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Sample records for activity significantly enhanced

  1. Significantly Enhanced Visible Light Photoelectrochemical Activity in TiO₂ Nanowire Arrays by Nitrogen Implantation.

    PubMed

    Wang, Gongming; Xiao, Xiangheng; Li, Wenqing; Lin, Zhaoyang; Zhao, Zipeng; Chen, Chi; Wang, Chen; Li, Yongjia; Huang, Xiaoqing; Miao, Ling; Jiang, Changzhong; Huang, Yu; Duan, Xiangfeng

    2015-07-08

    Titanium oxide (TiO2) represents one of most widely studied materials for photoelectrochemical (PEC) water splitting but is severely limited by its poor efficiency in the visible light range. Here, we report a significant enhancement of visible light photoactivity in nitrogen-implanted TiO2 (N-TiO2) nanowire arrays. Our systematic studies show that a post-implantation thermal annealing treatment can selectively enrich the substitutional nitrogen dopants, which is essential for activating the nitrogen implanted TiO2 to achieve greatly enhanced visible light photoactivity. An incident photon to electron conversion efficiency (IPCE) of ∼10% is achieved at 450 nm in N-TiO2 without any other cocatalyst, far exceeding that in pristine TiO2 nanowires (∼0.2%). The integration of oxygen evolution reaction (OER) cocatalyst with N-TiO2 can further increase the IPCE at 450 nm to ∼17% and deliver an unprecedented overall photocurrent density of 1.9 mA/cm(2), by integrating the IPCE spectrum with standard AM 1.5G solar spectrum. Systematic photoelectrochemical and electrochemical studies demonstrated that the enhanced PEC performance can be attributed to the significantly improved visible light absorption and more efficient charge separation. Our studies demonstrate the implantation approach can be used to reliably dope TiO2 to achieve the best performed N-TiO2 photoelectrodes to date and may be extended to fundamentally modify other semiconductor materials for PEC water splitting.

  2. Cationic Polymethacrylate-Modified Liposomes Significantly Enhanced Doxorubicin Delivery and Antitumor Activity

    PubMed Central

    Wang, Wenxi; Shao, Anna; Zhang, Nan; Fang, Jinzhang; Ruan, Jennifer Jin; Ruan, Benfang Helen

    2017-01-01

    Liposome (LP) encapsulation of doxorubicin (DOX) is a clinically validated method for cancer drug delivery, but its cellular uptake is actually lower than the free DOX. Therefore, we modified DOX-LP with a cationic polymer (Eudragit RL100; ER) to improve its cellular uptake and antitumor activity. The resulting DOX-ERLP was a 190 nm nanoparticle that was absorbed efficiently and caused cancer cell death in 5 hrs. Growth as measured by the MTT assay or microscopic imaging demonstrated that DOX-ERLP has at least a two-fold greater potency than the free DOX in inhibiting the growth of a DOX resistant (MCF7/adr) cell and an aggressive liver cancer H22 cell. Further, its in vivo efficacy was tested in H22-bearing mice, where four injections of DOX-ERLP reduced the tumor growth by more than 60% and caused an average of 60% tumor necrosis, which was significantly better than the DOX and DOX-LP treated groups. Our work represents the first use of polymethacrylate derivatives for DOX liposomal delivery, demonstrating the great potential of cationic polymethacrylate modified liposomes for improving cancer drug delivery. PMID:28225062

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Appropriate Fe (II) Addition Significantly Enhances Anaerobic Ammonium Oxidation (Anammox) Activity through Improving the Bacterial Growth Rate

    PubMed Central

    Liu, Yiwen; Ni, Bing-Jie

    2015-01-01

    The application of anaerobic ammonium oxidation (Anammox) process is often limited by the slow growth rate of Anammox bacteria. As the essential substrate element that required for culturing Anammox sludge, Fe (II) is expected to affect Anammox bacterial growth. This work systematically studied the effects of Fe (II) addition on Anammox activity based on the kinetic analysis of specific growth rate using data from batch tests with an enriched Anammox sludge at different dosing levels. Results clearly demonstrated that appropriate Fe (II) dosing (i.e., 0.09 mM) significantly enhanced the specific Anammox growth rate up to 0.172 d−1 compared to 0.118 d−1 at regular Fe (II) level (0.03 mM). The relationship between Fe (II) concentration and specific Anammox growth rate was found to be well described by typical substrate inhibition kinetics, which was integrated into currently well-established Anammox model to describe the enhanced Anammox growth with Fe (II) addition. The validity of the integrated Anammox model was verified using long-term experimental data from three independent Anammox reactors with different Fe (II) dosing levels. This Fe (II)-based approach could be potentially implemented to enhance the process rate for possible mainstream application of Anammox technology, in order for an energy autarchic wastewater treatment. PMID:25644239

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

    PubMed Central

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

    2015-01-01

    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. PMID:25652244

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

    PubMed

    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.

  7. Enhanced activity of the free radical producing enzyme xanthine oxidase in hypoxic rat liver. Regulation and pathophysiologic significance.

    PubMed Central

    Brass, C A; Narciso, J; Gollan, J L

    1991-01-01

    It has been widely proposed that conversion of xanthine dehydrogenase (XDH) to its free radical-producing form, xanthine oxidase (XOD), underlies ischemic/reperfusion injury, although the relationship of this conversion to hypoxia and its physiologic control have not been defined. This study details the time course and control of this enzymatic interconversion. In a functionally intact, isolated perfused rat liver model, mean % XOD activity increased as a function of both the duration (25 to 45% in 3 h) and degree (r = 0.97) of hypoxia. This process was markedly accelerated in ischemic liver by an overnight fast (45 vs. 30% at 2 h), and by imposing a short period of in vivo ischemia (cardiopulmonary arrest 72%). Moreover, only under these conditions was there a significant rise in the XOD activity due to the conformationally altered XDH molecule (XODc, 18%), as well as concomitant morphologic injury. Neither circulating white blood cells nor thrombosis appeared to contribute to the effects of in vivo ischemia on enzyme conversion. Thus, it is apparent that conversion to the free radical-producing state, with high levels of XOD activity and concurrent cellular injury, can be achieved during a relatively short period of hypoxia under certain well-defined physiologic conditions, in a time course consistent with its purported role in modulating reperfusion injury. These data also suggest that the premorbid condition of organ donors (e.g., nutritional status and relative state of hypoxia) is important in achieving optimal organ preservation. Images PMID:1991828

  8. A nanotherapy strategy significantly enhances anticryptosporidial activity of an inhibitor of bifunctional thymidylate synthase-dihydrofolate reductase from Cryptosporidium.

    PubMed

    Mukerjee, Anindita; Iyidogan, Pinar; Castellanos-Gonzalez, Alejandro; Cisneros, José A; Czyzyk, Daniel; Ranjan, Amalendu Prakash; Jorgensen, William L; White, A Clinton; Vishwanatha, Jamboor K; Anderson, Karen S

    2015-01-01

    Cryptosporidiosis, a gastrointestinal disease caused by protozoans of the genus Cryptosporidium, is a common cause of diarrheal diseases and often fatal in immunocompromised individuals. Bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) from Cryptosporidium hominis (C. hominis) has been a molecular target for inhibitor design. C. hominis TS-DHFR inhibitors with nM potency at a biochemical level have been developed however drug delivery to achieve comparable antiparasitic activity in Cryptosporidium infected cell culture has been a major hurdle for designing effective therapies. Previous mechanistic and structural studies have identified compound 906 as a nM C. hominis TS-DHFR inhibitor in vitro, having μM antiparasitic activity in cell culture. In this work, proof of concept studies are presented using a nanotherapy approach to improve drug delivery and the antiparasitic activity of 906 in cell culture. We utilized PLGA nanoparticles that were loaded with 906 (NP-906) and conjugated with antibodies to the Cryptosporidium specific protein, CP2, on the nanoparticle surface in order to specifically target the parasite. Our results indicate that CP2 labeled NP-906 (CP2-NP-906) reduces the level of parasites by 200-fold in cell culture, while NP-906 resulted in 4.4-fold decrease. Moreover, the anticryptosporidial potency of 906 improved 15 to 78-fold confirming the utility of the antibody conjugated nanoparticles as an effective drug delivery strategy.

  9. Significant enhancement in the photocatalytic activity of N, W co-doped TiO2 nanomaterials for promising environmental applications.

    PubMed

    Thind, Sapanbir S; Wu, Guosheng; Tian, Min; Chen, Aicheng

    2012-11-30

    In this work, a mesoporous N, W co-doped TiO(2) photocatalyst was synthesized via a one-step solution combustion method, which utilized urea as the nitrogen source and sodium tungstate as the tungsten source. The photocatalytic activity of the N, W co-doped TiO(2) photocatalyst was significantly enhanced by a facile UV pretreatment approach and was evaluated by measuring the rate of photodegradation of Rhodamine B under both UV and visible (λ > 420) light. Following the UV pretreatment, the UV photocatalytic activity of the N, W co-doped TiO(2) was doubled. In terms of visible light activity, the UV pretreatment resulted in an extraordinary >12 fold improvement. In order to gain insight into this substantial enhancement, the N, W co-doped TiO(2) photocatalysts were studied using x-ray diffraction, transmission electron microscopy, N(2) physisorption, UV-vis absorbance spectroscopy and x-ray photoelectron spectroscopy prior to and following the UV pretreatment. Our experimental results have revealed that this significant augmentation of photocatalytic activity may be attributed to several synergetic factors, including increase of the specific surface area, reduction of the band gap energy and the removal of carbon impurities.

  10. Powerful Complex Immunoadjuvant Based on Synergistic Effect of Combined TLR4 and NOD2 Activation Significantly Enhances Magnitude of Humoral and Cellular Adaptive Immune Responses

    PubMed Central

    Dzharullaeva, Alina S.; Tukhvatulina, Natalia M.; Shcheblyakov, Dmitry V.; Shmarov, Maxim M.; Dolzhikova, Inna V.; Stanhope-Baker, Patricia; Naroditsky, Boris S.; Gudkov, Andrei V.; Logunov, Denis Y.; Gintsburg, Alexander L.

    2016-01-01

    Binding of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) activates innate immune responses and contributes to development of adaptive immunity. Simultaneous stimulation of different types of PRRs can have synergistic immunostimulatory effects resulting in enhanced production of molecules that mediate innate immunity such as inflammatory cytokines, antimicrobial peptides, etc. Here, we evaluated the impact of combined stimulation of PRRs from different families on adaptive immunity by generating alum-based vaccine formulations with ovalbumin as a model antigen and the Toll-like receptor 4 (TLR4) agonist MPLA and the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist MDP adsorbed individually or together on the alum-ovalbumin particles. Multiple in vitro and in vivo readouts of immune system activation all showed that while individual PRR agonists increased the immunogenicity of vaccines compared to alum alone, the combination of both PRR agonists was significantly more effective. Combined stimulation of TLR4 and NOD2 results in a stronger and broader transcriptional response in THP-1 cells compared to individual PRR stimulation. Immunostimulatory composition containing both PRR agonists (MPLA and MDP) in the context of the alum-based ovalbumin vaccine also enhanced uptake of vaccine particles by bone marrow derived dendritic cells (BMDCs) and promoted maturation (up-regulation of expression of CD80, CD86, MHCII) and activation (production of cytokines) of BMDCs. Finally, immunization of mice with vaccine particles containing both PRR agonists resulted in enhanced cellular immunity as indicated by increased proliferation and activation (IFN-γ production) of splenic CD4+ and CD8+ T cells following in vitro restimulation with ovalbumin and enhanced humoral immunity as indicated by higher titers of ovalbumin-specific IgG antibodies. These results indicate that combined stimulation of TLR4 and NOD2

  11. Powerful Complex Immunoadjuvant Based on Synergistic Effect of Combined TLR4 and NOD2 Activation Significantly Enhances Magnitude of Humoral and Cellular Adaptive Immune Responses.

