple with lumen-scale eddies to enhance absorption at the epithelium of the small intestine. Using a multigrid strategy within the lattice-Boltzmann framework, we model a macro-scale cavity flow with microscale ``villi'' in pendular motion on the lower surface and evaluate the couplings between macro and micro-scale fluid motions, scalar mixing, and uptake of passive scalar at the villi surface. We study the influences of pendular frequency, villous length, and villous groupings on absorption rate. The basic mechanism underlying the enhancement of absorption rate by a villous-induced ``micro-mixing layer'' (MML) is the microscale ``pumping'' of low concentration fluid from between groups of villi coupled with the return of high concentration fluid into the villi groups from the macroscale flow. The MML couples with the macrosacle eddies through a diffusion layer that separates micro and macro mixed layers. The absorption rate increases with frequency of villi oscillation due to enhanced vertical pumping. We discover a critical villus length above which absorption rate increases significantly. The absorption is influenced by villus groupings in a complex way due to the interference between vertical and horizontal geometry vs. MML scales. We conclude that optimized villi motility can enhance absorption and may underlie an explanation for the existence of villi in the gut. [Supported by NSF

  3. Tramadol does not enhance sedation induced by acepromazine in dogs.

    Science.gov (United States)

    Monteiro, Eduardo R; Lobo, Renan B; Nunes, Juarez S; Rangel, Julia P P; Bitti, Flavia S

    2016-10-01

    The sedative effect of acepromazine combined with 2 doses of tramadol [3 and 5 mg/kg body weight (BW)] was compared with the sedative effect of acepromazine alone in dogs and the effects of each sedative protocol on cardiorespiratory variables were examined. This was a prospective, randomized, blinded, crossover study. Each of 6 dogs received 3 treatments at 1-week intervals. During all anesthetic episodes, dogs received 0.05 mg/kg BW acepromazine. Approximately 25 min later, dogs were given physiological saline (control) or tramadol [3 mg/kg BW (TR3) or 5 mg/kg BW (TR5)]. All drugs were administered intravenously. Variables evaluated included heart rate (HR), respiratory rate (RR), systolic, mean, and diastolic blood pressures (SAP, MAP, and DAP), and sedation [by use of a simple descriptive scale (SDS, range: 0 to 3) and a numeric rating scale (NRS, range: 0 to 10)]. Variables were recorded 25 min after acepromazine and for 80 min after saline or tramadol. Acepromazine administration resulted in mild sedation in most dogs and decreased RR, SAP, MAP, and DAP in all treatments. Tramadol administration did not significantly increase SDS or NRS scores compared to acepromazine alone. The only exception to this rule was observed at 20 min after TR3, when NRS was higher in this group than in the control treatment. Administration of tramadol (TR3 and TR5) decreased HR. Under the conditions of this study, sedation induced by acepromazine with tramadol was similar to that of acepromazine alone. The main adverse effects of the combination were a decrease in blood pressure and HR, without clinical significance.

  4. Enhanced decomposition of dyes by hemin-ACF with significant improvement in pH tolerance and stability

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Yuyuan, E-mail: yyy0571@126.com; Mao, Yajun; Huang, Qunfeng; Wang, Lie; Huang, Zhengfu; Lu, Wangyang; Chen, Wenxing, E-mail: wxchen@zstu.edu.cn

    2014-01-15

    Highlights: • ACF-supported hemin allowed enhanced decomposition of dyes compared with bare hemin. • Hemin-ACF exhibited excellent pH tolerance over a wide pH range from acidic to alkaline. • The introduction of ACF accelerated the generation of reactive species by electron transfer from ACF to hemin. -- Abstract: In this study, we evaluated a novel heterogeneous catalytic system (hemin-ACF/H{sub 2}O{sub 2}) based on activated carbon fiber supported hemin for the rapid removal of dyes. Contrast experiments, effects of pH and temperature, and sustained catalytic stability of hemin-ACF for the catalytic decomposition of azo dye RR195 used as a model pollutant were investigated. Surprisingly, the introduction of ACF significantly enhanced the decomposition of dyes by hemin with an obvious improvement in pH tolerance and stability. Inhibition and probe studies combined with electron paramagnetic resonance (EPR) were conducted to ascertain the role of several radicals (·OH, O{sub 2}·{sup −}/HO{sub 2}·, {sup 1}O{sub 2} and Fe{sup IV}=O) on dye degradation. ACF are rich in free electrons, and the π-conjugated macrocyclic structure of hemin may present convenient channels for the transfer of free electrons from the ACF, promoting the generation of hydroxyl radicals and high-valence iron species. These results are promising because they offer new insight for the application of hemin as a catalyzer upon treatment of organic pollutants and contribute to identification of the interaction between support material and catalyzer from a new perspective.

  5. 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

  6. Combination of Human Fas (CD95/Apo-1) Ligand with Adriamycin Significantly Enhances the Efficacy of Antitumor Response

    Institute of Scientific and Technical Information of China (English)

    Zhongchen Liu; Ruizhen Liu; Jinhua Qiu; Ping Yin; Fanghong Luo; Jinhua SU; Wenzhu Li; Caixia Chen; Xin Fan; Jiakai Zhang; Guohong Zhuang

    2009-01-01

    The prognosis of hepatocellular carcinoma (HCC) is poor, even with the combined treatment of curative resection and adjuvant chemoradiotherapy. To solve this problem, many biologic therapies have been investigated. Fas ligand (FasL, CD95L) is mainly expressed in activated T lymphocytes and natural killer (NK) cells, and plays a central role in both cell-mediated immunity and immune downregnlation. Several studies have shown that FasL is expressed in HCC. In the present report, we prepared recombinant human pET-22b(+)/FasL protein and investigated the effect of FasL on HCC cells in vitro and on tumor growth in a murine HCC tumor model. The well-known cytotoxic chemotherapeutic reagent adriamycin (ADM) served as a control. We found that FasL effectively suppressed the viability of H22 tumor cells and significantly induced the apoptosis of H22 cells. The apoptotic levels of cells treated with FasL-ADM were significantly higher than those treated with FasL or ADM alone, and the FasL-ADM combination resulted in a more than additive effect on tumor growth delay in this model. The results suggested that combined treatment of FasL and other chemotherapeutic agents 5 be a new approach to improve the efficacy of chemotherapy for HCC. Cellular & Molecular Immunology. 2009;6(3):167-174.

  7. Acellular bone marrow extracts significantly enhance engraftment levels of human hematopoietic stem cells in mouse xeno-transplantation models.

    Directory of Open Access Journals (Sweden)

    Kazem Zibara

    Full Text Available Hematopoietic stem cells (HSC derived from cord blood (CB, bone marrow (BM, or mobilized peripheral blood (PBSC can differentiate into multiple lineages such as lymphoid, myeloid, erythroid cells and platelets. The local microenvironment is critical to the differentiation of HSCs and to the preservation of their phenotype in vivo. This microenvironment comprises a physical support supplied by the organ matrix as well as tissue specific cytokines, chemokines and growth factors. We investigated the effects of acellular bovine bone marrow extracts (BME on HSC in vitro and in vivo. We observed a significant increase in the number of myeloid and erythroid colonies in CB mononuclear cells (MNC or CB CD34+ cells cultured in methylcellulose media supplemented with BME. Similarly, in xeno-transplantation experiments, pretreatment with BME during ex-vivo culture of HSCs induced a significant increase in HSC engraftment in vivo. Indeed, we observed both an increase in the number of differentiated myeloid, lymphoid and erythroid cells and an acceleration of engraftment. These results were obtained using CB MNCs, BM MNCs or CD34(+ cells, transplanted in immuno-compromised mice (NOD/SCID or NSG. These findings establish the basis for exploring the use of BME in the expansion of CB HSC prior to HSC Transplantation. This study stresses the importance of the mechanical structure and soluble mediators present in the surrounding niche for the proper activity and differentiation of stem cells.

  8. Mechanism of regulation of 'chromosome kissing' induced by Fob1 and its physiological significance.

    Science.gov (United States)

    Choudhury, Malay; Zaman, Shamsu; Jiang, James C; Jazwinski, S Michal; Bastia, Deepak

    2015-06-01

    Protein-mediated "chromosome kissing" between two DNA sites in trans (or in cis) is known to facilitate three-dimensional control of gene expression and DNA replication. However, the mechanisms of regulation of the long-range interactions are unknown. Here, we show that the replication terminator protein Fob1 of Saccharomyces cerevisiae promoted chromosome kissing that initiated rDNA recombination and controlled the replicative life span (RLS). Oligomerization of Fob1 caused synaptic (kissing) interactions between pairs of terminator (Ter) sites that initiated recombination in rDNA. Fob1 oligomerization and Ter-Ter kissing were regulated by intramolecular inhibitory interactions between the C-terminal domain (C-Fob1) and the N-terminal domain (N-Fob1). Phosphomimetic substitutions of specific residues of C-Fob1 counteracted the inhibitory interaction. A mutation in either N-Fob1 that blocked Fob1 oligomerization or C-Fob1 that blocked its phosphorylation antagonized chromosome kissing and recombination and enhanced the RLS. The results provide novel insights into a mechanism of regulation of Fob1-mediated chromosome kissing. © 2015 Choudhury et al.; Published by Cold Spring Harbor Laboratory Press.

  9. Mechanism of regulation of ‘chromosome kissing’ induced by Fob1 and its physiological significance

    Science.gov (United States)

    Choudhury, Malay; Zaman, Shamsu; Jiang, James C.; Jazwinski, S. Michal

    2015-01-01

    Protein-mediated “chromosome kissing” between two DNA sites in trans (or in cis) is known to facilitate three-dimensional control of gene expression and DNA replication. However, the mechanisms of regulation of the long-range interactions are unknown. Here, we show that the replication terminator protein Fob1 of Saccharomyces cerevisiae promoted chromosome kissing that initiated rDNA recombination and controlled the replicative life span (RLS). Oligomerization of Fob1 caused synaptic (kissing) interactions between pairs of terminator (Ter) sites that initiated recombination in rDNA. Fob1 oligomerization and Ter–Ter kissing were regulated by intramolecular inhibitory interactions between the C-terminal domain (C-Fob1) and the N-terminal domain (N-Fob1). Phosphomimetic substitutions of specific residues of C-Fob1 counteracted the inhibitory interaction. A mutation in either N-Fob1 that blocked Fob1 oligomerization or C-Fob1 that blocked its phosphorylation antagonized chromosome kissing and recombination and enhanced the RLS. The results provide novel insights into a mechanism of regulation of Fob1-mediated chromosome kissing. PMID:26063576

  10. Contrast-induced nephropathy in patients with renal insufficiency undergoing contrast-enhanced MDCT

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Ryusuke; Hayashi, Hiromitsu; Sugizaki, Ken-ichi; Yoshida, Tamiko; Okazaki, Emi; Kumita, Shin-ichiro; Owan, Chojin [Nippon Medical School, Department of Radiology, Graduate School of Medicine, Tokyo (Japan)

    2012-10-15

    To evaluate the safety of contrast-enhanced MDCT in patients with renal impairment. We conducted a retrospective review of 938 patients with stable renal insufficiency (eGFR between 15 and 60 ml/min) who underwent contrast-enhanced MDCT. SCr levels were measured at baseline and 48-72 h after contrast medium administration. The incidence of contrast-induced nephropathy (CIN) in the total study population was assessed. As a control group, 1,164 separate patients with renal insufficiency who did not receive contrast medium for CT were also reviewed. The overall incidence of CIN in the patient population with renal insufficiency was 6.1 %; the incidence was 4.4 %, 10.5 % and 10.0 % for patients whose eGFR was 45-60, 30-45 and {<=}30 ml/min, respectively (P < 0.01). In the control group, 5.8 % of patients showed an increase in the SCr level from the baseline. The increase in the SCr level showed no significant difference between the patients who received CM and those who did not (P = 0.82) The risk of CIN from contrast-enhanced MDCT in patients with renal insufficiency appeared to be low, and there was no significant difference in the incidence of CIN in comparison with patients who did not receive CM. (orig.)

  11. Drug-induced sleep endoscopy changes snoring management plan very significantly compared to standard clinical evaluation.

    Science.gov (United States)

    Pilaete, Karen; De Medts, Joris; Delsupehe, Kathelijne Godelieve

    2014-05-01

    Drug-induced sleep endoscopy (DISE) is a new tool in the work-up of patients with sleep-disordered breathing (SDB). We assessed the impact of DISE on the treatment plan of snoring patients. This is a single institution prospective longitudinal clinical trial. The setting is a private teaching hospital. A consecutive series of 100 snoring patients prospectively underwent a standardised questionnaire, clinical examination, rhinomanometry, allergy skin prick testing, DISE and polysomnography. Management plan before and after DISE evaluation was compared. In 61 patients (excluding 16 patients sent for continuous positive airway pressure, three patients refused sleep endoscopy and 20 were lost to follow-up), we compared the treatment plans. DISE showed single level airway collapse in 13 and multilevel collapse in 48 patients. The site of flutter did not add additional information as compared to the pattern and the location of the collapse. After DISE, the initial management plan changed in 41% of patients irrespective of the type of initial management plan. The only somewhat accurate initial treatment plan was uvulopalatopharyngoplasty (unchanged in 11/13 patients). Excluding moderate to severe obstructive sleep apnea patients DISE is an indispensable tool in treatment decision in all SDB patients. We suggest to simplify the protocol for DISE reporting.

  12. Significant modulation of the hepatic proteome induced by exposure to low temperature in Xenopus laevis

    Directory of Open Access Journals (Sweden)

    Kazumichi Nagasawa

    2013-08-01

    The African clawed frog, Xenopus laevis, is an ectothermic vertebrate that can survive at low environmental temperatures. To gain insight into the molecular events induced by low body temperature, liver proteins were evaluated at the standard laboratory rearing temperature (22°C, control and a low environmental temperature (5°C, cold exposure. Using nano-flow liquid chromatography coupled with tandem mass spectrometry, we identified 58 proteins that differed in abundance. A subsequent Gene Ontology analysis revealed that the tyrosine and phenylalanine catabolic processes were modulated by cold exposure, which resulted in decreases in hepatic tyrosine and phenylalanine, respectively. Similarly, levels of pyruvate kinase and enolase, which are involved in glycolysis and glycogen synthesis, were also decreased, whereas levels of glycogen phosphorylase, which participates in glycogenolysis, were increased. Therefore, we measured metabolites in the respective pathways and found that levels of hepatic glycogen and glucose were decreased. Although the liver was under oxidative stress because of iron accumulation caused by hepatic erythrocyte destruction, the hepatic NADPH/NADP ratio was not changed. Thus, glycogen is probably utilized mainly for NADPH supply rather than for energy or glucose production. In conclusion, X. laevis responds to low body temperature by modulating its hepatic proteome, which results in altered carbohydrate metabolism.

  13. Xenobiotic-induced apoptosis: significance and potential application as a general biomarker of response

    Science.gov (United States)

    Sweet, Leonard I.; Passino-Reader, Dora R.; Meier, Peter G.; Omann, Geneva M.

    1999-01-01

    The process of apoptosis, often coined programmed cell death, involves cell injury induced by a variety of stimuli including xenobiotics and is morphologically, biochemically, and physiologically distinct from necrosis. Apoptotic death is characterized by cellular changes such as cytoplasm shrinkage, chromatin condensation, and plasma membrane asymmetry. This form of cell suicide is appealing as a general biomarker of response in that it is expressed in multiple cell systems (e.g. immune, neuronal, hepatal, intestinal, dermal, reproductive), is conserved phylogenetically (e.g. fish, rodents, birds, sheep, amphibians, roundworms, plants, humans), is modulated by environmentally relevant levels of chemical contaminants, and indicates a state of stress of the organism. Further, apoptosis is useful as a biomarker as it serves as a molecular control point and hence may provide mechanistic information on xenobiotic stress. Studies reviewed here suggest that apoptosis is a sensitive and early indicator of acute and chronic chemical stress, loss of cellular function and structure, and organismal health. Examples are provided of the application of this methodology in studies of health of lake trout (Salvelinus namaycush) in the Laurentian Great Lakes.

  14. Dendritic cells enhance UHMWPE wear particle-induced osteoclast differentiation of macrophages.

    Science.gov (United States)

    Cang, Dingwei; Guo, Kaijin; Zhao, Fengchao

    2015-10-01

    Ultra-high molecular weight polyethylene (UHMWPE) has been widely used in large joint replacement. Osteolysis induced by the UHMWPE wear particles is one of the main causes of replacement failure. This study aims to elucidate whether dendritic cells play a role in UHMWPE particle-induced osteolysis. An in vitro Raw 264.7 and DC 2.4 coculture system was employed to examine the effects of dendritic cells on the inflammatory and osteoclastogenic responses of Raw 264.7 toward UHMWPE particles. The expression of cytokines, NF-κB, and osteoclast marker genes was analyzed by ELISA, western blot, or quantitative PCR. The osteoclast differentiation was measured by TRAP staining and flow cytometry. UHMWPE particles induced Raw 264.7 cells to differentiate into osteoclasts, which was enhanced by coculturing with DC 2.4 cells. DC 2.4 cells augmented UHMWPE particle-elicited activation of NF-κB signaling, higher levels of TNF-α and MCP-1, and an increased expression of MMP-9, Calcr, and Ctsk, though DC 2.4 coculture alone did not significantly cause the aforementioned changes. These results suggest that dendritic cells, among other immune cells recruited by UHMWPE particle induced inflammation, could further exacerbate inflammation and osteolysis.

  15. PYRROLIDINE DITHIOCARBAMATE INHIBITS NF-ΚB ACTIVATION AND ENHANCES TNF-INDUCED APOPTOSIS IN HUMAN BREAST CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    涂刚; 姚榛祥

    2004-01-01

    Objective: To determine whether pyrrolidine dithio- carbamate(PDTC) enhances TNFκ-induced apoptosis in cultured breast cancer cells and explore the role of NF-κB in TNFα-induced apoptosis. Methods: Human breast cancer cell lines MCF-7 and MDA-MB-435s were treated with TNFα, PDTC and combination therapy. Cell survivals were determined by MTT assay. Apoptosis was detected by TUNEL and flow cytometry. NF-κ B DNA binding activity was detected using electrophoresis mobility shift assay (EMSA). Western blots were performed to demonstrate IκBα(Inhibitor protein of nuclear factor(B) phosphorylation and degradation. Results: Cell growth was not suppressed by either TNFα(2000 U/ml or less) or PDTC alone. Both cell lines treated with TNFα(2000 U/ml) combined with PDTC(50 μmol/L) showed significant growth inhibition. PDTC inhibited TNFα-induced IκBα phosphorylation and degradation in both cell lines. EMSA showed that PDTC continuously inhibited TNFα induced NF-κB DNA binding activity. TNFα induced apoptosis (TUNEL) was increased significantly when both cells were pretreated with PDTC, and this was confirmed by Flow cytometry. Conclusion: PDTC enhances TNFα-induced apoptosis via inhibiting IκBα phosphorylation and degradation in human breast cancer cells. NF-κB protects against TNFα-induced apoptosis.

  16. The significance of Gd-DTPA enhanced MRI for lumbar disc herniation; The relationship between nerve root enhancement and clinical manifestations

    Energy Technology Data Exchange (ETDEWEB)

    Taneichi, Hiroshi; Abumi, Kuniyoshi; Hirachi, Kazuhiko; Kaneda, Kiyoshi (Hokkaido Univ., Sapporo (Japan). School of Medicine)

    1993-04-01

    The purpose of this study was twofold: to determine the ability of Gd-DTPA enhanced MRI to enhance the nerve root and to determine its clinical value in lumbar disc herniation. One hundred and fifteen patients underwent enhanced MRI before and after surgery. Disturbed nerve root was demonstrated on enhanced MRI before surgery in 39.1% (45/115). Nerve root enhancement was occasionally associated with severe leg pain, but not associated with the degree of paralysis. Nerve root enhancement early after surgery was positive in 27 of 46 patients (58.7%), revealing no clinical usefulness of enhanced MRI. Non-damaged nerve root was enhanced in 7 patients (5.9%). This may reflect enhancement of root vein. Nerve root enhancement has the potential for visualizing endoneurial edema resulting from compression and inflammation of the nerve root. Enhanced MRI demonstrated lesions within the nerve root, allowing identification of damaged nerve root and diagnosis of lumbar disc herniation. (N.K.).

  17. Olanzapine-high potency antipsychotic drug inducing significant weight gain: A case report

    Directory of Open Access Journals (Sweden)

    Marić Nađa P.

    2008-01-01

    Full Text Available INTRODUCTION Olanzapine is a second generation antipsychotic (SGA with a high level of therapeutic effectiveness in schizophrenia and other psychotic disorders. Along with the positive therapeutic effects, an increase of the body weight frequently occurs. According to the literature, the average weight gain is about 6-7 kg during several months of treatment. This could be valued as a moderate weight increase. CASE OUTLINE This article presents a case of a young female with schizophrenia, without clinical improvement with several antipsychotics (clozapine, risperidone, haloperidol and with the occurrence of significant neurological side effects. The treatment started with olanzapine (baseline was associated with good initial response (PANSS reduction 20% in the first two weeks and the improvement was maintained further on (PANSS reduction 50% after 16 weeks. Significant increase (20 kg, 40% in weight appeared during the following 16 weeks (BMI at baseline 17.9 kg/m2; BMI 16 weeks later 25.1 kg/m2. CONCLUSION High effectiveness of olanzapine in schizophrenia symptoms reduction was accompanied by a significant weight gain. However, this drug leads to impaired glucoregulation, dyslipidaemia etc. It also increases the risk of diabetes and cardio-vascular diseases, i.e. the main causes of mortality in schizophrenia after a suicide. Therefore, clinicians are suggested to focus on possible predictors of weight gain during olanzapine therapy, and act accordingly in order to prevent serious health consequences.

  18. Hypoxia-inducible factor-1α and semaphorin4D genes involved with tumor-associated macrophage-induced metastatic behavior and clinical significance in colon cancer.

    Science.gov (United States)

    Mu, Linjun; Wang, Jinshen; Chen, Yuezhi; Li, Leping; Guo, Xiaobo; Zheng, Sheng; Jing, Changqing

    2014-01-01

    Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha (HIF-1α) plays a pivotal role in this process. Recently identified pro-angiogenic factor, semaphorin4D (Sema4D) also promotes angiogenesis and enhances invasive proliferation in some tumors. Furthermore, tumor-associated macrophages (TAMs) can increase the expression of HIF-1α and Sema4D in cancer cells and thus influence tumor growth and progression. The purpose of this study was to evaluate the effect of TAMs on the expression of Sema4D and HIF-1α and the impact of biologic behavior in colon cancer cells. Immunohistochemistry was used to analyze HIF-1α and Sema4D expression in 86 curatively resected colon cancer samples and 52 normal colon tissues samples. The relationship between their expression and clinicopathological factors was analyzed. Furthermore, macrophage-tumor cell interactions, such as metastasis, angiogenesis, were also studied using in vitro co-culture systems. Statistical analysis was performed using SPSS 17.0 software (SPSS Inc., USA). Differences between two groups were analyzed with Student's t test. HIF-1α (58%) and Sema4D (60%) were expressed at a significantly higher level in tumors than in normal tissues (P TNM stages (P 0.05). Sema4D expression was correlated with that of HIF-1α (r = 0.567, P colon cancer cells and subsequently increased their migration and invasion. HIF-1α and Sema4D expression are closely related to lymphatic metastasis, specific histological types and TNM stages in colon cancer. Furthermore, TAMs promote migration and invasion of colon cancer cells and endothelial tube formation, possibly through up-regulation of HIF-1α and Sema4D.

  19. Character, distribution, and ecological significance of storm wave-induced scour in Rhode Island Sound, USA

    Science.gov (United States)

    McMullen, Katherine Y.; Poppe, Lawrence J.; Parker, Castle E.

    2015-04-01

    Multibeam bathymetry, collected during NOAA hydrographic surveys in 2008 and 2009, is coupled with USGS data from sampling and photographic stations to map the seabed morphology and composition of Rhode Island Sound along the US Atlantic coast, and to provide information on sediment transport and benthic habitats. Patchworks of scour depressions cover large areas on seaward-facing slopes and bathymetric highs in the sound. These depressions average 0.5-0.8 m deep and occur in water depths reaching as much as 42 m. They have relatively steep well-defined sides and coarser-grained floors, and vary strongly in shape, size, and configuration. Some individual scour depressions have apparently expanded to combine with adjacent depressions, forming larger eroded areas that commonly contain outliers of the original seafloor sediments. Where cobbles and scattered boulders are present on the depression floors, the muddy Holocene sands have been completely removed and the winnowed relict Pleistocene deposits exposed. Low tidal-current velocities and the lack of obstacle marks suggest that bidirectional tidal currents alone are not capable of forming these features. These depressions are formed and maintained under high-energy shelf conditions owing to repetitive cyclic loading imposed by high-amplitude, long-period, storm-driven waves that reduce the effective shear strength of the sediment, cause resuspension, and expose the suspended sediments to erosion by wind-driven and tidal currents. Because epifauna dominate on gravel floors of the depressions and infauna are prevalent in the finer-grained Holocene deposits, it is concluded that the resultant close juxtaposition of silty sand-, sand-, and gravel-dependent communities promotes regional faunal complexity. These findings expand on earlier interpretations, documenting how storm wave-induced scour produces sorted bedforms that control much of the benthic geologic and biologic diversity in Rhode Island Sound.

  20. Character, distribution, and ecological significance of storm wave-induced scour in Rhode Island Sound, USA

    Science.gov (United States)

    McMullen, Katherine Y.; Poppe, Lawrence J.; Parker, Castle E.

    2015-01-01

    Multibeam bathymetry, collected during NOAA hydrographic surveys in 2008 and 2009, is coupled with USGS data from sampling and photographic stations to map the seabed morphology and composition of Rhode Island Sound along the US Atlantic coast, and to provide information on sediment transport and benthic habitats. Patchworks of scour depressions cover large areas on seaward-facing slopes and bathymetric highs in the sound. These depressions average 0.5-0.8 m deep and occur in water depths reaching as much as 42 m. They have relatively steep well-defined sides and coarser-grained floors, and vary strongly in shape, size, and configuration. Some individual scour depressions have apparently expanded to combine with adjacent depressions, forming larger eroded areas that commonly contain outliers of the original seafloor sediments. Where cobbles and scattered boulders are present on the depression floors, the muddy Holocene sands have been completely removed and the winnowed relict Pleistocene deposits exposed. Low tidal-current velocities and the lack of obstacle marks suggest that bidirectional tidal currents alone are not capable of forming these features. These depressions are formed and maintained under high-energy shelf conditions owing to repetitive cyclic loading imposed by high-amplitude, long-period, storm-driven waves that reduce the effective shear strength of the sediment, cause resuspension, and expose the suspended sediments to erosion by wind-driven and tidal currents. Because epifauna dominate on gravel floors of the depressions and infauna are prevalent in the finer-grained Holocene deposits, it is concluded that the resultant close juxtaposition of silty sand-, sand-, and gravel-dependent communities promotes regional faunal complexity. These findings expand on earlier interpretations, documenting how storm wave-induced scour produces sorted bedforms that control much of the benthic geologic and biologic diversity in Rhode Island Sound.

  1. Inhibition of SGK1 enhances mAR-induced apoptosis in MCF-7 breast cancer cells.

    Science.gov (United States)

    Liu, Guilai; Honisch, Sabina; Liu, Guoxing; Schmidt, Sebastian; Pantelakos, Stavros; Alkahtani, Saad; Toulany, Mahmoud; Lang, Florian; Stournaras, Christos

    2015-01-01

    Functional membrane androgen receptors (mAR) have previously been described in MCF-7 breast cancer cells. Their stimulation by specific testosterone albumin conjugates (TAC) activate rapidly non-genomic FAK/PI3K/Rac1/Cdc42 signaling, trigger actin reorganization and inhibit cell motility. PI3K stimulates serum and glucocorticoid inducible kinase SGK1, which in turn regulates the function of mAR. In the present study we addressed the role of SGK1 in mAR-induced apoptosis. TAC-stimulated mAR activation elicited apoptosis of MCF-7 cells, an effect significantly potentiated by concomitant incubation of the cells with TAC and the specific SGK1 inhibitors EMD638683 and GSK650394. In line with this, TAC and EMD638683 activated caspase-3. These effects were insensitive to the classical androgen receptor (iAR) antagonist flutamide, pointing to iAR-independent, mAR-induced responses. mAR activation and SGK1 inhibition further considerably augmented the radiation-induced apoptosis of MCF-7 cells. Moreover, TAC- and EMD638683 triggered early actin polymerization in MCF-7 cells. Blocking actin restructuring with cytochalasin B abrogated the TAC- and EMD638683-induced pro-apoptotic responses. Further analysis of the molecular signaling revealed late de-phosphorylation of FAK and Akt. Our results demonstrate that mAR activation triggers pro-apoptotic responses in breast tumor cells, an effect significantly enhanced by SGK1 inhibition, involving actin reorganization and paralleled by down-regulation of FAK/Akt signaling.

  2. Pyrrolidine dithiocarbamate Inhibits NF- κB Activation and Enhance TNFα- Induced Apoptosis in Human Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    TU Gang(涂刚); YAO Zhenxiang(姚榛祥); DONG Pujiang(董浦江)

    2002-01-01

    Objective: Tumor necrosis factor α(TNFα) induced apoptosis is limited by its coactivation of nuclear factor kappa B(NF- κB) -dependent antiapoptosis genes. We examined whether pyrrolidine dithiocarbamate (PDTC) enhance TNFα - induced apoptosis in cultured breast cancer cells and explored the role of NF - κB in TNFα - induced apoptosis. Methods: Human breast cancer cell lines MCF-7 and MDA - MB -435s were treated with TNFα、 PDTC and combination therapy . Induction of apoptosis was detected by TUNEL staining and flow cytometry. NF- κB DNA binding activity was detected using electrophoresis mobility shift assay(EMSA) . Western blots of cytoplasmic lysates were performed to demonstrate IκBα (Inhibitor protein of nuclear factor κB) phosphorylation and degradation. Results:TNFα-induced IκBo phosphorylation and degradation, which was inhibited by PDTC in both cell lines. TNFα-induced apoptosis (TUNEL) increased significantly when both cells were pretreated with PDTC. Flow cytometry also confirmed this. EMSA showed that PDTC continuously inhibited TNFo-induced NF- κB DNA binding activity . Conclusions:PDTC enhances TNFo-induced apoptosis whileinhibiting IκBα phosphorylation and degradation in human breast cancer cells. NF - κB has a protective role on TNFα-induced apoptosis.

  3. Suppression of narrow-band transparency in a metasurface induced by a strongly enhanced electric field

    CERN Document Server

    Tamayama, Yasuhiro; Yasui, Kanji

    2015-01-01

    We realize a suppression of an electromagnetically induced transparency (EIT) like transmission in a metasurface induced by a local electric field that is strongly enhanced based on two approaches: squeezing of electromagnetic energy in resonant metasurfaces and enhancement of electromagnetic energy density associated with a low group velocity. The EIT-like metasurface consists of a pair of radiatively coupled cut-wire resonators, and it can effect both field enhancement approaches simultaneously. The strongly enhanced local electric field generates an air discharge plasma at either of the gaps of the cut-wire resonators, which causes the EIT-like metasurface to change into two kinds of Lorentz type metasurfaces.

  4. 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.

  5. Graphene nanoplatelets induced heterogeneous bimodal structural magnesium matrix composites with enhanced mechanical properties.

    Science.gov (United States)

    Xiang, Shulin; Wang, Xiaojun; Gupta, Manoj; Wu, Kun; Hu, Xiaoshi; Zheng, Mingyi

    2016-12-12

    In this work, graphene nanoplatelets (GNPs) reinforced magnesium (Mg) matrix composites were synthesised using the multi-step dispersion route. Well-dispersed but inhomogeneously distributed GNPs were obtained in the matrix. Compared with the monolithic alloy, the nanocomposites exhibited dramatically enhanced Young's modulus, yield strength and ultimate tensile strength and relatively high plasticity, which mainly attributed to the significant heterogeneous laminated microstructure induced by the addition of GNPs. With increasing of the concentration of GNPs, mechanical properties of the composites were gradually improved. Especially, the strengthening efficiency of all the composites exceeded 100%, which was significantly higher than that of carbon nanotubes reinforced Mg matrix composites. The grain refinement and load transfer provided by the two-dimensional and wrinkled surface structure of GNPs were the dominated strengthening mechanisms of the composites. This investigation develops a new method for incorporating GNPs in metals for fabricating high-performance composites.

  6. Glandular epithelial AR inactivation enhances PTEN deletion-induced uterine pathology.

    Science.gov (United States)

    Choi, Jaesung Peter; Zheng, Yu; Handelsman, David J; Simanainen, Ulla

    2016-05-01

    Phosphatase and tensin homolog (PTEN) deletion induces uterine pathology, whereas androgen actions via androgen receptor (AR) support uterine growth and therefore may modify uterine cancer risk. We hypothesized that the androgen actions mediated via uterine glandular epithelial AR could modify PTEN deletion-induced uterine pathology. To test our hypothesis, we developed uterine glandular epithelium-specific PTEN and/or AR knockout mouse models comparing the uterine pathology among wild-type (WT), glandular epithelium-specific AR inactivation (ugeARKO), PTEN deletion (ugePTENKO), and the combined PTEN and AR knockout (ugePTENARKO) female mice. The double knockout restricted to glandular epithelium showed that AR inactivation enhanced PTEN deletion-induced uterine pathology with development of intraepithelial neoplasia by 20 weeks of age. In ugePTENARKO, 6/10 (60%) developed intraepithelial neoplasia, whereas 3/10 (30%) developed only glandular hyperplasia in ugePTENKO uterus. No uterine pathology was observed in WT (n=8) and ugeARKO (n=7) uteri. Uterine weight was significantly (P=0.002) increased in ugePTENARKO (374±97 mg (mean±s.e.)) compared with WT (97±6 mg), ugeARKO (94±12 mg), and ugePTENKO (205±33 mg). Estrogen receptor alpha (ERα) and P-AKT expression was modified by uterine pathology but did not differ between ugePTENKO and ugePTENARKO, suggesting that its expressions are not directly affected by androgens. However, progesterone receptor (PR) expression was reduced in ugePTENARKO compared to ugePTENKO uterus, suggesting that PR expression could be regulated by glandular epithelial AR inactivation. In conclusion, glandular epithelial AR inactivation (with persistent stromal AR action) enhanced PTEN deletion-induced uterine pathology possibly by downregulating PR expression in the uterus.