    PubMed

    Tukhvatulin, Amir I; Dzharullaeva, Alina S; Tukhvatulina, Natalia M; Shcheblyakov, Dmitry V; Shmarov, Maxim M; Dolzhikova, Inna V; Stanhope-Baker, Patricia; Naroditsky, Boris S; Gudkov, Andrei V; Logunov, Denis Y; Gintsburg, Alexander L

    2016-01-01

    Binding of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) activates innate immune responses and contributes to development of adaptive immunity. Simultaneous stimulation of different types of PRRs can have synergistic immunostimulatory effects resulting in enhanced production of molecules that mediate innate immunity such as inflammatory cytokines, antimicrobial peptides, etc. Here, we evaluated the impact of combined stimulation of PRRs from different families on adaptive immunity by generating alum-based vaccine formulations with ovalbumin as a model antigen and the Toll-like receptor 4 (TLR4) agonist MPLA and the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist MDP adsorbed individually or together on the alum-ovalbumin particles. Multiple in vitro and in vivo readouts of immune system activation all showed that while individual PRR agonists increased the immunogenicity of vaccines compared to alum alone, the combination of both PRR agonists was significantly more effective. Combined stimulation of TLR4 and NOD2 results in a stronger and broader transcriptional response in THP-1 cells compared to individual PRR stimulation. Immunostimulatory composition containing both PRR agonists (MPLA and MDP) in the context of the alum-based ovalbumin vaccine also enhanced uptake of vaccine particles by bone marrow derived dendritic cells (BMDCs) and promoted maturation (up-regulation of expression of CD80, CD86, MHCII) and activation (production of cytokines) of BMDCs. Finally, immunization of mice with vaccine particles containing both PRR agonists resulted in enhanced cellular immunity as indicated by increased proliferation and activation (IFN-γ production) of splenic CD4+ and CD8+ T cells following in vitro restimulation with ovalbumin and enhanced humoral immunity as indicated by higher titers of ovalbumin-specific IgG antibodies. These results indicate that combined stimulation of TLR4 and NOD2

  12. Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

    PubMed

    Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

    2016-04-04

    The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

  13. Mono- and disaccharides enhance the activity and enantioselectivity of Burkholderia cepacia lipase in organic solvent but do not significantly affect its conformation.

    PubMed

    Secundo, Francesco; Carrea, Giacomo

    2005-11-20

    Sucrose, trehalose, and mannitol were colyophilized with lipase from Burkholderia cepacia and their effects on the activity and enantioselectitivity of the enzyme evaluated using as model reactions the transesterification between n-octanol or 6-methyl-5-hepten-2-ol with vinyl acetate. The lipase co-lyophilized with sugars showed an activity which was up to 4.7-fold higher (at a sugar/lipase ratio >or= 20) than that observed without sugar. Analogously, lipase enantioselectivity, expressed as the enantiomeric ratio, increased up to 2.8-fold in the presence of sugars. The conformation of the lipase was investigated by means of Fourier transform infrared spectroscopy (FT/IR) in water and as lyophilized powder. The infrared spectra of lyophilized lipase in the presence and, even more so, in the absence of sugars were different from that of the enzyme in water. In particular, the band at around 1,654/cm, typically assigned to alpha-helix, was less intense in the lyophilized samples. Nevertheless, the enzyme in the presence of sugars showed a decrease of the bands at 1,614-1,620/cm and at 1,680-1,695/cm that indicates a lower content of intermolecular beta-sheets (typical of protein aggregates). Additionally the increase of the component at 1,546/cm in the amide II region is consistent with a hydrogen bond pattern of the enzyme more similar to that shown in water. These results suggest that although sugars are not able to fully preserve the native secondary structure, they might contribute to reduce the conformational changes caused by protein/protein interactions. These factors in combinations with others (e.g., ability to reduce deleterious interactions between the enzyme and inert supports) make sugars (both mono- and disaccharides) an interesting class of additives for improving the performance of biocatalysts in organic solvents.

  14. Reducing Human-Tsetse Contact Significantly Enhances the Efficacy of Sleeping Sickness Active Screening Campaigns: A Promising Result in the Context of Elimination

    PubMed Central

    Courtin, Fabrice; Camara, Mamadou; Rayaisse, Jean-Baptiste; Kagbadouno, Moise; Dama, Emilie; Camara, Oumou; Traoré, Ibrahima S.; Rouamba, Jérémi; Peylhard, Moana; Somda, Martin B.; Leno, Mamadou; Lehane, Mike J.; Torr, Steve J.; Solano, Philippe; Jamonneau, Vincent; Bucheton, Bruno

    2015-01-01

    Background Control of gambiense sleeping sickness, a neglected tropical disease targeted for elimination by 2020, relies mainly on mass screening of populations at risk and treatment of cases. This strategy is however challenged by the existence of undetected reservoirs of parasites that contribute to the maintenance of transmission. In this study, performed in the Boffa disease focus of Guinea, we evaluated the value of adding vector control to medical surveys and measured its impact on disease burden. Methods The focus was divided into two parts (screen and treat in the western part; screen and treat plus vector control in the eastern part) separated by the Rio Pongo river. Population census and baseline entomological data were collected from the entire focus at the beginning of the study and insecticide impregnated targets were deployed on the eastern bank only. Medical surveys were performed in both areas in 2012 and 2013. Findings In the vector control area, there was an 80% decrease in tsetse density, resulting in a significant decrease of human tsetse contacts, and a decrease of disease prevalence (from 0.3% to 0.1%; p=0.01), and an almost nil incidence of new infections (<0.1%). In contrast, incidence was 10 times higher in the area without vector control (>1%, p<0.0001) with a disease prevalence increasing slightly (from 0.5 to 0.7%, p=0.34). Interpretation Combining medical and vector control was decisive in reducing T. b. gambiense transmission and in speeding up progress towards elimination. Similar strategies could be applied in other foci. PMID:26267667

  15. Histone H2A significantly enhances in vitro DNA transfection.

    PubMed Central

    Balicki, D.; Beutler, E.

    1997-01-01

    BACKGROUND: Gene transfer is a potential treatment modality of genetic disease. Efficient, practical methods of DNA transfection are currently under investigation. MATERIALS AND METHODS: A beta-galactosidase reporter plasmid interacted electrostatically with histones, poly-L-Lys, poly-L-Arg, and a combination of poly-L-Lys and poly-L-Arg. This complex was then used to transfect COS-7 cells. beta-galactosidase activity was quantified and used to compare the efficiency of gene transfection in vitro. A comparison was also made of DNA transfection with the most active histone subclass, i.e., histone H2A, in the absence and presence of an anionic liposome. RESULTS: There was a marked increase in DNA transfection in the presence of histone H2A when compared with the control, whereas each of the other histones and polycations showed little, if any, effect. The extent of activation depends strongly on the DNA/histone ratio and is also a function of the molarity of the final Tris-acetate, pH 8, solution. The anionic liposomes used demonstrated an inhibitory effect. CONCLUSIONS: Histone H2A significantly enhances in vitro DNA transfection whereas other histones and anionic liposomes do not. A study of the difference between histone H2A and other histone subclasses may serve to clarify some of the mechanisms and the essential components of efficient gene delivery. PMID:9407553

  16. Enhanced NIF neutron activation diagnostics.

    PubMed

    Yeamans, C B; Bleuel, D L; Bernstein, L A

    2012-10-01

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the (89)Zr/(89 m)Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  17. Enhanced NIF neutron activation diagnostics

    SciTech Connect

    Yeamans, C. B.; Bleuel, D. L.; Bernstein, L. A.

    2012-10-15

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the {sup 89}Zr/{sup 89m}Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  18. Porcine JAB1 significantly enhances apoptosis induced by staurosporine

    PubMed Central

    Jiang, P; Wang, J; Kang, Z; Li, D; Zhang, D

    2013-01-01

    c-Jun activation domain-binding protein-1 (JAB1), also known as the subunit 5 of the COP9 signalosome, is a multifunctional protein that regulates cell proliferation, apoptosis and oncogenesis by interacting with and subsequently degrading a large number of proteins. Although human JAB1 (hJAB1) has been studied for a long time, studies on porcine JAB1 (pJAB1) have never been reported. In the present study, we cloned and characterized the pJAB1 gene. The genomic structure of the pJAB1 gene was determined. The open-reading frame of pJAB1 encoded 334 amino acids. The deduced amino acid sequence was highly similar to homologs in other species. Furthermore, the tertiary structure analysis and phylogenetic analysis indicated that JAB1 was highly conservative among species. pJAB1 may interact with several proteins according to protein–protein interactions analysis. In addition, pJAB1 was found to be universally expressed in porcine tissues. Subcellular localization analysis showed that GFP–pJAB1 fusion protein distributed specifically in the cytoplasm. Flow cytometric analysis proved that pJAB1 significantly enhanced apoptosis induced by staurosporine, which at least partially depended on the activation of caspase-9 and caspase-3. This study is useful for understanding the function of pJAB1 and offers a potential molecular model for the investigation of diseases related to hJAB1. PMID:24091666

  19. Cyclase inhibitor tripropylamine significantly enhanced lycopene accumulation in Blakeslea trispora.

    PubMed

    Wang, Yanlong; Chen, Xiwen; Hong, Xiao; Du, Shipeng; Liu, Chunxiao; Gong, Wenfang; Chen, Defu

    2016-11-01

    Lycopene is a member of carotenoids that exhibits strong antioxidant activity. In this study, on the basis of screening suitable strain combination [ATCC 14271(+) and ATCC 14272(-)] and establishing the optimal inoculation proportion of mated culture (1/2, +/-, w/w) for carotenoid production, the efficiency of compounds, mainly tertiary amines, on enhancing the lycopene content of Blakeslea trispora was systematically assessed. Of these compounds, tripropylamine showed the best enhancing effect, and then sequentially followed by triethylamine, tributylamine, trimethylamine, diisopropylamine, and isopropylamine. After treated with 1.8 g/L tripropylamine for two days, the lycopene proportion was increased from 1.7% to 90.1%, while the β-carotene proportion was decreased from 91.1% to 6.4% of the total carotenoids. In this case, the lycopene and total carotenoid contents were increased to 83.2 and 92.4 mg/gDW, which were 315.8- and 5.9-fold of that of the untreated control, respectively; while the growth of mycelia was only decreased at 6.0 g/L tripropylamine. Gene expression analysis showed that all the tested genes, especially genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase (hmgr) and isopentenyl pyrophosphate isomerase (ipi) in mevalonate pathway, as well as phytoene desaturase (carB) in carotenoid biosynthesis process were upregulated. Therefore, tripropylamine enhanced lycopene content of B. trispora by inhibiting the cyclase activity, and by upregulating the expression of genes associated with terpenoid biosynthesis. Besides, a possible association between the structure and the lycopene-enhancing capability of these compounds was also discussed.

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

    PubMed

    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.

  1. Nanostructures Significantly Enhance Thermal Transport across Solid Interfaces.

    PubMed

    Lee, Eungkyu; Zhang, Teng; Yoo, Taehee; Guo, Zhi; Luo, Tengfei

    2016-12-28

    The efficiency of thermal transport across solid interfaces presents large challenges for modern technologies such as thermal management of electronics. In this paper, we report the first demonstration of significant enhancement of thermal transport across solid interfaces by introducing interfacial nanostructures. Analogous to fins that have been used for macroscopic heat transfer enhancement in heat exchangers, the nanopillar arrays patterned at the interface help interfacial thermal transport by the enlarged effective contact area. Such a benefit depends on the geometry of nanopillar arrays (e.g., pillar height and spacing), and a thermal boundary conductance enhancement by as much as ∼88% has been measured using the time-domain thermoreflectance technique. Theoretical analysis combined with low-temperature experiments further indicates that phonons with low frequency are less influenced by the interfacial nanostructures due to their large transmissivity, but the benefit of the nanostructure is fully developed at room temperature where higher frequency phonons dominate interfacial thermal transport. The findings from this work can potentially be generalized to benefit real applications such as the thermal management of electronics.

  2. Significant enhancement of photovoltage in artificially designed perovskite oxide structures

    NASA Astrophysics Data System (ADS)

    Zhou, Wen-jia; Jin, Kui-juan; Guo, Hai-zhong; He, Xu; He, Meng; Xu, Xiu-lai; Lu, Hui-bin; Yang, Guo-zhen

    2015-03-01

    La0.9Sr0.1MnO3/insulator/SrNb0.007Ti0.993O3 multilayer and La0.9Sr0.1MnO3/SrNb0.007Ti0.993O3/In2O3:SnO2(ITO)/La0.9Sr0.1MnO3/SrNb0.007Ti0.993O3 multilayer structures were designed to enhance the photovoltage. The photovoltages of these two structures under an illumination of 308 nm laser are 410 and 600 mV, respectively. The latter is 20 times larger than that (30 mV) observed in La0.9Sr0.1MnO3/SrNb0.007Ti0.993O3 single junction. The origin of such significant enhancement of photovoltage is discussed in this letter. These results suggest that the photoelectric property of perovskite oxides could be much improved by artificial structure designing. The enhanced photovoltaic effects have potential applications in the ultraviolet photodetection and solar cells.

  3. A Hybrid Actuation System Demonstrating Significantly Enhanced Electromechanical Performance

    NASA Technical Reports Server (NTRS)

    Su, Ji; Xu, Tian-Bing; Zhang, Shujun; Shrout, Thomas R.; Zhang, Qiming

    2004-01-01

    A hybrid actuation system (HYBAS) utilizing advantages of a combination of electromechanical responses of an electroactive polymer (EAP), an electrostrictive copolymer, and an electroactive ceramic single crystal, PZN-PT single crystal, has been developed. The system employs the contribution of the actuation elements cooperatively and exhibits a significantly enhanced electromechanical performance compared to the performances of the device made of each constituting material, the electroactive polymer or the ceramic single crystal, individually. The theoretical modeling of the performances of the HYBAS is in good agreement with experimental observation. The consistence between the theoretical modeling and experimental test make the design concept an effective route for the development of high performance actuating devices for many applications. The theoretical modeling, fabrication of the HYBAS and the initial experimental results will be presented and discussed.

  4. Significant Quantum Effects in Hydrogen Activation

    SciTech Connect

    Kyriakou, Georgios; Davidson, Erlend R.; Peng, Guowen; Roling, Luke T.; Singh, Suyash; Boucher, Matthew B.; Marcinkowski, Matthew D.; Mavrikakis, Manos; Michaelides, Angelos; Sykes, E. Charles H.

    2014-03-31

    Dissociation of molecular hydrogen is an important step in a wide variety of chemical, biological, and physical processes. Due to the light mass of hydrogen, it is recognized that quantum effects are often important to its reactivity. However, understanding how quantum effects impact the reactivity of hydrogen is still in its infancy. Here, we examine this issue using a well-defined Pd/Cu(111) alloy that allows the activation of hydrogen and deuterium molecules to be examined at individual Pd atom surface sites over a wide range of temperatures. Experiments comparing the uptake of hydrogen and deuterium as a function of temperature reveal completely different behavior of the two species. The rate of hydrogen activation increases at lower sample temperature, whereas deuterium activation slows as the temperature is lowered. Density functional theory simulations in which quantum nuclear effects are accounted for reveal that tunneling through the dissociation barrier is prevalent for H2 up to 190 K and for D2 up to 140 K. Kinetic Monte Carlo simulations indicate that the effective barrier to H2 dissociation is so low that hydrogen uptake on the surface is limited merely by thermodynamics, whereas the D2 dissociation process is controlled by kinetics. These data illustrate the complexity and inherent quantum nature of this ubiquitous and seemingly simple chemical process. Examining these effects in other systems with a similar range of approaches may uncover temperature regimes where quantum effects can be harnessed, yielding greater control of bond-breaking processes at surfaces and uncovering useful chemistries such as selective bond activation or isotope separation.

  5. Significant Quantum Effects in Hydrogen Activation

    PubMed Central

    2014-01-01

    Dissociation of molecular hydrogen is an important step in a wide variety of chemical, biological, and physical processes. Due to the light mass of hydrogen, it is recognized that quantum effects are often important to its reactivity. However, understanding how quantum effects impact the reactivity of hydrogen is still in its infancy. Here, we examine this issue using a well-defined Pd/Cu(111) alloy that allows the activation of hydrogen and deuterium molecules to be examined at individual Pd atom surface sites over a wide range of temperatures. Experiments comparing the uptake of hydrogen and deuterium as a function of temperature reveal completely different behavior of the two species. The rate of hydrogen activation increases at lower sample temperature, whereas deuterium activation slows as the temperature is lowered. Density functional theory simulations in which quantum nuclear effects are accounted for reveal that tunneling through the dissociation barrier is prevalent for H2 up to ∼190 K and for D2 up to ∼140 K. Kinetic Monte Carlo simulations indicate that the effective barrier to H2 dissociation is so low that hydrogen uptake on the surface is limited merely by thermodynamics, whereas the D2 dissociation process is controlled by kinetics. These data illustrate the complexity and inherent quantum nature of this ubiquitous and seemingly simple chemical process. Examining these effects in other systems with a similar range of approaches may uncover temperature regimes where quantum effects can be harnessed, yielding greater control of bond-breaking processes at surfaces and uncovering useful chemistries such as selective bond activation or isotope separation. PMID:24684530

  6. Cytochrome bd Displays Significant Quinol Peroxidase Activity

    PubMed Central

    Al-Attar, Sinan; Yu, Yuanjie; Pinkse, Martijn; Hoeser, Jo; Friedrich, Thorsten; Bald, Dirk; de Vries, Simon

    2016-01-01

    Cytochrome bd is a prokaryotic terminal oxidase that catalyses the electrogenic reduction of oxygen to water using ubiquinol as electron donor. Cytochrome bd is a tri-haem integral membrane enzyme carrying a low-spin haem b558, and two high-spin haems: b595 and d. Here we show that besides its oxidase activity, cytochrome bd from Escherichia coli is a genuine quinol peroxidase (QPO) that reduces hydrogen peroxide to water. The highly active and pure enzyme preparation used in this study did not display the catalase activity recently reported for E. coli cytochrome bd. To our knowledge, cytochrome bd is the first membrane-bound quinol peroxidase detected in E. coli. The observation that cytochrome bd is a quinol peroxidase, can provide a biochemical basis for its role in detoxification of hydrogen peroxide and may explain the frequent findings reported in the literature that indicate increased sensitivity to hydrogen peroxide and decreased virulence in mutants that lack the enzyme. PMID:27279363

  7. Significantly enhanced osteoblast response to nano-grained pure tantalum

    PubMed Central

    Huo, W. T.; Zhao, L. Z.; Yu, S.; Yu, Z. T.; Zhang, P. X.; Zhang, Y. S.

    2017-01-01

    Tantalum (Ta) metal is receiving increasing interest as biomaterial for load-bearing orthopedic applications and the synthetic properties of Ta can be tailored by altering its grain structures. This study evaluates the capability of sliding friction treatment (SFT) technique to modulate the comprehensive performances of pure Ta. Specifically, novel nanocrystalline (NC) surface with extremely small grains (average grain size of ≤20 nm) was fabricated on conventional coarse-grained (CG) Ta by SFT. It shows that NC surface possessed higher surface hydrophilicity and enhanced corrosion resistance than CG surface. Additionally, the NC surface adsorbed a notably higher percentage of protein as compared to CG surface. The in vitro results indicated that in the initial culture stages (up to 24 h), the NC surface exhibited considerably enhanced osteoblast adherence and spreading, consistent with demonstrated superior hydrophilicity on NC surface. Furthermore, within the 14 days culture period, NC Ta surface exhibited a remarkable enhancement in osteoblast cell proliferation, maturation and mineralization as compared to CG surface. Ultimately, the improved osteoblast functions together with the good mechanical and anti-corrosion properties render the SFT-processed Ta a promising alternative for the load-bearing bone implant applications. PMID:28084454

  8. Noise enhanced activity in a complex network

    NASA Astrophysics Data System (ADS)

    Choudhary, Anshul; Kohar, Vivek; Sinha, Sudeshna

    2014-09-01

    We consider the influence of local noise on a generalized network of populations having positive and negative feedbacks. The population dynamics at the nodes is nonlinear, typically chaotic, and allows cessation of activity if the population falls below a threshold value. We investigate the global stability of this large interactive system, as indicated by the average number of nodal populations that manage to remain active. Our central result is that the probability of obtaining active nodes in this network is significantly enhanced under fluctuations. Further, we find a sharp transition in the number of active nodes as noise strength is varied, along with clearly evident scaling behaviour near the critical noise strength. Lastly, we also observe noise induced temporal coherence in the active sub-network, namely, there is an enhancement in synchrony among the nodes at an intermediate noise strength.

  9. Surgical enhancement of facial beauty and its psychological significance.

    PubMed

    Baig, Moghees A

    2004-10-01

    Facial beauty is easier to recognize than to define. It is widely agreed that beauty is an evolutionary adoption for ensuring the survival of the species, because physical attractiveness is rated as more vital in mate selection. It includes a combination of qualities, starting from the grace of form to the charm of the colours that delight the sight and other senses. It does not have any norms however individual or societal assessment of attractiveness is greatly influenced by cultural standards. Several soft and hard tissue surgical procedures are therefore performed around the world each year. In this 12 years study from 1992 to 2004 the types of orthognathic surgical procedures performed and their psychological impact on the patients' well-being have been evaluated. By carefully structured interviews and psychosomatic evaluations It has been clinically demonstrated that psychological analysis is as important as soft and hard tissue parameters for patients undergoing surgical procedures to enhance facial beauty.

  10. A DNA/HDAC dual-targeting drug CY190602 with significantly enhanced anticancer potency

    PubMed Central

    Liu, Chuan; Ding, Hongyu; Li, Xiaoxi; Pallasch, Christian P; Hong, Liya; Guo, Dianwu; Chen, Yi; Wang, Difei; Wang, Wei; Wang, Yajie; Hemann, Michael T; Jiang, Hai

    2015-01-01

    Genotoxic drugs constitute a major treatment modality for human cancers; however, cancer cells' intrinsic DNA repair capability often increases the threshold of lethality and renders these drugs ineffective. The emerging roles of HDACs in DNA repair provide new opportunities for improving traditional genotoxic drugs. Here, we report the development and characterization of CY190602, a novel bendamustine-derived drug with significantly enhanced anticancer potency. We show that CY190602's enhanced potency can be attributed to its newly gained ability to inhibit HDACs. Using this novel DNA/HDAC dual-targeting drug as a tool, we further explored HDAC's role in DNA repair. We found that HDAC activities are essential for the expression of several genes involved in DNA synthesis and repair, including TYMS, Tip60, CBP, EP300, and MSL1. Importantly, CY190602, the first-in-class example of such DNA/HDAC dual-targeting drugs, exhibited significantly enhanced anticancer activity in vitro and in vivo. These findings provide rationales for incorporating HDAC inhibitory moieties into genotoxic drugs, so as to overcome the repair capacity of cancer cells. Systematic development of similar DNA/HDAC dual-targeting drugs may represent a novel opportunity for improving cancer therapy. PMID:25759362

  11. A DNA/HDAC dual-targeting drug CY190602 with significantly enhanced anticancer potency.

    PubMed

    Liu, Chuan; Ding, Hongyu; Li, Xiaoxi; Pallasch, Christian P; Hong, Liya; Guo, Dianwu; Chen, Yi; Wang, Difei; Wang, Wei; Wang, Yajie; Hemann, Michael T; Jiang, Hai

    2015-03-09

    Genotoxic drugs constitute a major treatment modality for human cancers; however, cancer cells' intrinsic DNA repair capability often increases the threshold of lethality and renders these drugs ineffective. The emerging roles of HDACs in DNA repair provide new opportunities for improving traditional genotoxic drugs. Here, we report the development and characterization of CY190602, a novel bendamustine-derived drug with significantly enhanced anticancer potency. We show that CY190602's enhanced potency can be attributed to its newly gained ability to inhibit HDACs. Using this novel DNA/HDAC dual-targeting drug as a tool, we further explored HDAC's role in DNA repair. We found that HDAC activities are essential for the expression of several genes involved in DNA synthesis and repair, including TYMS, Tip60, CBP, EP300, and MSL1. Importantly, CY190602, the first-in-class example of such DNA/HDAC dual-targeting drugs, exhibited significantly enhanced anticancer activity in vitro and in vivo. These findings provide rationales for incorporating HDAC inhibitory moieties into genotoxic drugs, so as to overcome the repair capacity of cancer cells. Systematic development of similar DNA/HDAC dual-targeting drugs may represent a novel opportunity for improving cancer therapy.

  12. Social isolation stress significantly enhanced the disruption of prepulse inhibition in mice repeatedly treated with methamphetamine.

    PubMed

    Dai, Hongmei; Okuda, Hirotomo; Iwabuchi, Kentaro; Sakurai, Eiko; Chen, Zhong; Kato, Motohisa; Iinuma, Kazuie; Yanai, Kazuhiko

    2004-10-01

    Repeated administration of methamphetamine (METH) causes reverse tolerance or behavioral sensitization in mice. However, the effects of social isolation stress on the METH-caused reverse tolerance have not been studied until now. The aim of this study was to investigate the effects of social isolation stress on METH-caused reverse tolerance by examining the prepulse inhibition of startle response (PPI). PPI was tested in socially isolated and grouped mice after repeated METH injections. Locomotor activity and PPI were also examined just after a four-week isolation rearing period as a control experiment. After completing behavioral experiments, the mice were sacrificed, and the contents of monoamines, including histamine in the brain, were measured. Social isolation stress significantly lowered the locomotion and disrupted PPI. Repeated injections of METH enhanced the effects of social isolation on PPI. The content of dopamine and histamine significantly increased in the cortex, and the turnover rate of dopamine decreased significantly. These findings demonstrate that social isolation stress significantly enhances METH-induced behavioral sensitization and that the altered histaminergic neuron system might play an important role in METH-induced behavioral sensitization in addition to dopaminergic and serotoninergic neurotransmission. Our data suggest that social isolation is involved in the development of METH-induced psychosis, schizophrenia, and other related psychiatric disorders.