  7. Significant enhancement of fatty acid composition in seeds of the allohexaploid, Camelina sativa, using CRISPR/Cas9 gene editing.

    Science.gov (United States)

    Jiang, Wen Zhi; Henry, Isabelle M; Lynagh, Peter G; Comai, Luca; Cahoon, Edgar B; Weeks, Donald P

    2017-05-01

    The CRISPR/Cas9 nuclease system is a powerful and flexible tool for genome editing, and novel applications of this system are being developed rapidly. Here, we used CRISPR/Cas9 to target the FAD2 gene in Arabidopsis thaliana and in the closely related emerging oil seed plant, Camelina sativa, with the goal of improving seed oil composition. We successfully obtained Camelina seeds in which oleic acid content was increased from 16% to over 50% of the fatty acid composition. These increases were associated with significant decreases in the less desirable polyunsaturated fatty acids, linoleic acid (i.e. a decrease from ~16% to enhanced oil composition in T3 and T4 generation Camelina seeds was associated with a combination of germ-line mutations and somatic cell mutations in FAD2 genes in each of the three Camelina subgenomes. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  8. "Fungal elicitors combined with a sucrose feed significantly enhance triterpene production of a Salvia fruticosa cell suspension".

    Science.gov (United States)

    Kümmritz, Sibylle; Louis, Marilena; Haas, Christiane; Oehmichen, Franz; Gantz, Stephanie; Delenk, Hubertus; Steudler, Susanne; Bley, Thomas; Steingroewer, Juliane

    2016-08-01

    Oleanolic (OA) and ursolic acid (UA) are plant secondary metabolites with diverse pharmacological properties. To reach reasonable productivities with plant cell suspension cultures, elicitation is a widely used strategy. Within the presented work, the effects of different elicitors on growth and production of OA and UA in a Salvia fruticosa cell suspension culture were examined. Beside commonly used elicitors like jasmonic acid (JA) and yeast extract, the influence of medium filtrates of the endophytic fungi Aspergillus niger and Trichoderma virens was investigated. The best eliciting effects were achieved with JA and fungal medium filtrates. Both increased the triterpene content by approximately 70 %. Since JA showed significant growth inhibition, the volumetric triterpene yield did not increase. But, adding fungal filtrates increased the volumetric triterpene yield by approximately 70 % to 32.6 mgOA l(-1) and 65.9 mgUA l(-1) for T. virens compared to the control with 19.4 mgOA l(-1) and 33.3 mgUA l(-1). An elicitation strategy combining fungal medium filtrate of T. virens with sucrose feeding significantly enhanced cell dry weight concentration to 22.2 g l(-1) as well as triterpene content by approximately 140 %. In total, this led to an approximately 500 % increase of volumetric triterpene yield referring to the control with final values of 112.9 mgOA l(-1) and 210.4 mgUA l(-1). Despite the doubled cultivation duration, productivities of 6.7 mgOA l(-1) day(-1) and 12.4 mgUA l(-1) day(-1) were reached. These results demonstrate methods by which increased productivities of triterpenes can be achieved to attain yields competing with intact plants.

  9. Engineered absorption enhancement and induced transparency in coupled molecular and plasmonic resonator systems.

    Science.gov (United States)

    Adato, Ronen; Artar, Alp; Erramilli, Shyamsunder; Altug, Hatice

    2013-06-12

    Coupled plasmonic resonators have become the subject of significant research interest in recent years as they provide a route to dramatically enhanced light-matter interactions. Often, the design of these coupled mode systems draws intuition and inspiration from analogies to atomic and molecular physics systems. In particular, they have been shown to mimic quantum interference effects, such as electromagnetically induced transparency (EIT) and Fano resonances. This analogy also been used to describe the surface-enhanced absorption effect where a plasmonic resonance is coupled to a weak molecular resonance. These important phenomena are typically described using simple driven harmonic (or linear) oscillators (i.e., mass-on-a-spring) coupled to each other. In this work, we demonstrate the importance of an essential interdependence between the rate at which the system can be driven by an external field and its damping rate through radiative loss. This link is required in systems exhibiting time-reversal symmetry and energy conservation. Not only does it ensure an accurate and physically consistent description of resonant systems but leads directly to interesting new effects. Significantly, we demonstrate this dependence to predict a transition between EIT and electromagnetically induced absorption that is solely a function of the ratio of the radiative to intrinsic loss rates in coupled resonator systems. Leveraging the temporal coupled mode theory, we introduce a unique and intuitive picture that accurately describes these effects in coupled plasmonic/molecular and fully plasmonic systems. We demonstrate our approach's key features and advantages analytically as well as experimentally through surface-enhanced absorption spectroscopy and plasmonic metamaterial applications.

  10. Vaccine-Induced Enhancement of EIAV Replication and Disease

    Science.gov (United States)

    1994-01-14

    including dengue virus, respiratory syncytial virus, and feline infectious peritonitis virus (Porterfield 1986). In many of these cases, the enhancement...funding was to initiate the expansion of ongoing research in which the equine infectious anemia virus (EIAV)/Shetland pony animal lentivirus system is...enhancement of EIAV replication and disease. 14. SUBJECT TERMS 15. NUMBER OF PAGES AIDS vaccines, equine infectious anemia virus, 16. PRICE CODE

  11. Wet air oxidation induced enhanced biodegradability of distillery effluent.

    Science.gov (United States)

    Malik, S N; Saratchandra, T; Tembhekar, P D; Padoley, K V; Mudliar, S L; Mudliar, S N

    2014-04-01

    The present study reports the feasibility of Wet Air Oxidation (WAO) as a pretreatment option for enhanced biodegradation of complex distillery effluent. Initially, the distillery effluent was pretreated by WAO at different process conditions (pressure, temperature and time) to facilitate enhancement in the biodegradability index (BI = BOD5: COD ratio). The biodegradability of WAO pretreated effluent was evaluated by subjecting it to aerobic biodegradation and anaerobic followed by aerobic biodegradation. Aerobic biodegradation of pretreated effluent with enhanced biodegradability index (BI = 0.4-0.8) showed enhanced COD reduction of up to 67.7%, whereas the untreated effluent (BI = 0.17) indicated poor COD reduction of only 22.5%. Anaerobic followed by aerobic biodegradation of pretreated effluent has shown up to 87.9% COD reduction, while the untreated effluent has shown only 43.1% COD reduction. Bio-kinetic parameters also confirmed the increased rate of bio-oxidation at enhanced BIs. The results indicate that the WAO pretreatment facilitates enhanced bio-oxidation/bio-degradation of complex effluents like the distillery spent wash.

  12. Sparingly-soluble phosphate rock induced significant plant growth and arsenic uptake by Pteris vittata from three contaminated soils.

    Science.gov (United States)

    Lessl, Jason T; Ma, Lena Q

    2013-05-21

    We evaluated the ability of As-hyperaccumulator Pteris vittata (PV) to remove As from As-contaminated soils over five harvests in 2.5 years in raised beds (162 kg soil/bed). We tested the hypothesis that a P-limiting environment would enhance PV growth and As uptake owing its unique ability to uptake P under As-rich environment. In Dec. 2009, PV was transplanted to three As-contaminated soils (pH of 5.5-7.2) containing 25-129 mg kg(-1) As, which was amended with sparingly-soluble phosphate rock (PR-soil) or soluble P fertilizer (P-soil). During the 2.5-year, PV obtained sufficient P (1882 vs 2225 mg kg(-1)) from PR-soils, with increased root biomass (33%) and root exudation (53%) compared to P-soils. In addition, its frond biomass increased by 20% consecutively with each harvest (six month interval) from 18 to 36 g plant(-1). Its frond biomass in PR-soils (52.2 g plant(-1) year(-1) or ∼12 mt ha(-1) year(-1)) averaged 39% more than that in P-soils. To our knowledge, this represented the largest PV frond biomass reported, demonstrating the unique ability of PV in using insoluble P from PR in alkaline soils. In addition to biomass increase, PV from PR-soils had ∼1.5 times more As in fronds (2540, 780, and 920 mg kg(-1)) than those from P-soils (1740, 570, and 400 mg kg(-1)), with soils containing 129, 25, and 30 mg kg(-1) As, respectively. The low available P in PR-soils induced substantial plant growth and As uptake by PV. This translated into significantly more As removal from soil, averaging 48% reduction in PR-soils and 36% in P-soils in 2.5 years. With multiple harvests and PR amendments, our results showed As removal by PV from contaminated soils was ∼7 times faster than published studies.

  13. 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.

  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. Inhibition of aldehyde dehydrogenase 2 activity enhances antimycin-induced rat cardiomyocytes apoptosis through activation of MAPK signaling pathway.

    Science.gov (United States)

    Zhang, Peng; Xu, Danling; Wang, Shijun; Fu, Han; Wang, Keqiang; Zou, Yunzeng; Sun, Aijun; Ge, Junbo

    2011-12-01

    Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial-specific enzyme, has been proved to be involved in oxidative stress-induced cell apoptosis, while little is known in cardiomyocytes. This study was aimed at investigating the role of ALDH2 in antimycin A-induced cardiomyocytes apoptosis by suppressing ALDH2 activity with a specific ALDH2 inhibitor Daidzin. Antimycin A (40μg/ml) was used to induce neonatal cardiomyocytes apoptosis. Daidzin (60μM) effectively inhibited ALDH2 activity by 50% without own effect on cell apoptosis, and significantly enhanced antimycin A-induced cardiomyocytes apoptosis from 33.5±4.4 to 56.5±6.4% (Hochest method, pdaidzin treated cardiomyocytes compared to the cells treated with antimycin A alone. These findings indicated that modifying mitochondrial ALDH2 activity/expression might be a potential therapeutic option on reducing oxidative insults induced cardiomyocytes apoptosis.

  16. Gamma-Glutamyl Cysteine Attenuates Tissue Damage and Enhances Tissue Regeneration in a rat Model of Lead-Induced Nephrotoxicity.

    Science.gov (United States)

    Salama, Samir A; Arab, Hany H; Maghrabi, Ibrahim A; Hassan, Memy H; AlSaeed, Mohammed S

    2016-09-01

    Lead is a biohazardous metal that is commonly involved in human illness including renal injury. Although it is a non-redox reactive metal, lead-induced renal injury is largely based on oxidative stress. The current work aimed at exploring the possible protective effect of γ-glutamyl cysteine (γGC) against lead-induced renal injury. Rats were allocated to normal and γGC control groups, lead-treated group, and lead and γGC-treated group. γGC alleviated lead-induced renal injury as evidenced by attenuation of histopathological aberration, amelioration of oxidative injury as demonstrated by significant reduction in lipid and protein oxidation, elevation of total antioxidant capacity, and glutathione level. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was significantly elevated. γGC significantly decreased levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β and the activity of the apoptotic marker caspase-3. In addition, γGC reduced kidney lead content, enhanced weight gain, and improved renal function as demonstrated by reduced serum levels of urea and creatinine. Importantly, γGC upregulated proliferating cell nuclear antigen (PCNA) expression, denoting enhanced renal regenerative capacity. Together, our findings highlight evidence for alleviating effects of γGC against lead-induced renal injury that is potentially mediated through diminution of oxidative tissue injury, reduction of inflammatory response, attenuation of apoptosis, and enhancement of renal regenerative capacity.

  17. 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.

  18. Inlet Cover Treatment to Enhance Zero NPSH Inducer Operation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Zero net positive suction head (NPSH)-capable hydrogen pump inducers are a critical component needed to lower the cost and increase the effectiveness of Nuclear...

  19. 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.

  20. (-)-Stepholodine induced enhancement of cardiac muscle contractions mediated by D1 receptors

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shu-yuan; LIU Zheng; HU Hui-sheng; SHI Zhen; CHEN Long

    2008-01-01

    Objective To investigate the effect of (-)-Stepholidine (SPD) on enhancing D1 receptor mediated contraction of cardiac muscle in isolated rat heart and to examine whether SPD has a direct effect on the heart dopamine D1 receptors. SPD an active ingredient of the Chinese herb Stephania intermedia, binds to dopamine D1 and D2 like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D(1/5) agonist and a D(2/4) antagonist, which could indicate unique antipsychotic properties. Methods Normal adult rat working hearts were isolated by Langendorff technique. Results SPD significantly increased the cardiac muscle contraction in a dose-dependent manner. The selective D1 dopamine receptor antagonist SCH23390 (1 μM) blocked the SPD induced heart contraction, however, neither the β-receptor antagonist propranolol (1 μM) nor the α1-receptor antagonist prazosin (1 μM) had any effect on blocking SPD induced heart contractions. Moreover, the L-type Ca2+ channel inhibitor nimodipine (1 μM) completely blocked the effect of SPD on cardiac muscle contraction. Conclusions SPD show the effect on enhancing contraction of isolated rat heart through activating L-type Ca2+ channel mediated by heart D1 receptors.

  1. Novel curcumin diclofenac conjugate enhanced curcumin bioavailability and efficacy in streptococcal cell wall-induced arthritis

    Directory of Open Access Journals (Sweden)

    S K Jain

    2014-01-01

    Full Text Available 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 (P<0.01 alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.

  2. 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.

  3. Pressure Induced Enhancement of Superconductivity in LaRu2P2

    Science.gov (United States)

    Li, Baoxuan; Lu, Pengchao; Liu, Jianzhong; Sun, Jian; Li, Sheng; Zhu, Xiyu; Wen, Hai-Hu

    2016-04-01

    To explore new superconductors beyond the copper-based and iron-based systems is very important. The Ru element locates just below the Fe in the periodic table and behaves like the Fe in many ways. One of the common thread to induce high temperature superconductivity is to introduce moderate correlation into the system. In this paper, we report the significant enhancement of superconducting transition temperature from 3.8 K to 5.8 K by using a pressure only of 1.74 ± 0.05 GPa in LaRu2P2 which has an iso-structure of the iron-based 122 superconductors. The ab-initio calculation shows that the superconductivity in LaRu2P2 at ambient pressure can be explained by the McMillan’s theory with strong electron-phonon coupling. However, it is difficult to interpret the enhancement of Tc versus pressure within this picture. Detailed analysis of the pressure induced evolution of resistivity and upper critical field Hc2(T) reveals that the increase of Tc with pressure may be accompanied by the involvement of extra electron-boson interaction. This suggests that the Ru-based system has some commonality as the Fe-based superconductors.

  4. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    OpenAIRE

    2009-01-01

    Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showe...

  5. Exam anxiety induces significant blood pressure and heart rate increase in college students.

    Science.gov (United States)

    Zhang, Zhihong; Su, Hai; Peng, Qiang; Yang, Qing; Cheng, Xiaoshu

    2011-01-01

    To investigate the relationship between the anxiety and blood pressure (BP) and heart rate (HR) increase in peri-exam period. Sixty-four college students(20.0 ± 0.1 year old) were included in this study. The BP and HR were measured in the morning and in the evening for 3 days during the prereview (ba), review, and exam periods. The BP and HR increase amplitudes (HRIA) of review and exam periods were from the difference of corresponding values and basic values, and the BPIA/baBP and HRIA/baHR were calculated. All of the students completed the Self-Rating Anxiety score (SAS) questionnaire the first day of the exam period. Scores over 50 points were used as the standard for anxiety. From the prereview to exam periods, the BP and HR increased gradually. The exam SBPIA (4.3 ± 1.3 vs. 0.3 ± 0.5 mmHg, P family hypertension group had higher anxiety score; meanwhile, their exam BPIAs and HRIAs were significantly higher than their corresponding group. The BP and HR increase in the review and exam period, anxiety is an important factor of BP and HR increase.

  6. 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

  7. Persistent CaMKII activation mediates learning-induced long-lasting enhancement of synaptic inhibition.

    Science.gov (United States)

    Ghosh, Sourav; Reuveni, Iris; Lamprecht, Raphael; Barkai, Edi

    2015-01-07

    Training rats in a particularly difficult olfactory-discrimination task results in acquisition of high skill to perform the task superbly, termed "rule learning" or "learning set." Such complex learning results in enhanced intrinsic neuronal excitability of piriform cortex pyramidal neurons, and in their excitatory synaptic interconnections. These changes, while subserving memory maintenance, must be counterbalanced by modifications that prevent overspreading of activity and uncontrolled synaptic strengthening. Indeed, we have previously shown that the average amplitude of GABAA-mediated miniature IPSCs (mIPSCs) in these neurons is enhanced for several days after learning, an enhancement mediated via a postsynaptic mechanism. To unravel the molecular mechanism of this long-term inhibition enhancement, we tested the role of key second-messenger systems in maintaining such long-lasting modulation. The calcium/calmodulin-dependent kinase II (CaMKII) blocker, KN93, significantly reduced the average mIPSC amplitude in neurons from trained rats only to the average pretraining level. A similar effect was obtained by the CaMKII peptide inhibitor, tatCN21. Such reduction resulted from decreased single-channel conductance and not in the number of activated channels. The PKC inhibitor, GF109203X, reduced the average mIPSC amplitude in neurons from naive, pseudo-trained, and trained animals, and the difference between the trained and control groups remained. Such reduction resulted from a decrease in the number of activated channels. The PKA inhibitor H89 dihydrochloride did not affect the average mIPSC amplitude in neurons from any of the three groups. We conclude that learning-induced enhancement of GABAA-mediated synaptic inhibition is maintained by persistent CaMKII activation.

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

    Directory of Open Access Journals (Sweden)

    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

  9. Enhancing Neoplasm Expression in Field Pea (Pisum sativum via Intercropping and its Significance to Pea Weevil (Bruchus pisorum Management

    Directory of Open Access Journals (Sweden)

    Abel eTeshome

    2016-05-01

    Full Text Available Neoplasm formation, a non-meristematic tissue growth on young field pea (Pisum sativum L. pods is triggered in the absence of UV light and/or in response to oviposition by pea weevil (Bruchus pisorum L.. This trait is expressed in some genotypes (Np genotypes of P. sativum and has the capacity to obstruct pea weevil larval entry into developing seeds. In the present study, 26% of the tested accessions depicted the trait when grown under greenhouse conditions. However, UV light inhibits full expression of this trait and subsequently it is inconspicuous at the field level. In order to investigate UV light impact on the expression of neoplasm, particular Np genotypes were subjected to UV lamp light exposure in the greenhouse and sunlight at the field level. Under these different growing conditions, the highest mean percentage of neoplastic pods was in the control chamber in the greenhouse (36% whereas in single and double UV lamp chambers, the percentage dropped to 10% and 15%, respectively. Furthermore, when the same Np genotypes were grown in the field, the percentage of neoplastic pods dropped significantly (7%. In order to enhance neoplastic expression at the field level, intercropping of Np genotypes with sorghum was investigated. As result, the percentage of neoplastic pods was threefold in intercropped Np genotypes as compared to those without intercropping. Therefore, intercropping neoplastic genotypes with other crops such as sorghum and maize can facilitate neoplasm formation, which in turn can minimize the success rate of pea weevil larvae entry into developing seeds. Greenhouse artificial infestation experiments showed that pea weevil damage in neoplastic genotypes is lower in comparison to wild type genotypes. Therefore, promoting neoplastic formation under field conditions via intercropping can serve as part of an integrated pea weevil management strategy especially for small scale farming systems.

  10. Enhancing Neoplasm Expression in Field Pea (Pisum sativum) via Intercropping and Its Significance to Pea Weevil (Bruchus pisorum) Management

    Science.gov (United States)

    Teshome, Abel; Bryngelsson, Tomas; Mendesil, Esayas; Marttila, Salla; Geleta, Mulatu

    2016-01-01

    Neoplasm formation, a non-meristematic tissue growth on young field pea (Pisum sativum L.) pods is triggered in the absence of UV light and/or in response to oviposition by pea weevil (Bruchus pisorum L.). This trait is expressed in some genotypes [neoplastic (Np) genotypes] of P. sativum and has the capacity to obstruct pea weevil larval entry into developing seeds. In the present study, 26% of the tested accessions depicted the trait when grown under greenhouse conditions. However, UV light inhibits full expression of this trait and subsequently it is inconspicuous at the field level. In order to investigate UV light impact on the expression of neoplasm, particular Np genotypes were subjected to UV lamp light exposure in the greenhouse and sunlight at the field level. Under these different growing conditions, the highest mean percentage of Np pods was in the control chamber in the greenhouse (36%) whereas in single and double UV lamp chambers, the percentage dropped to 10 and 15%, respectively. Furthermore, when the same Np genotypes were grown in the field, the percentage of Np pods dropped significantly (7%). In order to enhance Np expression at the field level, intercropping of Np genotypes with sorghum was investigated. As result, the percentage of Np pods was threefold in intercropped Np genotypes as compared to those without intercropping. Therefore, intercropping Np genotypes with other crops such as sorghum and maize can facilitate neoplasm formation, which in turn can minimize the success rate of pea weevil larvae entry into developing seeds. Greenhouse artificial infestation experiments showed that pea weevil damage in Np genotypes is lower in comparison to wild type genotypes. Therefore, promoting Np formation under field conditions via intercropping can serve as part of an integrated pea weevil management strategy especially for small scale farming systems. PMID:27242855

  11. Enhanced therapeutic efficacy and amelioration of cisplatin-induced nephrotoxicity by quercetin in 1,2-dimethyl hydrazine-induced colon cancer in rats.

    Science.gov (United States)

    Li, Qing-Chun; Liang, Yun; Hu, Guang-Rui; Tian, Yuan

    2016-01-01

    The aim of quercetin treatment in combination of cisplatin (CP)-induced nephrotoxicity as well on 1,2-dimethyl hydrazine (DMH)-induced colon cancer. In this study, animals are exposed to DMH hydrochloride to induce colon cancer. In these groups, nephrotoxicity was assessed with the help of blood urea nitrogen, urea, and creatinine. The antitumor activity of quercetin and CP assessed with the help of number of aberrant crypts and foci formation. Tumor size in different treatment group determined with the help of vernier caliper. CP is one of the most widely used antineoplastic drugs against colon cancer, but it has a major dose-limiting drawbacks of causing nephrotoxicity. Therefore, there is a need for a novel therapeutic regimen which will reduce the nephrotoxicity and enhance the anticancer activity of CP. The protective effect of quercetin on CP-induced nephrotoxicity is well-known. Moreover, quercetin is proven to have antitumor activity in colon cancer. Keeping all the facts in view, this study was conceived to evaluate the role of quercetin on therapeutic efficacy and nephrotoxicity of CP in DMH-induced colon cancer in male Sprague-Dawley rats. Treatment of quercetin with CP (7.5 mg/kg) prevents the CP-induced nephrotoxicity along with enhance the anticancer activity confirmed by the reduction of aberrant crypt foci number. Treatment of CP and quercetin alone leads to significant increase in the anticancer activity as compared to control colon tumor rats. In DMH-induced colon cancer model, combination of quercetin and CP ameliorates CP-induced nephrotoxicity as well as enhanced antitumor activity.

  12. 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.

  13. Tactile cues significantly modulate the perception of sweat-induced skin wetness independently of the level of physical skin wetness.

    Science.gov (United States)

    Filingeri, Davide; Fournet, Damien; Hodder, Simon; Havenith, George

    2015-06-01

    Humans sense the wetness of a wet surface through the somatosensory integration of thermal and tactile inputs generated by the interaction between skin and moisture. However, little is known on how wetness is sensed when moisture is produced via sweating. We tested the hypothesis that, in the absence of skin cooling, intermittent tactile cues, as coded by low-threshold skin mechanoreceptors, modulate the perception of sweat-induced skin wetness, independently of the level of physical wetness. Ten males (22 yr old) performed an incremental exercise protocol during two trials designed to induce the same physical skin wetness but to induce lower (TIGHT-FIT) and higher (LOOSE-FIT) wetness perception. In the TIGHT-FIT, a tight-fitting clothing ensemble limited intermittent skin-sweat-clothing tactile interactions. In the LOOSE-FIT, a loose-fitting ensemble allowed free skin-sweat-clothing interactions. Heart rate, core and skin temperature, galvanic skin conductance (GSC), and physical (w(body)) and perceived skin wetness were recorded. Exercise-induced sweat production and physical wetness increased significantly [GSC: 3.1 μS, SD 0.3 to 18.8 μS, SD 1.3, P 0.05). However, the limited intermittent tactile inputs generated by the TIGHT-FIT ensemble reduced significantly whole-body and regional wetness perception (P < 0.01). This reduction was more pronounced when between 40 and 80% of the body was covered in sweat. We conclude that the central integration of intermittent mechanical interactions between skin, sweat, and clothing, as coded by low-threshold skin mechanoreceptors, significantly contributes to the ability to sense sweat-induced skin wetness.

  14. Electronically induced contrast enhancement in whisker S1 cortical response fields.

    Science.gov (United States)

    von Kraus, Lee M; Francis, Joseph T

    2014-01-01

    The ability of an organism to specifically attend to relevant sensory information during learning and subsequent performance of a task is highly dependent on the release of the neurotransmitter Acetylcholine (ACh). Electrophysiological studies have shown that pairing endogenous ACh with specific visual or auditory stimuli induces long lasting enhancements of subsequent cortical responses to the previously paired stimulus. In this study we present data suggesting that similar effects can be elicited in the rat whisker sensory system. Specifically, we show that pairing whisker deflection with electrical stimulation of the magnocellular basal nucleus (BN: a natural source of cortical ACh) causes an increase in the center-surround contrast of the treated whisker's cortical response field (CRF). Meanwhile, deflections of whiskers distant from the treated whisker show overall increased response magnitudes, but non-significant changes in contrast between principle vs. surround barrel responses. Control trials, in which BN stimulation was not paired with whisker deflection, showed similar lack of contrast enhancement. These results indicate that BN stimulation, paired with incoming whisker information, selectively increases the paired whisker's CRF center-surround contrast, while unpaired BN stimulation causes a more general increases in S1 responsiveness, without contrast modulation. Enhanced control over whisker sensory pathway attentional mechanisms has the potential to facilitate a more effective transfer of desired information to the animal's neural processing circuitry, thereby allowing experimental evaluation of more complex behavior and cognition than was previously possible.

  15. Puerarin Ameliorates D-Galactose Induced Enhanced Hippocampal Neurogenesis and Tau Hyperphosphorylation in Rat Brain.

    Science.gov (United States)

    Hong, Xiao-Ping; Chen, Tao; Yin, Ni-Na; Han, Yong-Ming; Yuan, Fang; Duan, Yan-Jun; Shen, Feng; Zhang, Yan-Hong; Chen, Ze-Bin

    2016-01-01

    Enhanced neurogenesis has been reported in the hippocampus of patients with Alzheimer's disease (AD), the most common neurodegenerative disorder characterized with amyloid-β (Aβ) aggregation, tau hyperphosphorylation, and progressive neuronal loss. Previously we reported that tau phosphorylation played an essential role in adult hippocampal neurogenesis, and activation of glycogen synthase kinase (GSK-3), a crucial tau kinase, could induce increased hippocampal neurogenesis. In the present study, we found that treatment of D-galactose rats with Puerarin could significantly improve behavioral performance and ameliorate the enhanced neurogenesis and microtubule-associated protein tau hyperphosphorylation in the hippocampus of D-galactose rat brains. FGF-2/GSK-3 signaling pathway might be involved in the effects of Puerarin on hippocampal neurogenesis and tau hyperphosphorylation. Our finding provides primary in vivo evidence that Puerarin can attenuate AD-like enhanced hippocampal neurogenesis and tau hyperphosphorylation. Our finding also suggests Puerarin can be served as a treatment for age-related neurodegenerative disorders, such as AD.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-05-01

    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.

  17. Genetic Phagocyte NADPH Oxidase Deficiency Enhances Nonviable Candida albicans-Induced Inflammation in Mouse Lungs.

    Science.gov (United States)

    Endo, Daiki; Fujimoto, Kenta; Hirose, Rika; Yamanaka, Hiroko; Homme, Mizuki; Ishibashi, Ken-Ichi; Miura, Noriko; Ohno, Naohito; Aratani, Yasuaki

    2017-02-01

    Patients with chronic granulomatous disease (CGD) have mutated phagocyte NADPH oxidase, resulting in reduced production of reactive oxygen species (ROS). While the mechanism underlying hyperinfection in CGD is well understood, the basis for inflammatory disorders that arise in the absence of evident infection has not been fully explained. This study aimed to evaluate the effect of phagocyte NADPH oxidase deficiency on lung inflammation induced by nonviable Candida albicans (nCA). Mice deficient in this enzyme (CGD mice) showed more severe neutrophilic pneumonia than nCA-treated wild-type mice, which exhibited significantly higher lung concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and keratinocyte-derived chemokine (KC). Neutralization of these proinflammatory mediators significantly reduced neutrophil infiltration. In vitro, production of IL-1β and TNF-α from neutrophils and that of KC from macrophages was enhanced in nCA-stimulated neutrophils from CGD mice. Expression of IL-1β mRNA was higher in the stimulated CGD neutrophils than in the stimulated wild-type cells, concomitant with upregulation of nuclear factor (NF)-κB and its upstream regulator extracellular-signal regulated kinase (ERK) 1/2. Pretreatment with an NADPH oxidase inhibitor significantly enhanced IL-1β production in the wild-type neutrophils stimulated with nCA. These results suggest that lack of ROS production because of NADPH oxidase deficiency results in the production of higher levels of proinflammatory mediators from neutrophils and macrophages, which may at least partly contribute to the exacerbation of nCA-induced lung inflammation in CGD mice.

  18. The changes and significance of T cell subsets and cytokines in the induced sputum in children with asthma

    Institute of Scientific and Technical Information of China (English)

    Zu-Hui Tian; Feng-Qiong Zuo; Wei Zhang

    2016-01-01

    Objective:To explore the changes and significance of T cell subsets and cytokines in the induced sputum in children with asthma.Methods:A total of 86 cases of children with asthma were selected as research objects in the observation group, while a total of 35 cases of healthy children were chosen as research objects in the control group. Lung function indexes including the ratio (FEV1%) of forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) and the maximum peak expiratory flow (PEF), and inflammatory cytokines in the induced sputum including interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and T cell subsets including Th1 cells, CD8+CD28- Treg cells, CD4+CD25+ Treg cells, Th2 cells and Th17 cells, and T cell subsets related cytokines including interferon-γ (IFN-γ), transforming growth factor-β (TGF-β), interleukin-4 (IL-4), and interleukin-17A (IL-17A) were all detected and compared between the two groups.Results:The levels of IL-8, TNF-α and IL-6 in the induced sputum in the observation group were significantly higher than those in the control group (P<0.05), while FEV1% and PEF were significantly decreased in the observation group compared with the control group (P<0.05); the number of Th1 cells, CD8+CD28- Treg cells and CD4+CD25+ Treg cells in the induced sputum was significantly lower, while the number of Th2 cells and Th17 cells was significantly higher in the observation group than that in the control group (P<0.05); the expression levels of IFN-γ from Th1 cells and TGF-β from Treg cells were significantly lower, while the expression levels of IL-4 from Th2 cells and IL-17A from Th17 cells were significantly higher in the observation group than those in the control group (P<0.05).Conclusions:The number of T cell subsets in the induced sputum in children with asthma is abnormal, showing increases in the number of the Th2 cells and Th17 cells as well as their related cytokines, and decreases in the

  19. HIV-1gp120 induces neuronal apoptosis through enhancement of 4-aminopyridine-senstive outward K+ currents.

    Directory of Open Access Journals (Sweden)

    Lina Chen

    Full Text Available Human immunodeficiency virus type 1 (HIV-1-associated dementia (HAD usually occurs late in the course of HIV-1 infection and the mechanisms underlying HAD pathogenesis are not well understood. Accumulating evidence indicates that neuronal voltage-gated potassium (Kv channels play an important role in memory processes and acquired neuronal channelopathies in HAD. To examine whether Kv channels are involved in HIV-1-associated neuronal injury, we studied the effects of HIV-1 glycoprotein 120 (gp120 on outward K+ currents in rat cortical neuronal cultures using whole-cell patch techniques. Exposure of cortical neurons to gp120 produced a dose-dependent enhancement of A-type transient outward K+ currents (IA. The gp120-induced increase of IA was attenuated by T140, a specific antagonist for chemokine receptor CXCR4, suggesting gp120 enhancement of neuronal IA via CXCR4. Pretreatment of neuronal cultures with a protein kinase C (PKC inhibitor, GF109203X, inhibited the gp120-induced increase of IA. Biological significance of gp120 enhancement of IA was demonstrated by experimental results showing that gp120-induced neuronal apoptosis, as detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay and caspase-3 staining, was attenuated by either an IA blocker 4-aminopyridine or a specific CXCR4 antagonist T140. Taken together, these results suggest that gp120 may induce caspase-3 dependent neuronal apoptosis by enhancing IA via CXCR4-PKC signaling.