  13. Alzheimer's Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells.

    PubMed

    Jiang, Qinghua; Jin, Shuilin; Jiang, Yongshuai; Liao, Mingzhi; Feng, Rennan; Zhang, Liangcai; Liu, Guiyou; Hao, Junwei

    2017-01-01

    The existing large-scale genome-wide association studies (GWAS) datasets provide strong support for investigating the mechanisms of Alzheimer's disease (AD) by applying multiple methods of pathway analysis. Previous studies using selected single nucleotide polymorphisms (SNPs) with several thresholds of nominal significance for pathway analysis determined that the threshold chosen for SNPs can reflect the disease model. Presumably, then, pathway analysis with a stringent threshold to define "associated" SNPs would test the hypothesis that highly associated SNPs are enriched in one or more particular pathways. Here, we selected 599 AD variants (P < 5.00E-08) to investigate the pathways in which these variants are enriched and the cell types in which these variants are active. Our results showed that AD variants are significantly enriched in pathways of the immune system. Further analysis indicated that AD variants are significantly enriched for enhancers in a number of cell types, in particular the B-lymphocyte, which is the most substantially enriched cell type. This cell type maintains its dominance among the strongest enhancers. AD SNPs also display significant enrichment for DNase in 12 cell types, among which the top 6 significant signals are from immune cell types, including 4 B cells (top 4 significant signals) and CD14+ and CD34+ cells. In summary, our results show that these AD variants with P < 5.00E-08 are significantly enriched in pathways of the immune system and active in immune cells. To a certain degree, the genetic predisposition for development of AD is rooted in the immune system, rather than in neuronal cells.

  14. -graphene nanocomposites and their enhanced photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Xian, Tao; Yang, Hua; Di, Lijing; Ma, Jinyuan; Zhang, Haimin; Dai, Jianfeng

    2014-06-01

    SrTiO3-graphene nanocomposites were prepared via photocatalytic reduction of graphene oxide by UV light-irradiated SrTiO3 nanoparticles. Fourier transformed infrared spectroscopy analysis indicates that graphene oxide is reduced into graphene. Transmission electron microscope observation shows that SrTiO3 nanoparticles are well assembled onto graphene sheets. The photocatalytic activity of as-prepared SrTiO3-graphene composites was evaluated by the degradation of acid orange 7 (AO7) under a 254-nm UV irradiation, revealing that the composites exhibit significantly enhanced photocatalytic activity compared to the bare SrTiO3 nanoparticles. This can be explained by the fact that photogenerated electrons are captured by graphene, leading to an increased separation and availability of electrons and holes for the photocatalytic reaction. Hydroxyl (·OH) radicals were detected by the photoluminescence technique using terephthalic acid as a probe molecule and were found to be produced over the irradiated SrTiO3 nanoparticles and SrTiO3-graphene composites; especially, an enhanced yield is observed for the latter. The influence of ethanol, KI, and N2 on the photocatalytic efficiency was also investigated. Based on the experimental results, ·OH, h+, and H2O2 are suggested to be the main active species in the photocatalytic degradation of AO7 by SrTiO3-graphene composites.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26832603

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2016-02-02

    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. OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer

    PubMed Central

    Weixler, Benjamin; Cremonesi, Eleonora; Sorge, Roberto; Muraro, Manuele Giuseppe; Delko, Tarik; Nebiker, Christian A.; Däster, Silvio; Governa, Valeria; Amicarella, Francesca; Soysal, Savas D.; Kettelhack, Christoph; von Holzen, Urs W.; Eppenberger-Castori, Serenella; Spagnoli, Giulio C.; Oertli, Daniel; Iezzi, Giandomenica; Terracciano, Luigi; Tornillo, Luigi

    2015-01-01

    Background OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation. Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in cancer immunotherapy. We explored the prognostic significance of tumor infiltration by OX40+ cells in a large colorectal cancer (CRC) collective. Methods OX40 gene expression was analyzed in 50 freshly excised CRC and corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657 clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3 mAbs by standard immunohistochemistry. The CRC cohort was randomly split into training and validation sets. Correlations between CRC infiltration by OX40+ cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical-pathological data and overall survival were comparatively evaluated. Results OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene expression. High CRC infiltration by OX40+ cells was significantly associated with favorable prognosis in training and validation sets in univariate, but not multivariate, Cox regression analysis. CRC with OX40high/CD8high infiltration were characterized by significantly prolonged overall survival, as compared to tumors with OX40low/CD8high, OX40high/CD8low or OX40low/CD8low infiltration in both uni- and multivariate analysis. In contrast, prognostic significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined evaluation. Irrespective of TNM stage, CRC with OX40high/CD8high density infiltrates showed an overall survival similar to that of all stage I CRC included in the study. Conclusions OX40high/CD8high density tumor infiltration represents an independent, favorable, prognostic marker in CRC with an overall survival similar to stage I cancers. PMID:26439988

  20. Overexpression of AKR1C3 significantly enhances human prostate cancer cells resistance to radiation

    PubMed Central

    Gao, Xian-Shu; Li, Yi; Yu, Hongliang; Xiong, Wei; Yu, Hao; Wang, Wen; Li, Yingbo; Teng, Yingqi; Zhou, Demin

    2016-01-01

    Aldo-keto reductase 1C3(AKR1C3) is an enzyme involved in prostaglandins metabolism. Studies suggest that AKR1C3 has a pivotal role in the radioresistance of esophageal cancer and non-small-cell lung cancer, yet the role of AKR1C3 in prostate cancer cells radiation resistance has not yet been clarified. In our study, we established a stable overexpressing AKR1C3 cell line (AKR1C3-over) derived from the prostate cell line DU145 and its control cell line (Control). We conducted colony formation assay to determine the role of AKR1C3 in radioresistance and we used its chemical inhibitor to detect whether it can restored the sensitivity of the acquired tumor cells. Flow cytometry assay was carried out to detect IR-induced ROS accumulation. Elisa was adopted to dedect the concentration of PGF2α in the suspension of the cells after 6GY radiation. Western blotting was used to dedect the MAPK and PPAR γ. The results demonstrated that overexpression of AKR1C3 in prostate cancer can result in radioresistance and suppression of AKR1C3 via its chemical inhibitor indocin restored the sensitivity of the acquired tumor cells. According to the flow cytometry assay, ROS was decreased by 80% in DU145-over cells. Also overexpression of AKR1C3 could result in the accumulation of prostaglandin F2α (PGF2α), which can not only promote prostate cancer cell 's proliferation but also could enhance prostate cancer cells resistance to radiation and activated the MAPK pathway and inhibited the expression of PPARγ. In conclusion, we found that overexpression of AKR1C3 significantly enhanced human prostate cancer cells resistance to radiation through activation of MAPK pathway. PMID:27385003

  1. Amorphous Semiconductor Nanowires Created by Site-Specific Heteroatom Substitution with Significantly Enhanced Photoelectrochemical Performance.

    PubMed

    He, Ting; Zu, Lianhai; Zhang, Yan; Mao, Chengliang; Xu, Xiaoxiang; Yang, Jinhu; Yang, Shihe

    2016-08-23

    Semiconductor nanowires that have been extensively studied are typically in a crystalline phase. Much less studied are amorphous semiconductor nanowires due to the difficulty for their synthesis, despite a set of characteristics desirable for photoelectric devices, such as higher surface area, higher surface activity, and higher light harvesting. In this work of combined experiment and computation, taking Zn2GeO4 (ZGO) as an example, we propose a site-specific heteroatom substitution strategy through a solution-phase ions-alternative-deposition route to prepare amorphous/crystalline Si-incorporated ZGO nanowires with tunable band structures. The substitution of Si atoms for the Zn or Ge atoms distorts the bonding network to a different extent, leading to the formation of amorphous Zn1.7Si0.3GeO4 (ZSGO) or crystalline Zn2(GeO4)0.88(SiO4)0.12 (ZGSO) nanowires, respectively, with different bandgaps. The amorphous ZSGO nanowire arrays exhibit significantly enhanced performance in photoelectrochemical water splitting, such as higher and more stable photocurrent, and faster photoresponse and recovery, relative to crystalline ZGSO and ZGO nanowires in this work, as well as ZGO photocatalysts reported previously. The remarkable performance highlights the advantages of the ZSGO amorphous nanowires for photoelectric devices, such as higher light harvesting capability, faster charge separation, lower charge recombination, and higher surface catalytic activity.

  2. Beyond Statistical Significance: Implications of Network Structure on Neuronal Activity

    PubMed Central

    Vlachos, Ioannis; Aertsen, Ad; Kumar, Arvind

    2012-01-01

    It is a common and good practice in experimental sciences to assess the statistical significance of measured outcomes. For this, the probability of obtaining the actual results is estimated under the assumption of an appropriately chosen null-hypothesis. If this probability is smaller than some threshold, the results are deemed statistically significant and the researchers are content in having revealed, within their own experimental domain, a “surprising” anomaly, possibly indicative of a hitherto hidden fragment of the underlying “ground-truth”. What is often neglected, though, is the actual importance of these experimental outcomes for understanding the system under investigation. We illustrate this point by giving practical and intuitive examples from the field of systems neuroscience. Specifically, we use the notion of embeddedness to quantify the impact of a neuron's activity on its downstream neurons in the network. We show that the network response strongly depends on the embeddedness of stimulated neurons and that embeddedness is a key determinant of the importance of neuronal activity on local and downstream processing. We extrapolate these results to other fields in which networks are used as a theoretical framework. PMID:22291581

  3. Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

    SciTech Connect

    John, George; Nagarajan, Subbiah; Chapman, Kent; Faure, Lionel; Koulen, Peter

    2016-10-25

    A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacylethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings. The subject matter disclosed herein relates to enhancers of amidohydrolase activity.

  4. A Novel Peptide from Soybean Protein Isolate Significantly Enhances Resistance of the Organism under Oxidative Stress

    PubMed Central

    Ma, Heran; Liu, Rui; Zhao, Ziyuan; Zhang, Zhixian; Cao, Yue; Ma, Yudan; Guo, Yi; Xu, Li

    2016-01-01

    Recent studies have indicated that protein hydrolysates have broad biological effects. In the current study we describe a novel antioxidative peptide, FDPAL, from soybean protein isolate (SPI). The aim of this study was to purify and characterize an antioxidative peptide from SPI and determine its antioxidative mechanism. LC–MS/MS was used to isolate and identify the peptide from SPI. The sequence of the peptide was determined to be Phe-Asp-Pro-Ala-Leu (FDPAL, 561 Da). FDPAL can cause significant enhancement of resistance to oxidative stress both in cells as well as simple organisms. In Caenorhabditis elegans (C. elegans), FDPAL can up-regulate the expression of certain genes associated with resistance. The antioxidant activity of this peptide can be attributed to the presence of a specific amino acid sequence. Results from our work suggest that FDPAL can facilitate potential applications of proteins carrying this sequence in the nutraceutical, bioactive material and clinical medicine areas, as well as in cosmetics and health care products. PMID:27455060

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

    PubMed

    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.

  6. The Significance of Ras Activity in Pancreatic Cancer Initiation

    PubMed Central

    Logsdon, Craig D.; Lu, Weiqin

    2016-01-01

    The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Rasmt alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Rasmt. Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Rasmt is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Rasmt activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Rasmt. Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Rasmt activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease. PMID:26929740

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

    SciTech Connect

    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 windows.

  8. Adaptive significance of right hemisphere activation in aphasic language comprehension

    PubMed Central

    Meltzer, Jed A.; Wagage, Suraji; Ryder, Jennifer; Solomon, Beth; Braun, Allen R.

    2013-01-01

    Aphasic patients often exhibit increased right hemisphere activity during language tasks. This may represent takeover of function by regions homologous to the left-hemisphere language networks, maladaptive interference, or adaptation of alternate compensatory strategies. To distinguish between these accounts, we tested language comprehension in 25 aphasic patients using an online sentence-picture matching paradigm while measuring brain activation with MEG. Linguistic conditions included semantically irreversible (“The boy is eating the apple”) and reversible (“The boy is pushing the girl”) sentences at three levels of syntactic complexity. As expected, patients performed well above chance on irreversible sentences, and at chance on reversible sentences of high complexity. Comprehension of reversible non-complex sentences ranged from nearly perfect to chance, and was highly correlated with offline measures of language comprehension. Lesion analysis revealed that comprehension deficits for reversible sentences were predicted by damage to the left temporal lobe. Although aphasic patients activated homologous areas in the right temporal lobe, such activation was not correlated with comprehension performance. Rather, patients with better comprehension exhibited increased activity in dorsal fronto-parietal regions. Correlations between performance and dorsal network activity occurred bilaterally during perception of sentences, and in the right hemisphere during a post-sentence memory delay. These results suggest that effortful reprocessing of perceived sentences in short-term memory can support improved comprehension in aphasia, and that strategic recruitment of alternative networks, rather than homologous takeover, may account for some findings of right hemisphere language activation in aphasia. PMID:23566891

  9. Adaptive significance of right hemisphere activation in aphasic language comprehension.

    PubMed

    Meltzer, Jed A; Wagage, Suraji; Ryder, Jennifer; Solomon, Beth; Braun, Allen R

    2013-06-01

    Aphasic patients often exhibit increased right hemisphere activity during language tasks. This may represent takeover of function by regions homologous to the left-hemisphere language networks, maladaptive interference, or adaptation of alternate compensatory strategies. To distinguish between these accounts, we tested language comprehension in 25 aphasic patients using an online sentence-picture matching paradigm while measuring brain activation with MEG. Linguistic conditions included semantically irreversible ("The boy is eating the apple") and reversible ("The boy is pushing the girl") sentences at three levels of syntactic complexity. As expected, patients performed well above chance on irreversible sentences, and at chance on reversible sentences of high complexity. Comprehension of reversible non-complex sentences ranged from nearly perfect to chance, and was highly correlated with offline measures of language comprehension. Lesion analysis revealed that comprehension deficits for reversible sentences were predicted by damage to the left temporal lobe. Although aphasic patients activated homologous areas in the right temporal lobe, such activation was not correlated with comprehension performance. Rather, patients with better comprehension exhibited increased activity in dorsal fronto-parietal regions. Correlations between performance and dorsal network activity occurred bilaterally during perception of sentences, and in the right hemisphere during a post-sentence memory delay. These results suggest that effortful reprocessing of perceived sentences in short-term memory can support improved comprehension in aphasia, and that strategic recruitment of alternative networks, rather than homologous takeover, may account for some findings of right hemisphere language activation in aphasia.

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

    PubMed

    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.

  11. Rural Enterprises, Incorporated report of significant activities and accomplishments

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The ongoing activities of Rural Enterprises, Inc. are presented. The function of Rural Enterprises is to bring innovation from its rudimentary conceptual stages to useful and productive ends by means of cooperation with government, business, and educational institutions.

  12. Routine Activities and Victimization at School: The Significance of Gender

    ERIC Educational Resources Information Center

    Popp, Ann Marie; Peguero, Anthony A.

    2011-01-01

    Routine activities theory has not fully considered the role of gender in shaping victimization and yet, the research literature clearly demonstrates that gender is associated with an individual's risk of victimization. In addition to the pervasive effect of gender on victimization, gender shapes an individual's daily routines and thus may create a…

  13. Active Dendrites Enhance Neuronal Dynamic Range

    PubMed Central

    Gollo, Leonardo L.; Kinouchi, Osame; Copelli, Mauro

    2009-01-01

    Since the first experimental evidences of active conductances in dendrites, most neurons have been shown to exhibit dendritic excitability through the expression of a variety of voltage-gated ion channels. However, despite experimental and theoretical efforts undertaken in the past decades, the role of this excitability for some kind of dendritic computation has remained elusive. Here we show that, owing to very general properties of excitable media, the average output of a model of an active dendritic tree is a highly non-linear function of its afferent rate, attaining extremely large dynamic ranges (above 50 dB). Moreover, the model yields double-sigmoid response functions as experimentally observed in retinal ganglion cells. We claim that enhancement of dynamic range is the primary functional role of active dendritic conductances. We predict that neurons with larger dendritic trees should have larger dynamic range and that blocking of active conductances should lead to a decrease in dynamic range. PMID:19521531

  14. On the validity versus utility of activity landscapes: are all activity cliffs statistically significant?

    PubMed Central

    2014-01-01

    Background Most work on the topic of activity landscapes has focused on their quantitative description and visual representation, with the aim of aiding navigation of SAR. Recent developments have addressed applications such as quantifying the proportion of activity cliffs, investigating the predictive abilities of activity landscape methods and so on. However, all these publications have worked under the assumption that the activity landscape models are “real” (i.e., statistically significant). Results The current study addresses for the first time, in a quantitative manner, the significance of a landscape or individual cliffs in the landscape. In particular, we question whether the activity landscape derived from observed (experimental) activity data is different from a randomly generated landscape. To address this we used the SALI measure with six different data sets tested against one or more molecular targets. We also assessed the significance of the landscapes for single and multiple representations. Conclusions We find that non-random landscapes are data set and molecular representation dependent. For the data sets and representations used in this work, our results suggest that not all representations lead to non-random landscapes. This indicates that not all molecular representations should be used to a) interpret the SAR and b) combined to generate consensus models. Our results suggest that significance testing of activity landscape models and in particular, activity cliffs, is key, prior to the use of such models. PMID:24694189

  15. Finding Significant Correlates of Conscious Activity in Rhythmic EEG

    NASA Astrophysics Data System (ADS)

    Durka, Piotr J.

    2005-12-01

    One of the important issues in designing an EEG-based brain-computer interface is an exact delineation of the rhythms, related to the intended or performed action. Traditionally, related bands were found by trial and error procedures seeking maximum reactivity. Even then, large values of ERD/ERS did not imply the statistical significance of the results. This paper presents complete methodology, allowing for a high-resolution presentation of the whole time-frequency picture of event-related changes in the energy density of signals, revealing the microstructure of rhythms, and determination of the time-frequency regions of energy changes, which are related to the intentions in a statistically significant way.

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

    PubMed

    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.

  17. Enhancing laboratory activities in nuclear medicine education.

    PubMed

    Grantham, Vesper; Martin, Chris; Schmitz, Casey

    2009-12-01

    Hands-on or active learning is important in nuclear medicine education. As more curricula start to require greater standards and as distance education expands, the effective use of laboratories in nuclear medicine education remains important in physics, instrumentation, and imaging but is often overlooked or underutilized. Laboratory exercises are a unique opportunity for nuclear medicine educators to facilitate students' critical thinking and problem-solving skills in a manner that often cannot occur in lectures or during online education. Given the lack of current laboratory tools and publications, there exists a requirement for nuclear medicine educators to develop, enhance, and monitor educational tools for laboratory exercises. Expanding technologies, variations in imaging and measurement systems, and the need to ensure that the taught technology is relevant to nuclear medicine students are issues faced by nuclear medicine educators. This article, based on principles of instructional design, focuses on the components and development of effective and enhanced nuclear medicine laboratories in our current educational environment.

  18. Prognotic significance of pretreatment proliferative activity in adult acute leukemia.

    PubMed

    Hart, J S; George, S L; Frei, E; Bodey, G P; Nickerson, R C; Freireich, E J

    1977-04-01

    A statistical analysis of the prognostic significance of eight pretreatment variables was undertaken for 71 previously untreated adult patients with acute leukemia seen at M.D. Anderson Hospital over a 5 1/2-year period. None of the patients had received any prior therapy. Nearly all of the patients (68 of the 71) were treated with 4- or 5-day courses of arabinosyl-cytosine alone or in combination with cyclophosphamide, vincristine (oncovin) and prednisone (COAP). The pretreatment variables studied were age at diagnosis, the percent labeling index of the bone marrow leukemic cells, diagnosis, the highest temperature prior to start of treatment, the marrow clot section cellularity and smear differential percent of blasts, percent absolute marrow leukemic cell infiltrate and absolute number of blasts X 10(3)/mm3 in the peripheral blood. Fifty-one patients had acute myeloblastic leukemia (AML) and 20 patients had acute lymphoblastic leukemia (ALL). Using a statistical regression model approach, the only variables found to be of significant prognostic importance with respect to the probability of complete remission for AML patients were the pretreatment percent labeling index, the age of the patient and the highest temperature prior to start of treatment. Unlike AML, the initial percent labeling index did not appear to be of prognostic significance for ALL patients. AML patients with high labeling indices (larger than or equal to 9%) and young patients in general (especially those less than 40 years old) had the best remission rates. With respect to the length of complete remission and survival for all patients, the only important variables were the pretreatment percent labeling index and the age of the patient, respectively. Once in complete remission, an initially high labeling index was an unfavorable sign with respect to length of remission, regardless of the patient's diagnosis. The results of this study are supportive of studies in experimental systems

  19. Enhancement of parkinsonian rigidity with contralateral hand activation

    PubMed Central

    Powell, Douglas; Hanson, Nicholas; Threlkeld, A. Joseph; Fang, Xiang; Xia, Ruiping

    2011-01-01

    Objective Quantify the enhancement of parkinsonian rigidity associated with a contralateral activation maneuver. Methods Twelve subjects with PD and eight controls participated in the study protocol. Subjects’ tested hand was displaced by a servo-motor throughout wrist flexion and extension motions of 60° without and with a concurrent gripping activation in the contralateral hand, referred to as passive and active conditions, respectively. Subjects with PD were tested in both OFF-Med and ON-Med states. Rigidity was quantified by integrating torque with position during both flexion and extension (torque resistance). ANOVA was performed to assess the effect of contralateral activation on rigidity. Results PD patients had significantly (0.038) enhanced torque resistance in OFF-Med compared to healthy controls and ON-MED. In the Active condition, differences in torque resistance were magnified (p=0.002). Medication substantially reduced differences in torque resistance between controls and PD patients in the passive and active conditions. Conclusions A contralateral activation maneuver substantially increases rigidity in patients with PD, specifically the OFF-MED state. Rigidity is reduced with the application of dopaminergic medication, even with the presence of a contralateral activation maneuver. Significance These data support the use of a contralateral activation maneuver as a tool in the diagnosis of PD. PMID:21330199

  20. The mother as hunter: significant reduction in foraging costs through enhancements of predation in maternal rats.

    PubMed

    Kinsley, Craig Howard; Blair, Jamie C; Karp, Natalie E; Hester, Naomi W; McNamara, Ilan M; Orthmeyer, Angela L; McSweeney, Molly C; Bardi, Massimo M; Karelina, Kate; Christon, Lillian M; Sirkin, Maxwell R; Victoria, Lindsay W; Skurka, Danielle J; Fyfe, Christian R; Hudepohl, Margaret B; Felicio, Luciano F; Franssen, R Adam; Meyer, Elizabeth E A; da Silva, Ilton S; Lambert, Kelly G

    2014-09-01

    In previous laboratory investigations, we have identified enhanced cognition and reduced stress in parous rats, which are likely adaptations in mothers needing to efficiently exploit resources to maintain, protect and provision their immature offspring. Here, in a series of seven behavioral tests on rats, we examined a natural interface between cognition and resource gathering: predation. Experiment 1 compared predatory behavior (toward crickets) in age-matched nulliparous mothers (NULLs) and postpartum lactating mothers (LACTs), revealing a highly significant enhancement of predation in LACT females (mean = -65s in LACTs, vs. -270s in NULLs). Experiment 2 examined the possibility that LACTs, given their increased metabolic rate, were hungrier, and thus more motivated to hunt; doubling the length of time of food deprivation in NULLs did not decrease their predatory latencies. Experiments 3-5, which examined sensory regulation of the effect, indicated that olfaction (anosmia), audition (blockade with white noise), and somatosensation (trimming the vibrissae) appear to play little role in the behavioral enhancement observed in the LACTs; Experiment 6 examined the possibility that visual augmentations may facilitate the improvements in predation; testing LACTs in a 0-lux environment eliminated the behavioral advantage (increasing their latencies from -65s to -212s), which suggests that temporary augmentation to the visual system may be important, and with hormone-neural alterations therein a likely candidate for further study. In contrast, testing NULLS in the 0-lux environment had the opposite effect, reducing their latency to catch the cricket (from -270s to -200s). Finally, Experiment 7 examined the development of predatory behavior in Early-pregnant (PREG), Mid-PREG, and Late-PREG females. Here, we observed a significant enhancement of predation in Mid-PREG and Late-PREG females--at a time when maternity-associated bodily changes would be expected to diminish

  1. LRRK2 autophosphorylation enhances its GTPase activity

    PubMed Central

    Liu, Zhiyong; Mobley, James A.; DeLucas, Lawrence J.; Kahn, Richard A.; West, Andrew B.