  20. Hippocampus-dependent cognitive enhancement induced by systemic gintonin administration

    Directory of Open Access Journals (Sweden)

    Sungmin Kim

    2016-01-01

    Conclusion: Our observations suggest that the systemic gintonin administration could successfully improve contextual memory formation at the molecular and synaptic levels as well as the behavioral level. Therefore, oral administration of gintonin may serve as an effective noninvasive, nonsurgical method of enhancing cognitive functions.

  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...

  2. Carbon nanotube-based coatings to induce flow enhancement in hydrophilic nanopores

    DEFF Research Database (Denmark)

    Wagemann, Enrique; Walther, Jens Honore; Zambrano, Harvey

    2016-01-01

    that carbon nanotubes (CNTs) feature ultrafast waterflow rates which result in flow enhancements of 1 to 5 orders of magnitude compared to Hagen-Poiseuille predictions. In the present study, CNT-based coatings are considered to induce water flow enhancement in silica nanopores with different radius. We......-walled carbon nanotubes implemented as coating material in silica nanopores....

  3. Clinical Significance of a Myeloperoxidase Gene Polymorphism and Inducible Nitric Oxide Synthase Expression in Cirrhotic Patients with Hepatopulmonary Syndrome

    Institute of Scientific and Technical Information of China (English)

    王燕颖; 王文多; 张艳霞; 赵欣; 杨东亮

    2010-01-01

    The clinical significance of a myeloperoxidase (MPO) gene polymorphism and inducible nitric oxide synthase (iNOS) expression in cirrhotic patients with hepatopulmonary syndrome (HPS) was explored. Enrolled subjects were divided into three groups according to their disease/health conditions: the HPS group (cirrhotic patients with HPS; n=63), the non-HPS group (cirrhotic patients without HPS; n=182), and the control group (healthy subjects without liver disease; n=35). The distribution of the MPO-463 G/A geno...

  4. Enhancement of taxol-induced apoptosis by inhibition of NF-κB with ursorlic acid

    Science.gov (United States)

    Li, Yunlong; Xing, Da

    2007-05-01

    Taxol is known to inhibit cell growth and triggers significant apoptosis in various cancer cells, and activation of proliferation factor NF-κB during Taxol-induced apoptosis is regarded as a main reason resulting in tumor cells resistance to Taxol. It has been found that ursorlic acid can inhibit the activation of NF-κB. In order to study whether ursorlic acid can enhance the Taxol-induced apoptosis, we use fluorescence resonance energy transfer (FRET) technique and probe SCAT3 to compare the difference of caspase-3 activation between Taxol alone and Taxol combined ursorlic acid. With laser scanning confocal microscopy, we find that ursorlic acid, a nontoxic food component, sensitizes ASTC-a-1 cells more efficiently to Taxol-induced apoptosis by advanced activation of caspase 3. The result also suggests that there would be a synergistic effect between Taxol and ursorlic acid, and the more detailed mechanism of synergistic effect needs to be clarified further, such as the correlations among NF-κB, Akt, caspase 8, which leads to the advanced activation of caspase 3 during combined treatment of Taxol and ursorlic acid. Moreover, this may be a new way to improve Taxol-dependent tumor therapy.

  5. Delayed contrast enhancement cardiac magnetic resonance imaging in trastuzumab induced cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Kirkpatrick Iain

    2008-01-01

    Full Text Available Abstract Background Trastuzumab (Herceptin, an antagonist to the human epidermal growth factor 2 (HER2 receptor significantly decreases the rates of breast cancer recurrence and mortality by 50%. Despite therapeutic benefits, the risk of cardiotoxicity with trastuzumab ranges from 10–15% when administered sequentially following anthraycline chemotherapy. Little is known about the utility of cardiac magnetic resonance (CMR in the assessment of trastuzumab mediated cardiomyopathy. Methods and results Between 2005–2006 inclusive, 160 breast cancer patients were identified at a single tertiary care oncology centre. Of the total population, 10 patients (mean age 40 ± 8 years were identified with trastuzumab induced cardiomyopathy, based on a LVEF less than 40% on serial MUGA or echocardiography. CMR was performed in all patients to determine LV volumes, systolic function and evidence of late gadolinium enhancement (LGE. At the time of diagnosis of trastuzumab induced cardiomyopathy, the mean LVEF was 29 ± 4%. Subepicardial linear LGE was present in the lateral portion of the left ventricles in all 10 patients. Conclusion LGE-CMR is a novel way of detecting early changes in the myocardium due to trastuzumab induced cardiotoxicity.

  6. Quercetin Attenuates Chronic Ethanol-Induced Hepatic Mitochondrial Damage through Enhanced Mitophagy.

    Science.gov (United States)

    Yu, Xiao; Xu, Yanyan; Zhang, Shanshan; Sun, Jian; Liu, Peiyi; Xiao, Lin; Tang, Yuhan; Liu, Liegang; Yao, Ping

    2016-01-05

    Emerging evidence suggested mitophagy activation mitigates ethanol-induced liver injury. However, the effect of ethanol on mitophagy is inconsistent. Importantly, the understanding of mitophagy status after chronic ethanol consumption is limited. This study evaluated the effect of quercetin, a naturally-occurring flavonoid, on chronic ethanol-induced mitochondrial damage focused on mitophagy. An ethanol regime to mice for 15 weeks (accounting for 30% of total calories) led to significant mitochondrial damage as evidenced by changes of the mitochondrial ultrastructure, loss of mitochondrial membrane potential and remodeling of membrane lipid composition, which was greatly attenuated by quercetin (100 mg/kg.bw). Moreover, quercetin blocked chronic ethanol-induced mitophagy suppression as denoted by mitophagosomes-lysosome fusion and mitophagy-related regulator elements, including LC3II, Parkin, p62 and voltage-dependent anion channel 1 (VDAC1), paralleling with increased FoxO3a nuclear translocation. AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase 2 (ERK2), instead of AKT and Sirtuin 1, were involved in quercetin-mediated mitophagy activation. Quercetin alleviated ethanol-elicited mitochondrial damage through enhancing mitophagy, highlighting a promising preventive strategy for alcoholic liver disease.

  7. Dendropanoxide induces autophagy through ERK1/2 activation in MG-63 human osteosarcoma cells and autophagy inhibition enhances dendropanoxide-induced apoptosis.

    Science.gov (United States)

    Lee, Ji-Won; Kim, Kyoung-Sook; An, Hyun-Kyu; Kim, Cheorl-Ho; Moon, Hyung-In; Lee, Young-Choon

    2013-01-01

    Anticancer effects of dendropanoxide (DP) newly isolated from leaves and stem of Dendropanax morbifera Leveille were firstly investigated in this study. DP inhibited cell proliferation and induced apoptosis in dose- and time-dependent manner in MG-63 human osteosarcoma cells, which was dependent on the release of cytochrome c to the cytosol and the activation of caspases. Moreover, the DP-treated cells exhibited autophagy, as characterized by the punctuate patterns of microtubule-associated protein 1 light chain 3 (LC3) by confocal microscopy and the appearance of autophagic vacuoles by MDC staining. The expression levels of ATG7, Beclin-1 and LC3-II were also increased by DP treatment. Inhibition of autophagy by 3-methyladenine (3-MA) and wortmannin (Wort) significantly enhanced DP-induced apoptosis. DP treatment also caused a time-dependent increase in protein levels of extracellular signal-regulated kinase 1 and 2 (ERK1/2), and inhibition of ERK1/2 phosphorylation with U0126 resulted in a decreased DP-induced autophagy that was accompanied by an increased apoptosis and a decreased cell viability. These results indicate a cytoprotective function of autophagy against DP-induced apoptosis and suggest that the combination of DP treatment with autophagy inhibition may be a promising strategy for human osteosarcoma control. Taken together, this study demonstrated for the first time that DP could induce autophagy through ERK1/2 activation in human osteosarcoma cells and autophagy inhibition enhanced DP-induced apoptosis.

  8. Dendropanoxide induces autophagy through ERK1/2 activation in MG-63 human osteosarcoma cells and autophagy inhibition enhances dendropanoxide-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Ji-Won Lee

    Full Text Available Anticancer effects of dendropanoxide (DP newly isolated from leaves and stem of Dendropanax morbifera Leveille were firstly investigated in this study. DP inhibited cell proliferation and induced apoptosis in dose- and time-dependent manner in MG-63 human osteosarcoma cells, which was dependent on the release of cytochrome c to the cytosol and the activation of caspases. Moreover, the DP-treated cells exhibited autophagy, as characterized by the punctuate patterns of microtubule-associated protein 1 light chain 3 (LC3 by confocal microscopy and the appearance of autophagic vacuoles by MDC staining. The expression levels of ATG7, Beclin-1 and LC3-II were also increased by DP treatment. Inhibition of autophagy by 3-methyladenine (3-MA and wortmannin (Wort significantly enhanced DP-induced apoptosis. DP treatment also caused a time-dependent increase in protein levels of extracellular signal-regulated kinase 1 and 2 (ERK1/2, and inhibition of ERK1/2 phosphorylation with U0126 resulted in a decreased DP-induced autophagy that was accompanied by an increased apoptosis and a decreased cell viability. These results indicate a cytoprotective function of autophagy against DP-induced apoptosis and suggest that the combination of DP treatment with autophagy inhibition may be a promising strategy for human osteosarcoma control. Taken together, this study demonstrated for the first time that DP could induce autophagy through ERK1/2 activation in human osteosarcoma cells and autophagy inhibition enhanced DP-induced apoptosis.

  9. In a randomized placebo-controlled add-on study orlistat significantly reduced clozapine-induced constipation.

    Science.gov (United States)

    Chukhin, Evgeny; Takala, Pirjo; Hakko, Helinä; Raidma, Mirjam; Putkonen, Hanna; Räsänen, Pirkko; Terevnikov, Viacheslav; Stenberg, Jan-Henry; Eronen, Markku; Joffe, Grigori

    2013-03-01

    Constipation is a common and potentially fatal side effect of clozapine treatment. Another important side effect of clozapine may also be significant weight gain. Orlistat is a weight-control medication that is known to induce loose stools as a common side effect. This study aimed to explore whether orlistat used to control clozapine-induced weight gain can simultaneously tackle clozapine-related constipation. In this 16-week randomized-controlled study, clozapine-treated patients received add-on orlistat (n=30) or add-on placebo (n=24). Colonic function was measured using the Bristol Stool Form Scale. There was a significant (P=0.039) difference in the prevalence of constipation in favor of orlistat over placebo in completers (n=40) at the endpoint. A decrease in the prevalence of constipation within the orlistat group (P=0.035) was observed (vs. no statistically significant changes in the placebo group). In clozapine-treated patients, orlistat may be beneficial not only for weight control but also as a laxative. As no established treatments for clozapine-induced constipation exist, orlistat can be considered for this population, although more studies are required.

  10. L-type calcium channel blockers enhance 5-HTP-induced antinociception in mice

    Institute of Scientific and Technical Information of China (English)

    Jian-hui LIANG; Jun-xu LI; Xu-hua WANG; Bi CHEN; Ying LU; Pan ZHANG; Rong HAN; Xiang-feng YE

    2004-01-01

    AIM: To investigate the involvement of L-type Ca2+ channels in antinociceptive action induced by the 5-HT precursor,5-hydroxytryptophan (5-HTP). METHODS: Female Kunming mice were treated with either 5-HTP (20-80 mg/kg,ip) alone, or the combination of 5-HTP and fluoxetine (2-8 mg/kg, ip), pargyline (15-60 mg/kg, ip), nimodipine (2.5-10 mg/kg, ip), nifedipine (2.5-10 mg/kg, ip), verapamil (2.5-10 mg/kg, ip), CaC12 (5-20 mmol/L, icv), or EGTA (0.5-3 mmol/L, icv) prior to the hot-plate test (55 ℃, hind-paw licking latency). In addition, locomotor activity in mice treated with 5-HTP alone was measured using an ambulometer with five activity boxes. RESULTS: Ip injection of 5-HTP alone had no influence on the spontaneous locomotor activity, whereas dose-dependently increased the latency to licking hind-paw in the hot-plate test in mice. The inhibitory effects of 5-HTP on nociceptive response were significantly enhanced by fluoxetine in the mouse hot-plate test. At a sub-effective dose, pargyline could cause a leftward shift in the dose-response curve of 5-HTP-induced antinociception. Co-administration with 5-HTP and nimodipine, nifedipine, or verapamil obviously potentiated the antinociceptive effects elicited by 5-HTP.Interestingly, 5-HTP-induced antinociception was antagonized by CaC12 and enhanced by EGTA injected icv in the mouse hot-plate test. CONCLUSION: These findings suggest that systemic administration of 5-HTP may yield the antinociceptive effects, which are related to Ca2+ influx from extracellular fluid through L-type Ca2+ channels.

  11. L-type calcium channel blockers enhance 5-HTP-induced antinociception in mice.

    Science.gov (United States)

    Liang, Jian-hui; Li, Jun-xu; Wang, Xu-hua; Chen, Bi; Lu, Ying; Zhang, Pan; Han, Rong; Ye, Xiang-feng

    2004-05-01

    To investigate the involvement of L-type Ca(2+) channels in antinociceptive action induced by the 5-HT precursor, 5-hydroxytryptophan (5-HTP). Female Kunming mice were treated with either 5-HTP (20-80 mg/kg, ip) alone, or the combination of 5-HTP and fluoxetine (2-8 mg/kg, ip), pargyline (15-60 mg/kg, ip), nimodipine (2.5-10 mg/kg, ip), nifedipine (2.5-10 mg/kg, ip), verapamil (2.5-10 mg/kg, ip), CaCl(2) (5-20 mmol/L, icv), or EGTA (0.5-3 mmol/L, icv) prior to the hot-plate test (55 degree, hind-paw licking latency). In addition, locomotor activity in mice treated with 5-HTP alone was measured using an ambulometer with five activity boxes. Ip injection of 5-HTP alone had no influence on the spontaneous locomotor activity, whereas dose-dependently increased the latency to licking hind-paw in the hot-plate test in mice. The inhibitory effects of 5-HTP on nociceptive response were significantly enhanced by fluoxetine in the mouse hot-plate test. At a sub-effective dose, pargyline could cause a leftward shift in the dose-response curve of 5-HTP-induced antinociception. Co-administration with 5-HTP and nimodipine, nifedipine, or verapamil obviously potentiated the antinociceptive effects elicited by 5-HTP. Interestingly, 5-HTP-induced antinociception was antagonized by CaCl(2) and enhanced by EGTA injected icv in the mouse hot-plate test. These findings suggest that systemic administration of 5-HTP may yield the antinociceptive effects, which are related to Ca(2+) influx from extracellular fluid through L-type Ca(2+) channels.

  12. Enhancement of photoprotection potential of catechin loaded nanoemulsion gel against UVA induced oxidative stress.

    Science.gov (United States)

    Harwansh, Ranjit K; Mukherjee, Pulok K; Kar, Amit; Bahadur, Shiv; Al-Dhabi, Naif Abdullah; Duraipandiyan, V

    2016-07-01

    The present study was aimed to develop a catechin (CA) loaded nanoemulsion based nano-gel for the protection of skin against ultraviolet radiation (UV) induced photo-damage and to ensure its enhanced skin permeability as well as bioavailability through transdermal route. The optimized nanoemulsion (CA-NE4) was prepared by spontaneous nano-emulsification method. It was composed of oil (ethyl oleate), Smix [surfactant (span 80) and co-surfactant (transcutol CG)] and aqueous system in an appropriate ratio of 15:62:23% w/w respectively. The CA-NE4 was characterized through assessment of droplet size, zeta potential, refractive index, transmission electron microscopy (TEM), UV, high performance thin layer chromatography (HPTLC) and Fourier transform infrared spectroscopy (FTIR) analysis. The average droplet size and zeta potential of CA-NE4 were found to be 98.6±1.01nm and -27.3±0.20mV respectively. The enhanced skin permeability was better with CA-NE4 based nano-gel (CA-NG4) [96.62%] compared to conventional gel (CA-CG) [53.01%] for a period of 24h. The enhanced % relative bioavailability (F) of CA (894.73), Cmax (93.79±6.19ngmL(-1)), AUC0-t∞ (2653.99±515.02nghmL(-1)) and Tmax (12.05±0.02h) was significantly obtained with CA-NG4 as compared to oral suspension for extended periods (72h). CA-NG4 could improve the level of cutaneous antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) and reduce the level of thiobarbituric acid reactive substances (TBRAS) against oxidative stress induced by UVA. Nano-gel formulation of CA showed sustained release profile and enhanced photoprotection potential due to its improved permeability as well as bioavailability (Pgel. Therefore, transdermal administration of nano-gel (CA-NG4) of CA offers a better way to develop the endogenous cutaneous protection system and thus could be an effective strategy for decreasing UV-induced oxidative damage in the skin tissues.

  13. 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

  14. Identification of promoters and enhancers induced by carbon nanotube exposure

    DEFF Research Database (Denmark)

    Bornholdt, Jette; Lilje, Berit; Saber, Anne Thoustrup

    Usage of carbon nanotubes (CNTs) is increasing in industry due to their mechanical and electrical properties. However, pulmonary exposure to CNTs induces, an asbestos-like toxicological response characterized by persistent inflammation, granuloma formation and fibrosis with low no-effect levels...

  15. Significant correlation between expression level of HSP gp96 and progression of hepatitis B virus induced diseases

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Zhu; Cheng-Lin Li; Zhen-Wei Lang; George F Gao; Po Tien

    2004-01-01

    AIM: Gp96, also known as Grp94, is a member of heat shock protein (HSP) family and binds repertoires of peptides thereof eliciting peptide-specific T cell immune responses.It predominantly locates inside the endoplasmic reticulum (ER) with some cell surface expression in certain cancerous cells. Previous studies have shown that gp96 expression level was up-regulated in tumor cells, including hepatocellular carcinoma (HCC). However, relationship between the extent of gp96 expression and disease progression especially HBV-induced chronic infection, cirrhosis and hepatocellular carcinoma, has not been addressed before. As primary HCC can be induced and progressed from chronic hepatitis B virus (HBV) infection and HBV-induced cirrhosis, we designed an immunohistochemical experiment to test the correlation between gp96 expression level and HBV-induced disease progression, from chronic HBV infection, cirrhosis to HCC.METHODS: We chose liver samples from different patients of hepatitis B virus induced diseases, including chronic hepatitis B (77 patients), cirrhosis (27 patients) and primary HCC (30 patients), to test the expression level of gp96 in different affected groups. Formalin-fixed, and paraffinembedded liver tissues taken from these patients were immuno-stained by using an anti-gp96 monoclonal antibody for the expression level of gp96 protein in the sections. In addition, Western blotting of whole cell lysates derived from established human embryonic liver cell lines and several human HCC cell lines (Huh7, HepG2, SSMC-7721) was compared with the expression of gp96.RESULTS: We found that the extent of elevated gp96expression was significantly correlated with the disease progression, and was the highest in HCC patients, lowest in chronic HBV infection and was that of the cirrhosis in the middle.CONCLUSION: Increased expression of gp96 might be used as a diagnostic or prognostic bio-marker for the HBV infection and HBV-induced diseases.

  16. Berberine augments ATP-induced inflammasome activation in macrophages by enhancing AMPK signaling

    Science.gov (United States)

    Xu, Li-Hui; Liang, Yi-Dan; Wei, Hong-Xia; Hu, Bo; Pan, Hao; Zha, Qing-Bing; Ouyang, Dong-Yun; He, Xian-Hui

    2017-01-01

    The isoquinoline alkaloid berberine possesses many pharmacological activities including antibacterial infection. Although the direct bactericidal effect of berberine has been documented, its influence on the antibacterial functions of macrophages is largely unknown. As inflammasome activation in macrophages is important for the defense against bacterial infection, we aimed to investigate the influence of berberine on inflammasome activation in murine macrophages. Our results showed that berberine significantly increased ATP-induced inflammasome activation as reflected by enhanced pyroptosis as well as increased release of caspase-1p10 and mature interleukin-1β (IL-1β) in macrophages. Such effects of berberine could be suppressed by AMP-activated protein kinase (AMPK) inhibitor compound C or by knockdown of AMPKα expression, indicating the involvement of AMPK signaling in this process. In line with increased IL-1β release, the ability of macrophages to kill engulfed bacteria was also intensified by berberine. This was corroborated by the in vivo finding that the peritoneal live bacterial load was decreased by berberine treatment. Moreover, berberine administration significantly improved survival of bacterial infected mice, concomitant with increased IL-1β levels and elevated neutrophil recruitment in the peritoneal cavity. Collectively, these data suggested that berberine could enhance bacterial killing by augmenting inflammasome activation in macrophages through AMPK signaling. PMID:27980220

  17. The prevalence and significance of renal perfusion defects in early kidney transplants quantified using 3D contrast enhanced ultrasound (CEUS).

    Science.gov (United States)

    Stenberg, Ben; Wilkinson, M; Elliott, S; Caplan, N

    2017-06-07

    Vascular complications are one of the most common causes of early kidney transplant dysfunction. Contrast enhanced ultrasound increases sensitivity to vascular changes. The aim of this study was to assess the prevalence and size of vascular abnormalities in early renal transplants using 3D CEUS and the significance of perfusion defects on renal function. Ninety-nine renal transplant patients underwent 3D CEUS after surgery to quantify perfusion defects as percentage total renal volume (TRV). Serum creatinine and estimated glomerular filtration rate (eGFR) were recorded up to 3 months post-surgery. Twenty participants had focal perfusion defects (0.2-43%TRV). There was a meaningful difference in patients with perfusion defects in eGFR at 1 month (90% CI 2.7-19.2 mL/min/1.73 m(2)) and 3 months (90% CI 1.9-19.6 mL/min/1.73 m(2)) and creatinine at 3 months (90% CI -56 - -8 μmol/L) using a predetermined clinical threshold. Perfusion defect size correlated well with both serum creatinine and eGFR at 3 months (R = 0.80, p ≤ 0.000 and 0.58, p = 0.038). No correlation was seen prior to 3 months. Perfusion defects in kidney transplants were more common than expected and were highly likely to reduce renal function at 1-3 months, and the size of the defect affected the degree of functional change at 3 months. • Perfusion defects were more common than previously thought. • Perfusion defects could be quantified using 3D CEUS. • The presence of even small perfusion defects may affect kidney function. • Size of perfusion defects correlated with subsequent kidney function at 3 months. • Potentially useful in informing clinician expectations of kidney function post-surgery.

  18. European corn borer (Ostrinia nubilalis) induced responses enhance susceptibility in maize.

    Science.gov (United States)

    Dafoe, Nicole J; Thomas, James D; Shirk, Paul D; Legaspi, Michelle E; Vaughan, Martha M; Huffaker, Alisa; Teal, Peter E; Schmelz, Eric A

    2013-01-01

    Herbivore-induced plant responses have been widely described following attack on leaves; however, less attention has been paid to analogous local processes that occur in stems. Early studies of maize (Zea mays) responses to stem boring by European corn borer (ECB, Ostrinianubilalis) larvae revealed the presence of inducible acidic diterpenoid phytoalexins, termed kauralexins, and increases in the benzoxazinoid 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one-glucose (HDMBOA-Glc) after 24 h of herbivory. Despite these rapidly activated defenses, larval growth was not altered in short-term feeding assays. Unexpectedly, ECB growth significantly improved in assays using stem tissue preconditioned by 48 h of larval tunneling. Correspondingly, measures of total soluble protein increased over 2.6-fold in these challenged tissues and were accompanied by elevated levels of sucrose and free linoleic acid. While microarray analyses revealed up-regulation of over 1100 transcripts, fewer individual protein increases were demonstrable. Consistent with induced endoreduplication, both wounding and ECB stem attack resulted in similar significant expansion of the nucleus, nucleolus and levels of extractable DNA from challenged tissues. While many of these responses are triggered by wounding alone, biochemical changes further enhanced in response to ECB may be due to larval secreted effectors. Unlike other Lepidoptera examined, ECB excrete exceedingly high levels of the auxin indole-3-acetic acid (IAA) in their frass which is likely to contact and contaminate the surrounding feeding tunnel. Stem exposure to a metabolically stable auxin, such as 2,4-dichlorophenoxyacetic acid (2,4-D), promoted significant protein accumulation above wounding alone. As a future testable hypothesis, we propose that ECB-associated IAA may function as a candidate herbivore effector promoting the increased nutritional content of maize stems.

  19. European corn borer (Ostrinia nubilalis induced responses enhance susceptibility in maize.

    Directory of Open Access Journals (Sweden)

    Nicole J Dafoe

    Full Text Available Herbivore-induced plant responses have been widely described following attack on leaves; however, less attention has been paid to analogous local processes that occur in stems. Early studies of maize (Zea mays responses to stem boring by European corn borer (ECB, Ostrinianubilalis larvae revealed the presence of inducible acidic diterpenoid phytoalexins, termed kauralexins, and increases in the benzoxazinoid 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one-glucose (HDMBOA-Glc after 24 h of herbivory. Despite these rapidly activated defenses, larval growth was not altered in short-term feeding assays. Unexpectedly, ECB growth significantly improved in assays using stem tissue preconditioned by 48 h of larval tunneling. Correspondingly, measures of total soluble protein increased over 2.6-fold in these challenged tissues and were accompanied by elevated levels of sucrose and free linoleic acid. While microarray analyses revealed up-regulation of over 1100 transcripts, fewer individual protein increases were demonstrable. Consistent with induced endoreduplication, both wounding and ECB stem attack resulted in similar significant expansion of the nucleus, nucleolus and levels of extractable DNA from challenged tissues. While many of these responses are triggered by wounding alone, biochemical changes further enhanced in response to ECB may be due to larval secreted effectors. Unlike other Lepidoptera examined, ECB excrete exceedingly high levels of the auxin indole-3-acetic acid (IAA in their frass which is likely to contact and contaminate the surrounding feeding tunnel. Stem exposure to a metabolically stable auxin, such as 2,4-dichlorophenoxyacetic acid (2,4-D, promoted significant protein accumulation above wounding alone. As a future testable hypothesis, we propose that ECB-associated IAA may function as a candidate herbivore effector promoting the increased nutritional content of maize stems.

  20. Enhanced External Counterpulsation Inducing Arterial Hemodynamic Variations and Its Chronic Effect on Endothelial Function

    Institute of Scientific and Technical Information of China (English)

    DU Jian-hang; WU Gui-fu; ZHENG Zhen-sheng; DAI Gang; FENG Ming-zhe

    2014-01-01

    To make clear the precise hemodynamic mechanism underlying the anti-atherogenesis benefit of enhanced external couterpulsation(EECP) treatment, and to investigate the proper role of some important hemodynamic factors during the atherosclerotic progress, a comprehensive study combining long-term animal experiment and numerical solving was conducted in this paper. An experimentally induced hypercholesterolemic porcine model was developed and the chronic EECP intervention was subjected. Basic hemodynamic measurement was performed in vivo, as well as the arterial endothelial samples were extracted for physiological examination. Meanwhile, a numerical model was introduced to solve the complex hemodynamic factors such as WSS and OSI. The results show that EECP treatment resulted in significant increase of the instant levels of arterial WSS, blood pressure, and OSI. During EECP treatment, the instant OSI level of the common carotid arteries over cardiac cycles raised to a mean value of 8.58 ×10-2 ±2.13 ×10-2. Meanwhile, the chronic intervention of EECP treatment significantly reduced the atherosclerotic lesions in abdominal aortas and the endothelial cellular adherence. The present study suggests that the unique blood flow pattern induced by EECP treatment and the augmentation of WSS level in cardiac cycles may be the most important hemodynamic mechanism that contribute to its anti-atherogenesis effect. And as one of the indices that cause great concern in current hemodynamic study, OSI may not play a key role during the initiation of atherosclerosis.

  1. Significance of liver biopsy for the evaluation of methotrexate-induced liver damage in patients with rheumatoid arthritis.

    Science.gov (United States)

    Osuga, Tatsuya; Ikura, Yoshihiro; Kadota, Chikara; Hirano, Seiichi; Iwai, Yasuhiro; Hayakumo, Takanobu

    2015-01-01

    It is well recognized that long-term administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA) can induce liver fibrosis via a steatohepatitis-like inflammatory process. Several non-invasive tests have been investigated as alternatives to liver biopsy, which is, however, still recognized as a final diagnostic modality to detect the MTX-induced liver damage. To clarify whether there is a significant discrepancy between clinical estimations and pathologic findings of this hepatic condition, we performed a following comparative study. Four RA patients (4 women, age 67-80 yr) with MTX-induced liver damage were reviewed. The severity of hepatic damage estimated clinically was compared with histopathologic findings. Consequently, the liver biopsies showed the relatively earlier stages of and milder degrees of hepatic damages than the clinical estimations. The histopathologic findings were more reliable and useful than any other clinical examinations, to plan and modify the treatment strategies, especially in cases of liver damages with multiple etiologies besides MTX. These findings suggest that liver biopsy is an unavoidable examination to assess precisely MTX-induced liver damage. Non-invasive tests may be useful to monitor the hepatic condition of RA patients receiving MTX but do not constitute an acceptable alternative to liver biopsy.

  2. Cognition Enhancing Activity of Sulforaphane Against Scopolamine Induced Cognitive Impairment in Zebra Fish (Danio rerio).

    Science.gov (United States)

    Rajesh, Venugopalan; Ilanthalir, Sakthivel

    2016-10-01

    Several epidemiological studies have shown that consumption of large quantities of vegetables especially cruciferous vegetables (Broccoli and Brussels sprouts) can protect against chronic diseases. Sulforaphane, an isothiocynate found in cruciferous vegetables has been demonstrated to have neuroprotective effects in several experimental paradigms. This study was undertaken to examine the effect of sulforaphane on cognitive impairment in zebra fish model using a novel method of fear conditioning. Initially, the normal behaviour of zebra fishes was studied in light-dark tank for 10 min daily for 10 days. Fishes were then divided into seven groups of twelve in each. Group I served as normal, group II served as fear conditioned control, group III and group IV were sulforaphane (25 µM/L) and piracetam (200 mg/L) treated respectively. Group V served as scopolamine (400 µM/L) induced memory impairment fishes. Group VI and VII were sulforaphane (25 µM/L) and piracetam (200 mg/L) treated scopolamine induced memory impairment groups respectively. In normal behavioural analysis, fishes preferred to stay in dark compartment. The average number of entries into the dark and time spent in dark were significantly more. Fishes in group II to VII were individually subjected to fear conditioning passive avoidance task and evaluated for learned task memory. It was observed that the average number of entries into dark and time spent in dark were significantly decreased. After exposure to respective treatment fishes in group III to VII were subjected to cognitive evaluation. There was no significant difference in cognition of group III and IV fishes exposed to sulforaphane and piracetam alone respectively. Fishes exposed to scopolamine showed a significant cognitive impairment. Sulforaphane exposure prior to scopolamine significantly retained the memory of learned task. These findings suggest that sulforaphane might be a promising therapeutic agent for cognitive enhancement in

  3. Inhibition of PLK1 in glioblastoma multiforme induces mitotic catastrophe and enhances radiosensitization

    Science.gov (United States)

    Tandle, Anita T.; Kramp, Tamalee; Kil, Whoon J; Halthore, Aditya; Gehlhaus, Kristen; Shankavaram, Uma; Tofilon, Philip J.; Caplen, Natasha J.; Camphausen, Kevin

    2013-01-01

    Glioblastoma multiforme (GBM) is the most common primary brain tumor in the USA with a median survival of approximately 14 months. Low survival rates are attributable to the aggressiveness of GBM and a lack of understanding of the molecular mechanisms underlying GBM. The disruption of signaling pathways regulated either directly or indirectly by protein kinases is frequently observed in cancer cells and thus the development of inhibitors of specific kinases has become a major focus of drug discovery in oncology. To identify protein kinases required for the survival of GBM we performed a siRNA-based RNAi screen focused on the human kinome in GBM. Inhibition of the polo-like kinase 1 (PLK1) induced a reduction in the viability in two different GBM cell lines. To assess the potential of inhibiting PLK1 as a treatment strategy for GBM we examined the effects of a small molecule inhibitor of PLK1, GSK461364A, on the growth of GBM cells. PLK1 inhibition arrested cells in the mitotic phase of the cell cycle and induced cell kill by mitotic catastrophe. GBM engrafts treated with GSK461364A showed statistically significant inhibition of tumor growth. Further, exposure of different GBM cells to RNAi or GSK461364A prior to radiation resulted in an increase in their radiosensitivity with dose enhancement factor ranging from 1.40 to 1.53 with no effect on normal cells. As a measure of DNA double strand breaks, γH2AX levels were significantly higher in the combined modality as compared to the individual treatments. This study suggests that PLK1 is an important therapeutic target for GBM and can enhance radiosensitivity in GBM. PMID:23790466

  4. Inhibition of polo-like kinase 1 in glioblastoma multiforme induces mitotic catastrophe and enhances radiosensitisation.

    Science.gov (United States)

    Tandle, Anita T; Kramp, Tamalee; Kil, Whoon J; Halthore, Aditya; Gehlhaus, Kristen; Shankavaram, Uma; Tofilon, Philip J; Caplen, Natasha J; Camphausen, Kevin

    2013-09-01

    Glioblastoma multiforme (GBM) is the most common primary brain tumour in the United States of America (USA) with a median survival of approximately 14 months. Low survival rates are attributable to the aggressiveness of GBM and a lack of understanding of the molecular mechanisms underlying GBM. The disruption of signalling pathways regulated either directly or indirectly by protein kinases is frequently observed in cancer cells and thus the development of inhibitors of specific kinases has become a major focus of drug discovery in oncology. To identify protein kinases required for the survival of GBM we performed a siRNA-based RNAi screen focused on the human kinome in GBM. Inhibition of the polo-like kinase 1 (PLK1) induced a reduction in the viability in two different GBM cell lines. To assess the potential of inhibiting PLK1 as a treatment strategy for GBM we examined the effects of a small molecule inhibitor of PLK1, GSK461364A, on the growth of GBM cells. PLK1 inhibition arrested cells in the mitotic phase of the cell cycle and induced cell kill by mitotic catastrophe. GBM engrafts treated with GSK461364A showed statistically significant inhibition of tumour growth. Further, exposure of different GBM cells to RNAi or GSK461364A prior to radiation resulted in an increase in their radiosensitivity with dose enhancement factor ranging from 1.40 to 1.53 with no effect on normal cells. As a measure of DNA double strand breaks, γH2AX levels were significantly higher in the combined modality as compared to the individual treatments. This study suggests that PLK1 is an important therapeutic target for GBM and can enhance radiosensitivity in GBM.