    2016-01-01

    The leucine-rich repeat kinase (LRRK)-2 protein contains nonoverlapping GTPase and kinase domains, and mutation in either domain can cause Parkinson disease. GTPase proteins are critical upstream modulators of many effector protein kinases. In LRRK2, this paradigm may be reversed, as the kinase domain phosphorylates its own GTPase domain. In this study, we found that the ameba LRRK2 ortholog ROCO4 phosphorylates the GTPase domain [termed Ras-of-complex (ROC) domain in this family] of human LRRK2 on the same residues as the human LRRK2 kinase. Phosphorylation of ROC enhances its rate of GTP hydrolysis [from kcat (catalytic constant) 0.007 to 0.016 min−1], without affecting GTP or GDP dissociation kinetics [koff = 0.093 and 0.148 min−1 for GTP and GDP, respectively). Phosphorylation also promotes the formation of ROC dimers, although GTPase activity appears to be equivalent between purified dimers and monomers. Modeling experiments show that phosphorylation induces conformational changes at the critical p-loop structure. Finally, ROC appears to be one of many GTPases phosphorylated in p-loop residues, as revealed by alignment of LRRK2 autophosphorylation sites with GTPases annotated in the phosphoproteome database. These results provide an example of a novel mechanism for kinase-mediated control of GTPase activity.—Liu, Z., Mobley, J. A., DeLucas, L. J., Kahn, R. A., West, A. B. LRRK2 autophosphorylation enhances its GTPase activity. PMID:26396237

  2. Mechanical and Electrical Properties of a Polyimide Film Significantly Enhanced by the Addition of Single-Wall Carbon Nanotubes

    NASA Technical Reports Server (NTRS)

    Meador, Michael A.

    2005-01-01

    Single-wall carbon nanotubes have been shown to possess a combination of outstanding mechanical, electrical, and thermal properties. The use of carbon nanotubes as an additive to improve the mechanical properties of polymers and/or enhance their thermal and electrical conductivity has been a topic of intense interest. Nanotube-modified polymeric materials could find a variety of applications in NASA missions including large-area antennas, solar arrays, and solar sails; radiation shielding materials for vehicles, habitats, and extravehicular activity suits; and multifunctional materials for vehicle structures and habitats. Use of these revolutionary materials could reduce vehicle weight significantly and improve vehicle performance and capabilities.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Aspirin can stimulate luminol-enhanced chemiluminescence of activated platelets.

    PubMed

    Gabbasov, Zufar; Ivanova, Oksana; Kogan-Yasny, Victor; Vasilieva, Elena

    2010-01-01

    A preliminary investigation was conducted into the influence of aspirin on the luminol-enhanced chemiluminescence of platelets stimulated with platelet-activating factor (PAF). Ten coronary artery disease patients and six volunteers without coronary artery disease were included in the study. All the patients received aspirin (daily dose, 100 mg) for at least 10 days before in vitro experiments. Luminol-enhanced luminescence of platelet-rich plasma samples mixed with a PAF solution was measured. After stimulation of platelets with PAF, we did not find a luminol-enhanced chemiluminescent response either in the non-coronary artery disease volunteers or in eight out of the 10 coronary artery disease patients examined. However, in samples from two patients where platelets were stimulated with PAF reactive oxygen species were formed. This ability was expressed as an intensive luminol-enhanced luminescence of activated platelets. Such a reaction was observed against the background of the administration of aspirin. The addition of aspirin to a test tube considerably enhanced the intensity of chemiluminescence. In one case, the cancellation of aspirin was accompanied by diminution of the intensity of luminol-enhanced chemiluminescence of platelets. The clinical significance of this phenomenon is unknown.

  6. Substrate co-doping modulates electronic metal-support interactions and significantly enhances single-atom catalysis.

    PubMed

    Shi, J L; Wu, J H; Zhao, X J; Xue, X L; Gao, Y F; Guo, Z X; Li, S F

    2016-11-24

    Transitional metal nanoparticles or atoms deposited on appropriate substrates can lead to highly economical, efficient, and selective catalysis. One of the greatest challenges is to control the electronic metal-support interactions (EMSI) between the supported metal atoms and the substrate so as to optimize their catalytic performance. Here, from first-principles calculations, we show that an otherwise inactive Pd single adatom on TiO2(110) can be tuned into a highly effective catalyst, e.g. for O2 adsorption and CO oxidation, by purposefully selected metal-nonmetal co-dopant pairs in the substrate. Such an effect is proved here to result unambiguously from a significantly enhanced EMSI. A nearly linear correlation is noted between the strength of the EMSI and the activation of the adsorbed O2 molecule, as well as the energy barrier for CO oxidation. Particularly, the enhanced EMSI shifts the frontier orbital of the deposited Pd atom upward and largely enhances the hybridization and charge transfer between the O2 molecule and the Pd atom. Upon co-doping, the activation barrier for CO oxidation on the Pd monomer is also reduced to a level comparable to that on the Pd dimer which was experimentally reported to be highly efficient for CO oxidation. The present findings provide new insights into the understanding of the EMSI in heterogeneous catalysis and can open new avenues to design and fabricate cost-effective single-atom-sized and/or nanometer-sized catalysts.

  7. Enhancing the catalytic activity of hydronium ions through constrained environments

    NASA Astrophysics Data System (ADS)

    Liu, Yuanshuai; Vjunov, Aleksei; Shi, Hui; Eckstein, Sebastian; Camaioni, Donald M.; Mei, Donghai; Baráth, Eszter; Lercher, Johannes A.

    2017-03-01

    The dehydration of alcohols is involved in many organic conversions but has to overcome high free-energy barriers in water. Here we demonstrate that hydronium ions confined in the nanopores of zeolite HBEA catalyse aqueous phase dehydration of cyclohexanol at a rate significantly higher than hydronium ions in water. This rate enhancement is not related to a shift in mechanism; for both cases, the dehydration of cyclohexanol occurs via an E1 mechanism with the cleavage of Cβ-H bond being rate determining. The higher activity of hydronium ions in zeolites is caused by the enhanced association between the hydronium ion and the alcohol, as well as a higher intrinsic rate constant in the constrained environments compared with water. The higher rate constant is caused by a greater entropy of activation rather than a lower enthalpy of activation. These insights should allow us to understand and predict similar processes in confined spaces.

  8. Enhancing the catalytic activity of hydronium ions through constrained environments

    PubMed Central

    Liu, Yuanshuai; Vjunov, Aleksei; Shi, Hui; Eckstein, Sebastian; Camaioni, Donald M.; Mei, Donghai; Baráth, Eszter; Lercher, Johannes A.

    2017-01-01

    The dehydration of alcohols is involved in many organic conversions but has to overcome high free-energy barriers in water. Here we demonstrate that hydronium ions confined in the nanopores of zeolite HBEA catalyse aqueous phase dehydration of cyclohexanol at a rate significantly higher than hydronium ions in water. This rate enhancement is not related to a shift in mechanism; for both cases, the dehydration of cyclohexanol occurs via an E1 mechanism with the cleavage of Cβ–H bond being rate determining. The higher activity of hydronium ions in zeolites is caused by the enhanced association between the hydronium ion and the alcohol, as well as a higher intrinsic rate constant in the constrained environments compared with water. The higher rate constant is caused by a greater entropy of activation rather than a lower enthalpy of activation. These insights should allow us to understand and predict similar processes in confined spaces. PMID:28252021

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    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.

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

    PubMed

    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.

  11. The significant adhesion enhancement of Ag-polytetrafluoroethylene antibacterial coatings by using of molecular bridge

    NASA Astrophysics Data System (ADS)

    Guo, Ruijie; Yin, Guangda; Sha, Xiaojuan; Zhao, Qi; Wei, Liqiao; Wang, Huifang

    2015-06-01

    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 sbnd SH groups. During electroless plating S which has lone pair electrons anchored Ag+ 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.

  12. Phanerochaete mutants with enhanced ligninolytic activity

    SciTech Connect

    Kakar, S.N.; Perez, A.; Gonzales, J.

    1993-06-01

    In addition to lignin, the white rot fungus Phanerochaete chrysosporium has the ability to degrade a wide spectrum of recalcitrant organopollutants in soils and aqueous media. Although some of the organic compounds are degraded under nonligninolytic conditions, most are degraded under ligninolytic conditions with the involvement of the extracellular enzymes, lignin peroxidases, and manganese-dependent peroxidases, which are produced as secondary metabolites triggered by conditions of nutrient starvation (e.g., nitrogen limitation). The fungus and its enzymes can thus provide alternative technologies for bioremediation, biopulping, biobleaching, and other industrial applications. The efficiency and effectiveness of the fungus can be enhanced by increasing production and secretion of the important enzymes in large quantities and as primary metabolites under enriched conditions. One way this can be achieved is through isolation of mutants that are deregulated or are hyperproducers or supersecretors of key enzymes under enriched conditions. Through ultraviolet-light and gamma-rays mutagenesis we have isolated a variety of mutants, some of which produce key enzymes of the ligninolytic system under high-nitrogen growth conditions. One of the mutants produced 272 units (U) of lignin peroxidases enzyme activity per liter after nine days under high nitrogen. The mutant and the parent strains produced up to 54 U/L and 62 U/L, respectively, of the enzyme activity under low-nitrogen growth conditions during this period. In some experiments the mutant showed 281 U/L of enzyme activity under high nitrogen after 17 days.

  13. How Soluble GARP Enhances TGFβ Activation

    PubMed Central

    Fridrich, Sven; Hahn, Susanne A.; Linzmaier, Marion; Felten, Matthias; Zwarg, Jenny; Lennerz, Volker; Tuettenberg, Andrea; Stöcker, Walter

    2016-01-01

    GARP (glycoprotein A repetitions predominant) is a cell surface receptor on regulatory T-lymphocytes, platelets, hepatic stellate cells and certain cancer cells. Its described function is the binding and accommodation of latent TGFβ (transforming growth factor), before the activation and release of the mature cytokine. For regulatory T cells it was shown that a knockdown of GARP or a treatment with blocking antibodies dramatically decreases their immune suppressive capacity. This confirms a fundamental role of GARP in the basic function of regulatory T cells. Prerequisites postulated for physiological GARP function include membrane anchorage of GARP, disulfide bridges between the propeptide of TGFβ and GARP and connection of this propeptide to αvβ6 or αvβ8 integrins of target cells during mechanical TGFβ release. Other studies indicate the existence of soluble GARP complexes and a functionality of soluble GARP alone. In order to clarify the underlying molecular mechanism, we expressed and purified recombinant TGFβ and a soluble variant of GARP. Surprisingly, soluble GARP and TGFβ formed stable non-covalent complexes in addition to disulfide-coupled complexes, depending on the redox conditions of the microenvironment. We also show that soluble GARP alone and the two variants of complexes mediate different levels of TGFβ activity. TGFβ activation is enhanced by the non-covalent GARP-TGFβ complex already at low (nanomolar) concentrations, at which GARP alone does not show any effect. This supports the idea of soluble GARP acting as immune modulator in vivo. PMID:27054568

  14. Occurrence of neutral endopeptidase activity in the cat carotid body and its significance in chemoreception.

    PubMed

    Kumar, G K; Runold, M; Ghai, R D; Cherniack, N S; Prabhakar, N R

    1990-05-28

    The carotid body contains both tachykinins and enkephalins. Neutral endopeptidase (NEP, E.C. 3.4.24.11), has been suggested to involve in the metabolism of these neuropeptides in several organs. In the present study we determined neutral endopeptidase activity of the cat carotid body and assessed its significance in chemoreception. The cytosolic and membrane fractions of the carotid body contained NEP-like activity whereas it occurred only in the membrane fractions of the superior cervical and the nodose ganglia. Phosphoramidon, thiorphan and metal ion chelators inhibited NEP-like activity of all the 3 tissues studied; other protease inhibitors, however, were ineffective. Close carotid body administration of phosphoramidon significantly potentiated the carotid body response to low PO2 but not to hypercapnia. The enhanced response to hypoxia following phosphoramidon was further augmented by naloxone, an enkephalin antagonist. These results demonstrate that the glomus tissue contains detectable amounts of NEP-like activity and its inhibition selectively affects the hypoxic response of the carotid body.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Transepithelial Transport of Curcumin in Caco-2 Cells Is significantly Enhanced by Micellar Solubilisation.

    PubMed

    Frank, Jan; Schiborr, Christina; Kocher, Alexa; Meins, Jürgen; Behnam, Dariush; Schubert-Zsilavecz, Manfred; Abdel-Tawab, Mona

    2017-03-01

    Curcumin, the active constituent of Curcuma longa L. (family Zingiberaceae), has gained increasing interest because of its anti-cancer, anti-inflammatory, anti-diabetic, and anti-rheumatic properties associated with good tolerability and safety up to very high doses of 12 g. Nanoscaled micellar formulations on the base of Tween 80 represent a promising strategy to overcome its low oral bioavailability. We therefore aimed to investigate the uptake and transepithelial transport of native curcumin (CUR) vs. a nanoscaled micellar formulation (Sol-CUR) in a Caco-2 cell model. Sol-CUR afforded a higher flux than CUR (39.23 vs. 4.98 μg min(-1) cm(-2), respectively). This resulted in a higher Papp value of 2.11 × 10(-6) cm/s for Sol-CUR compared to a Papp value of 0.56 × 10(-6) cm/s for CUR. Accordingly a nearly 9.5 fold higher amount of curcumin was detected on the basolateral side at the end of the transport experiments after 180 min with Sol-CUR compared to CUR. The determined 3.8-fold improvement in the permeability of curcumin is in agreement with an up to 185-fold increase in the AUC of curcumin observed in humans following the oral administration of the nanoscaled micellar formulation compared to native curcumin. The present study demonstrates that the enhanced oral bioavailability of micellar curcumin formulations is likely a result of enhanced absorption into and increased transport through small intestinal epithelial cells.

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

    PubMed

    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.

  19. Significantly different coagulation factor activities underlying the variability of 'normal' activated partial thromboplastin time.

    PubMed

    Park, Kyoung-Jin; Kwon, Eui-Hoon; Ma, Youngeun; Park, In-Ae; Kim, Seon-Woo; Kim, Sun-Hee; Kim, Hee-Jin

    2012-01-01

    The activated partial thromboplastin time (aPTT) is a widely used coagulation screening test in routine laboratories. The aPTT level in the control population varies and is reflected by the reference interval. However, there have been no studies to investigate the coagulation status determining the variability of the aPTT. The aim of this study was to investigate the coagulation factor activities underlying the variability of aPTT in the population. The study participants were reference individuals with prothrombin time and aPTT within reference intervals. The aPTT was determined using STA-PTT Automate (Diagnostica Stago, Asnieres, France; local reference interval, 29.1-41.9 s). Those with aPTT within the marginal ranges of reference interval were selected for factor assays. We defined the lower marginal group as the lowest 10 percentile of reference interval (29.1-30.9 s) and the upper marginal group as the highest 10 percentile (38.0-41.9 s). Activities of factor II, V, VIII, IX, X, XI, and XII were determined in both groups. The lower marginal and upper marginal groups consisted of 220 and 209 individuals, respectively. All coagulation factors were significantly higher in the lower marginal than in the upper marginal group (P = 0.0127 for factor II and P < 0.0001 for the others). Multiple logistic regression analyses revealed factor XII and VIII were two strongest contributors determining the aPTT level, whereas factor XI was not significantly different between the groups (P = 0.095). This study firstly demonstrated significantly different coagulation factor activities underlying the variability of aPTT in reference individuals. The results suggested the possibility of disease association or phenotypic contribution of variable coagulation activities in the population.

  20. Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

    SciTech Connect

    Sakata, K.; Kurata, C.; Taguchi, T.; Suzuki, S.; Kobayashi, A.; Yamazaki, N.; Rydzewski, A.; Takada, Y.; Takada, A. )

    1990-10-01

    To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01).

  1. Enhancement of bismuth antibacterial activity with lipophilic thiol chelators.

    PubMed Central

    Domenico, P; Salo, R J; Novick, S G; Schoch, P E; Van Horn, K; Cunha, B A

    1997-01-01

    bacteria. The activity, solubility, and stability of BisBAL were strongly dependent on the pH, temperature, and molar ratio. Chelation of bismuth with certain thiol agents enhanced the solubility and lipophilicity of this cationic heavy metal, thereby significantly enhancing its potency and versatility as an antibacterial agent. PMID:9257744

  2. An active principle of Nigella sativa L., thymoquinone, showing significant antimicrobial activity against anaerobic bacteria

    PubMed Central

    Randhawa, Mohammad Akram; Alenazy, Awwad Khalaf; Alrowaili, Majed Gorayan; Basha, Jamith

    2017-01-01

    Aim/Background: Thymoquinone (TQ) is the major active principle of Nigella sativa seed (black seed) and is known to control many fungi, bacteria, and some viruses. However, the activity of TQ against anaerobic bacteria is not well demonstrated. Anaerobic bacteria can cause severe infections, including diarrhea, aspiration pneumonia, and brain abscess, particularly in immunodeficient individuals. The present study aimed to investigate the in vitro antimicrobial activity of TQ against some anaerobic pathogens in comparison to metronidazole. Methods: Standard, ATCC, strains of four anaerobic bacteria (Clostridium difficile, Clostridium perfringens, Bacteroides fragilis, and Bacteroides thetaiotaomicron), were initially isolated on special Brucella agar base (with hemin and vitamin K). Then, minimum inhibitory concentrations (MICs) of TQ and metronidazole were determined against these anaerobes when grown in Brucella agar, using serial agar dilution method according to the recommended guidelines for anaerobic organisms instructed by the Clinical and Laboratory Standards Institute. Results: TQ showed a significant antimicrobial activity against anaerobic bacteria although much weaker than metronidazole. MICs of TQ and metronidazole against various anaerobic human pathogens tested were found to be between 10-160 mg/L and 0.19-6.25 mg/L, respectively. Conclusions: TQ controlled the anaerobic human pathogenic bacteria, which supports the use of N. sativa in the treatment of diarrhea in folk medicine. Further investigations are in need for determination of the synergistic effect of TQ in combination with metronidazole and the activity of derivatives of TQ against anaerobic infections. PMID:28163966

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Individual versus Significant Other-Enhanced Brief Motivational Intervention for Alcohol in Emergency Care

    PubMed Central

    Monti, Peter M.; Colby, Suzanne M.; Mastroleo, Nadine R.; Barnett, Nancy P.; Gwaltney, Chad J.; Apodaca, Timothy R.; Rohsenow, Damaris J.; Magill, Molly; Gogineni, Aruna; Mello, Michael J.; Biffl, Walter L.; Cioffi, William G.

    2014-01-01

    Objective Effects of brief motivational interventions (BMIs) for heavy drinkers identified by alcohol-related emergency department (ED) visits are mixed. The successes of including significant others (SOs) in behavioral treatment suggest that involving SOs in ED-delivered BMI might prove beneficial. This study investigated the relative efficacy of an SO-enhanced Motivational Intervention (SOMI) compared to an Individual Motivational Intervention (IMI) to address heavy drinking in emergency care settings. Method ED (n = 317) or trauma unit (n = 89) patients were randomly assigned to receive either an IMI or an SOMI and were re-assessed at 6 and 12 months for alcohol consumption, alcohol-related consequences, and perceived alcohol-specific SO support. Results GEE analyses showed consistent reductions over time for both alcohol consumption and consequences. At one-year follow up, the average reduction in total drinks consumed per week was greater for patients in the SOMI condition than the IMI condition. In SOMI, 9.4% more patients moved to within the national guidelines for weekly drinking than did IMI patients. Frequency of heavy drinking and negative alcohol consequences showed no differential effects of intervention. Conclusions Emergence of a modest treatment effect at 12 months suggests that SO involvement in the SOMI condition may have led to more sustained positive influence on patient drinking than in the IMI condition. Implications and limitations regarding SO involvement in brief treatment are discussed. PMID:25111430

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26997140

  8. Hotspots of aberrant enhancer activity punctuate the colorectal cancer epigenome

    PubMed Central

    Cohen, Andrea J.; Saiakhova, Alina; Corradin, Olivia; Luppino, Jennifer M.; Lovrenert, Katreya; Bartels, Cynthia F.; Morrow, James J.; Mack, Stephen C.; Dhillon, Gursimran; Beard, Lydia; Myeroff, Lois; Kalady, Matthew F.; Willis, Joseph; Bradner, James E.; Keri, Ruth A.; Berger, Nathan A.; Pruett-Miller, Shondra M.; Markowitz, Sanford D.; Scacheri, Peter C.

    2017-01-01

    In addition to mutations in genes, aberrant enhancer element activity at non-coding regions of the genome is a key driver of tumorigenesis. Here, we perform epigenomic enhancer profiling of a cohort of more than forty genetically diverse human colorectal cancer (CRC) specimens. Using normal colonic crypt epithelium as a comparator, we identify enhancers with recurrently gained or lost activity across CRC specimens. Of the enhancers highly recurrently activated in CRC, most are constituents of super enhancers, are occupied by AP-1 and cohesin complex members, and originate from primed chromatin. Many activate known oncogenes, and CRC growth can be mitigated through pharmacologic inhibition or genome editing of these loci. Nearly half of all GWAS CRC risk loci co-localize to recurrently activated enhancers. These findings indicate that the CRC epigenome is defined by highly recurrent epigenetic alterations at enhancers which activate a common, aberrant transcriptional programme critical for CRC growth and survival. PMID:28169291

  9. Significant metal enhanced fluorescence of Ag2S quantum dots in the second near-infrared window

    NASA Astrophysics Data System (ADS)

    Theodorou, I. G.; Jawad, Z. A. R.; Qin, H.; Aboagye, E. O.; Porter, A. E.; Ryan, M. P.; Xie, F.

    2016-06-01

    The amplification of light in NIR-II from Ag2S QDs via metal enhanced fluorescence (MEF) is reported for the first time. Significant fluorescence enhancement of over 100 times for Ag2S QDs deposited on Au-nanostructured arrays, paves the way for novel sensing and imaging applications based on Ag2S QDs, with improved detection sensitivity and contrast enhancement.The amplification of light in NIR-II from Ag2S QDs via metal enhanced fluorescence (MEF) is reported for the first time. Significant fluorescence enhancement of over 100 times for Ag2S QDs deposited on Au-nanostructured arrays, paves the way for novel sensing and imaging applications based on Ag2S QDs, with improved detection sensitivity and contrast enhancement. Electronic supplementary information (ESI) available: Detailed description of experimental methods. See DOI: 10.1039/c6nr03220f

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Eastward electrojet enhancements during substorm activity

    NASA Astrophysics Data System (ADS)

    D'Onofrio, M.; Partamies, N.; Tanskanen, E.

    2014-11-01

    In this study, we use a semi-automatic routine to identify negative and positive bays in the IMAGE magnetometer data during seven months in 2003. The IMAGE stations have been divided into three latitude regions to monitor the time evolution and temporal relationship between the regions during substorms. In particular, we focus on the events where both positive and negative ground magnetic deflections are observed in different latitude regions. We found 101 events in total. We examine separately a subset of 32 events, for which the local electrojet index values are larger than the global ones, suggesting that the strongest activity at that time takes place within or very close to the local time sector of IMAGE. We systematically analyze the temporal difference and the intensity of the positive and negative bays. Our results show that the magnitude of the positive bay is on average about half of that of the negative bay. Two thirds of the positive bays within the IMAGE network peak earlier than the negative bays. Because the positive and negative bays occur meridionally very close together, we suggest that the enhancements of the westward current at the poleward part of the auroral oval and the eastward current within the return flow are very tightly coupled through field-aligned currents and closing horizontal currents. The substorm current system appears as a superposition on the large-scale current pattern in the vicinity of the evening sector shear flow region.

  12. Enhanced-performance active fiber composites

    NASA Astrophysics Data System (ADS)

    Gentilman, Richard L.; McNeal, Kelley; Schmidt, Gerald E.; Pizzochero, Alessandro E.; Rossetti, George A., Jr.

    2003-08-01

    Active fiber composites (AFCs) find applications in a variety of industrial, commercial, and aerospace markets as both actuators and sensors. Among the key attributes of AFCs relative to conventional monolithic piezoceramic actuators are high strain energy density, unidirectional response, conformability, and robustness. Recently, performance enhancements in AFCs have been demonstrated through the use of a modified injection molding process to produce piezoceramic modules with multiple identical fibers of a uniform rectangular cross section. AFC actuators made from Type II PZT fiber modules exhibit free micro-strains of 1830 +/- 30 ppm at a peak-peak E-field drive of 26.1 kV/cm, and show exceptional part-to-part uniformity. In addition, AFCs made from injection molded PMN-PT fiber modules show a low-field d33 of 650 pm/V. The successful incorporation of PMN-PT materials into AFCs also demonstrates the viability of using highly textured ceramic PMN-PT piezofibers, for which even larger increases in strain response are expected.