  5. 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

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

    Science.gov (United States)

    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; de Oliveira, Antonio Carlos P; Moraes, Marcio F D; Moreira, Fabricio A

    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 CB1 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 CB1 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.

  7. 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.

  8. 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.

  9. HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis

    Science.gov (United States)

    Tenhunen, Jyrki; Tonnessen, Tor Inge

    2017-01-01

    Severe acute pancreatitis (SAP) starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT) during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly) gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS) can lead to multiple organ dysfunction syndrome (MODS) during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs) are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP. PMID:28316860

  10. HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Runkuan Yang

    2017-01-01

    Full Text Available Severe acute pancreatitis (SAP starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS can lead to multiple organ dysfunction syndrome (MODS during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP.

  11. Sustained systemic delivery of green tea polyphenols by polymeric implants significantly diminishes benzo[a]pyrene-induced DNA adducts.

    Science.gov (United States)

    Cao, Pengxiao; Vadhanam, Manicka V; Spencer, Wendy A; Cai, Jian; Gupta, Ramesh C

    2011-06-20

    The polyphenolics in green tea are believed to be the bioactive components. However, poor bioavailability following ingestion limits their efficacy in vivo. In this study, polyphenon E (poly E), a standardized green tea extract, was administered by sustained-release polycaprolactone implants (two, 2-cm implants; 20% drug load) grafted subcutaneously or via drinking water (0.8% w/v) to female S/D rats. Animals were treated with continuous low dose of benzo[a]pyrene (BP) via subcutaneous polymeric implants (2 cm; 10% load) and euthanized after 1 and 4 weeks. Analysis of lung DNA by (32)P-postlabeling resulted in a statistically significant reduction (50%; p = 0.023) of BP-induced DNA adducts in the implant group; however, only a modest (34%) but statistically insignificant reduction occurred in the drinking water group at 1 week. The implant delivery system also showed significant reduction (35%; p = 0.044) of the known BP diolepoxide-derived DNA adduct after 4 weeks. Notably, the total dose of poly E administered was >100-fold lower in the implant group than the drinking water group (15.7 versus 1,632 mg, respectively). Analysis of selected phase I, phase II, and nucleotide excision repair enzymes at both mRNA and protein levels showed no significant modulation by poly E, suggesting that the reduction in the BP-induced DNA adducts occurred presumably due to known scavenging of the antidiolepoxide of BP by the poly E catechins. In conclusion, our study demonstrated that sustained systemic delivery of poly E significantly reduced BP-induced DNA adducts in spite of its poor bioavailability following oral administration.

  12. Quercetin enhances TRAIL-induced apoptosis in prostate cancer cells via increased protein stability of death receptor 5

    Science.gov (United States)

    Jung, Young-Hwa; Heo, Jeonghoon; Lee, Yong J.; Kwon, Taeg Kyu; Kim, Young-Ho

    2010-01-01

    Aims Quercetin has been shown to enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of prostate cancer cells via mechanisms that include upregulation of death receptor (DR) 5, a protein reported to play an important role in sensitizing cancer cells to apoptosis. We aimed to determine the specific mechanisms underlying quercetin-induced DR5 expression. Main methods Human prostate cancer cells were exposed to quercetin and TRAIL. Trypan blue assays and terminal transferase dUTP nick-end labeling (TUNEL) assays evaluated changes in TRAIL resistance after quercetin treatment, and flow cytometry examined quercetin-induced death receptor expression in DU-145 cells. Western blotting, reverse transcription-polymerase chain reaction (RT-PCR) and transiently transfection were utilized to confirm apoptotic patterns of prostate cancer cells. Key findings After stimulation with quercetin, DU-145 cells exhibited stronger sensitization to TRAIL. Quercetin treatment enhanced TRAIL-induced activation proteins in the caspase pathway, such as poly (ADP-ribose) polymerase (PARP), caspase-3, and caspase-9. Quercetin dose-dependently increased DR5 levels in prostate cancer cells, which was mediated by increased transcription and protein stability, but not mRNA stability. Ectopic expression of DR5 dose-dependently increased TRAIL-induced apoptosis. Significance Our results showed that the role of quercetin and TRAIL combination therapy may provide a novel strategy for treating prostate cancer by overcoming critical mechanisms of apoptosis resistance. PMID:20096292

  13. Temperature enhancement induced by ionosphere heating in low altitude region

    Institute of Scientific and Technical Information of China (English)

    Bin Xu; Jian Wu; Zhensen Wu; Jun Wu; Haiqin Che; Yubo Yan; Kun Xue

    2008-01-01

    The assumption that the electron temperature is approximately equal to the ion temperature is not rational during the high frequency (HF) heating in low ionosphere region. Thus, using the theoretical formula of incoherent scatter spectra with collisional plasma, the incoherent scatter data are analyzed during ionosphere heating at 91.7 km height on August 15th 2006. The enhancements of electron temperature are obtained, and the incremental percent is up to 37% and 46% at the universal time of 10:22 and 10:30, respectively. By using the same initialization value, the ionosphere heating process is simulated by Ohmic theory and the experimental results are basically consistent with the simulation.

  14. 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.

  15. High glucose induces podocyte injury via enhanced (prorenin receptor-Wnt-β-catenin-snail signaling pathway.

    Directory of Open Access Journals (Sweden)

    Caixia Li

    Full Text Available (Prorenin receptor (PRR expression is upregulated in diabetes. We hypothesized that PRR contributes to podocyte injury via activation of Wnt-β-catenin-snail signaling pathway. Mouse podocytes were cultured in normal (5 mM or high (25 mM D-glucose for 3 days. Compared to normal glucose, high glucose significantly decreased mRNA and protein expressions of podocin and nephrin, and increased mRNA and protein expressions of PRR, Wnt3a, β-catenin, and snail, respectively. Confocal microscopy studies showed significant reduction in expression and reorganization of podocyte cytoskeleton protein, F-actin, in response to high glucose. Transwell functional permeability studies demonstrated significant increase in albumin flux through podocytes monolayer with high glucose. Cells treated with high glucose and PRR siRNA demonstrated significantly attenuated mRNA and protein expressions of PRR, Wnt3a, β-catenin, and snail; enhanced expressions of podocin mRNA and protein, improved expression and reorganization of F-actin, and reduced transwell albumin flux. We conclude that high glucose induces podocyte injury via PRR-Wnt-β-catenin-snail signaling pathway.

  16. Cavitationally induced biodegradability enhancement of a distillery wastewater.

    Science.gov (United States)

    Padoley, K V; Saharan, Virendra Kumar; Mudliar, S N; Pandey, R A; Pandit, Aniruddha B

    2012-06-15

    Hydrodynamic cavitation (HC) was evaluated as a pretreatment option for the complex/recalcitrant biomethanated distillery wastewater (B-DWW). The effect of various process parameters such as inlet pressure, dilution and reaction time on reduction of COD/TOC and enhancement of biodegradability index (BI:BOD(5):COD ratio) of the B-DWW was studied with an aim to maximize the biodegradability index and reducing the toxicity of the distillery wastewater. It was observed that higher operating pressure (13 bar) yielded the maximum BI whereas the lower pressure (5 bar) is suitable for the reduction in the toxicity of B-DWW. The toxicity of the distillery wastewater was analyzed by measuring the COD, TOC and color of the wastewater sample. The HC pretreatment under optimized conditions leads to a BI of 0.32, COD and TOC reduction of 32.24% and 31.43%, respectively along with a color reduction by 48%. These results indicate the potential of HC as a pretreatment option for enhancing the biodegradability index of the recalcitrant wastewater such as B-DWW along with reduced toxicity of wastewater as observed from COD, TOC and color reduction profile under optimized conditions.

  17. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of β-2 Microglobulin Levels

    OpenAIRE

    Fujisawa, Naoaki; Oya, Soichi; Mori, Harushi; Matsui, Toru

    2015-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of β-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to expe...

  18. ADDITIVE-INDUCED ENHANCEMENT OF OPTICAL CLARITY OF POLYACRYLAMIDE HYDROGEL

    Institute of Scientific and Technical Information of China (English)

    Jeffery Franklin; Zhi Yuan Wang

    2003-01-01

    The aqueous polymerization of acrylamide and crosslinking with N,N-methylenebisacrylamide afforded hydrogels displaying high levels of light scattering (poor optical clarity). Enhancement of the optical clarity within a polyacrylamide (PAm) hydrogel was accomplished through the implementation of"refractive index matching", Water-soluble additives were utilised to better match the refractive index inhomogeneities throughout a given hydrogel. This resulted in lower light scattering within the system and hence improved clarity. Amino acids, sugars, polymers, and other water-soluble additives such as glycerol were investigated by this methodology. Most additives investigated displayed potential for effectively reducing the light scattering within a PAm hydrogel as a function of increased additive concentration. On increasing the refractive index of the water medium, the overall refractive index of a PAm hydrogel was also observed to increase. This provided a quantitative means of determining the effectiveness of a given additive for improving the optical clarity within a hydrogel.

  19. Large-Eddy Simulations of Flapping-Induced Lift Enhancement

    Science.gov (United States)

    Franck, Jennifer; Swartz, Sharon; Breuer, Kenneth

    2011-11-01

    This work isolates the heaving motion of flapping flight in order to numerically investigate the fluid-structure interaction at Reynolds numbers relevant to birds and bats. Although there has been much focus on insect flight, larger vertebrates fly at a higher Reynolds number, which leads to different dynamics in terms of flow separation, reattachment, and high-lift mechanisms. In this work, an incompressible large-eddy simulation is used to simulate the periodic heaving of a flat plate at various angles of attack. It is found that the heaving motion can increase the average lift when compared with the steady flow, more so than is expected from the relative angle of attack. The additional lift is attributed to the vortex dynamics at the leading edge. The lift enhancement and flow features are compared with experimental results.

  20. Photon drag enhancement by a slow-light moving medium via electromagnetically-induced transparency amplification

    Science.gov (United States)

    Iqbal, Azmat; Khan, Naveed; Bacha, Bakht Amin; Rahman, Amin Ur; Ahmad, Afaq

    2017-09-01

    Recently, a considerable enhancement has been observed in the celebrated Fresnel-Fizeau light drag by innovative experimental and theoretical approaches because of its fundamental and practical interest in the emerging technology of quantum optics and photonics. We present a semiclassical density matrix approach on the demonstration of light drag in a slow-light moving medium comprising five-level single tripod atomic configuration. To accomplish this, we introduce Kerr-type nonlinearity that leads to electromagnetically-induced transparency amplification under resonance conditions. By switching ON Kerr-type nonlinearity effect, we observe a prominent transparency window in probe field's absorption spectrum whose width and amplitude can be controlled further by the intensity of Kerr field and control field. The incorporation of Kerr field also switches light propagation from superluminal to subluminal domain. We predict a significant enhancement both in the lateral and the rotary photon drag owing to drag of light linear polarization state subjected to translation and rotation of the host medium, respectively. Consistent with earlier results, light drag considerably depends on both transverse and angular velocity of the host medium. In regime of subluminal propagation, light polarization state drags along the medium motion while in the superluminal propagation region it drags opposite to the medium motion.

  1. Light-Induced Conversion of Chemical Permeability to Enhance Electron and Molecular Transfer in Nanoscale Assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Balgley, Renata; de Ruiter, Graham; Evmenenko, Guennadi; Bendikov, Tatyana; Lahav, Michal; van der Boom, Milko E.

    2016-12-21

    In this paper, we demonstrate how photochemically enhancing the permeability of metal–organic assemblies results in a significant enhancement of the electrochemical activity of metal complexes located within the assembly. The molecular assemblies consist of different layers of redox-active metal complexes ([M(mbpy-py)3][PF6]2; M = Ru or Os) that are separated by redox-inactive spacers consisting of 1,4-bis[2-(4-pyridyl)ethenyl]benzene (BPEB) and PdCl2 of variable thicknesses (0–13.4 nm). UV-irradiation (λ = 254 nm) of our assemblies induces a photochemical reaction in the redox-inactive spacer increasing the permeability of the assembly. The observed increase was evident by trapping organic (nBu4NBF4) and inorganic (NiCl2) salts inside the assemblies, and by evaluating the electrochemical response of quinones absorbed inside the molecular assemblies before and after UV irradiation. The increase in permeability is reflected by higher currents and a change in the directionality of electron transfer, i.e., from mono- to bidirectional, between the redox-active metal complexes and the electrode surface. The supramolecular structure of the assemblies dominates the overall electron transfer properties and overrules possible electron transfer mediated by the extensive π-conjugation of its individual organic components.

  2. 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.

  3. 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

  4. Noise induced enhancement of network reciprocity in social dilemmas

    CERN Document Server

    Zhang, Gui-Qing; Wang, Lin

    2013-01-01

    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 a 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.

  5. Cardiovascular responses induced by obstructive apnea are enhanced in hypertensive rats due to enhanced chemoreceptor responsivity.

    Directory of Open Access Journals (Sweden)

    Juliana M M Angheben

    Full Text Available Spontaneously hypertensive rats (SHR, like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. The effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY. Blood pressure increased by 57±3 mmHg during apnea in SHR and by 28±3 mmHg in WKY (p<0.05, n = 14/13. The respiratory effort increased by 53±6 mmHg in SHR and by 34±5 mmHg in WKY. The heart rate fell by 209±19 bpm in SHR and by 155±16 bpm in WKY. The carotid chemoreceptors were then inactivated by the ligation of the carotid body artery, and apneas were induced two days later. The inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. The apnea-induced hypertension was 11±4 mmHg in SHR and 8±4 mmHg in WKY. The respiratory effort was 15±2 mmHg in SHR and 15±2 mmHg in WKY. The heart rate fell 63±18 bpm in SHR and 52±14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. In conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea.

  6. 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.

  7. 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.

  8. Inducible DNA - protein interactions of the murine kappa immunoglobulin enhancer in intact cells: comparison with in vitro interactions

    Energy Technology Data Exchange (ETDEWEB)

    Hromas, R.; Pauli, U.; Marcuzzi, A.; Lafrenz, D.; Nick, H.; Stein, J.; Stein, G.; Ness, B.V.

    1988-02-11

    The large intron of the kappa immunoglobulin gene contains a cis-acting enhancer element, which is important in the tissue-specific expressions of the gene. The authors have confirmed the binding activity of a sequence-specific factor present in lymphoid extracts derived from cell lines expressing, or induced to express, the kappa gene. They have extended these studies to show the binding activity is present in normal activated splenic B cells as well as lambda producing cells, and have demonstrated by DNAse footprint analysis full, protection of a sequence containing the 11 bp homology to the SV-40 core enhancer. They have compared these in vitro binding studies with an analysis of protein-DNA interactions in intact murine cell lines using genomic sequencing techniques. They demonstrate significant alterations in DMS reactivity of DNA in the murine 70Z/3 cell line after it is induced to kappa expression. These alterations occur at guanine residues which are part of the 11 bp core sequence, and are identical to those observed in cells constitutively expressing kappa. This provides direct evidence for the induced binding of the tissue specific factor to intact chromatin. In intact chromatin they also observed significant alteration in the reactivity of a guanine, 3' of the core sequence, which is part of a potential secondary DNA structure, and protection of four residues that are part of a region homologous to the heavy chain enhancer.

  9. Inducible DNA-protein interactions of the murine kappa immunoglobulin enhancer in intact cells: comparison with in vitro interactions.

    Science.gov (United States)

    Hromas, R; Pauli, U; Marcuzzi, A; Lafrenz, D; Nick, H; Stein, J; Stein, G; Van Ness, B

    1988-01-01

    The large intron of the kappa immunoglobulin gene contains a cis-acting enhancer element, which is important in the tissue-specific expression of the gene. We have confirmed the binding activity of a sequence-specific factor present in lymphoid extracts derived from cell lines expressing, or induced to express, the kappa gene. We have extended these studies to show the binding activity is present in normal activated splenic B cells as well as lambda producing cells, and have demonstrated by DNAse footprint analysis full protection of a sequence containing the 11 bp homology to the SV-40 core enhancer. We have compared these in vitro binding studies with an analysis of protein-DNA interactions in intact murine cell lines using genomic sequencing techniques. We demonstrate significant alterations in DMS reactivity of DNA in the murine 70Z/3 cell line after it is induced to kappa expression. These alterations occur at guanine residues which are part of the the 11 bp core sequence, and are identical to those observed in cells constitutively expressing kappa. This provides direct evidence for the induced binding of the tissue specific factor to intact chromatin. In intact chromatin we also observed significant alteration in the reactivity of a guanine, 3' of the core sequence, which is part of a potential secondary DNA structure, and protection of four residues that are part of a region homologous to the heavy chain enhancer. Images PMID:2830597

  10. Ghrelin enhances glucose-induced insulin secretion in scheduled meal-fed sheep.

    Science.gov (United States)

    Takahashi, H; Kurose, Y; Kobayashi, S; Sugino, T; Kojima, M; Kangawa, K; Hasegawa, Y; Terashima, Y

    2006-04-01

    The purpose of this study was to investigate the effects of physiologic levels of ghrelin on insulin secretion and insulin sensitivity (glucose disposal) in scheduled fed-sheep, using the hyperglycemic clamp and hyperinsulinemic euglycemic clamp respectively. Twelve castrated Suffolk rams (69.8 +/- 0.6 kg) were conditioned to be fed alfalfa hay cubes (2% of body weight) once a day. Three hours after the feeding, synthetic ovine ghrelin was intravenously administered to the animals at a rate of 0.025 and 0.05 mug/kg body weight (BW) per min for 3 h. Concomitantly, the hyperglycemic clamp or the hyperinsulinemic euglycemic clamp was carried out. In the hyperglycemic clamp, a target glucose concentration was clamped at 100 mg/100 ml above the initial level. In the hyperinsulinemic euglycemic clamp, insulin was intravenously administered to the animals for 3 h at a rate of 2 mU/kg BW per min. Basal glucose concentrations (44+/- 1 mg/dl) were maintained by variably infusing 100 mg/dl glucose solution. In both clamps, plasma ghrelin concentrations were dose-dependently elevated and maintained at a constant level within the physiologic range. Ghrelin infusions induced a significant (ANOVA; P ghrelin-infused animals. In the hyperinsulinemic euglycemic clamp, glucose infusion rate, an index of insulin sensitivity, was not affected by ghrelin infusion. In conclusion, the present study has demonstrated for the first time that ghrelin enhances glucose-induced insulin secretion in the ruminant animal.

  11. Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy.

    Science.gov (United States)

    Hong, Zai-Fa; Zhao, Wen-Xiu; Yin, Zhen-Yu; Xie, Cheng-Rong; Xu, Ya-Ping; Chi, Xiao-Qin; Zhang, Sheng; Wang, Xiao-Min

    2015-01-01

    Cholangiocarcinoma (CCA), a devastating cancer with a poor prognosis, is resistant to the currently available chemotherapeutic agents. Capsaicin, the major pungent ingredient found in hot red chili peppers of the genus Capsicum, suppresses the growth of several malignant cell lines. Our aims were to investigate the role and mechanism of capsaicin with respect to the sensitivity of CCA cells to chemotherapeutic agents. The effect of capsaicin on CCA tumor sensitivity to 5-fluorouracil (5-FU) was assessed in vitro in CCA cells and in vivo in a xenograft model. The drug sensitivity of QBC939 to 5-FU was significantly enhanced by capsaicin compared with either agent alone. In addition, the combination of capsaicin with 5-FU was synergistic, with a combination index (CI) capsaicin. Moreover, the decrease in AKT and S6 phosphorylation induced by 5-FU was effectively reversed by capsaicin, indicating that capsaicin inhibits 5-FU-induced autophagy by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in CCA cells. Taken together, these results demonstrate that capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.

  12. Memory modulation in the classroom: selective enhancement of college examination performance by arousal induced after lecture.

    Science.gov (United States)

    Nielson, Kristy A; Arentsen, Timothy J

    2012-07-01

    Laboratory studies examining moderate physiological or emotional arousal induced after learning indicate that it enhances memory consolidation. Yet, no studies have yet examined this effect in an applied context. As such, arousal was induced after a college lecture and its selective effects were examined on later exam performance. Participants were divided into two groups who either watched a neutral video clip (n=66) or an arousing video clip (n=70) after lecture in a psychology course. The final examination occurred two weeks after the experimental manipulation. Only performance on the group of final exam items that covered material from the manipulated lecture were significantly different between groups. Other metrics, such as the midterm examination and the total final examination score, did not differ between groups. The results indicate that post-lecture arousal selectively increased the later retrieval of lecture material, despite the availability of the material for study before and after the manipulation. The results reinforce the role of post-learning arousal on memory consolidation processes, expanding the literature to include a real-world learning context. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Enhanced Expression of Aquaporin-9 in Rat Brain Edema Induced by Bacterial Lipopolysaccharides

    Institute of Scientific and Technical Information of China (English)

    Huaili WANG; Runming JIN; Peichao TIAN; Zhihong ZHUO

    2009-01-01

    To investigate the role of AQP9 in brain edema,the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide (LPS) was examined.Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals.Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection,with maximum value appearing at 12 h,which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals.The further correlation analysis revealed strong positive correlations among the brain water content,the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals.These results suggested that the regulation of AQP9 expression may play important roles in water movement and in brain metabolic homeostasis associated with the pathophysiology of brain edema induced by LPS injection.

  14. Enhanced two-photon emission in coupled metal nanoparticles induced by conjugated polymers.

    Science.gov (United States)

    Guan, Zhenping; Polavarapu, Lakshminarayana; Xu, Qing-Hua

    2010-12-01

    Interactions between noble metal (Ag and Au) nanoparticles and conjugated polymers as well as their one- and two-photon emission have been investigated. Ag and Au nanoparticles exhibited extraordinary quenching effects on the fluorescence of cationic poly(fluorinephenylene). The quenching efficiency by 37-nm Ag nanoparticles is ∼19 times more efficient than that by 13-nm Au nanoparticles, and 9-10 orders of magnitude more efficient than typical small molecule dye-quencher pairs. On the other hand, the cationic conjugated polymers induce the aggregate formation and plasmonic coupling of the metal nanoparticles, as evidenced by transmission electron microscopy images and appearance of a new longitudinal plasmon band in the near-infrared region. The two-photon emissions of Ag and Au nanoparticles were found to be significantly enhanced upon addition of conjugated polymers, by a factor of 51-times and 9-times compared to the isolated nanoparticles for Ag and Au, respectively. These studies could be further extended to the applications of two-photon imaging and sensing of the analytes that can induce formation of metal nanoparticle aggregates, which have many advantages over the conventional one-photon counterparts.

  15. 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.

  16. INVESTIGATION OF THROMBOMODULIN AND PLASMINOGEN ACTIVATOR INHIBITOR TYPE-I IN PREGNANCY INDUCED HYPERTENSION AND ITS CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    马水清; 白春梅; 边旭明

    2001-01-01

    Objective. To measure tbe circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type-Ⅰ(PAI-I) in women with pregnancy induced hypertension (PIH).``Methods. Blood samples were drawn from 97 pregnant women in their third trimester, grouped as 25 mild PIH, 26 moderate PIH, 22 severe PIH and 24 normotensive healthy pregnant women for determining levels of TM by ELISA, PAI-I by colorimetric assay methods, and creatinine (Cr) in serum by biochemical method.``Results. Circulating levels of TM, PAId and TM/Cr ratio increased with increasing severity of PIH. There were no significant differences between mild and normotensive pregnant women. The parameters were significantly changed in the moderate and severe PIH groups.``Conclv, sion. TM and PAI-Ⅰ may serve as meaningful clinical markers for the assessment of the endothelial damage in PIH,which is very important in evaluating and following the development of PIH.

  17. INVESTIGATION OF THROMBOMODULIN AND PLASMINOGEN ACTIVATOR INHIBITOR TYPE-I IN PREGNANCY INDUCED HYPERTENSION AND ITS CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    马水清; 白春梅; 边旭明

    2001-01-01

    Objective. To measure the circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type-I (PAI-I) inwomen with pregnancy induced hypertension (PIH). Methods. Blood samples were drawn from 97 pregnant women in their third trimester, grouped as 25 mild PIH, 26 moderate PIH, 22 severe PIH and 24 normotensive healthy pregnant women for determining levels of TM by ELISA, PAI-I by colorimetric assay methods, and creatinine (Cr) in serum by biochemical method. Results. Circulating levels of TM, PAI-I and TM/Cr ratio increased with increasing severity of PIH. There were no significant differences between mild and normotensive pregnant women. The parameters were significantly changed in the moderate and severe PIH groups. Conclusion. TM and PAI-I may serve as meaningful clinical markers for the assessment of the endothelial damage in PIH,which is very important in evaluating and following the development of PIH.

  18. Expression and clinical significance of CD73 and hypoxia-inducible factor-1α in gastric carcinoma.

    Science.gov (United States)

    Lu, Xiao-Xia; Chen, Yi-Tian; Feng, Bing; Mao, Xiao-Bei; Yu, Bo; Chu, Xiao-Yuan

    2013-03-28

    To investigate the expression of CD73 and hypoxia-inducible factor-1α (HIF-1α) in human gastric carcinoma, and explore their clinical significance and prognostic value. CD73 and HIF-1α expressions were detected by immunohistochemistry in consecutive sections of tissue samples from 68 gastric carcinoma patients. The peritumor tissues 2 cm away from the tumor were obtained and served as controls. The presence of CD73 and HIF-1α was analyzed by immunohistochemistry using the Envision technique. CD73 and HIF-1α expressions in gastric carcinoma were significantly higher than those in gastric mucosal tissues as control (P gastric carcinoma by both multivariate Cox regression analysis (P = 0.021) and receiver operating characteristic curves (P = 0.001). CD73 expression correlates closely with HIF-1α expression in gastric carcinoma. CD73 could be an independent prognostic indicator for gastric carcinoma.

  19. Residual force enhancement following eccentric induced muscle damage.

    Science.gov (United States)

    Power, Geoffrey A; Rice, Charles L; Vandervoort, Anthony A

    2012-06-26

    During lengthening of an activated skeletal muscle, the force maintained following the stretch is greater than the isometric force at the same muscle length. This is termed residual force enhancement (RFE), but it is unknown how muscle damage following repeated eccentric contractions affects RFE. Using the dorsiflexors, we hypothesised muscle damage will impair the force generating sarcomeric structures leading to a reduction in RFE. Following reference maximal voluntary isometric contractions (MVC) in 8 young men (26.5±2.8y) a stretch was performed at 30°/s over a 30° ankle excursion ending at the same muscle length as the reference MVCs (30° plantar flexion). Surface electromyography (EMG) of the tibialis anterior and soleus muscles was recorded during all tasks. The damage protocol involved 4 sets of 25 isokinetic (30°/s) lengthening contractions. The same measures were collected at baseline and immediately post lengthening contractions, and for up to 10min recovery. Following the lengthening contraction task, there was a 30.3±6.4% decrease in eccentric torque (Pmuscle damage (Pmuscle function compared to isometric actions succeeding damage. Thus, active force of cross-bridges is decreased because of impaired excitation-contraction coupling but force generated during stretch remains intact because force contribution from stretched sarcomeric structures is less impaired.

  20. Lipopolysaccharide-induced biliary factors enhance invasion of Salmonella enteritidis in a rat model.

    Science.gov (United States)

    Islam, A F; Moss, N D; Dai, Y; Smith, M S; Collins, A M; Jackson, G D

    2000-01-01

    In this study, the role of the hepatobiliary system in the early pathogenesis of Salmonella enteritidis infection was investigated in a rat model. Intravenous (i.v.) challenge with lipopolysaccharide (LPS) has previously been shown to enhance the translocation of normal gut flora. We first confirmed that LPS can similarly promote the invasion of S. enteritidis. Oral infection of outbred Australian Albino Wistar rats with 10(6) to 10(7) CFU of S. enteritidis led to widespread tissue invasion after days. If animals were similarly challenged after intravenous administration of S. enteritidis LPS (3 to 900 microg/kg of body weight), significant invasion of the livers and mesenteric lymph nodes (MLN) occurred within 24 h, with invasion of the liver increasing in a dose-dependent fashion (P < 0.01). If bile was prevented from reaching the intestine by bile duct ligation or cannulation, bacterial invasion of the liver and MLN was almost totally abrogated (P < 0.001). As i.v. challenge with LPS could induce the delivery of inflammatory mediators into the bile, biliary tumor necrosis factor alpha (TNF-alpha) concentrations were measured by bioassay. Biliary concentrations of TNF-alpha rose shortly after LPS challenge, peaked with a mean concentration of 27.0 ng/ml at around 1 h postchallenge, and returned to baseline levels (3.1 ng/ml) after 2.5 h. Although TNF-alpha cannot be directly implicated in the invasion process, we conclude that the invasiveness of the enteric pathogen S. enteritidis is enhanced by the presence of LPS in the blood and that this enhanced invasion is at least in part a consequence of the delivery of inflammatory mediators to the gastrointestinal tract by the hepatobiliary system.

  1. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of β-2 Microglobulin Levels.

    Science.gov (United States)

    Fujisawa, Naoaki; Oya, Soichi; Mori, Harushi; Matsui, Toru

    2015-11-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of β-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to experience numbness in all fingers of his left hand one year ago, which gradually extended to his body trunk and legs on both sides. Magnetic resonance imaging demonstrated numerous small enhancing spots scattered in his brain and spinal cord. CSF levels of β-2 microglobulin were elevated; although this often indicates central nervous system involvement in leukemia and lymphoma, the lesions were diagnosed as CLIPPERS based on the pathological findings from a biopsy specimen. We emphasize the importance of biopsy to differentiate between CLIPPERS and malignant lymphoma because the temporary radiological response to steroid might be the same in both diseases but the treatment strategies regarding the use of steroid are quite different.

  2. Distribution of late gadolinium enhancement in various types of cardiomyopathies:Significance in differential diagnosis, clinical features and prognosis

    Institute of Scientific and Technical Information of China (English)

    Hiroshi; Satoh; Makoto; Sano; Kenichiro; Suwa; Takeji; Saitoh; Mamoru; Nobuhara; Masao; Saotome; Tsuyoshi; Urushida; Hideki; Katoh; Hideharu; Hayashi

    2014-01-01

    The recent development of cardiac magnetic resonance(CMR)techniques has allowed detailed analyses of cardiac function and tissue characterization with high spatial resolution.We review characteristic CMR features in ischemic and non-ischemic cardiomyopathies(ICM and NICM),especially in terms of the location and distribution of late gadolinium enhancement(LGE).CMR in ICM shows segmental wall motion abnormalities or wall thinning in a particular coronary arterial territory,and the subendocardial or transmural LGE.LGE in NICM generally does not correspond to any particular coronary artery distribution and is located mostly in the mid-wall to subepicardial layer.The analysis of LGE distribution is valuable to differentiate NICM with diffusely impaired systolic function,including dilated cardiomyopathy,end-stage hypertrophic cardiomyopathy(HCM),cardiac sarcoidosis,and myocarditis,and those with diffuse left ventricular(LV)hypertrophy including HCM,cardiac amyloidosis and Anderson-Fabry disease.A transient low signal intensity LGE in regions of severe LV dysfunction is a particular feature of stress cardiomyopathy.In arrhythmogenic right ventricular cardiomyopathy/dysplasia,an enhancement of right ventricular(RV)wall with functional and morphological changes of RV becomes apparent.Finally,the analyses of LGE distribution have potentials to predict cardiac outcomes and response to treatments.

  3. 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.

  4. Fatty acid synthase as a factor required for exercise-induced cognitive enhancement and dentate gyrus cellular proliferation.

    Science.gov (United States)

    Chorna, Nataliya E; Santos-Soto, Iván J; Carballeira, Nestor M; Morales, Joan L; de la Nuez, Janneliz; Cátala-Valentin, Alma; Chornyy, Anatoliy P; Vázquez-Montes, Adrinel; De Ortiz, Sandra Peña

    2013-01-01

    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.

  5. 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.

  6. Implantation induced extended defects and transient enhanced diffusion in silicon

    Energy Technology Data Exchange (ETDEWEB)

    Chen, J.; Liu, J.; Listebarger, J.; Krishnamoorthy, W.; Zhang, L.; Jones, K.S. [Univ. of Florida, Gainesville, FL (United States)

    1995-08-01

    Transient enhanced diffusion (TED) of dopant in silicon caused by point defects during annealing of implanted. Si has become one of the essential concerns in miniaturization of silicon device technology. In order to control and minimize the TED effect, a fundamental understanding of the evolution of the point defects upon annealing and the interaction between point defects and extended defects and their effects on dopant diffusion is necessary. Our studies were carried out by two parts; (1) For understanding the evolution of <311> and <110> defects, B{sup +} and Si{sup +} implantation at energies (from 5 keV to 40 keV) and doses in the range from 5 x 10{sup 12} to 1 x 10{sup 14}/cm{sup 2} were used. The annealing kinetics were investigated using a N{sub 2} ambient with temperatures for time ranging from 500{degrees}C to 1100{degrees}C for time ranging from 3 min to 3 hours. A matrix of implant energy vs. dose on formation threshold of <311> and <110> defect, interstitials napped and dissolved condition were obtained. (2) For Understanding the interaction between Type II dislocation loop and point defect a B doped buried marker layer was used. The oxidation of silicon surface used as a interstitials injection source and a buried type II loop layer as a point defect detector used to quantify the flux of interstitials injected. Combining the flux measured by loops and dopant diffusion the D{sub I} C{sub I} was determined. The diffusion limited kinetics was concluded. The TED from <311> and EOR (End of Range) <110> defect was studied using 8keV B{sup +} implanted Si to a dose of the le14 and 190keV Ge{sub +} implanted to a dose of le15. Subsequent anneals are done for 5 min and 30 min, respectively, These defects affect dopant diffusion by trapping and releasing point defects.

  7. Significant decrease in thermal conductivity of multi-walled carbon nanotube induced by inter-wall van der Waals interactions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xue; Zhou, Wu-Xing, E-mail: wuxingzhou@hnu.edu.cn; Chen, Xue-Kun; Liu, Yue-Yang; Chen, Ke-Qiu, E-mail: keqiuchen@hnu.edu.cn

    2016-05-06

    The thermal transport properties of multi-walled carbon nanotubes (MWCNTs) were investigated by using non-equilibrium molecular dynamics simulation. The results show that the thermal conductivity of MWCNTs decreases significantly comparing to that of single-walled carbon nanotubes (SWCNTs) due to the inter-wall van der Waals interactions. The more interesting is a fact that the thermal conductance of MWCNTs is significantly greater than the thermal conductance summation of each SWCNTs. This is because the thermal conductance of a carbon nanotube protected by an outer tube is much larger than that of one that is not protected. Moreover, we also studied the thermal flux distribution of MWCNTs, and found that the outer tube plays a dominant role in heat energy transfer. - Highlights: • Significant decrease in thermal conductivity of multi-walled carbon nanotube induced by inter-wall interactions. • The thermal conductivity of the inner tube is increased significantly due to protected by outer tube. • The outer tube plays a dominant role in heat energy transfer in multi-walled carbon nanotube.

  8. High Glucose Enhances Isoflurane-Induced Neurotoxicity by Regulating TRPC-Dependent Calcium Influx.

    Science.gov (United States)

    Liu, ZhongJie; Ma, ChangQing; Zhao, Wei; Zhang, QingGuo; Xu, Rui; Zhang, HongFei; Lei, HongYi; Xu, ShiYuan

    2017-01-06

    Isoflurane is a commonly used inhalational anesthetic that can induce neurotoxicity via elevating cytosolic calcium (Ca(2+)). High glucose regulates the expression of a family of non-selective cation channels termed transient receptor potential canonical (TRPC) channels that may contribute to Ca(2+) influx. In the present study, we investigated whether high glucose enhances isoflurane-induced neurotoxicity by regulating TRPC-dependent Ca(2+) influx. First, we evaluated toxic damage in mice primary cultured hippocampal neurons and human neuroblastoma cells (SH-SY5Y cells) after hyperglycemia and isoflurane exposure. Next, we investigated cytosolic Ca(2+) concentrations, TRPC mRNA expression levels and tested the effect of the TRPC channel blocker SKF96365 on cytosolic Ca(2+) levels in cells treated with high glucose or/and isoflurane. Finally, we employed knocked down TRPC6 to demonstrate the role of TRPC in high glucose-mediated enhancement of isoflurane-induced neurotoxicity. The results showed that high glucose could enhance isoflurane-induecd toxic damage in primary hippocampal neurons and SH-SY5Y cells. High glucose enhanced the isoflurane-induced increase of cytosolic Ca(2+) in SH-SY5Y cells. High glucose elevated TRPC mRNA expression, especially that of TRPC6. SKF96365 and knock down of TRPC6 were able to inhibit the high glucose-induced increase of cytosolic Ca(2+) and decrease isoflurane-induced neurotoxicity in SH-SY5Y cells cultured with high glucose. Our findings indicate that high glucose could elevate TRPC expression, thus increasing Ca(2+) influx and enhancing isoflurane-induced neurotoxicity.

  9. Growth Enhancement of Radish Sprouts Induced by Low Pressure O2 Radio Frequency Discharge Plasma Irradiation

    Science.gov (United States)

    Kitazaki, Satoshi; Koga, Kazunori; Shiratani, Masaharu; Hayashi, Nobuya

    2012-01-01

    We studied growth enhancement of radish sprouts (Raphanus sativus L.) induced by low pressure O2 radio frequency (RF) discharge plasma irradiation. The average length of radish sprouts cultivated for 7 days after O2 plasma irradiation is 30-60% greater than that without irradiation. O2 plasma irradiation does not affect seed germination. The experimental results reveal that oxygen related radicals strongly enhance growth, whereas ions and photons do not.

  10. Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy.

    Directory of Open Access Journals (Sweden)

    Zai-Fa Hong

    Full Text Available Cholangiocarcinoma (CCA, a devastating cancer with a poor prognosis, is resistant to the currently available chemotherapeutic agents. Capsaicin, the major pungent ingredient found in hot red chili peppers of the genus Capsicum, suppresses the growth of several malignant cell lines. Our aims were to investigate the role and mechanism of capsaicin with respect to the sensitivity of CCA cells to chemotherapeutic agents. The effect of capsaicin on CCA tumor sensitivity to 5-fluorouracil (5-FU was assessed in vitro in CCA cells and in vivo in a xenograft model. The drug sensitivity of QBC939 to 5-FU was significantly enhanced by capsaicin compared with either agent alone. In addition, the combination of capsaicin with 5-FU was synergistic, with a combination index (CI < 1, and the combined treatment also suppressed tumor growth in the CCA xenograft to a greater extent than 5-FU alone. Further investigation revealed that the autophagy induced by 5-FU was inhibited by capsaicin. Moreover, the decrease in AKT and S6 phosphorylation induced by 5-FU was effectively reversed by capsaicin, indicating that capsaicin inhibits 5-FU-induced autophagy by activating the phosphoinositide 3-kinase (PI3K/protein kinase B (AKT/mammalian target of rapamycin (mTOR pathway in CCA cells. Taken together, these results demonstrate that capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.

  11. Significance of Cystatin C for Early Diagnosis of Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography.

    Science.gov (United States)

    Wang, Mian; Zhang, Li; Yue, Rongzheng; You, Guiying; Zeng, Rui

    2016-08-22

    BACKGROUND Contrast-induced nephropathy is acute kidney injury caused by contrast medium exposure. Serum creatinine is the clinical diagnostic standard, but it does not yield quick results. The serum level of cystatin C is stable and it can reflect renal function sensitively. The study aimed to assess the usefulness of cystatin C for early diagnosis of contrast-induced nephropathy in patients undergoing coronary angiography. MATERIAL AND METHODS We included 300 patients who underwent CAG. According to the sCr at 48 h, patients were divided into 2 groups: CIN group and non-CIN group. Their demographics and basal renal function were recorded. Changes in sCr, Cys C, and e GFR were compared at the same time. ROC analysis was used to assess the sensitivity and specificity of Cys C in the early diagnosis of CIN. RESULTS Comparison of basal renal function and serum level of Cys C showed no significant differences between the 2 groups. Serum level of Cys C increased significantly at 24 h (p<0.001), and sCr increased significantly at 48 h. ROC analysis showed that the AUC of the change in Cys C between baseline and 24 h was 0.936 (95% CI: 0.879-0.992, p=0.000) and the optimum cut-off level was 0.26 mg/L (sensitivity=89.7% and specificity=95.6%). CONCLUSIONS The concentration change of Cys C is better than sCr as a biomarker in the early detection of CIN.

  12. Trehalose enhances osmotic tolerance and suppresses lysophosphatidylcholine-induced acrosome reaction in ram spermatozoon.

    Science.gov (United States)

    Ahmad, E; Naseer, Z; Aksoy, M; Küçük, N; Uçan, U; Serin, I; Ceylan, A

    2015-09-01

    This study was aimed to investigate the influence of trehalose on osmotic tolerance and the ability of ram spermatozoon to undergo acrosome reaction induced by lysophosphatidylcholine (LPC). In experiment 1, the diluted ejaculates were exposed to anisosmotic fructose solutions (70, 500, 750 and 1000 mOsm l(-1) ) with or without 50 mm trehalose. The presence of trehalose in hyperosmotic conditions enhanced (P ram spermatozoon and suppresses their ability to undergo LPC and cryo-induced acrosome reaction.

  13. 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.

  14. Taxifolin enhances andrographolide-induced mitotic arrest and apoptosis in human prostate cancer cells via spindle assembly checkpoint activation.

    Science.gov (United States)

    Zhang, Zhong Rong; Al Zaharna, Mazen; 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.

  15. The enhanced anticoagulation for graphene induced by COOH(+) ion implantation.

    Science.gov (United States)

    Liu, Xiaoqi; Cao, Ye; Zhao, Mengli; Deng, Jianhua; Li, Xifei; Li, Dejun

    2015-01-01

    Graphene may have attractive properties for some biomedical applications, but its potential adverse biological effects, in particular, possible modulation when it comes in contact with blood, require further investigation. Little is known about the influence of exposure to COOH(+)-implanted graphene (COOH(+)/graphene) interacting with red blood cells and platelets. In this paper, COOH(+)/graphene was prepared by modified Hummers' method and implanted by COOH(+) ions. The structure and surface chemical and physical properties of COOH(+)/graphene were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement. Systematic evaluation of anticoagulation, including in vitro platelet adhesion assays and hemolytic assays, proved that COOH(+)/graphene has significant anticoagulation. In addition, at the dose of 5 × 10(17) ions/cm(2), COOH(+)/graphene responded best on platelet adhesion, aggregation, and platelet activation.

  16. Chronic ethanol feeding promotes azoxymethane and dextran sulfate sodium-induced colonic tumorigenesis potentially by enhancing mucosal inflammation.

    Science.gov (United States)

    Shukla, Pradeep K; Chaudhry, Kamaljit K; Mir, Hina; Gangwar, Ruchika; Yadav, Nikki; Manda, Bhargavi; Meena, Avtar S; Rao, RadhaKrishna

    2016-03-07

    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.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Hans Rempel

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

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

    Science.gov (United States)

    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.

  20. 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

  1. A novel multi-stage subunit vaccine against paratuberculosis induces significant immunity and reduces bacterial burden in tissues (P4304)

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Aagaard, Claus; Riber, Ulla;

    2013-01-01

    Effective control of paratuberculosis is hindered by lack of a vaccine preventing infection, transmission and without diagnostic interference with tuberculosis. We have developed a novel multi-stage recombinant subunit vaccine in which a fusion of four early expressed MAP antigens is combined...... with a MAP protein expressed in latent infection (FET11 vaccine). FET11 vaccine proteins were formulated with CAF01 adjuvant and injected to MAP challenged calves at two different ages. 28 calves divided into two FET11 vaccine groups, a commercial vaccine and a control group were used in the study...... and followed for a year. The FET11 vaccine induced a significant T cell response against constituent vaccine proteins characterized by a high percentage of CD4+ T cells and participation of polyfunctional CD4+ T cells. Of the two different age groups, late FET11 vaccination conferred protective immunity...

  2. Clinically significant and practical! Enhancing precision does make a difference. Reply to McGlinchey and Jacobson, Hsu, and Speer

    NARCIS (Netherlands)

    Hageman, WJJM; Arrindell, WA

    1999-01-01

    Based on a secondary analysis of the Jacobson and Truax [Jacobson, N.S. & Truax, P. (1991). Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology, 59, 12-19.] data using both their own traditional approach

  3. Clinically significant and practical! Enhancing precision does make a difference. Reply to McGlinchey and Jacobson, Hsu, and Speer

    NARCIS (Netherlands)

    Hageman, WJJM; Arrindell, WA

    1999-01-01

    Based on a secondary analysis of the Jacobson and Truax [Jacobson, N.S. & Truax, P. (1991). Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology, 59, 12-19.] data using both their own traditional approach

  4. Significantly enhanced hydrogen desorption properties of Mg(AlH42 nanoparticles synthesized using solvent free strategy

    Directory of Open Access Journals (Sweden)

    Xuezhang Xiao

    2017-02-01

    Full Text Available Mg(AlH42 nanoparticles with a particle size less than 10 nm have been successfully synthesized by mechanochemical method using LiAlH4 and MgCl2 as raw materials together with LiCl buffering additive. In comparison to Mg(AlH42 microparticles, Mg(AlH42 nanoparticles exhibit a faster hydrogen desorption kinetics and lower desorption temperature. The hydrogen desorption temperatures of the first and second dehydrogenation steps are 80 and 220 °C for the Mg(AlH42 nanoparticles, which are about 65 and 60 °C, respectively, lower than those of Mg(AlH42 microparticles. The decomposition activation energy is reduced from 135 kJ/mol for Mg(AlH42 microparticles to 105.3 kJ/mol for Mg(AlH42 nanoparticles. It is proposed that the shortened diffusion distance and enhanced diffusivity of Mg(AlH42/MgH2 nanoparticles provide an energy destabilization for lowering the dehydrogenation temperature, and thus being the key factor for promoting the hydrogen desorption kinetics. More importantly, it is demonstrated that the dehydrided nano MgH2 hydride with a particle size below 10 nm can be formed after rehydrogenation process, resulting in the good cycling hydrogen desorption performance of nano MgH2.

  5. Significantly Enhanced Hydrogen Evolution Activity of Freestanding Pd-Ru Distorted Icosahedral Clusters with less than 600 Atoms.

    Science.gov (United States)

    Dai, Zhihui; Liu, Suli; Zhang, Qinghua; Bao, Jianchun; Li, Yafei; Gu, Lin

    2017-07-24

    Freestanding metal nanoclusters can tune, precisely and effectively, the Gibbs free energy (ΔGH) of atomic hydrogen on the surface of materials. This enables the enhancement of hydrogen evolution activity. In this paper, we report a study of freestanding Pd-Ru distorted icosahedral clusters (ico-clusters) with less than 600 atoms using a simple one-pot synthesis method. This Pd-Ru ico-cluster can be used as an efficient electrocatalyst for the hydrogen evolution reaction (HER) in acidic water, which is a promising alternative to Pt. The experimental and theoretical results suggest that the fcc freestanding Pd-Ru distorted ico-clusters with less than 600 atoms ensure increased active edges and distorted defect sites that reduce the coordination number for the atoms on the catalyst surface. Furthermore, Ru is a more effective hydrogen dissociation source, while Pd has a better hydrogen storage function. Pd-Ru can tune the ΔGH of atomic hydrogen adsorbed on a catalyst and reach an optimal equilibrium state that improves the HER performance. Our studies represent a robust approach towards the development of freestanding Pd-Ru distorted ico-clusters and advanced catalysts with non-Pt content for HER and many other heterogeneous reactions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. TRPC6 enhances angiotensin II-induced albuminuria.

    LENUS (Irish Health Repository)

    Eckel, Jason

    2011-03-01

    Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS). The mechanisms by which TRPC6 mutations cause kidney disease are not well understood. We used TRPC6-deficient mice to examine the function of TRPC6 in the kidney. We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals. Glomerular histomorphology revealed no abnormalities on both light and electron microscopy. To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days. Although both groups developed similar levels of hypertension, TRPC6-deficient mice had significantly less albuminuria, especially during the early phase of the infusion; this suggested that TRPC6 adversely influences the glomerular filter. We used whole-cell patch-clamp recording to measure cell-membrane currents in primary cultures of podocytes from both wild-type and TRPC6-deficient mice. In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude. Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.

  7. Tumor necrosis factor-alpha induced enhancement of cryosurgery

    Science.gov (United States)

    Goel, Raghav; Paciotti, Guilio F.; Bischof, John C.

    2008-02-01

    Local recurrence of cancer after cryosurgery is related to the inability to monitor and predict destruction of cancer (temperatures > -40°C) within an iceball. We previously reported that a cytokine adjuvant TNF-α could be used to achieve complete cancer destruction at the periphery of an iceball (0 to -40°C). This study is a further development of that work in which cryosurgery was performed using cryoprobes operating at temperatures > -40°C. LNCaP Pro 5 tumor grown in a dorsal skin fold chamber (DSFC) was frozen at -6°C after TNF-α incubation for 4 or 24 hours. Tumors grown in the hind limb were frozen with a probe tip temperature of -40°C, 4 or 24 hours after systemic injection with TNF-α. Both cryosurgery alone or TNF-α treatment alone caused only a minimal damage to the tumor tissue at the conditions used in the study. The combination of TNF-α and cryosurgery produced a significant damage to the tumor tissue in both the DSFC and the hind limb model system. This augmentation in cryoinjury was found to be time-dependent with 4-hour time period between the two treatments being more effective than 24-hour. These results suggests the possibility of cryotreatment at temperatures > -40°C with the administration of TNF-α.

  8. Radiation-induced bystander effect in healthy G{sub 0} human lymphocytes: Biological and clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Belloni, Paola; Latini, Paolo [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo De Lellis, I-01100 Viterbo (Italy); Palitti, Fabrizio, E-mail: palitti@unitus.it [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo De Lellis, I-01100 Viterbo (Italy)

    2011-08-01

    To study the bystander effects, G{sub 0} human peripheral blood lymphocytes were X-irradiated with 0.1, 0.5 and 3 Gy. After 24 h, cell-free conditioned media from irradiated cultures were transferred to unexposed lymphocytes. Following 48 h of medium transfer, viability, induction of apoptosis, telomere shortening, reactive oxygen species (ROS) levels and micronuclei (after stimulation) were analyzed. A statistically significant decrement in cell viability, concomitant with the loss of mitochondrial membrane potential, telomere shortening, increases in hydrogen peroxide (H{sub 2}O{sub 2}) and superoxide anion (O{sub 2}{sup -}) with depletion of intracellular glutathione (GSH) level, and higher frequencies of micronuclei, were observed in bystander lymphocytes incubated with medium from 0.5 and 3 Gy irradiated samples, compared to lymphocytes unexposed. Furthermore, no statistically significant difference between the response to 0.5 and 3 Gy of irradiation in bystander lymphocytes, was found. However, when lymphocytes were irradiated with 0.1 Gy, no bystander effect with regard to viability, apoptosis, telomere length, and micronuclei was observed, although a high production of ROS level persisted. Radiation in the presence of the radical scavenger dimethyl sulfoxide (DMSO) suppressed oxidative stress induced by 3 Gy of X-rays with the effective elimination of bystander effects, suggesting a correlation between ROS and bystander signal formation in irradiated cells. The data propose that bystander effect might be mostly due to the reactions of radiation induced free radicals on DNA, with the existence of a threshold at which the bystander signal is not operative (0.1 Gy dose of X-rays). Our results may have clinical implications for health risk associated with radiation exposure.

  9. Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis

    Institute of Scientific and Technical Information of China (English)

    Hui-jie MA; Xin-li HUANG; Yan LIU; Ya-min FAN

    2012-01-01

    Aim:We speculated that the enhanced apoptosis of polymorphonuclear neutrophil (PMN) might be responsible for the inhibition of PMN infiltration in the lung.This study was designed to investigate the effects of sulfur dioxide (SO2) on PMN apoptosis in vivo and in vitro,which may mediate the protective action of SO2 on pulmonary diseases.Methods:Acute lung injury (ALI) was induced by intratracheally instillation of lipopolysaccharide (LPS,100 μg/100 g.in 200 μL saline) in adult male SD rats.SO2 solution (25 μmol/kg) was administered intraperitoneally 30 min before LPS treatment.The rats were killed 6 h after LPS treatment.Lung tissues were collected for histopathologic study and SO2 concentration assay.Bronchoalveolar lavage fluid (BALF) was collected for the measurement of PMN apoptosis.For in vitro experiments,rat peripheral blood PMNs were cultured and treated with LPS (30 mg/L) and S02 (10,20 and 30 μmol/L) for 6 h,and apoptosis-related protein expression was detected by Western blotting,and apoptosis rate was measured with flow cytometry.Results:LPS treatment significantly reduced the SO2 concentrations in the lung tissue and peripheral blood,as compared with the control group.Pretreatment with SO2 prevented LPS-induced reduction of the SO2 concentration in the lung tissue and peripheral blood.LPS treatment significantly reduced PMN apoptosis both in vivo and in vitro,which could be prevented by the pretreatment with SO2.The protein levels of caspase-3 and Bax was significantly increased,but Bcl-2 was decreased by the pretreatment with SO2,as compared with LPS administration alone.Conclusion:SO2 plays an important role as the modulator of PMN apoptosis during LPS-induced ALl,which might be one of the mechanisms underlying the protective action of SO2 on pulmonary diseases.

  10. Mussel-inspired Fluoro-Polydopamine Functionalization of Titanium Dioxide Nanowires for Polymer Nanocomposites with Significantly Enhanced Energy Storage Capability

    OpenAIRE

    Guanyao Wang; Xingyi Huang; Pingkai Jiang

    2017-01-01

    High-dielectric-constant polymer nanocomposites are demonstrated to show great promise as energy storage materials. However, the large electrical mismatch and incompatibility between nanofillers and polymer matrix usually give rise to significantly reduced breakdown strength and weak energy storage capability. Therefore, rational selection and elaborate functionalization of nanofillers to optimize the performance of polymer nanocomposites are vital. Herein, inspired by adhesive proteins in mu...

  11. Glucose significantly enhances enterotoxigenic Escherichia coli adherence to intestinal epithelial cells through its effects on heat-labile enterotoxin production.

    Directory of Open Access Journals (Sweden)

    Prageeth Wijemanne

    Full Text Available The present study tested whether exposure of enterotoxigenic Escherichia coli (ETEC to glucose at different concentrations in the media results in increased bacterial adherence to host cells through increased heat-labile enterotoxin (LT production, thereby suggesting the effects are physiological. Porcine-origin ETEC strains grown in Casamino acid yeast extract medium containing different concentrations of glucose were washed and inoculated onto IPEC-J2 porcine intestinal epithelial cells to test for effects on adherence and host cell cAMP concentrations. Consistent with previous studies, all LT+ strains had higher ETEC adherence to IPEC-J2 cells than did LT- strains. Adherence of the LT- but not the LT+ strains was increased by pre-incubating the IPEC-J2 cells with LT and decreased by co-incubation with GM1 ganglioside in a dose-dependent manner (P<0.05. To determine whether the glucose concentration of the cell culture media has an effect on adherence, IPEC-J2 cells were inoculated with LT+ or LT- strains in cell culture media containing a final glucose concentration of 0, 0.25, 0.5, 1.0 or 2.0%, and incubated for 4 h. Only media containing 0.25% glucose resulted in increased adherence and cAMP levels, and this was limited to IPEC-J2 cells inoculated with LT+ strains. This study supports the hypothesis that glucose, at a concentration optimal for LT expression, enhances bacterial adherence through the promotion of LT production. Hence, these results establish the physiological relevance of the effects of glucose on LT production and provide a basis for how glucose intake may influence the severity of ETEC infection.

  12. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Oluwafemi O. Oguntibeju

    2016-01-01

    Full Text Available Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ- induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg aqueous solution was administered (daily orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC, ferric reducing antioxidant power (FRAP, catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  13. 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...

  14. 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 stu

  15. Inhibition of autophagy by 3-MA enhances endoplasmic reticulum stress-induced apoptosis in human nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Song, Lele; Liu, Hao; Ma, Linyan; Zhang, Xudng; Jiang, Zhiwen; Jiang, Chenchen

    2013-10-01

    Radiotherapy and adjuvant cisplatin chemotherapy are the mainstream treatments for nasopharyngeal carcinoma (NPC), which effectively improve the outcome and reduce tumor recurrence. However, the resistance mechanism(s) involved in radiotherapy and chemotherapy, which is the main barrier in NPC treatment, remains undefined. Therefore, there is an urgent requirement for the identification of new therapeutic strategies or adjuvant drugs. In the present study, the effects of autophagy inhibitors on endoplasmic reticulum (ER) stress-induced autophagy was investigated. Combining 3-methyladenine (3-MA) with cisplatin (DDP), ionizing radiation (IR), 2-deoxy-D-glucose (2-DG) or tunicamycin (TM) resulted in enhanced cell death, as revealed by MTT and colony formation assays. Flow cytometry results demonstrated that the sensitivity of NPC cells to DDP- and IR-induced apoptosis was not significant. DDP, IR, 2-DG and TM induced ER stress and autophagy. Using fluorescence microscopy, 3-MA was identified to increase the apoptotic cell death induced by DDP, IR, 2-DG or TM. In addition, 3-MA inhibited the increased autophagy induced by DDP, IR, 2-DG or TM, as demonstrated by western blot analysis and immunocytochemistry results. Results of the present study indicate that autophagy acts as a protective mechanism response to the apoptosis induced by DDP, IR, 2-DG or TM.

  16. Chronic morphine treatment enhances sciatic nerve stimulation-induced immediate early gene expression in the rat dorsal horn.

    Science.gov (United States)

    Bojovic, Ognjen; Bramham, Clive R; Tjølsen, Arne

    2015-01-01

    Synaptic plasticity is a property of neurons that can be induced by conditioning electrical stimulation (CS) of afferent fibers in the spinal cord. This is a widely studied property of spinal cord and hippocampal neurons. CS has been shown to trigger enhanced expression of immediate early gene proteins (IEGPs), with peak increases observed 2 hour post stimulation. Chronic morphine treatment has been shown to promoteinduce opioid-induced hyperalgesia, and also to increase CS-induced central sensitization in the dorsal horn. As IEGP expression may contribute to development of chronic pain states, we aimed to determine whether chronic morphine treatment affects the expression of IEGPs following sciatic nerve CS. Changes in expression of the IEGPs Arc, c-Fos or Zif268 were determined in cells of the lumbar dorsal horn of the spinal cord. Chronic Morphine pretreatment over 7 days led to a significant increase in the number of IEGP positive cells observed at both 2 h and 6 h after CS. The same pattern of immunoreactivity was obtained for all IEGPs, with peak increases occurring at 2 h post CS. In contrast, morphine treatment alone in sham operated animals had no effect on IEGP expression. We conclude that chronic morphine treatment enhances stimulus-induced expression of IEGPs in the lumbar dorsal horn. These data support the notion that morphine alters gene expression responses linked to nociceptive stimulation and plasticity.

  17. Anti-Helicobacter pylori therapy significantly reduces Helicobacter pylori-induced gastric mucosal damage in Mongolian gerbils

    Institute of Scientific and Technical Information of China (English)

    Chun-Chao Chang; Sheng-Hsuan Chen; Gi-Shih Lien; Yuarn-Jang Lee; Horng-Yuan Lou; Ching-Ruey Hsieh; Chia-Lang Fang; Shiann Pan

    2005-01-01

    AIM: To investigate the effectiveness of 4 d' anti-Helicobacter pyloritherapy on the H pylori-infected Mongolian gerbils based on physiological and pathological changes.METHODS: We used 6-wk-old male gerbils orally inoculated with H pylori (ATCC43504, 2x108 CFU/mL).Seven weeks after H pylori inoculation, the animals of study group received 4 d' anti-H pylori triple therapy (H pylorieradicated group). Seven days later, all animals of the H pylori-eradicated and control groups (H pylori-infected& H pylori-uninfected groups) were sacrificed. We examined gastric mucosal lesions macroscopically, studied gastritis microscopically and determined the stomach weight ratio, myeloperoxidase (MPO) activity and prostaglandin (PG) E2 level.RESULTS: The results showed that both macroscopic and histological gastric damages were significantly less in H pylori-eradicated group than H pylori-infected group.Stomach weight ratio, MPO activity and PGE2 levels were significantly higher in H pylori-infected group than those in the other two groups.CONCLUSION: Four days' anti-H pylori therapy was effective in the improvement of H pylori-induced gastric lesions in Mongolian gerbils.

  18. Soil mulching significantly enhances yields and water and nitrogen use efficiencies of maize and wheat: a meta-analysis.

    Science.gov (United States)

    Qin, Wei; Hu, Chunsheng; Oenema, Oene

    2015-11-20

    Global crop yields are limited by water and nutrient availability. Soil mulching (with plastic or straw) reduces evaporation, modifies soil temperature and thereby affects crop yields. Reported effects of mulching are sometimes contradictory, likely due to differences in climatic conditions, soil characteristics, crop species, and also water and nitrogen (N) input levels. Here we report on a meta-analysis of the effects of mulching on wheat and maize, using 1310 yield observations from 74 studies conducted in 19 countries. Our results indicate that mulching significantly increased yields, WUE (yield per unit water) and NUE (yield per unit N) by up to 60%, compared with no-mulching. Effects were larger for maize than wheat, and larger for plastic mulching than straw mulching. Interestingly, plastic mulching performed better at relatively low temperature while straw mulching showed the opposite trend. Effects of mulching also tended to decrease with increasing water input. Mulching effects were not related to soil organic matter content. In conclusion, soil mulching can significantly increase maize and wheat yields, WUE and NUE, and thereby may contribute to closing the yield gap between attainable and actual yields, especially in dryland and low nutrient input agriculture. The management of soil mulching requires site-specific knowledge.

  19. Biological designer self-assembling peptide nanofiber scaffolds significantly enhance osteoblast proliferation, differentiation and 3-D migration.

    Directory of Open Access Journals (Sweden)

    Akihiro Horii

    Full Text Available A class of self-assembling peptide nanofiber scaffolds has been shown to be an excellent biological material for 3-dimension cell culture and stimulating cell migration into the scaffold, as well as for repairing tissue defects in animals. We report here the development of several peptide nanofiber scaffolds designed specifically for osteoblasts. We designed one of the pure self-assembling peptide scaffolds RADA16-I through direct coupling to short biologically active motifs. The motifs included osteogenic growth peptide ALK (ALKRQGRTLYGF bone-cell secreted-signal peptide, osteopontin cell adhesion motif DGR (DGRGDSVAYG and 2-unit RGD binding sequence PGR (PRGDSGYRGDS. We made the new peptide scaffolds by mixing the pure RAD16 and designer-peptide solutions, and we examined the molecular integration of the mixed nanofiber scaffolds using AFM. Compared to pure RAD16 scaffold, we found that these designer peptide scaffolds significantly promoted mouse pre-osteoblast MC3T3-E1 cell proliferation. Moreover, alkaline phosphatase (ALP activity and osteocalcin secretion, which are early and late markers for osteoblastic differentiation, were also significantly increased. We demonstrated that the designer, self-assembling peptide scaffolds promoted the proliferation and osteogenic differentiation of MC3T3-E1. Under the identical culture medium condition, confocal images unequivocally demonstrated that the designer PRG peptide scaffold stimulated cell migration into the 3-D scaffold. Our results suggest that these designer peptide scaffolds may be very useful for promoting bone tissue regeneration.

  20. Loss-induced Enhanced Transmission in Anisotropic Density-near-zero Acoustic Metamaterials

    Science.gov (United States)

    Shen, Chen; Jing, Yun

    2016-11-01

    Anisotropic density-near-zero (ADNZ) acoustic metamaterials are investigated theoretically and numerically in this paper and are shown to exhibit extraordinary transmission enhancement when material loss is induced. The enhanced transmission is due to the enhanced propagating and evanescent wave modes inside the ADNZ medium thanks to the interplay of near-zero density, material loss, and high wave impedance matching in the propagation direction. The equi-frequency contour (EFC) is used to reveal whether the propagating wave mode is allowed in ADNZ metamaterials. Numerical simulations based on plate-type acoustic metamaterials with different material losses were performed to demonstrate collimation and subwavelength imaging enabled by the induced loss in ADNZ media. This work provides a different way for manipulating acoustic waves.

  1. Loss-induced enhanced transmission in anisotropic density-near-zero acoustic metamaterials

    CERN Document Server

    Shen, Chen

    2016-01-01

    Anisotropic density-near-zero (ADNZ) acoustic metamaterials are investigated theoretically and numerically in this letter and are shown to exhibit extraordinary transmission enhancement when material loss is induced. The enhanced transmission is due to the enhanced propagating and evanescent wave modes inside the ADNZ medium thanks to the interplay of near-zero density, material loss, and high wave impedance matching in the propagation direction. The equi-frequency contour (EFC) is used to reveal whether the propagating wave mode is allowed in ADNZ metamaterials. Numerical simulations based on plate-type acoustic metamaterials with different material losses were performed to demonstrate collimation enabled by the induced loss in ADNZ media. This work provides a different way for manipulating acoustic waves.

  2. Loss-induced Enhanced Transmission in Anisotropic Density-near-zero Acoustic Metamaterials.

    Science.gov (United States)

    Shen, Chen; Jing, Yun

    2016-11-25

    Anisotropic density-near-zero (ADNZ) acoustic metamaterials are investigated theoretically and numerically in this paper and are shown to exhibit extraordinary transmission enhancement when material loss is induced. The enhanced transmission is due to the enhanced propagating and evanescent wave modes inside the ADNZ medium thanks to the interplay of near-zero density, material loss, and high wave impedance matching in the propagation direction. The equi-frequency contour (EFC) is used to reveal whether the propagating wave mode is allowed in ADNZ metamaterials. Numerical simulations based on plate-type acoustic metamaterials with different material losses were performed to demonstrate collimation and subwavelength imaging enabled by the induced loss in ADNZ media. This work provides a different way for manipulating acoustic waves.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Xu; Liu Xiaoli; Sun Jialun [State Key Laboratory of Bioactive Materials, School of Physics, Nankai University, Tianjin 300073 (China); He Shuojie [State Key Laboratory of Bioactive Materials, School of Physics, Nankai University, Tianjin 300073 (China); Department of Physics, Pusan National University, Pusan (Korea, Republic of); Lee, Imshik [State Key Laboratory of Bioactive Materials, School of Physics, Nankai University, Tianjin 300073 (China)], E-mail: ilee@nankai.edu.cn2; Pak, Hyuk Kyu [Department of Physics, Pusan National University, Pusan (Korea, Republic of)

    2008-09-15

    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{sup *}. 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{sup *}-values disappears. It seems that the enhanced mechanical property was recover able under no additional mechanical stimulus.

  4. Low-dose spiruchostatin-B, a potent histone deacetylase inhibitor enhances radiation-induced apoptosis in human lymphoma U937 cells via modulation of redox signaling.

    Science.gov (United States)

    Rehman, Mati Ur; Jawaid, Paras; Zhao, Qing Li; Li, Peng; Narita, Koichi; Katoh, Tadashi; Shimizu, Tadamichi; Kondo, Takashi

    2016-06-01

    Spiruchostatin B (SP-B), is a potent histone deacetylase (HDAC) inhibitor, in addition to HDAC inhibition, the pharmacological effects of SP-B are also attributed to its ability to produce intracellular reactive oxygen species (ROS), particularly H2O2. In this study, we investigated the effects of low dose (non-toxic) SP-B on radiation-induced apoptosis in human lymphoma U937 cells in vitro. The treatment of cells with low-dose SP-B induced the acetylation of histones, however, does not induce apoptosis. Whereas, the combined treatment with SP-B and radiation significantly enhanced the radiation-induced apoptosis, suggesting the potential role of this combined treatment for future radiation therapy. Interestingly, the enhancement of apoptosis was accompanied by significant increased in the ROS generation. Pre-treatment with an antioxidant, N-acetyl-l-cysteine (NAC) significantly inhibited the enhancement of apoptosis induced by combined treatment, indicating that ROS play an essential role. It was also found that SP-B combined with radiation caused the activation of death receptor and intrinsic apoptotic pathways, via modulation of ROS-mediated signaling. Moreover, SP-B also significantly enhanced the radiation-induced apoptosis in other lymphoma cell lines such as Molt-4 and HL-60. Taken together, our findings suggest that the low-dose SP-B enhances radiation-induced apoptosis via modulation of redox signaling because of its ability to serve as an intracellular ROS generating agent, mainly (H2O2 or [Formula: see text]). This study provides further insights into the mechanism of action of SP-B with radiation and demonstrates that SP-B can be used as a future novel sensitizer for radiation therapy.

  5. The endoplasmic reticulum stress inducer thapsigargin enhances the toxicity of ZnO nanoparticles to macrophages and macrophage-endothelial co-culture.

    Science.gov (United States)

    Chen, Gui; Shen, Yuexin; Li, Xiyue; Jiang, Qin; Cheng, Shanshan; Gu, Yuxiu; Liu, Liangliang; Cao, Yi

    2017-03-01

    It was recently shown that exposure to ZnO nanoparticles (NPs) could induce endoplasmic reticulum (ER) stress both in vivo and in vitro, but the role of ER stress in ZnO NP induced toxicity remains unclear. Because macrophages are sensitive to ER stress, we hypothesized that stressing macrophages with ER stress inducer could enhance the toxicity of ZnO NPs. In this study, the effects of ER stress inducer thapsigargin (TG) on the toxicity of ZnO NPs to THP-1 macrophages were investigated. The results showed that TG enhanced ZnO NP induced cytotoxicity as revealed by water soluble tetrazolium-1 (WST-1) and neutral red uptake assays, but not lactate dehydrogenase (LDH) assay. ZnO NPs dose-dependently enhanced the accumulation of intracellular Zn ions without the induction of reactive oxygen species (ROS), and the presence of TG did not significantly affect these effects. In the co-culture, exposure of THP-1 macrophages in the upper chamber to ZnO NPs and TG significantly reduced the viability of human umbilical vein endothelial cells (HUVECs) in the lower chamber, but the release of tumor necrosis factor α (TNFα) was not induced. In summary, our data showed that stressing THP-1 macrophages with TG enhanced the cytotoxicity of ZnO NPs to macrophages and macrophage-endothelial co-cultures.

  6. 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.

  7. A more robust model of the biodiesel reaction, allowing identification of process conditions for significantly enhanced rate and water tolerance.

    Science.gov (United States)

    Eze, Valentine C; Phan, Anh N; Harvey, Adam P

    2014-03-01

    A more robust kinetic model of base-catalysed transesterification than the conventional reaction scheme has been developed. All the relevant reactions in the base-catalysed transesterification of rapeseed oil (RSO) to fatty acid methyl ester (FAME) were investigated experimentally, and validated numerically in a model implemented using MATLAB. It was found that including the saponification of RSO and FAME side reactions and hydroxide-methoxide equilibrium data explained various effects that are not captured by simpler conventional models. Both the experiment and modelling showed that the "biodiesel reaction" can reach the desired level of conversion (>95%) in less than 2min. Given the right set of conditions, the transesterification can reach over 95% conversion, before the saponification losses become significant. This means that the reaction must be performed in a reactor exhibiting good mixing and good control of residence time, and the reaction mixture must be quenched rapidly as it leaves the reactor.

  8. IP3-mediated octopamine-induced synaptic enhancement of crayfish LG neurons.

    Science.gov (United States)

    Araki, Makoto; Nagayama, Toshiki

    2012-08-01

    The biogenic amines, octopamine and serotonin, modulate the synaptic activity of the lateral giant interneuron (LG) circuitry of the crayfish escape behavior. Bath application of both octopamine and serotonin enhances the synaptic responses of LG to sensory stimulation. We have shown previously (Araki et al. J Neurophysiol 94:2644-2652, 2005) that a serotonin-induced enhancement of the LG response was mediated by an increase in cAMP levels following activation of adenylate cyclase; however, octopamine acts independently. Here, we clarify how octopamine enhances the LG response during sensory stimulation using physiological and pharmacological analyses. When phospholipase C inhibitor U-73122 was directly injected into the LG before biogenic amine application, it abolished the enhancing effect of octopamine on direct sensory input to the LG, but did not block indirect input via sensory interneurons or the effect of serotonin. Direct injection of IP(3), and its analogue adenophostin A, into the LG increased the synaptic response of the LG to sensory stimulation. Thus, IP(3) mediates octopamine-induced synaptic enhancement of the LG, but serotonin acts independently. These results indicate that both octopamine and serotonin enhance the synaptic responses of the LG to sensory stimulation, but that they activate two different signaling cascades in the LG.

  9. The prognostic significance of hypoxia inducing factor 1-α in oropharyngeal cancer in relation to human papillomavirus status.

    Science.gov (United States)

    Hong, Angela; Zhang, Mei; Veillard, Anne-Sophie; Jahanbani, Jahanfar; Lee, C Soon; Jones, Deanna; Harnett, Gerald; Clark, Jonathan; Elliott, Michael; Milross, Chris; Rose, Barbara

    2013-04-01

    This study examines the prognostic significance of hypoxia inducing factor-1α (HIF-1α) expression in relation to human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (SCC). Clinical details on 233 oropharyngeal SCCs were extracted from institutional databases. Recurrence in any form or death from any cause was recorded for a median of 51 months after diagnosis. HIF-1α expression was evaluated by semiquantitative immunohistochemistry and HPV status was determined by HPV E6-targeted multiplex real-time PCR and p16 immunohistochemistry. Determinants of recurrence and mortality hazards were modeled using Cox regression with censoring at dates of last follow-up. The HIF-1α positivity rate was 58.8%. HIF-1α positivity was associated with higher T category (T3/T4 vs. T1/T2, 64.2% vs. 48.4%, p=0.001) and lower grade (Grade 1-2 vs. 3, 62% vs. 46.9%, p=0.001). There was no significant association between HIF-1α expression and HPV status. After adjustment for clinico-pathological variables, HPV status but not HIF-1α was a strong predictor of outcome. The combination of HPV and HIF-1α was not a prognostic variable but the worst outcomes were seen in those with HPV negative and HIF-1α positive cancers. There was no statistically significant evidence of an interaction between HPV and HIF-1α. The degree of hypoxia as measured by HIF-1α expression does not differ between HPV positive and HPV negative cancers. The role of hypoxia in HPV negative oropharyngeal cancer warrants further investigation. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  10. Biodegradable polylactide microspheres enhance specific immune response induced by Hepatitis B surface antigen.

    Science.gov (United States)

    Qiu, Shaohui; Wei, Qiang; Liang, Zhenglun; Ma, Guanghui; Wang, Lianyan; An, Wenqi; Ma, Xiaowei; Fang, Xin; He, Peng; Li, Hemin; Hu, Zhongyu

    2014-01-01

    Hepatitis B (HB) infection caused by Hepatitis B virus (HBV) is the most common liver disease in the world. HB vaccine, when administered in conjunction with alum adjuvants, induces Th2 immunity that confers protection against HBV. However, currently available vaccine formulations and adjuvants do not elicit adequate Th1 and CTL responses that are important for prevention of maternal transmission of the virus. Microspheres synthesized from poly (D, L-lactide-co-glycolide) (PLGA) or poly (D, L-lactide) (PLA) polymers have been considered as promising tools for in vivo delivery of antigens and drugs. Here we describe PLA microspheres synthesized by premix membrane emulsification method and their application in formulating a new microsphere based HB vaccine. To evaluate the immunogenicity of this microsphere vaccine, BALB/c mice were immunized with microsphere vaccine and a series of immunological assays were conducted. Results of Enzyme-linked ImmunoSpot (ELISPOT) assays revealed that the number of interferon-gamma (IFN-γ)-producing splenocytes and CD8(+) T cells increased significantly in the microsphere vaccine group. Microsphere vaccine group showed enhanced specific cell lysis when compared with HB surface antigen (HBsAg) only group in (51)Cr cytotoxicity assays. Moreover, microsphere vaccine elicited a comparable level of antibody production as that of HB vaccine administered with alum adjuvant. We show that phagocytosis of HBsAg by dendritic cells is more pronounced in microsphere vaccine group when compared with other control groups. These results clearly demonstrate the potential of using PLA microspheres as effective HB vaccine adjuvants for an enhanced Th1 immune response.

  11. Motavizumab, A Neutralizing Anti-Respiratory Syncytial Virus (Rsv Monoclonal Antibody Significantly Modifies The Local And Systemic Cytokine Responses Induced By Rsv In The Mouse Model

    Directory of Open Access Journals (Sweden)

    Jafri Hasan S

    2007-10-01

    Full Text Available Abstract Motavizumab (MEDI-524 is a monoclonal antibody with enhanced neutralizing activity against RSV. In mice, motavizumab suppressed RSV replication which resulted in significant reduction of clinical parameters of disease severity. We evaluated the effect of motavizumab on the local and systemic immune response induced by RSV in the mouse model. Balb/c mice were intranasally inoculated with 106.5 PFU RSV A2 or medium. Motavizumab was given once intraperitoneally (1.25 mg/mouse as prophylaxis, 24 h before virus inoculation. Bronchoalveolar lavage (BAL and serum samples were obtained at days 1, 5 (acute and 28 (long-term post inoculation and analyzed with a multiplex assay (Beadlyte Upstate, NY for simultaneous quantitation of 18 cytokines: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, KC (similar to human IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, TNF-α, MCP-1, RANTES, IFN-γ and GM-CSF. Overall, cytokine concentrations were lower in serum than in BAL samples. By day 28, only KC was detected in BAL specimens at low concentrations in all groups. Administration of motavizumab significantly reduced (p

  12. Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5

    OpenAIRE

    INOUE, Hiroki; WAIWUT, PORNTHIP; Saiki, Ikuo; Shimada, Yutaka; Sakurai, Hiroaki

    2011-01-01

    Pharmacological studies have revealed that lignans isolated from Schisandra chinensis, including gomisin N, show anticancer, anti-hepatotoxic, anti-oxidative and anti-inflammatory activities. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an important member of the tumor necrosis factor superfamily with great potential in cancer therapy. The present study investigated whether pretreatment with gomisin N significantly enhanced TRAIL-induced cleavage of caspase-3, caspase-8 ...

  13. Mussel-inspired Fluoro-Polydopamine Functionalization of Titanium Dioxide Nanowires for Polymer Nanocomposites with Significantly Enhanced Energy Storage Capability.

    Science.gov (United States)

    Wang, Guanyao; Huang, Xingyi; Jiang, Pingkai

    2017-02-22

    High-dielectric-constant polymer nanocomposites are demonstrated to show great promise as energy storage materials. However, the large electrical mismatch and incompatibility between nanofillers and polymer matrix usually give rise to significantly reduced breakdown strength and weak energy storage capability. Therefore, rational selection and elaborate functionalization of nanofillers to optimize the performance of polymer nanocomposites are vital. Herein, inspired by adhesive proteins in mussels, a facile modification by fluoro-polydopamine is employed to reinforce the compatibility of TiO2 nanowires in the fluoropolymer matrix. The loading of 2.5 vol % f-DOPA@TiO2 NWs leads to an ultrahigh discharged energy density of 11.48 J cm(-3) at 530 MV m(-1), more than three times of commercial biaxial-oriented polypropylene (BOPP, 3.56 J cm(-3) at 600 MV m(-1)). A gratifying high energy density of 9.12 J cm(-3) has also been obtained with nanofiller loading as high as 15 vol % at 360 MV m(-1), which is nearly double to that of pure P(VDF-HFP) (4.76 J cm(-3) at 360 MV m(-1)). This splendid energy storage capability seems to rival or exceed most of previously reported nano-TiO2 based nanocomposites. The methods presented here provide deep insights into the design of polymer nanocomposites for energy storage applications.

  14. Mussel-inspired Fluoro-Polydopamine Functionalization of Titanium Dioxide Nanowires for Polymer Nanocomposites with Significantly Enhanced Energy Storage Capability

    Science.gov (United States)

    Wang, Guanyao; Huang, Xingyi; Jiang, Pingkai

    2017-02-01

    High-dielectric-constant polymer nanocomposites are demonstrated to show great promise as energy storage materials. However, the large electrical mismatch and incompatibility between nanofillers and polymer matrix usually give rise to significantly reduced breakdown strength and weak energy storage capability. Therefore, rational selection and elaborate functionalization of nanofillers to optimize the performance of polymer nanocomposites are vital. Herein, inspired by adhesive proteins in mussels, a facile modification by fluoro-polydopamine is employed to reinforce the compatibility of TiO2 nanowires in the fluoropolymer matrix. The loading of 2.5 vol % f-DOPA@TiO2 NWs leads to an ultrahigh discharged energy density of 11.48 J cm-3 at 530 MV m-1, more than three times of commercial biaxial-oriented polypropylene (BOPP, 3.56 J cm-3 at 600 MV m-1). A gratifying high energy density of 9.12 J cm-3 has also been obtained with nanofiller loading as high as 15 vol % at 360 MV m-1, which is nearly double to that of pure P(VDF-HFP) (4.76 J cm-3 at 360 MV m-1). This splendid energy storage capability seems to rival or exceed most of previously reported nano-TiO2 based nanocomposites. The methods presented here provide deep insights into the design of polymer nanocomposites for energy storage applications.

  15. Artificial neural networks incorporating cost significant Items towards enhancing estimation for (life-cycle costing of construction projects

    Directory of Open Access Journals (Sweden)

    Ayedh Alqahtani

    2013-09-01

    Full Text Available Industrial application of life-cycle cost analysis (LCCA is somewhat limited, with techniques deemed overly theoretical, resulting in a reluctance to realise (and pass onto the client the advantages to be gained from objective (LCCA comparison of (subcomponent material specifications. To address the need for a user-friendly structured approach to facilitate complex processing, the work described here develops a new, accessible framework for LCCA of construction projects; it acknowledges Artificial Neural Networks (ANNs to compute the whole-cost(s of construction and uses the concept of cost significant items (CSI to identify the main cost factors affecting the accuracy of estimation. ANNs is a powerful means to handle non-linear problems and subsequently map between complex input/output data, address uncertainties. A case study documenting 20 building projects was used to test the framework and estimate total running costs accurately. Two methods were used to develop a neural network model; firstly a back-propagation method was adopted (using MATLAB SOFTWARE; and secondly, spread-sheet optimisation was conducted (using Microsoft Excel Solver. The best network was established as consisting of 19 hidden nodes, with the tangent sigmoid used as a transfer function of NNs model for both methods. The results find that in both neural network models, the accuracy of the developed NNs model is 1% (via Excel-solver and 2% (via back-propagation respectively.

  16. 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

  17. ERK signaling mediates enhanced angiotensin Ⅱ-induced rat aortic constriction following chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    GUO Xue-ling; DENG Yan; SHANG Jin; LIU Kui; XU Yong-jian; LIU Hui-guo

    2013-01-01

    Background Obstructive sleep apnea (OSA) has been recognized as an independent risk factor for systemic hypertension.The study investigated the functional consequences of chronic intermittent hypoxia (CIH) on aortic constriction induced by angiotensin Ⅱ (Ang Ⅱ) and the possible signaling involving ERK1/2 and contractile proteins such as myosin light chain kinase (MLCK),myosin phosphatase targeting subunit (MYPT1) and myosin light chain (MLC).Methods Male Wistar rats were randomly divided into CIH group and normoxia group and exposed to either CIH procedure or air-air cycles.Phosphorylation of ERK1/2,MYPT1 and MLC was assessed by Western blotting following constrictor studies in the presence or absence of PD98059 (10 μmol/L).Results CIH-exposure resulted in more body weight gain and elevated blood pressure,which could be attenuated by pretreatment with PD98059.Endothelium-removed aortic rings from CIH rats exhibited higher constrictor sensitivity to Ang Ⅱ (Emax:(138.56±5.78)% versus (98.45±5.31)% of KCI; pD2:7.98±0.14 versus 8.14±0.05,respectively).CIH procedure exerted complex effects on ERK expressions (total ERK1/2 decreased whereas the ratio of phosphorylated to total ERK1/2increased).CIH aortas had higher MLCK mRNA and basal phosphorylation of MYPT1 and MLC.In parallel to greater increases in phosphorylation of ERK1/2,MYPT1 and MLC,Ang Ⅱ-induced aortic constriction was significantly enhanced in CIH rats,which was largely reversed by PD98059.However vascular constriction of normoxia rats remained unchanged despite similar but smaller changing tendency of proteins phosphorylation.Conclusion These data suggest that CIH exposure results in aortic hyperresponsiveness to Ang Ⅱ,presumably owing to more activated ERK1/2 signaling pathway.

  18. Novel ZnO:Ag nanocomposites induce significant oxidative stress in human fibroblast malignant melanoma (Ht144 cells

    Directory of Open Access Journals (Sweden)

    Syeda Arooj

    2015-02-01

    Full Text Available The use of photoactive nanoparticles (NPs such as zinc oxide (ZnO and its nanocomposites has become a promising anticancer strategy. However, ZnO has a low photocatalytic decomposition rate and the incorporation of metal ions such as silver (Ag improves their activity. Here different formulations of ZnO:Ag (1, 3, 5, 10, 20 and 30% Ag were synthesized by a simple co-precipitation method and characterized by powder X-ray diffraction, scanning electron microscopy, Rutherford back scattering and diffuse reflectance spectroscopy for their structure, morphology, composition and optical band gap. The NPs were investigated with regard to their different photocatalytic cytotoxic effects in human malignant melanoma (HT144 and normal (HCEC cells. The ZnO:Ag nanocomposites killed cancer cells more efficiently than normal cells under daylight exposure. Nanocomposites having higher Ag content (10, 20 and 30% were more toxic compared to low Ag content (1, 3 and 5%. For HT144, under daylight exposure, the IC50 values were ZnO:Ag (10%: 23.37 μg/mL, ZnO:Ag (20%: 19.95 μg/mL, and ZnO:Ag (30%: 15.78 μg/mL. ZnO:Ag (30% was toxic to HT144 (IC50: 23.34 μg/mL in dark as well. The three nanocomposites were further analyzed with regard to their ability to generate reactive oxygen species (ROS and induce lipid peroxidation. The particles led to an increase in levels of ROS at cytotoxic concentrations, but only HT144 showed strongly induced MDA level. Finally, NPs were investigated for the ROS species they generated in vitro. A highly significant increase of 1O2 in the samples exposed to daylight was observed. Hydroxyl radical species, HO•, were also generated to a lesser extent. Thus, the incorporation of Ag into ZnO NPs significantly improves their photo-oxidation capabilities. ZnO:Ag nanocomposites could provide a new therapeutic option to selectively target cancer cells.

  19. Nogo receptor inhibition enhances functional recovery following lysolecithin-induced demyelination in mouse optic chiasm.

    Directory of Open Access Journals (Sweden)

    Fereshteh Pourabdolhossein

    Full Text Available BACKGROUND: Inhibitory factors have been implicated in the failure of remyelination in demyelinating diseases. Myelin associated inhibitors act through a common receptor called Nogo receptor (NgR that plays critical inhibitory roles in CNS plasticity. Here we investigated the effects of abrogating NgR inhibition in a non-immune model of focal demyelination in adult mouse optic chiasm. METHODOLOGY/PRINCIPAL FINDINGS: A focal area of demyelination was induced in adult mouse optic chiasm by microinjection of lysolecithin. To knock down NgR levels, siRNAs against NgR were intracerebroventricularly administered via a permanent cannula over 14 days, Functional changes were monitored by electrophysiological recording of latency of visual evoked potentials (VEPs. Histological analysis was carried out 3, 7 and 14 days post demyelination lesion. To assess the effect of NgR inhibition on precursor cell repopulation, BrdU was administered to the animals prior to the demyelination induction. Inhibition of NgR significantly restored VEPs responses following optic chiasm demyelination. These findings were confirmed histologically by myelin specific staining. siNgR application resulted in a smaller lesion size compared to control. NgR inhibition significantly increased the numbers of BrdU+/Olig2+ progenitor cells in the lesioned area and in the neurogenic zone of the third ventricle. These progenitor cells (Olig2+ or GFAP+ migrated away from this area as a function of time. CONCLUSIONS/SIGNIFICANCE: Our results show that inhibition of NgR facilitate myelin repair in the demyelinated chiasm, with enhanced recruitment of proliferating cells to the lesion site. Thus, antagonizing NgR function could have therapeutic potential for demyelinating disorders such as Multiple Sclerosis.

  20. Significantly elevated dielectric permittivity of Si-based semiconductor/polymer 2-2 composites induced by high polarity polymers

    Science.gov (United States)

    Feng, Yefeng; Gong, Honghong; Xie, Yunchuan; Wei, Xiaoyong; Zhang, Zhicheng

    2016-02-01

    To disclose the essential influence of polymer polarity on dielectric properties of polymer composites filled with semiconductive fillers, a series of Si-based semiconductor/polymer 2-2 composites in a series model was fabricated. The dielectric permittivity of composites is highly dependant on the polarity of polymer layers as well as the electron mobility in Si-based semiconductive sheets. The huge dielectric permittivity achieved in Si-based semiconductive sheets after being coated with high polarity polymer layers is inferred to originate from the strong induction of high polarity polymers. The increased mobility of the electrons in Si-based semiconductive sheets coated by high polarity polymer layers should be responsible for the significantly enhanced dielectric properties of composites. This could be facilely achieved by either increasing the polarity of polymer layers or reducing the percolative electric field of Si-based semiconductive sheets. The most promising 2-2 dielectric composite was found to be made of α-SiC with strong electron mobility and poly(vinyl alcohol) (PVA) with high polarity, and its highest permittivity was obtained as 372 at 100 Hz although the permittivity of α-SiC and PVA is 3-5 and 15, respectively. This work may help in the fabrication of high dielectric constant (high-k) composites by tailoring the induction effect of high polarity polymers to semiconductors.

  1. Impaired Bcl3 up-regulation leads to enhanced lipopolysaccharide-induced interleukin (IL)-23P19 gene expression in IL-10(-/-) mice.

    Science.gov (United States)

    Mühlbauer, Marcus; Chilton, Paula M; Mitchell, Thomas C; Jobin, Christian

    2008-05-23

    Genetic and biochemical analyses show that IL-23p19 plays a central role in mediating bacteria-induced colitis in interleukin-10-deficient (IL-10(-/-)) mice. The molecular mechanisms responsible for the dysregulated innate host response leading to enhanced IL-23 gene expression in IL-10(-/-) mice are poorly understood. In this study, we investigated the role of Bcl3 in controlling LPS-induced IL-23p19 gene expression in bone marrow-derived dendritic cells (BMDC) isolated from IL-10(-/-) mice. We report higher IL-23p19 mRNA accumulation and protein secretion in LPS-stimulated BMDC isolated from IL-10(-/-) compared with WT mice. Lipopolysaccharide (LPS)-induced B cell leukemia 3 (Bcl3) expression was strongly impaired (90% decrease) in IL-10(-/-) BMDC compared with WT BMDC. Chromatin immunoprecipitation demonstrated enhanced RelA binding to the IL-23p19 promoter in IL-10(-/-) compared with WT BMDC. Bcl3 overexpression decreased LPS-induced IL-23p19 gene expression in IL-10(-/-) BMDC, which correlated with enhanced NF-kappaB p50 binding and decreased RelA binding to the gene promoter. Conversely, Bcl3 knockdown enhanced LPS-induced IL-23p19 gene expression in WT BMDC. Moreover, LPS-induced IL-23p19 gene expression was significantly enhanced in Bcl3(-/-) BMDC compared with WT BMDC. In conclusion, enhanced LPS-induced IL-23p19 gene expression in IL-10(-/-) mice is due to impaired Bcl3 expression leading to diminished p50 and enhanced RelA recruitment to the IL-23p19 promoter.

  2. Thermal conductivity enhancement of laser induced graphene foam upon P3HT infiltration

    Science.gov (United States)

    Smith, M. K.; Luong, D. X.; Bougher, T. L.; Kalaitzidou, K.; Tour, J. M.; Cola, B. A.

    2016-12-01

    Significant research has been dedicated to the exploration of high thermal conductivity polymer composite materials with conductive filler particles for use in heat transfer applications. However, poor particle dispersibility and interfacial phonon scattering have limited the effective composite thermal conductivity. Three-dimensional foams with high ligament thermal conductivity offer a potential solution to the two aforementioned problems but are traditionally fabricated through expensive and/or complex manufacturing methods. Here, laser induced graphene foams, fabricated through a simple and cost effective laser ablation method, are infiltrated with poly(3-hexylthiophene) in a step-wise fashion to demonstrate the impact of polymer on the thermal conductivity of the composite system. Surprisingly, the addition of polymer results in a drastic (250%) improvement in material thermal conductivity, enhancing the graphene foam's thermal conductivity from 0.68 W/m-K to 1.72 W/m-K for the fully infiltrated composite material. Graphene foam density measurements and theoretical models are utilized to estimate the effective ribbon thermal conductivity as a function of polymer filling. Here, it is proposed that the polymer solution acts as a binding material, which draws graphene ligaments together through elastocapillary coalescence and bonds these ligaments upon drying, resulting in greatly reduced contact resistance within the foam and an effective thermal conductivity improvement greater than what would be expected from the addition of polymer alone.

  3. Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced apoptosis in K562 cells.

    Directory of Open Access Journals (Sweden)

    Li-Li Song

    Full Text Available Despite considerable efficacy of arsenic trioxide (As2O3 in acute promyelocytic leukemia (APL treatment, other non-APL leukemias, such as chronic myeloid leukemia (CML, are less sensitive to As2O3 treatment. However, the underlying mechanism is not well understood. Here we show that relative As2O3-resistant K562 cells have significantly lower ROS levels than As2O3-sensitive NB4 cells. We compared the expression of several antioxidant enzymes in these two cell lines and found that peroxiredoxin 1/2/6 and catalase are expressed at high levels in K562 cells. We further investigated the possible role of peroxirdoxin 1/2/6 and catalase in determining the cellular sensitivity to As2O3. Interestingly, knockdown of peroxiredoxin 1/2/6 did not increase the susceptibility of K562 cells to As2O3. On the contrary, knockdown of catalase markedly enhanced As2O3-induced apoptosis. In addition, we provide evidence that overexpression of BCR/ABL cannot increase the expression of PRDX 1/2/6 and catalase. The current study reveals that the functional role of antioxidant enzymes is cellular context and treatment agents dependent; targeting catalase may represent a novel strategy to improve the efficacy of As2O3 in CML treatment.

  4. RO 90-7501 enhances TLR3 and RLR agonist induced antiviral response.

    Directory of Open Access Journals (Sweden)

    Fang Guo

    Full Text Available Recognition of virus infection by innate pattern recognition receptors (PRRs, including membrane-associated toll-like receptors (TLR and cytoplasmic RIG-I-like receptors (RLR, activates cascades of signal transduction pathways leading to production of type I interferons (IFN and proinflammatory cytokines that orchestrate the elimination of the viruses. Although it has been demonstrated that PRR-mediated innate immunity plays an essential role in defending virus from infection, it also occasionally results in overwhelming production of proinflammatory cytokines that cause severe inflammation, blood vessel leakage and tissue damage. In our efforts to identify small molecules that selectively enhance PRR-mediated antiviral, but not the detrimental inflammatory response, we discovered a compound, RO 90-7501 ('2'-(4-Aminophenyl-[2,5'-bi-1H-benzimidazol]-5-amine, that significantly promoted both TLR3 and RLR ligand-induced IFN-β gene expression and antiviral response, most likely via selective activation of p38 mitogen-activated protein kinase (MAPK pathway. Our results thus imply that pharmacological modulation of PRR signal transduction pathways in favor of the induction of a beneficial antiviral response can be a novel therapeutic strategy.

  5. Fenofibrate Treatment Enhances Antioxidant Status and Attenuates Endothelial Dysfunction in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Murat Olukman

    2010-01-01

    Full Text Available Diabetic endothelial dysfunction is accompanied by increased oxidative stress and upregulated proinflammatory and inflammatory mediators in the vasculature. Activation of peroxisome proliferator-activated receptor-alpha (PPAR-α results in antioxidant and anti-inflammatory effects. This study was designed to investigate the effect of fenofibrate, a PPAR-α activator, on the endothelial dysfunction, oxidative stress, and inflammation in streptozotocin diabetic rats. Diabetic rats received fenofibrate (150 mg kg−1 day−1 for 4 weeks. Fenofibrate treatment restored the impaired endothelium-dependent relaxation and increased basal nitric oxide availability in diabetic aorta, enhanced erythrocyte/liver superoxide dismutase and catalase levels, ameliorated the abnormal serum/aortic thiobarbituric acid reactive substances, and prevented the increased aortic myeloperoxidase without a significant change in serum total cholesterol and triglyceride levels. It did not affect the decreased total homocysteine level and the increased tumor necrosis factor-α level in the serum of diabetic rats. Fenofibrate-induced prevention of the endothelial function seems to be related to its potential antioxidant and antiinflammatory activity.

  6. Small-Molecule XIAP Inhibitors Enhance γ-Irradiation-Induced Apoptosis in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Sri Hari Krishna Vellanki

    2009-08-01

    Full Text Available Because evasion of apoptosis can cause radioresistance of glioblastoma, there is a need to design rational strategies that counter apoptosis resistance. In the present study, we investigated the potential of targeting the antiapoptotic protein XIAP for the radiosensitization of glioblastoma. Here, we report that small-molecule XIAP inhibitors significantly enhance γ-irradiation-induced loss of viability and apoptosis and cooperate with γ-irradiation to suppress clonogenic survival of glioblastoma cells. Analysis of molecular mechanisms reveals that XIAP inhibitors act in concert with γ-irradiation to cause mitochondrial outer membrane permeabilization, caspase activation, and caspasedependent apoptosis. Importantly, XIAP inhibitors also sensitize primary cultured glioblastoma cells derived from surgical specimens as well as glioblastoma-initiating stemlike cancer stem cells for γ-irradiation. In contrast, they do not increase the toxicity of γ-irradiation on some nonmalignant cells of the central nervous system, including rat neurons or glial cells, pointing to some tumor selectivity. In conclusion, by demonstrating for the first time that smallmolecule XIAP inhibitors increase the radiosensitivity of glioblastoma cells while sparing normal cells of the central nervous system, our findings build the rationale for further (preclinical development of XIAP inhibitors in combination with γ-irradiation in glioblastoma.

  7. 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.

  8. Emission enhancement using two orthogonal targets in double pulse laser-induced breakdown spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Ake, C. [Laboratorio de Fotofisica, Centro de Ciencias Aplicadas y Desarrollo Tecnologico, Universidad Nacional Autonoma de Mexico, Apartado Postal 70-186, Mexico D.F., C.P. 04510 (Mexico)], E-mail: citlali.sanchez@ccadet.unam.mx; Bolanos, Marduk [Laboratorio de Fotofisica, Centro de Ciencias Aplicadas y Desarrollo Tecnologico, Universidad Nacional Autonoma de Mexico, Apartado Postal 70-186, Mexico D.F., C.P. 04510 (Mexico); Ramirez, C.Z. [Colegio de Ciencias y Humanidades Plantel Sur, Universidad Nacional Autonoma de Mexico (Mexico)

    2009-09-15

    The enhancement of emission intensity resulting from the interaction between two laser-induced plasmas on two orthogonal targets was investigated using double pulse laser-induced breakdown spectroscopy (LIBS) at 0.7 Pa, by means of time-resolved spectroscopy and fast photography. The results showed that the interaction between both plasmas improved carbon emission intensity in comparison to a single laser-induced plasma. For all the carbon lines of interest 477.2 nm (CI), 426.7 nm (CII), and 473.4 nm (C{sub 2} Swan band head), the intensity enhancement showed a maximum at a delay between lasers in the range from 2 to 5 {mu}s; moreover it increased with the fluence of the first laser. On the other hand, in the case of C{sub 2} the intensity enhancement reached a maximum at 5 mm from the target; however it decreased with increasing fluence of the second laser. The largest intensity enhancement found was twofold for atomic species and sixfold for molecular species.

  9. Choice of study endpoint significantly impacts the results of breast cancer trials evaluating chemotherapy-induced nausea and vomiting.

    Science.gov (United States)

    Ng, Terry; Mazzarello, Sasha; Wang, Zhou; Hutton, Brian; Dranitsaris, George; Vandermeer, Lisa; Smith, Stephanie; Clemons, Mark

    2016-01-01

    Multiple endpoints can be used to evaluate chemotherapy-induced nausea and vomiting (CINV). These endpoints reflect the various combinations of vomiting, nausea and rescue antiemetic use in the acute (0-24 h), delayed (>24-120 h) and overall (0-120 h) periods after chemotherapy. As the choice of outcome measure could potentially change the interpretation of clinical trial results, we evaluated CINV rates using different endpoints on a single dataset from a prospective cohort. Data from 177 breast cancer patients receiving anthracycline and cyclophosphamide-based chemotherapy was used to calculate CINV control rates using the 15 most commonly reported CINV endpoints. As nausea remains such a significant symptom, we explored the frequency at which pharmaceutical and non-pharmaceutical company-funded studies included measures of nausea in their primary study endpoint. CINV control rates ranged from 12.5 %, 95 % (CI 7.6-17.4 %) for total control (no vomiting, no nausea and no rescue medication) in the overall period to 77.4 %, 95 % (CI 71.2-83.6 %) for no vomiting in the overall period. Similar differences were found in the acute and delayed periods. Non-pharmaceutical company-funded trials were more likely to include a measure of nausea in the primary study outcome (9/18, 50 %) than pharmaceutical-funded trials (1/12, 8.3 %). The choice of trial endpoint has an important impact on reported CINV control rates and could significantly impact on interpretation of the results. Primary endpoints of studies, including those mandated by regulatory bodies, should account for nausea to reflect patient experience. Reporting of endpoints should be more comprehensive to allow for cross-trial comparisons.

  10. Significance of the first transcribed nucleoside of capped RNA for ligand-induced folding of the cap-binding complex

    Science.gov (United States)

    Worch, Remigiusz; Niedzwiecka, Anna; Stepinski, Janusz; Jankowska-Anyszka, Marzena; Mazza, Catherine; Darzynkiewicz, Edward; Cusack, Stephen; Stolarski, Ryszard

    2005-05-01

    Many proteins, including those that bind RNA, change conformation upon binding a ligand, a phenomenon known as induced fit. CBP20, the small subunit of the nuclear cap-binding complex (CBC), recognizes specifically the 5' cap of eukaryotic mRNA and snRNA. The N- and C-terminal regions of the CBP20 subunit of the human nuclear cap-binding complex only acquire a proper fold in complex with capped RNA. The cap is composed of 7-methylguanosine linked by a 5'-to-5' triphosphate bridge to the first transcribed nucleoside of the RNA. The significance of the latter for the capped RNA-CBC association and local folding of CBC has been characterized by emission spectroscopy. Fluorescence titration of CBC has been performed for three selected, mono- and dinucleotide mRNA 5' cap analogues. The measured values of the equilibrium association constant and the corresponding Gibbs free energy depend on the type of the first transcribed nucleoside (purine or pyrimidine), and decrease ~10-fold in the case of a mononucleotide analogue, 7-methylguanosine triphosphate. However, the total quenching of the intrinsic protein fluorescence is similar for each analogue. Changes of the solvent-accessible CBC hydrophobic surface of CBC on binding of the structurally different cap analogues have been followed using bis-ANS fluorescent probe.

  11. Significance and Expression of Serum and Glucocorticoid-inducible Kinase in Kidney of Mice with Diabetic Nephropathy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate the expression and the role of three isoforms of Serum and Glucocorticoidinducible Kinase (SGK) in experimental diabetic nephropathy (DN), 12 male C57BL/6 mice of 8-weeks-old were divided into two groups. Streptozotocin (STZ)-induced diabetic nephropathy and normal controls were analyzed at the end of the 4th week after the induction of diabetes. Renal hemodynamics and histological studies were performed. The expression of SGK1 mRNA, SGK2 mRNA and SGK3 mRNA of kidney cortex were measured by RT-PCR, and the cortical SGK1 protein was detected with Western blotting. Our results showed that the blood glucose, blood HbA1c, 24-h urinary protein, creatinine clearance and the renal index were all increased in DN group. More extracellular matrix (ECM) accumulation was observed. The level of cortical SGK1 mRNA and protein were up-regulated in DN group in comparison with control group. SGK2 and SGK3 mRNA were elevated in DN mice. In DN, mRNA level of three SGK isoforms and SGK1 protein were increased significantly. It is concluded that SGKs may contribute to the early renal injury of DN.

  12. PUMA gene transfection can enhance the sensitivity of epirubicin-induced apoptosis of MCF-7 breast cancer cells.

    Science.gov (United States)

    Sun, C-G; Zhuang, J; Teng, W-J; Wang, Z; Du, S-S

    2015-05-29

    We explored whether p53 upregulated modulator of apoptosis (PUMA) gene transfection could enhance the sensitivity of epirubicin-induced apoptosis of MCF-7 breast cancer cells. The liposome-mediated recombinant eukaryotic expression vector PU-MA-pCDNA3 and empty vector plasmid were stably transfected into MCF-7 cells. Epirubicin (0.01-100 μM) was applied to MCF-7, MCF-7/PUMA, and MCF-7/pCDNA3 cells for 72 h. The MTT assay was used to calculate the cell survival rate in each group, and the 50% inhibitory concentration (IC50) was calculated. The IC50 values of epirubicin in MCF-7, MCF-7/PUMA, and MCF-7/pCDNA3 cells were 13 ± 1.4, 1.8 ± 0.2, and 10.7 ± 1.3 μM, respectively. The sensitivity of MCF-7/PUMA cells to epirubicin increased 7.2-fold. Epirubicin induced apoptosis in MCF-7 cells dose-dependently, but MCF-7/PUMA cell-induced apoptosis was more significant compared to controls. Low concentrations of epirubicin (0.1 μM) caused low levels of apoptosis of MCF-7/pCDNA3 (1.15 ± 0.26%) and MCF-7 cells (0.9 ± 0.24%), but significantly induced apoptosis of MCF-7/PUMA cells (6.44 ± 1.46%). High epirubicin concentration (1 μM) induced apoptosis in each group, but the epirubicin MCF-7/PUMA apoptosis rate (35.47 ± 9.36%) was significantly higher than that of MCF-7 (12.6 ± 3.73%) and MCF-7/ pCDNA3 (15.2 ± 5.17%) cells (P PUMA protein expression in MCF-7/PUMA cells was significantly higher than that in MCF-7 and MCF-7/pCDNA3 cells by Western blot analysis. There-fore, stable transfection of PUMA can significantly enhance epirubicin-induced apoptosis sensitivity of MCF-7 breast cancer cells.

  13. Lysosome dysfunction enhances oxidative stress-induced apoptosis through ubiquitinated protein accumulation in Hela cells.

    Science.gov (United States)

    Yu, Chunyan; Huang, Xiaowei; Xu, Ye; Li, Hongyan; Su, Jing; Zhong, Jiateng; Kang, Jinsong; Liu, Yuhe; Sun, Liankun

    2013-01-01

    The role of lysosomal system in oxidative stress-induced apoptosis in cancer cells is not fully understood. Menadione is frequently used as oxidative stress model. It is indicated that menadione could induce autophagy in Hela cells. In the present study, we examined whether the lysosomal inhibitor, ammonium chloride (NH(4)Cl) could prevent the autophagy flux by inhibiting the fusion of autophagosomes with lysosomes and enhance apoptosis induced by menadione via mitochondrial pathway. The results demonstrated generation and accumulation of reactive oxygen species and increased levels of ubiquitinated proteins and GRP78 in cells treated with both menadione and NH(4)Cl. Our data indicates that lysosomal system through autophagy plays an important role in preventing menadione-induced apoptosis in Hela cells by clearing misfolded proteins, which alleviates endoplasmic reticulum stress.

  14. Enhancement of acoustic streaming induced flow on a focused surface acoustic wave device: Implications for biosensing and microfluidics

    Science.gov (United States)

    Singh, Reetu; Sankaranarayanan, Subramanian K. R. S.; Bhethanabotla, Venkat R.

    2010-01-01

    Fluid motion induced on the surface of 100 MHz focused surface acoustic wave (F-SAW) devices with concentric interdigital transducers (IDTs) based on Y-cut Z-propagating LiNbO3 substrate was investigated using three-dimensional bidirectionally coupled finite element fluid-structure interaction models. Acoustic streaming velocity fields and induced forces for the F-SAW device are compared with those for a SAW device with uniform IDTs (conventional SAW). Both, qualitative and quantitative differences in the simulation derived functional parameters, such as device displacements amplitudes, fluid velocity, and streaming forces, are observed between the F-SAW and conventional SAW device. While the conventional SAW shows maximum fluid recirculation near input IDTs, the region of maximum recirculation is concentrated near the focal point of the F-SAW device. Our simulation results also indicate acoustic energy focusing by the F-SAW device leading to maximized device surface displacements, fluid velocity, and streaming forces near the focal point located in the center of the delay path, in contrast to the conventional SAW exhibiting maximized values of these parameters near the input IDTs. Significant enhancement in acoustic streaming is observed in the F-SAW device when compared to the conventional ones; the increase in streaming velocities was computed to be 352% and 216% for tangential velocities in propagation and transverse directions, respectively, and 353% for the normal velocity. Consequently, the induced streaming force for F-SAW is 480% larger than that for conventional SAW. In biosensing applications, this allows for the removal of smaller submicron sized particles by F-SAW which are otherwise difficult to remove using the conventional SAW. The F-SAW presents an order of magnitude reduction in the smallest removable particle size compared to the conventional device. Our results indicate that the acoustic energy focusing and streaming enhancement brought about by

  15. 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.

  16. A visible light-induced photocatalytic silver enhancement reaction for gravimetric biosensors

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Wooree; Yim, Changyong; Jung, Namchul; Joo, Jinmyoung; Jeon, Sangmin [Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang (Korea, Republic of); Seo, Hyejung; Lee, Soo Suk; Park, Jae Chan, E-mail: jeons@postech.ac.kr [Samsung Advanced Institute of Technology (SAIT), Suwon (Korea, Republic of)

    2011-10-07

    We have developed a novel microgravimetric immunosensor using a WO{sub 3} nanoparticle-modified immunoassay and a silver enhancement reaction. When the nanoparticles in silver ion solution (i.e. AgNO{sub 3}) are exposed to visible light, the silver ions are photocatalytically reduced and form a metallic silver coating on the nanoparticles. This silver coating consequently induces changes in the mass and light absorption spectrum. Although photocatalytic reduction reactions can be achieved using ultraviolet (UV) light and TiO{sub 2} nanoparticles as described in our previous publication (Seo et al 2010 Nanotechnology 21 505502), the use of UV light in biosensing applications has drawbacks in that UV light can damage proteins. In addition, conventional quartz crystal substrates must be passivated to prevent undesirable silver ion reduction on their gold-coated sensing surfaces. We addressed these problems by adopting a visible light-induced photocatalytic silver enhancement method using WO{sub 3} nanoparticles and lateral field excited (LFE) quartz crystals. As a proof-of-concept demonstration of the technique, streptavidin was adsorbed onto an LFE quartz crystal, and its mass was enhanced with biotinylated WO{sub 3} nanoparticles, this being followed by a photocatalytic silver enhancement reaction. The mass change due to the enhancement was found to be > 30 times greater than the mass change obtained with the streptavidin alone.

  17. A visible light-induced photocatalytic silver enhancement reaction for gravimetric biosensors.

    Science.gov (United States)

    Ko, Wooree; Yim, Changyong; Jung, Namchul; Joo, Jinmyoung; Jeon, Sangmin; Seo, Hyejung; Lee, Soo Suk; Park, Jae Chan

    2011-10-07

    We have developed a novel microgravimetric immunosensor using a WO(3) nanoparticle-modified immunoassay and a silver enhancement reaction. When the nanoparticles in silver ion solution (i.e.  AgNO(3)) are exposed to visible light, the silver ions are photocatalytically reduced and form a metallic silver coating on the nanoparticles. This silver coating consequently induces changes in the mass and light absorption spectrum. Although photocatalytic reduction reactions can be achieved using ultraviolet (UV) light and TiO(2) nanoparticles as described in our previous publication (Seo et al 2010 Nanotechnology 21 505502), the use of UV light in biosensing applications has drawbacks in that UV light can damage proteins. In addition, conventional quartz crystal substrates must be passivated to prevent undesirable silver ion reduction on their gold-coated sensing surfaces. We addressed these problems by adopting a visible light-induced photocatalytic silver enhancement method using WO(3) nanoparticles and lateral field excited (LFE) quartz crystals. As a proof-of-concept demonstration of the technique, streptavidin was adsorbed onto an LFE quartz crystal, and its mass was enhanced with biotinylated WO(3) nanoparticles, this being followed by a photocatalytic silver enhancement reaction. The mass change due to the enhancement was found to be > 30 times greater than the mass change obtained with the streptavidin alone.

  18. Glioblastoma Presenting with Steroid-Induced Pseudoregression of Contrast Enhancement on Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Marcus D. Mazur

    2012-01-01

    Full Text Available Corticosteroid-induced reduction in contrast enhancement on radiographic imaging is most commonly associated with lymphoma but has been reported in other entities, including glioma. This finding may represent a diagnostic dilemma. Concern that steroid-induced cytotoxicity obscures histological diagnosis of suspected lymphoma may lead to postponement of a biopsy. If glioma is not considered in the differential diagnosis, reduction in tumor contrast enhancement may be misinterpreted as disease regression rather than a transient radiographic change. We report a case of a patient with an enhancing right temporoparietal mass adjacent to the atrium of the lateral ventricle. After treatment with dexamethasone was started, the mass exhibited marked reduction in contrast enhancement, with symptom improvement. The clinical course suggested lymphoma, and surgery was not performed. Subsequent screening for extra-axial lymphoma was negative. Two weeks later, the patient developed worsening symptoms, and repeat T1-weighted imaging showed interval increase in size and enhancement. The findings suggested a possible diagnosis of malignant glioma. The patient underwent a stereotactic-guided craniotomy for excision of the right temporoparietal mass lesion. Final histological diagnosis was glioblastoma multiforme, World Health Organization grade IV.

  19. Autophagy inhibition enhances RAD001-induced cytotoxicity in human bladder cancer cells

    Directory of Open Access Journals (Sweden)

    Lin JF

    2016-04-01

    treatment.Results: Advanced bladder cancer cells (5637, HT1376, and T24 were more resistant to RAD001 than RT4. Autophagy flux detected by the expression of LC3-II showed RAD001-induced autophagy. AVO formation was detected in cells treated with RAD001 and was inhibited by the addition of 3-MA or Baf A1. Cotreatment of RAD001 with autophagy inhibitors further reduced cell viability and induced apoptosis in bladder cancer cells.Conclusion: Our results indicate that simultaneous inhibition of the mTOR and autophagy pathway significantly enhances apoptosis, and it is suggested to be a new therapeutic paradigm for the treatment of bladder cancer. Keywords: autophagy, apoptosis, bladder cancer, chloroquine, RAD001

  20. Changes and significance of occludin expression in rats with blood-brain barrier injury induced by microwave radiation

    Directory of Open Access Journals (Sweden)

    Xiang LI

    2011-07-01

    Full Text Available Objective To observe the changes in occludin expression in hippocampus of rats injured by long-term microwave exposure at low dosage,and explore the mechanism of the effect of occludin on microwave-induced blood-brain barrier(BBB injury.Methods A total of 156 male Wistar rats were assigned into 4 groups(39 each according to the microwave dosage they received(0,2.5,5 and 10 mW/cm2.Irradiation was given 5 times/week and 6 minutes for each exposure for one month.Five rats of each group were sacrificed at each time point(6h and day 7,14,30 and 60 after irradiation,the structural changes in hippocampus tissues BBB were observed by light and electron microscopy.Another 3 rats of each group were sacrificed after an intravenous injection of 2% Evans blue(EB at the time points of 6h and day 7 and 30 after irradiation,and the change in BBB permeability was examined by laser scanning confocal microscopy.Western blotting,real-time PCR and image analysis were used to detect the gene and protein expression of occludin in hippocampus of rats.Results After microwave irradiation in doses of 2.5,5 and 10 mW/cm2,respectively,on day 7,14 and 30,the astrocytes were found to be swollen,the capillary gaps of hippocampus were broadened and tight junction(TJ structure was inconspicuous or widened.In sham-group(0 mW/cm2,the red fluorescence of EB was limited in lumens of blood vessels,while in 5 and 10 mW/cm2 groups,Evans blue was dispersed surrounding the blood vessels at 6h and day 7 till day 30 in an irradiation dose-dependent manner.In 5 and 10 mW/cm2 groups,the expression of occludin protein in hippocampus decreased at day 14(P 0.05.In the 2.5,5 and 10 mW/cm2 groups,mRNA expression of occludin began to significantly decrease at day 7 and 14 and it lowered to the nadir at day 30(P 0.05.Conclusions A long-term microwave irradiation with dosage of 2.5 to 10 mW/cm2 may destroy the structure of BBB of rats’ hippocampus and increase permeability in a radiation

  1. The enhancement of propyl gallate-induced apoptosis in HeLa cells by a proteasome inhibitor MG132.

    Science.gov (United States)

    You, Bo Ra; Park, Woo Hyun

    2011-03-01

    Propyl gallate (PG) used in processed food and medicinal preparations has been shown to induce cell death in normal and cancer cells. The inhibition of proteasome function has emerged as a useful strategy to maneuver apoptosis. Here, we investigated the combined effects of PG and MG132 (a proteasome inhibitor) on HeLa cells in relation to cell growth, cell death, reactive oxygen species (ROS) and glutathione (GSH). PG induced growth inhibition and apoptosis in HeLa cells, accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm), activation of caspase 3 and PARP cleavage. The levels of ROS and GSH depletion were increased in PG-treated HeLa cells. MG132 intensified apoptosis and PARP cleavage in PG-treated HeLa cells. MG132 also increased ROS levels including mitochondrial O2•-, MMP (ΔΨm) loss and GSH depletion in PG-treated HeLa cells. PG induced a G1 phase arrest of the cell cycle in HeLa cells, which was significantly prevented by MG132. MG132 alone inhibited HeLa cell growth via inducing the cell cycle arrests and triggering apoptosis. Conclusively, the inhibition of proteasome by MG132 plays a role as an enhancement factor in PG-induced apoptosis of HeLa cells via increasing ROS levels and GSH depletion.

  2. NOXA-induced alterations in the Bax/Smac axis enhance sensitivity of ovarian cancer cells to cisplatin.

    Directory of Open Access Journals (Sweden)

    Chao Lin

    Full Text Available Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy.

  3. NOXA-induced alterations in the Bax/Smac axis enhance sensitivity of ovarian cancer cells to cisplatin.

    Science.gov (United States)

    Lin, Chao; Zhao, Xin-yu; Li, Lei; Liu, Huan-yi; Cao, Kang; Wan, Yang; Liu, Xin-yu; Nie, Chun-lai; Liu, Lei; Tong, Ai-ping; Deng, Hong-xin; Li, Jiong; Yuan, Zhu; Wei, Yu-quan

    2012-01-01

    Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy.

  4. Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

    Science.gov (United States)

    Wang, Min; Sun, Guibo; Wu, Ping; Chen, Rongchang; Yao, Fan; Qin, Meng; Luo, Yun; Sun, Hong; Zhang, Qiang; Dong, Xi; Sun, Xiaobo

    2013-01-01

    Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO) without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2) cells and human cervical cancer (HeLa) cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose) polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects. PMID:23662152

  5. Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

    Directory of Open Access Journals (Sweden)

    Min Wang

    2013-01-01

    Full Text Available Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2 cells and human cervical cancer (HeLa cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects.

  6. Iron Deficiency-induced Increase of Root Branching Contributes to the Enhanced Root Ferric Chelate Reductase Activity

    Institute of Scientific and Technical Information of China (English)

    Chong-Wei Jin; Wei-Wei Chen; Zhi-Bin Meng; Shao-Jian Zheng

    2008-01-01

    In various plant species, Fe deficiency increases lateral root branching. However, whether this morphological alteration contributes to the Fe deficiency-induced physiological responses still remains to be demonstrated. In the present research, we demonstrated that the lateral root development of red clover (Trifolium pretense L.) was significantly enhanced by Fe deficient treatment, and the total lateral root number correlated well with the Fe deficiency-induced ferric chelate reductase (FCR) activity. By analyzing the results from Dasgan et al. (2002), we also found that although the two tomato genotypes line227/1 (P1) and Roza (P2) and their reciprocal F1 hybrid lines ("P1 × P2" and "P2 × P1 ") were cultured under two different lower Fe conditions (10-6 and 10-7 M FeEDDHA), their FCR activities are significantly correlated with the lateral root number. More interestingly, the -Fe chlorosis tolerant ability of these four tomato lines displays similar trends with the lateral root density. Taking these results together, it was proposed that the Fe deficiency-induced increases of the lateral root should play an important role in resistance to Fe deficiency, which may act as harnesses of a useful trait for the selection and breeding of more Fe-efficiant crops among the genotypes that have evolved a Fe deficiency-induced Fe uptake system.

  7. Enhancing thermally induced effects on atomic force microscope cantilevers using optical microcavities

    Science.gov (United States)

    Duy Vy, Nguyen; Iida, Takuya

    2016-12-01

    A theory of enhancing thermally induced effects on atomic force microscope cantilevers with respect to the input power is proposed. An optical microcavity is used to increase the absorbed power and radiation pressure on thin films. We show that the response to the input power is enhanced up to an order of magnitude for cantilevers of ∼200 µm in length and ∼0.5 µm in thickness. A decrease in the absorbed power in the presence of cantilever deflection increases system endurability with respect to the input power. The study gives methods for amplifying and tuning vibration amplitudes in amplitude modulation modes with high sensitivity and low controlling input power.

  8. Chitin enhances serum IgE in Aspergillus fumigatus induced allergy in mice

    DEFF Research Database (Denmark)

    Dubey, Lalit Kumar; Moeller, Jesper Bonnet; Schlosser, Anders;

    2015-01-01

    in the lungs, measured as the total cell efflux in BAL, EPO and chitinase production. However, chitin enhanced the total IgE, specific IgE and specific IgG1 production as efficiently as alum. Pre-treatment with chitin but not with alum depressed the concentration of the Th2 cytokines IL-4 and IL-13 in BAL...... fluid. These results shows that chitin, in spite of a reduction of the Th2 cytokine levels in the lungs, enhanced the total and specific IgE production in A. fumigatus culture filtrate induced allergy....

  9. 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

  10. Blocking autophagic flux enhances matrine-induced apoptosis in human hepatoma cells.

    Science.gov (United States)

    Wang, Li; Gao, Chun; Yao, Shukun; Xie, Bushan

    2013-11-25

    Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC). Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V-FITC/PI double-staining assay), the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1) both autophagy and apoptosis could be induced by treatment with matrine; (2) using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3) autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

  11. Blocking Autophagic Flux Enhances Matrine-Induced Apoptosis in Human Hepatoma Cells

    Directory of Open Access Journals (Sweden)

    Li Wang

    2013-11-01

    Full Text Available Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC. Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V–FITC/PI double-staining assay, the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1 both autophagy and apoptosis could be induced by treatment with matrine; (2 using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3 autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

  12. 5-fluorouracil-based therapy induces endovascular injury having potential significance to development of clinically overt cardiotoxicity

    DEFF Research Database (Denmark)

    Jensen, Søren Astrup; Sørensen, Jens Benn

    2012-01-01

    This study aimed to elucidate the influence of 5-fluorouracil (5-FU)-based therapy on the vascular endothelium and its association with 5-FU-induced heart ischemia.......This study aimed to elucidate the influence of 5-fluorouracil (5-FU)-based therapy on the vascular endothelium and its association with 5-FU-induced heart ischemia....

  13. CB1 cannabinoid receptors are involved in neuroleptic-induced enhancement of brain neurotensin

    Directory of Open Access Journals (Sweden)

    Parichehr Hassanzadeh

    2014-03-01

    Full Text Available Objective(s: Targeting the neuropeptide systems has been shown to be useful for the development of more effective antipsychotic drugs. Neurotensin, an endogenous neuropeptide, appears to be involved in the mechanism of action of antipsychotics. However, the available data provide conflicting results and the mechanism(s by which antipsychotics affect brain neurotensin neurotransmission have not been identified. Therefore, we aimed to investigate the effects of fluphenazine and amisulpride on brain regional contents of neurotensin considering the role of cannabinoid CB1 receptors which interact with neurotensin neurotransmission. Materials and Methods:Fluphenazine (0.5, 1, and 3 mg/kg or amisulpride (3, 5, and 10 mg/kg were administered intraperitoneally to male Wistar rats either for one day or 28 consecutive days.Twenty four hours after the last injection of drug or vehicle, neurotensin contents were determined in the mesocorticolimbic and nigrostriatal dopamine regions by radioimmunoassay. In the case of any significant change, the effect of pre-treatment with CB1 receptor antagonist, AM251 was investigated. Results:Chronic, but not acute, treatment with the highest dose of fluphenazine or amisulpride resulted in significant enhancement of neurotensin contents in the prefronatal cortex and nucleus accumbens. Fluphenazine also elevated neurotensin levels in the anterior and posterior caudate nuclei and substantia nigra. Neither amisulpride nor fluphenazine affected neurotensin contents in the amygdala or hippocampus. Pre-treatment with AM251 (3 mg/kg prevented the neuroleptic-induced elevation of neurotensin. AM251 showed no effect by itself. Conclusion:The brain neurotensin under the regulatory action of CB1 receptors is involved in[T1]  the effects of amisulpride and fluphenazine.

  14. Ion irradiation induced enhancement of out-of-plane magnetic anisotropy in ultrathin Co films

    Energy Technology Data Exchange (ETDEWEB)

    Mazalski, P.; Kurant, Z.; Maziewski, A. [Faculty of Physics, University of Bialystok, Bialystok (Poland); Liedke, M. O.; Fassbender, J. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Baczewski, L. T.; Wawro, A. [Institute of Physics, Polish Academy of Science, Warszawa (Poland)

    2013-05-07

    Ga{sup +} or He{sup +} irradiated MBE grown ultrathin films of sapphire/Pt/Co(d{sub Co})/Pt(d{sub Pt}) were studied using polar Kerr effect in wide ranges of both cobalt d{sub Co} and platinum d{sub Pt} thicknesses as well as ion fluences F. Two branches of increased magnetic anisotropy and enhanced Kerr rotation angle induced by Ga{sup +} or He{sup +} irradiation are clearly visible in two-dimensional (d{sub Co}, LogF) diagrams. Only Ga{sup +} irradiation induces two branches of out-of-plane magnetization state.

  15. Semiconductor quantum dots enhanced graphene/CdTe heterostructure solar cells by photo-induced doping

    CERN Document Server

    Li, Xiaoqiang; Wang, Peng; Xu, Zhijuan; Zhong, Huikai; Wu, Zhiqian; Lin, Shisheng

    2015-01-01

    Photo-induced doping is employed into graphene based solar cell through designing of a novel type of solar cell based on graphene/CdTe Schottky heterostructure. By coating a layer of ultrathin CdSe quantum dots onto graphene/CdTe heterostructure, the performance of the graphene/CdTe solar cell is improved by about 50%. Photo-induced doping is mainly accounted for this enhancement, as evidenced by resistance, photoluminescence and quantum efficiency measurements. This work demonstrates a general and feasible way of designing novel type of solar cells based on two dimensional materials/semiconductor heterostructures.

  16. Enhanced acceleration of injected electrons in a laser-beat-wave-induced plasma channel.

    Science.gov (United States)

    Tochitsky, S Ya; Narang, R; Filip, C V; Musumeci, P; Clayton, C E; Yoder, R B; Marsh, K A; Rosenzweig, J B; Pellegrini, C; Joshi, C

    2004-03-05

    Enhanced energy gain of externally injected electrons by a approximately 3 cm long, high-gradient relativistic plasma wave (RPW) is demonstrated. Using a CO2 laser beat wave of duration longer than the ion motion time across the laser spot size, a laser self-guiding process is initiated in a plasma channel. Guiding compensates for ionization-induced defocusing (IID) creating a longer plasma, which extends the interaction length between electrons and the RPW. In contrast to a maximum energy gain of 10 MeV when IID is dominant, the electrons gain up to 38 MeV energy in a laser-beat-wave-induced plasma channel.

  17. Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic Catastrophe and Tumor Growth Delay in Glioblastoma.

    Science.gov (United States)

    Gordon, Ira K; Lu, Jie; Graves, Christian A; Huntoon, Kristin; Frerich, Jason M; Hanson, Ryan H; Wang, Xiaoping; Hong, Christopher S; Ho, Winson; Feldman, Michael J; Ikejiri, Barbara; Bisht, Kheem; Chen, Xiaoyuan S; Tandle, Anita; Yang, Chunzhang; Arscott, W Tristram; Ye, Donald; Heiss, John D; Lonser, Russell R; Camphausen, Kevin; Zhuang, Zhengping

    2015-07-01

    Protein phosphatase 2A (PP2A) is a tumor suppressor whose function is lost in many cancers. An emerging, though counterintuitive, therapeutic approach is inhibition of PP2A to drive damaged cells through the cell cycle, sensitizing them to radiotherapy. We investigated the effects of PP2A inhibition on U251 glioblastoma cells following radiation treatment in vitro and in a xenograft mouse model in vivo. Radiotherapy alone augmented PP2A activity, though this was significantly attenuated with combination LB100 treatment. LB100 treatment yielded a radiation dose enhancement factor of 1.45 and increased the rate of postradiation mitotic catastrophe at 72 and 96 hours. Glioblastoma cells treated with combination LB100 and radiotherapy maintained increased γ-H2AX expression at 24 hours, diminishing cellular repair of radiation-induced DNA double-strand breaks. Combination therapy significantly enhanced tumor growth delay and mouse survival and decreased p53 expression 3.68-fold, compared with radiotherapy alone. LB100 treatment effectively inhibited PP2A activity and enhanced U251 glioblastoma radiosensitivity in vitro and in vivo. Combination treatment with LB100 and radiation significantly delayed tumor growth, prolonging survival. The mechanism of radiosensitization appears to be related to increased mitotic catastrophe, decreased capacity for repair of DNA double-strand breaks, and diminished p53 DNA-damage response pathway activity.

  18. 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.

  19. 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.

  20. LRRK2 enhances oxidative stress-induced neurotoxicity via its kinase activity.

    Science.gov (United States)

    Heo, Hye Young; Park, Ji-Min; Kim, Cy-Hyun; Han, Baek Soo; Kim, Kwang-Soo; Seol, Wongi

    2010-02-15

    LRRK2 is an autosomal dominant gene whose mutations cause familial Parkinson's disease (PD). The LRRK2 protein contains a functional kinase and a GTPase domain. PD phenotypes caused by LRRK2 mutations are similar to those of idiopathic PD, implying that LRRK2 is an important participant in PD pathogenesis. Of LRRK2's PD-specific mutations, the G2019S is the most frequently observed one. Its over-expression is known to increase kinase activity and neurotoxicity compared to wild type (WT) LRRK2. Here, using a simple colorimetric cell viability assay, we analyzed LRRK2's neurotoxicity in dopaminergic SN4741 cells following treatment with hydrogen peroxide. When WT, G2019S, or empty vector was expressed in SN4741 cells, cell death was modestly and significantly increased in the order of G2019S>WT>vector. When these transfected cells were treated with hydrogen peroxide to mimic oxidative stress, cellular neurotoxicity was enhanced in the same order (i.e. G2019S>WT>vector). Moreover, incubation of SN4741 cells with conditioned medium from cells expressing G2019S and subjected to hydrogen peroxide treatment exhibited 10-15% more cell death than conditioned medium from cells transfected with vector or WT, suggesting that G2019S-expressing cells secrete a factor(s) affecting viability of neighboring cells. The kinase domain was mapped to be responsible for oxidative stress-induced neurotoxicity. In addition, over-expression of WT and G2019S LRRK2 lead to a weak, but significant, increase in intracellular reactive oxygen species (ROS) in the order of G2019S>WT as measured by DCFH-DA assay in both the presence and absence of H(2)O(2) treatment. Furthermore, in G2019S-expressing cells, co-expression of the anti-oxidant protein DJ-1 or ERK inhibitor treatment restored survival rate to a level similar to that of cells transfected with control vector under H(2)O(2) treatment. Taken together, our data suggest that the LRRK2 kinase domain increases the generation of ROS and causes

  1. Enhanced emission and photoconductivity due to photo-induced charge transfer from Au nanoislands to ZnO

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Shang-Hsuan; Chan, Ching-Hsiang; Liang, Ching-Tarng [Research Center for Applied Sciences, Academia Sinica, Taipei 115, Taiwan (China); Chien, Ching-Hang; Yaseen, Mohammad Tariq [Research Center for Applied Sciences, Academia Sinica, Taipei 115, Taiwan (China); Nano Science and Technology Program, TIGP, Academia Sinica, Taipei 115, Taiwan (China); Department of Engineering and System Science, National Tsing Hua University, Hsinchu 300, Taiwan (China); Chang, Yia-Chung, E-mail: yiachang@gate.sinica.edu.tw [Research Center for Applied Sciences, Academia Sinica, Taipei 115, Taiwan (China); Department of Physics, National Cheng Kung University, Tainan 701, Taiwan (China)

    2016-01-25

    We report systematic studies based on photoluminescence, Hall, and photoconductivity measurements together with theoretical modeling in order to identify mechanisms for the photo-induced charge transfer effects in ZnO thin film incorporated with the Au nano-islands (AuNIs). Significant enhancement of near band edge emission and improvement in conductivity of ZnO/AuNIs samples after illumination are observed, which are attributed to the photo-induced hot electrons in Au which are then transferred into the conduction band of ZnO as long as the excitation energy is higher than the offset between the ZnO conduction-band minimum and Au Fermi level. Our experimental results are consistent with the general features predicted by first principles calculations.

  2. Expression of early growth response factor-1 in rats with cerulein-induced acute pancreatitis and its significance

    Institute of Scientific and Technical Information of China (English)

    Lan-Bo Gong; Li He; Yang Liu; Xue-Qing Chen; Bo Jiang

    2005-01-01

    AIM: To observe the expressions of early growth response factor-1 (Egr-L) and tissue factor (TF) in rats with cerulein-induced acute pancreatitis and to explore its significance.METHODS: A large dose of cerulein was used to create the experimental acute pancreatitis model in rats. The changes of Egr-1 mRNA and protein in rats were observed during 30 min to 4 h after the treatment and immunohistochemical method was used to observe the localized expression of Egr-1 in tissues. In addition to the mRNA expression of Egr-1 target gene, TF was also observed. A blank control group, and a bombesinadministered group were used for comparison.RESULTS: After the stimulation of a large dose of cerulein,the rats showed typical inflammatory changes of acute pancreatitis. Thirty minutes after the stimulation, the mRNA expression of Egr-1 in the pancreatic tissue reached its peak and then declined, while the expression of Egr-1protein reached its peak 2 h after the stimulation.Histologically, 2 h after the stimulation, almost all pancreatic acinar cells had the expression of Egr-1 protein,which was focused in the nuclei. The mRNA expression of TF occurred 1 h after the stimulation and gradually increased within 4 h. However, a large dose of bombesin only stimulated the pancreatic tissue to produce a little mRNA expression of Egr-1 and no mRNA expression of Egr-1 protein and TF.CONCLUSION: Egr-1 as a pro-inflammatory transcription factor may play an important role in the pathogenesis of acute pancreatitis by modulating the expression of TF.

  3. Electric field-induced emission enhancement and modulation in individual CdSe nanowires.

    Science.gov (United States)

    Vietmeyer, Felix; Tchelidze, Tamar; Tsou, Veronica; Janko, Boldizsar; Kuno, Masaru

    2012-10-23

    CdSe nanowires show reversible emission intensity enhancements when subjected to electric field strengths ranging from 5 to 22 MV/m. Under alternating positive and negative biases, emission intensity modulation depths of 14 ± 7% are observed. Individual wires are studied by placing them in parallel plate capacitor-like structures and monitoring their emission intensities via single nanostructure microscopy. Observed emission sensitivities are rationalized by the field-induced modulation of carrier detrapping rates from NW defect sites responsible for nonradiative relaxation processes. The exclusion of these states from subsequent photophysics leads to observed photoluminescence quantum yield enhancements. We quantitatively explain the phenomenon by developing a kinetic model to account for field-induced variations of carrier detrapping rates. The observed phenomenon allows direct visualization of trap state behavior in individual CdSe nanowires and represents a first step toward developing new optical techniques that can probe defects in low-dimensional materials.

  4. Bacteria-induced or bacterial product-induced preterm parturition in mice and rabbits is preceded by a significant fall in serum progesterone concentrations.

    Science.gov (United States)

    Fidel, P I; Romero, R; Maymon, E; Hertelendy, F

    1998-01-01

    Bacterial products are thought to induce labor by stimulating the production of pro-inflammatory cytokines and prostaglandins in gestational tissues, leading to the onset of preterm parturition. Progesterone withdrawal is a prerequisite of parturition in many species. Yet a role for progesterone in the mechanisms responsible for preterm parturition, in the setting of infection, is unclear. The current studies were conducted to determine if a fall in serum progesterone concentrations occurs before the onset of bacterial product-induced preterm parturition in animals. Accordingly, pregnant mice at day 15 (70% gestation) were injected i.p. with Escherichia coli lipopolysaccharide (LPS; 50 microg/mouse) and timed-pregnant rabbits were inoculated transcervically with a suspension of E. coli to cause an ascending intrauterine infection. Control animals in both groups received equal volumes of sterile phosphate-buffered saline (PBS) solution. Blood specimens were collected at regular intervals and serum progesterone levels were determined by RIA. Within 14 h of LPS administration, mice delivered their pups. The median concentrations of serum progesterone were significantly lower at 1 h, 4 h, 10 h, and at the onset of preterm parturition (11-12 h) after LPS injection, compared to that in animals given PBS. Similarly, E. coli-inoculated rabbits delivered 1-2 days posttranscervical inoculation and demonstrated 60% decrease in serum progesterone within 12-24 h of inoculation compared to those given PBS. Parturition in both control groups occurred at term, following typical progesterone withdrawal. It is concluded that LPS administration to pregnant mice and ascending intrauterine infection in pregnant rabbits is associated with a dramatic fall in serum progesterone concentrations prior to the onset of parturition.

  5. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin.

    Science.gov (United States)

    Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2013-05-01

    Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in adenosine triphosphate (ATP) production. Previously, we showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. Energy-dependent DNA repair is a key determinant of cellular survival after exposure to DNA-damaging agents such as UV radiation. Hence, in this study we investigated whether nicotinamide protection from cellular energy loss influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and exposed them to low-dose solar-simulated UV (ssUV). Excision repair was quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased both the proportion of cells undergoing excision repair and the repair rate in each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by comet assay in keratinocytes and with immunohistochemistry in human skin. Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to be due to enhancement of DNA repair. These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention.

  6. Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming.

    Directory of Open Access Journals (Sweden)

    Nicolas Christoforou

    Full Text Available Transient overexpression of defined combinations of master regulator genes can effectively induce cellular reprogramming: the acquisition of an alternative predicted phenotype from a differentiated cell lineage. This can be of particular importance in cardiac regenerative medicine wherein the heart lacks the capacity to heal itself, but simultaneously contains a large pool of fibroblasts. In this study we determined the cardio-inducing capacity of ten transcription factors to actuate cellular reprogramming of mouse embryonic fibroblasts into cardiomyocyte-like cells. Overexpression of transcription factors MYOCD and SRF alone or in conjunction with Mesp1 and SMARCD3 enhanced the basal but necessary cardio-inducing effect of the previously reported GATA4, TBX5, and MEF2C. In particular, combinations of five or seven transcription factors enhanced the activation of cardiac reporter vectors, and induced an upregulation of cardiac-specific genes. Global gene expression analysis also demonstrated a significantly greater cardio-inducing effect when the transcription factors MYOCD and SRF were used. Detection of cross-striated cells was highly dependent on the cell culture conditions and was enhanced by the addition of valproic acid and JAK inhibitor. Although we detected Ca(2+ transient oscillations in the reprogrammed cells, we did not detect significant changes in resting membrane potential or spontaneously contracting cells. This study further elucidates the cardio-inducing effect of the transcriptional networks involved in cardiac cellular reprogramming, contributing to the ongoing rational design of a robust protocol required for cardiac regenerative therapies.

  7. Exercise training-induced bradycardia: evidence for enhanced parasympathetic regulation without changes in intrinsic sinoatrial node function

    Science.gov (United States)

    Cagnoli, Kristen L.; Csepe, Thomas; Li, Ning; Wright, Patrick; Mohler, Peter J.; Fedorov, Vadim V.

    2015-01-01

    The mechanisms responsible for exercise-induced reductions in baseline heart rate (HR), known as training bradycardia, remain controversial. Therefore, changes in cardiac autonomic regulation and intrinsic sinoatrial nodal (SAN) rate were evaluated using dogs randomly assigned to either a 10- to 12-wk exercise training (Ex, n = 15) or an equivalent sedentary period (Sed, n = 10). Intrinsic HR was revealed by combined autonomic nervous system (ANS) blockade (propranolol + atropine, iv) before and after completion of the study. At the end of the study, SAN function was further evaluated by examining the SAN recovery time (SNRT) following rapid atrial pacing and the response to adenosine in anesthetized animals. As expected, both the response to submaximal exercise and baseline HR significantly (P heart rate variability (HRV; e.g., high-frequency R-R interval variability) significantly (P change in the Sed group. Atropine also induced significantly (P changes in both groups. In contrast, neither intrinsic HR (Ex before, 141.2 ± 6.7; Ex after, 146.0 ± 8.0 vs. Sed before, 143.3 ± 11.1; Sed after, 141.0 ± 11.3 beats per minute), the response to adenosine, corrected SNRT, nor atrial fibrosis and atrial fibrillation inducibility differed in the Ex group vs. the Sed group. These data suggest that in a large-animal model, training bradycardia results from an enhanced cardiac parasympathetic regulation and not from changes in intrinsic properties of the SAN. PMID:25749448

  8. Puerarin enhances superoxide dismutase activity and inhibits RAGE and VEGF expression in retinas of STZ-induced early diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Fang Chen; Hong-Quan Zhang; Jun Zhu; Kai-Yang Liu; Hong Cheng; Guo-Li Li; Shan Xu; Wei-Hong Lv; Zheng-Gao Xie

    2012-01-01

    Objective:To investigate the effects of puerarin on the activity of superoxide dismutase (SOD), and expressions of advanced glycation end-product (AGE) receptor (RAGE) and vascular endothelial growth factor (VEGF) in retinas of streptozotocin (STZ)-induced early diabetic rats. Methods: Diabetic rat models were established by inducing diabetes via intra-peritoneal injection of STZ. Rats were randomly divided into normal (control), diabetic (DM), and DM+puerarin groups. After intra-gastric administration of puerarin (500 mg/kg/day for 4 weeks), levels of SOD and malondialdehyde (MDA) were determined in serum and retina. mRNA and protein expression levels of RAGE and VEGF in retinas were determined by real-time polymerase chain reaction (RT-PCR) (mRNA) and Western blot analysis (protein levels). Results:There was significantly lower SOD activity and significantly higher MDA in serum and retinas of the DM group compared with the two other groups (P<0.05). After treatment with puerarin, SOD activity increased and MDA content decreased in this group (P<0.05). mRNA and protein expression levels of RAGE and VEGF in the DM group were significantly higher than those of the other groups (P<0.05), and decreased after puerarin treatment (P<0.05). Conclusions: Puerarin is able to enhance SOD activity, and inhibit RAGE and VEGF expressions in retinas of STZ-induced early diabetic rats.

  9. 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.

  10. 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

    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...... 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)....

  11. Fermentation enhances Ginkgo biloba protective role on gamma-irradiation induced neuroinflammatory gene expression and stress hormones in rat brain.

    Science.gov (United States)

    Ismail, Amel F M; El-Sonbaty, Sawsan M

    2016-05-01

    Ionizing radiation has attracted a lot of attention due to its beneficial and possible harmful effects to the human population. The brain displays numerous biochemical and functional alterations after exposure to irradiation, which induces oxidative-stress through generation of reactive oxygen species (ROS). The present study evaluated the neuro-protective role of fermented Ginkgo biloba (FGb) leaf extract, compared to non-fermented G. biloba (Gb) leaf extract against γ-irradiation (6Gy) in the rats' brain. The changes of the Gb phytochemical constituents after fermentation, using Aspergillus niger were evaluated by Gas Chromatography-Mass Spectrometry. The results showed a significant decrease in superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and elevation of the calcium level in the brain cytosolic fraction of γ-irradiated rats. Further, significant increases in the malondialdehyde (MDA), the stress hormones (catecholamines); epinephrine (EN), norepinephrine (NE) and dopamine (DA) levels and the interleukin-1-beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) gene expression relative ratio in parallel with a significant decrease in the glutathione (GSH) content and DNA fragmentation in the brain tissues of the γ-irradiated rats were observed. The pre-treatment with Gb extract significantly amended these biochemical parameters. Meanwhile, the pre-treatment with the FGb showed more improvement, compared to Gb, of these biochemical parameters in the brain of γ-irradiated rats, which could be attributed to the enhancement of its antioxidant activity after fermentation. These findings suggested that fermentation enhances the protective effect of Gb in the brain on the neuroinflammation, release of the stress hormones, apoptosis and oxidative damage induced by γ-irradiation. fermentation improved the bio-activities of Gb leaf extract and thus enhanced the in-vivo antioxidant, anti-apoptotic and anti-inflammatory activities, leading to

  12. Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Choe, Tae-Boo [Department of Microbiological Engineering, Kon-Kuk University, Gwangjin-gu, Seoul (Korea, Republic of); Hong, Seok-Il [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Yi, Jae-Youn [Laboratory of Modulation of Radiobiological Responses, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Lee, Hyun-Gyu [Department of Microbiology and Immunology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Lee, Yun-Han, E-mail: yhlee87@yuhs.ac [Department of Radiation Oncology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Park, In-Chul, E-mail: parkic@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of)

    2014-07-11

    Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

  13. 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.

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

    Science.gov (United States)

    Liraz, Ori; Rosenblum, Kobi; Barkai, Edi

    2009-01-01

    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.

  15. The memory-enhancing effect of erucic acid on scopolamine-induced cognitive impairment in mice.

    Science.gov (United States)

    Kim, Eunji; Ko, Hae Ju; Jeon, Se Jin; Lee, Sunhee; Lee, Hyung Eun; Kim, Ha Neul; Woo, Eun-Rhan; Ryu, Jong Hoon

    2016-03-01

    Erucic acid is a monounsaturated omega-9 fatty acid isolated from the seed of Raphanus sativus L. that is known to normalize the accumulation of very long chain fatty acids in the brains of patients suffering from X-linked adrenoleukodystrophy. Here, we investigated whether erucic acid enhanced cognitive function or ameliorated scopolamine-induced memory impairment using the passive avoidance, Y-maze and Morris water maze tasks. Erucic acid (3mg/kg, p.o.) enhanced memory performance in normal naïve mice. In addition, erucic acid (3mg/kg, p.o.) ameliorated scopolamine-induced memory impairment, as assessed via the behavioral tasks. We then investigated the underlying mechanism of the memory-enhancing effect of erucic acid. The administration of erucic acid increased the phosphorylation levels of phosphatidylinositide 3-kinase (PI3K), protein kinase C zeta (PKCζ), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB) and additional protein kinase B (Akt) in the hippocampus. These results suggest that erucic acid has an ameliorative effect in mice with scopolamine-induced memory deficits and that the effect of erucic acid is partially due to the activation of PI3K-PKCζ-ERK-CREB signaling as well as an increase in phosphorylated Akt in the hippocampus. Therefore, erucic acid may be a novel therapeutic agent for diseases associated with cognitive deficits, such as Alzheimer's disease.

  16. SIRT1 Overexpression in Mouse Hippocampus Induces Cognitive Enhancement Through Proteostatic and Neurotrophic Mechanisms.

    Science.gov (United States)

    Corpas, Rubén; Revilla, Susana; Ursulet, Suzanna; Castro-Freire, Marco; Kaliman, Perla; Petegnief, Valérie; Giménez-Llort, Lydia; Sarkis, Chamsy; Pallàs, Mercè; Sanfeliu, Coral

    2017-09-01

    SIRT1 induces cell survival and has shown neuroprotection against amyloid and tau pathologies in Alzheimer's disease (AD). However, protective effects against memory loss or the enhancement of cognitive functions have not yet been proven. We aimed to investigate the benefits induced by SIRT1 overexpression in the hippocampus of the AD mouse model 3xTg-AD and in control non-transgenic mice. A lentiviral vector encoding mouse SIRT1 or GFP, selectively transducing neurons, was injected into the dorsal CA1 hippocampal area of 4-month-old mice. Six-month overexpression of SIRT1 fully preserved learning and memory in 10-month-old 3xTg-AD mice. Remarkably, SIRT1 also induced cognitive enhancement in healthy non-transgenic mice. Neuron cultures of 3xTg-AD mice, which show traits of AD-like pathology, and neuron cultures from non-transgenic mice were also transduced with lentiviral vectors to analyze beneficial SIRT1 mechanisms. We uncovered novel pathways of SIRT1 neuroprotection through enhancement of cell proteostatic mechanisms and activation of neurotrophic factors not previously reported such as GDNF, present in both AD-like and healthy neurons. Therefore, SIRT1 may increase neuron function and resilience against AD.

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

    Energy Technology Data Exchange (ETDEWEB)

    Laduca, F.M.; Bell, W.R.; Bettigole, R.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA) State Univ. of New York, Buffalo (USA))

    1987-11-01

    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 ({sup 3}H)serotonin, or alter the dose-responsive binding of {sup 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.

  18. Gomisin N isolated from Schisandra chinensis significantly induces anti-proliferative and pro-apoptotic effects in hepatic carcinoma.

    Science.gov (United States)

    Yim, Su Youn; Lee, You Jin; Lee, Yoen Kyung; Jung, Seung Eun; Kim, Ji Ha; Kim, Hak Jin; Son, Beung Gu; Park, Young Hoon; Lee, Young Guen; Choi, Young Whan; Hwang, Dae Youn

    2009-01-01

    Lignans isolated from Schisandria chinensis have been prescribed as anti-cancer and anti-hepatitis treatments in Chinese medicine. To investigate the applications of lignans isolated from Schisandria chinensis in hepatic carcinoma therapy, their apoptotic ability was screened using a cell proliferation assay. Compared to the other lignans, gomisin N induced high apoptotic levels in hepatic carcinoma. Cell morphology and flow cytometric analysis demonstrated that this lignan induced cell death at high concentrations, but did not induce any changes at low concentrations. In addition, the expression levels of Bcl-2 and Bax proteins, which are involved in the apoptotic pathway, were markedly increased in only the 320 µM-treated group compared to the vehicle and other concentration groups, while the expression level of p53 protein remained unchanged in this group. These results suggest that gomisin N is an anti-cancer drug candidate capable of inhibiting the proliferation and inducing the apoptosis of human hepatic carcinomas.

  19. Richtmyer-Meshkov Instability Induced Mixing Enhancement in the Scramjet Combustor with a Central Strut

    Directory of Open Access Journals (Sweden)

    Qingchun Yang

    2014-01-01

    Full Text Available Experimental and numerical study of Richtmyer-Meshkov instability (RMI induced mixing enhancement has been conducted in a liquid-fueled scramjet engine with a central strut. To generate the RMI in the scramjet engine, transverse high temperature jets are employed downstream the strut injector. Compared to the transverse ordinary temperature jet, the jet penetration into the supersonic airstream of high temperature jet increases by 60%. The numerical results indicate that the RMI phenomenon markedly enhances the mixing efficiency (up to 43%, which is necessary to initiate the chemical reactions. Ground experiments were carried out in the combustor, which verify the numerical method from the perspective of wall pressures of the combustor. In particular, the experiment results indicate that the RMI can benefit flame-holding due to the mixing enhancement.

  20. ENHANCEMENT OF RADIATION-INDUCED APOPTOSIS IN RAJI CELL LINE BY BC1-2 ANTISENSE OLIGODEOXYNUCLEOTIDE

    Institute of Scientific and Technical Information of China (English)

    HE Dong-mei; ZHANG Huan

    2005-01-01

    Objective: To investigate whether the Bc1-2 antisense oligonucleotide(ASODN) may enhance radiation-induced apoptosis in Raji cell line. Methods: Cell surviving fraction was determined using the trypan blue dye exclusion assay. The expression level of bc1-2 protein was assayed by immunofluorescence using fluoresce isothiocyanate label. Apoptosis was detected by Giemsa staining and flow cytomertric cell cycle analysis. Results: It was found that Bc1-2 ASODN combined with radiation had significantly reduced the number of viable cells (P<0.05). There was no difference on cell survival between mismatch Bc1-2 oligodeoxynucleotide/radiation combination and radiation-treated cells alone. Bc1-2 ASODN combined with radiation could significantly inhibit expression of Bc1-2 protein in Raji cells (P<0.05). Cells treated with Bc1-2 ASODN combined with radiation at 72 h displayed classic apoptotic changes. Apoptosis rates of Raji cells treated with Bc1-2 oligodeoxynucleotide/radiation combination and radiation-treated cells alone, respectively. Conclusion: Bc1-2 antisense oligonucleotide can enhance radiation-induced apoptosis in Raji cell line.

  1. 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.

  2. Synthetic Beta-Lactam Antibiotic as a Selective Breast Cancer Cell Apoptosis Inducer: Significance in Breast Cancer Prevention and Treatment

    Science.gov (United States)

    2005-04-01

    954. 48 Wan SB, Chen D, Dou OP, and Chan TH. Study of the green tea polyphenols catechin -3-gallate (CG) and epicatechin-3-gallate (ECG) as proteasome... tea polyphenol epigallocatechin inhibits [26] Coultas L, Strasser A. The molecular control of DNA damage-induced DNA replication and consequently...Pommier Y. [20] Nam S, Smith DM, Dou QP. Ester bond-containing tea polyphenols Protein-linked DNA strand breaks induced by NSC 314622, a novel potently

  3. Pressure induced manifold enhancement of Li-kinetics in FCC fullerene.

    Science.gov (United States)

    Das, Deya; Han, Sang Soo; Lee, Kwang-Ryeol; Singh, Abhishek K

    2014-10-21

    The reduction of the diffusion energy barrier for Li in electrodes is one of the required criteria to achieve better performances in Li ion batteries. Using density functional theory based calculations, we report a pressure induced manifold enhancement of Li-kinetics in bulk FCC fullerene. Scanning of the potential energy surface reveals a diffusion path with a low energy barrier of 0.62 eV, which reduces further under the application of hydrostatic pressure. The pressure induced reduction in the diffusion barrier continues till a uniform volume strain of 17.7% is reached. Further enhancement of strain increases the barrier due to the repulsion caused by C-C bond formation between two neighbouring fullerenes. The decrease in the barrier is attributed to the combined effect of charge transfer triggered by the enhanced interaction of Li with the fullerene as well as the change in profile of the local potential, which becomes more attractive for Li. The lowering of the barrier leads to an enhancement of two orders of magnitude in Li diffusivity at room temperature making pressurized bulk fullerene a promising artificial solid electrolyte interface (SEI) for a faster rechargeable battery.

  4. Metabotropic glutamate subtype 5 receptors modulate fear-conditioning induced enhancement of prepulse inhibition in rats.

    Science.gov (United States)

    Zou, Dan; Huang, Juan; Wu, Xihong; Li, Liang

    2007-02-01

    Non-startling acoustic events presented shortly before an intense startling sound can inhibit the acoustic startle reflex. This phenomenon is called prepulse inhibition (PPI), and is widely used as a model of sensorimotor gating. The present study investigated whether PPI can be modulated by fear conditioning, whose acquisition can be blocked by the specific antagonist of metabotropic glutamate receptors subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)-pyridine (MPEP). The results show that a gap embedded in otherwise continuous noise sounds, which were delivered by two spatially separated loudspeakers, could inhibit the startle reflex induced by an intense sound that was presented 50 ms after the gap. The inhibitory effect depended on the duration of the gap, and was enhanced by fear conditioning that was introduced by temporally pairing the gap with footshock. Intraperitoneal injection of MPEP (0.5 or 5mg/kg) 30 min before fear conditioning blocked the enhancing effect of fear conditioning on PPI, but did not affect either the baseline startle magnitude or PPI if no fear conditioning was introduced. These results indicate that PPI is enhanced when the prepulse signifies an aversive event after fear conditioning. Also, mGlu5Rs play a role in preserving the fear-conditioning-induced enhancement of PPI.

  5. Nuclear factor-kappa B inhibition can enhance apoptosis of differentiated thyroid cancer cells induced by 131I.

    Directory of Open Access Journals (Sweden)

    Zhaowei Meng

    Full Text Available OBJECTIVE: To evaluate changes of nuclear factor-kappa B (NF-κB during radioiodine 131 ((131I therapy and whether NF-κB inhibition could enhance (131I-induced apoptosis in differentiated thyroid cancer (DTC cells in a synergistic manner. METHODS: Three human DTC cell lines were used. NF-κB inhibition was achieved by using a NF-κB inhibitor (Bay 11-7082 or by p65 siRNA transfection. Methyl-thiazolyl-tetrazolium assay was performed for cell viability assessment. DNA-binding assay, luciferase reporter assay, and Western blot were adopted to determine function and expression changes of NF-κB. Then NF-κB regulated anti-apoptotic factors XIAP, cIAP1, and Bcl-xL were measured. Apoptosis was analyzed by Western blot for caspase 3 and PARP, and by flow cytometry as well. An iodide uptake assay was performed to determine whether NF-κB inhibition could influence radioactive iodide uptake. RESULTS: The methyl-thiazolyl-tetrazolium assay showed significant decrease of viable cells by combination therapy than by mono-therapies. The DNA-binding assay and luciferase reporter assay showed enhanced NF-κB function and reporter gene activities due to (131I, yet significant suppression was achieved by NF-κB inhibition. Western blot proved (131I could increase nuclear NF-κB concentration, while NF-κB inhibition reduced NF-κB concentration. Western blot also demonstrated significant up-regulation of XIAP, cIAP1, and Bcl-xL after (131I therapy. And inhibition of NF-κB could significantly down-regulate these factors. Finally, synergism induced by combined therapy was displayed by significant enhancements of cleaved caspase 3 and PARP from Western blot, and of Annexin V positively staining from flow cytometry. The iodine uptake assay did not show significant changes when NF-κB was inhibited. CONCLUSION: We demonstrated that (131I could induce NF-κB activation, which would attenuate (131I efficacy in DTC cells. NF-κB inhibition by Bay 11-7082 or by p65 si

  6. Optimally enhanced optical emission in laser-induced breakdown spectroscopy by combining spatial confinement and dual-pulse irradiation.

    Science.gov (United States)

    Guo, L B; Zhang, B Y; He, X N; Li, C M; Zhou, Y S; Wu, T; Park, J B; Zeng, X Y; Lu, Y F

    2012-01-16

    In laser-induced breakdown spectroscopy (LIBS), a pair of aluminum-plate walls were used to spatially confine the plasmas produced in air by a first laser pulse (KrF excimer laser) from chromium (Cr) targets with a second laser pulse (Nd:YAG laser at 532 nm, 360 mJ/pulse) introduced parallel to the sample surface to re-excite the plasmas. Optical emission enhancement was achieved by combing the spatial confinement and dual-pulse LIBS (DP-LIBS), and then optimized by adjusting the distance between the two walls and the interpulse delay time between both laser pulses. A significant enhancement factor of 168.6 for the emission intensity of the Cr lines was obtained at an excimer laser fluence of 5.6 J/cm(2) using the combined spatial confinement and DP-LIBS, as compared with an enhancement factor of 106.1 was obtained with DP-LIBS only. The enhancement mechanisms based on shock wave theory and reheating in DP-LIBS are discussed.

  7. Penetration pathways induced by low-frequency sonophoresis with physical and chemical enhancers: iron oxide nanoparticles versus lanthanum nitrates.

    Science.gov (United States)

    Lee, Sang Eun; Choi, Ki Ju; Menon, Gopinathan K; Kim, Hyun Jung; Choi, Eung Ho; Ahn, Sung Ku; Lee, Seung Hun

    2010-04-01

    Low-frequency sonophoresis (LFS) has been shown to disrupt the structure of stratum corneum (SC) lipid bilayers and enhance SC permeability. In this study, we examined the penetration pathway of lanthanum nitrate (LaNO(3)) tracer in viable epidermis after combined treatment of LFS and tape stripping (TS), as a physical enhancer, or oleic acid (OA) application, as a chemical enhancer, using transmission electron microscopy (TEM). As a positive control, we visualized the passive diffusion pathway of LaNO(3) and iron oxide (Fe(3)O(4)) nanoparticles after the incision of hairless mouse skin. Next, we applied LFS immediately after TS or OA application and visualized the penetration pathway of LaNO(3). Each treatment showed restricted penetration to the SC-stratum granulosum (SG) interface or upper SG layer. However, the additional application of LFS induced diffuse intracellular distribution of LaNO(3) throughout the viable epidermis. Quantitative analysis also revealed that combined treatment significantly increases LaNO(3) penetration into viable epidermis when compared with each treatment. Our ultrastructural findings show the synergistic effect of LFS and TS or OA application on transdermal drug delivery. We also found that this combined treatment enhances the penetration of LaNO(3) through the viable epidermis through an intracellular pathway.

  8. Amino acid substitutions in the FXYD motif enhance phospholemman-induced modulation of cardiac L-type calcium channels.

    Science.gov (United States)

    Guo, Kai; Wang, Xianming; Gao, Guofeng; Huang, Congxin; Elmslie, Keith S; Peterson, Blaise Z

    2010-11-01

    We have found that phospholemman (PLM) associates with and modulates the gating of cardiac L-type calcium channels (Wang et al., Biophys J 98: 1149-1159, 2010). The short 17 amino acid extracellular NH(2)-terminal domain of PLM contains a highly conserved PFTYD sequence that defines it as a member of the FXYD family of ion transport regulators. Although we have learned a great deal about PLM-dependent changes in calcium channel gating, little is known regarding the molecular mechanisms underlying the observed changes. Therefore, we investigated the role of the PFTYD segment in the modulation of cardiac calcium channels by individually replacing Pro-8, Phe-9, Thr-10, Tyr-11, and Asp-12 with alanine (P8A, F9A, T10A, Y11A, D12A). In addition, Asp-12 was changed to lysine (D12K) and cysteine (D12C). As expected, wild-type PLM significantly slows channel activation and deactivation and enhances voltage-dependent inactivation (VDI). We were surprised to find that amino acid substitutions at Thr-10 and Asp-12 significantly enhanced the ability of PLM to modulate Ca(V)1.2 gating. T10A exhibited a twofold enhancement of PLM-induced slowing of activation, whereas D12K and D12C dramatically enhanced PLM-induced increase of VDI. The PLM-induced slowing of channel closing was abrogated by D12A and D12C, whereas D12K and T10A failed to impact this effect. These studies demonstrate that the PFXYD motif is not necessary for the association of PLM with Ca(V)1.2. Instead, since altering the chemical and/or physical properties of the PFXYD segment alters the relative magnitudes of opposing PLM-induced effects on Ca(V)1.2 channel gating, PLM appears to play an important role in fine tuning the gating kinetics of cardiac calcium channels and likely plays an important role in shaping the cardiac action potential and regulating Ca(2+) dynamics in the heart.

  9. Gene-carried hepatoma targeting complex induced high gene transfection efficiency with low toxicity and significant antitumor activity

    Directory of Open Access Journals (Sweden)

    Zhao QQ

    2012-06-01

    was confirmed and the vector showed low cytotoxicity and strong targeting specificity to liver tumors in vitro. The in vivo study results showed that interleukin-12 delivered by the new gene vector CPT/DNA significantly enhanced the antitumor effect on ascites tumor-bearing imprinting control region mice as compared with polyethylenimine (25 kDa, CP, and other controls, which further demonstrate the targeting specificity of the new synthesized polymer.Conclusion: The synthesized CPT copolymer was proven to be an effective liver cancer-targeted vector for therapeutic gene delivery, which could be a potential candidate for targeted cancer gene therapy.Keywords: targeting, peptide, polyethylenimine, chitosan, antitumor

  10. Magnetic domain-wall velocity enhancement induced by a transverse magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jusang, E-mail: jsyang@physics.utexas.edu [Department of Physics, The University of Texas at Austin, Austin, TX 78712-1081 (United States); Beach, Geoffrey S.D. [Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Knutson, Carl; Erskine, James L. [Department of Physics, The University of Texas at Austin, Austin, TX 78712-1081 (United States)

    2016-01-01

    Spin dynamics of field-driven domain walls (DWs) guided by permalloy nanowires are studied by high-speed magneto-optic polarimetry and numerical simulations. DW velocities and spin configurations are determined as functions of longitudinal drive field, transverse bias field, and nanowire width. Nanowires having cross-sectional dimensions large enough to support vortex wall structures exhibit regions of drive-field strength (at zero bias field) that have enhanced DW velocity resulting from coupled vortex structures that suppress oscillatory motion. Factor of 10 enhancements of the DW velocity are observed above the critical longitudinal drive-field (that marks the onset of oscillatory DW motion) when a transverse bias field is applied. Nanowires having smaller cross-sectional dimensions that support transverse wall structures also exhibit a region of higher mobility above the critical field, and similar transverse-field induced velocity enhancement but with a smaller enhancement factor. The bias-field enhancement of DW velocity is explained by numerical simulations of the spin distribution and dynamics within the propagating DW that reveal dynamic stabilization of coupled vortex structures and suppression of oscillatory motion in the nanowire conduit resulting in uniform DW motion at high speed. The enhanced velocity and drive field range are achieved at the expense of a less compact DW spin distribution. - Highlights: • The transverse magnetic fields can dramatically enhance the domain wall velocity. • The numerical simulation exhibits the four distinct dynamic modes. • Coupled multiple vortex structures within the domain wall become dynamically stable. • The enhanced domain wall velocity is explained by numerical simulations.

  11. Flow-Induced Deformation of a Flexible Thin Structure as Manifestation of Heat Transfer Enhancement

    CERN Document Server

    Soti, Atul Kumar; Sheridan, John

    2015-01-01

    Flow-induced deformation of thin structures coupled with convective heat transfer has potential applications in energy harvesting and is important for understanding functioning of several biological systems. We numerically demonstrate large-scale flow-induced deformation as an effective passive heat transfer enhancement technique. An in-house, strongly-coupled fluid-structure interaction (FSI) solver is employed in which flow and structure solvers are based on sharp-interface immersed boundary and finite element method, respectively. In the present work, we validate convective heat transfer module of the in-house FSI solver against several benchmark examples of conduction and convective heat transfer including moving structure boundaries. The thermal augmentation is investigated as well as quantified for the flow-induced deformation of an elastic thin plate attached to lee side of a rigid cylinder in a heated channel laminar flow. We show that the wake vortices past the plate sweep higher sources of vorticity...

  12. Selective block of IKs plays a