  13. Stiff substrates enhance cultured neuronal network activity.

    PubMed

    Zhang, Quan-You; Zhang, Yan-Yan; Xie, Jing; Li, Chen-Xu; Chen, Wei-Yi; Liu, Bai-Lin; Wu, Xiao-an; Li, Shu-Na; Huo, Bo; Jiang, Lin-Hua; Zhao, Hu-Cheng

    2014-08-28

    The mechanical property of extracellular matrix and cell-supporting substrates is known to modulate neuronal growth, differentiation, extension and branching. Here we show that substrate stiffness is an important microenvironmental cue, to which mouse hippocampal neurons respond and integrate into synapse formation and transmission in cultured neuronal network. Hippocampal neurons were cultured on polydimethylsiloxane substrates fabricated to have similar surface properties but a 10-fold difference in Young's modulus. Voltage-gated Ca(2+) channel currents determined by patch-clamp recording were greater in neurons on stiff substrates than on soft substrates. Ca(2+) oscillations in cultured neuronal network monitored using time-lapse single cell imaging increased in both amplitude and frequency among neurons on stiff substrates. Consistently, synaptic connectivity recorded by paired recording was enhanced between neurons on stiff substrates. Furthermore, spontaneous excitatory postsynaptic activity became greater and more frequent in neurons on stiff substrates. Evoked excitatory transmitter release and excitatory postsynaptic currents also were heightened at synapses between neurons on stiff substrates. Taken together, our results provide compelling evidence to show that substrate stiffness is an important biophysical factor modulating synapse connectivity and transmission in cultured hippocampal neuronal network. Such information is useful in designing instructive scaffolds or supporting substrates for neural tissue engineering.

  14. Electrophoretic Particle Guidance Significantly Enhances Olfactory Drug Delivery: A Feasibility Study

    PubMed Central

    Xi, Jinxiang; Si, Xiuhua A.; Gaide, Rachel

    2014-01-01

    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. PMID:24497957

  15. Significant enhancement in atmospheric biweekly disturbance over Northeast Asia during the recent warming hiatus

    NASA Astrophysics Data System (ADS)

    Li, Sang; Gong, Daoyi; Qu, Jingxuan

    2016-08-01

    Based on daily 500-hPa geopotential height from ERA-Interim reanalysis data, this study analyzed the day-to-day circulation variance in cold season (October-March) by composite and correlation analysis. Two same-length time periods were compared, namely, the hiatus period (1999-2013) and the rapid warming period (1984-1998). Spectral analysis revealed that over the mid-high latitudes of the Northern Hemisphere, the most outstanding peak in the daily 500-hPa geopotential height variance was of quasi-biweekly timescale (about 10-20 days), accounting for about 32% of the total variance. During the warming hiatus, quasibiweekly disturbance (QBD) changed remarkably in Northeast Asia. On average, within the domain 42°-50 °N, 128°-142 °E, the QBD variance changed from 1860 m2 in the rapid warming period to 2475 m2 in the hiatus period, increasing by about 33% and statistically significant at the 95% confidence level. Lead-lag analysis showed that the QBD signal could be traced back by about 14 days, with an origin around the Ural Mountains. Then, the signal developed and propogated southeastward, with its location about 10 days prior to its peak in West Siberia, and about 6 days prior to its peak in the Sayan Mountains, and finally moving to Northeast Asia. By comparing the propagation process between the two periods, we found that the propagation paths were basically the same, but there were evident differences in the intensity of the signals. The intensification of QBD may have been related to the increased energy conversion from mean flow to QBD transients. The frequency of low-temperature extremes in negative QBD phases was much higher than under normal conditions or in positive phases. Associated with the enhanced QBD, the probability of extreme low temperature increased from 19% during the rapid warming period to 27% during the warming hiatus.

  16. Significant enhancement of PEDOT thin film adhesion to inorganic solid substrates with EDOT-acid.

    PubMed

    Wei, Bin; Liu, Jinglin; Ouyang, Liangqi; Kuo, Chin-Chen; Martin, David C

    2015-07-22

    With its high conductivity, tunable surface morphology, relatively soft mechanical response, high chemical stability, and excellent biocompatibility, poly(3,4-ethylenedioxythiophene) (PEDOT) has become a promising coating material for a variety of electronic biomedical devices. However, the relatively poor adhesion of PEDOT to inorganic metallic and semiconducting substrates still poses challenges for long-term applications. Here, we report that 2,3-dihydrothieno(3,4-b)(1,4)dioxine-2-carboxylic acid (EDOT-acid) significantly improves the adhesion between PEDOT thin films and inorganic solid electrodes. EDOT-acid molecules were chemically bonded onto activated oxide substrates via the chemisorption of the carboxylic groups. PEDOT was then polymerized onto the EDOT-acid modified substrates, forming covalently bonded coatings. The adsorption of EDOT-acid onto the electrode surfaces was characterized by cyclic voltammetry (CV), contact angle measurements, atomic force microscopy, and X-ray photoelectron spectroscopy. The electrical properties of the subsequently coated PEDOT films were studied by electrochemical impedance spectroscopy and CV. An aggressive ultrasonication test confirmed the significantly improved adhesion and mechanical stability of the PEDOT films on electrodes with EDOT-acid treatment over those without treatment.

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

    PubMed

    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.

  18. In trans promoter activation by enhancers in transient transfection.

    PubMed

    Smirnov, N A; Akopov, S B; Didych, D A; Nikolaev, L G

    2017-03-01

    Earlier, it was reported that the strong cytomegalovirus enhancer can activate the cytomegalovirus promoter in trans, i.e. as a separate plasmid co-transfected with a promoter-reporter gene construct. Here we demonstrate that the ability of enhancers to activate promoters in trans in transient transfection experiments is a property of not only viral regulatory elements but also of various genomic enhancers and promoters. Enhancer-promoter activation in trans is promoter- and cell type-specific, and accompanied by physical interaction between promoter and enhancer as revealed by chromosome conformation capture assays. Thus, promoter activation in transient co-transfection of promoters and enhancers shares a number of important traits with long-distance promoter activation by enhancers in living cells and may therefore serve as a model of this fundamental cellular process.

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

    NASA Astrophysics Data System (ADS)

    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

  20. Significant enhancement of the Stille reaction with a new combination of reagents-copper(I) iodide with cesium fluoride.

    PubMed

    Mee, Simon P H; Lee, Victor; Baldwin, Jack E

    2005-05-20

    The combination of copper(I) iodide and cesium fluoride significantly enhances the Stille reaction. After extensive optimisation, a variety of electronically unfavourable and sterically hindered substrates were coupled in very high yields under mild conditions.

  1. Reliability enhancement activities for the TANSO interferometer

    NASA Astrophysics Data System (ADS)

    Châteauneuf, François; Soucy, Marc-André; Perron, Gaétan; Lévesque, Luc; Tanii, Jun

    2006-08-01

    The Greenhouse gases Observing SATellite (GOSAT) is designed to monitor the global distribution of carbon dioxide (CO II) from orbit. It is a joint project of Japan Aerospace Exploration Agency, the Ministry of Environment (MOE), and the National Institute for Environmental Studies (NIES). JAXA is responsible for the satellite and instrument development, MOE is involved in the instrument development, and NIES is responsible for the satellite data retrieval. It is scheduled to be launched in 2008. As existing ground monitoring stations are limited and still unevenly distributed, the satellite observation has advantages of global and frequent observations. The objective of the mission is in response to COP3 (Kyoto Protocol): Observation of Green House Gases (GHGs) including CO II with 1% relative accuracy in sub-continental spatial resolution and to identify the GHGs source and sink from the data obtained by GOSAT in conjunction with the data from the ground instruments, with simulated models. In order to detect the CO II variation of boundary layers, the technique to measure the column density and the retrieval algorithm to remove cloud and aerosol contamination are investigated. The simultaneous observation of methane (CH 4), which is the second largest contribution molecule, is studied. A Thermal And Near infrared Sensor for carbon Observation (TANSO) based on a Fourier transform spectrometer (FTS) with high optical throughput and spectral resolution is currently under design for the GOSAT mission. This paper presents an overview of the design of the TANSO interferometer as well as key reliability enhancement activities conducted during the design phase.

  2. Enhanced liposome-mediated activity of piperacillin against staphylococci.

    PubMed Central

    Nacucchio, M C; Bellora, M J; Sordelli, D O; D'Aquino, M

    1985-01-01

    This study showed that encapsulation of the beta-lactam antibiotic piperacillin (PIP) by liposomes prepared with phosphatidylcholine and cholesterol (1:1) protected the drug from hydrolysis by staphylococcal beta-lactamase. This was demonstrated by growth inhibition of Staphylococcus aureus in the presence of the liposomal preparation containing PIP at a 50% MIC. Growth inhibition was also seen when exogenous beta-lactamase was added. Furthermore, adsorption of PIP onto the surface of liposomes containing buffer conferred a significant degree of protection against enzymatic hydrolysis of the drug, thus enhancing its antistaphylococcal activity. PMID:3872624

  3. Enhancement of Buckling Load with the Use of Active Materials

    NASA Technical Reports Server (NTRS)

    Yuan, F. G.

    2002-01-01

    In this paper, active buckling control of a beam using piezoelectric materials is investigated. Under small deformation, mathematical models are developed to describe the behavior of the beams subjected to an axial compressive load with geometric imperfections and load eccentricities under piezoelectric force. Two types of supports, simply supported and clamped, of the beam with a partially bonded piezoelectric actuator are used to illustrate the concept. For the beam with load eccentricities and initial geometric imperfections, the load- carrying capacity can be significantly enhanced by counteracting moments from the piezoelectric actuator. For the single piezoelectric actuator, using static feedback closed-loop control, the first buckling load can be eliminated. In the case of initially straight beams, analytical solutions of the enhanced first critical buckling load due to the increase of bending stiffness by piezoelectric actuators are derived based on linearized buckling analysis.

  4. Schistosomes Enhance Plasminogen Activation: The Role of Tegumental Enolase

    PubMed Central

    Figueiredo, Barbara C.; Da'dara, Akram A.; Oliveira, Sergio C.; Skelly, Patrick J.

    2015-01-01

    Schistosoma mansoni is a blood fluke parasite that causes schistosomiasis, a debilitating disease of global public health importance. These relatively large parasites are able to survive prolonged periods in the human vasculature without inducing stable blood clots around them. We show here that the intravascular life stages (schistosomula and adult males and females) can all promote significant plasminogen (PLMG) activation in the presence of tissue plasminogen activator (tPA). This results in the generation of the potent fibrinolytic agent plasmin which could degrade blood clots forming around the worms in vivo. We demonstrate that S. mansoni enolase (SmEno) is a host-interactive tegumental enzyme that, in recombinant form, can bind PLMG and promote its activation. Like classical members of the enolase protein family, SmEno can catalyze the interconversion of 2-phospho-D-glycerate (2-PGA) and phosphoenolpyruvate (PEP). The enzyme has maximal activity at pH 7.5, requires Mg2+ for optimal activity and can be inhibited by NaF but not mefloquin. Suppressing expression of the SmEno gene significantly diminishes enolase mRNA levels, protein levels and surface enzyme activity but, surprisingly, does not affect the ability of the worms to promote PLMG activation. Thus, while SmEno can enhance PLMG activation, our analysis suggests that it is not the only contributor to the parasite’s ability to perform this function. We show that the worms possess several other PLMG-binding proteins in addition to SmEno and these may have a greater importance in schistosome-driven PLMG activation. PMID:26658895

  5. Growth enhancement and gene expression of Arabidopsis thaliana irradiated with active oxygen species

    NASA Astrophysics Data System (ADS)

    Watanabe, Satoshi; Ono, Reoto; Hayashi, Nobuya; Shiratani, Masaharu; Tashiro, Kosuke; Kuhara, Satoru; Inoue, Asami; Yasuda, Kaori; Hagiwara, Hiroko

    2016-07-01

    The characteristics of plant growth enhancement effect and the mechanism of the enhancement induced by plasma irradiation are investigated using various active species in plasma. Active oxygen species in oxygen plasma are effective for growth enhancement of plants. DNA microarray analysis of Arabidopsis thaliana indicates that the genes coding proteins that counter oxidative stresses by eliminating active oxygen species are expressed at significantly high levels. The size of plant cells increases owing to oxygen plasma irradiation. The increases in gene expression levels and cell size suggest that the increase in the expression level of the expansin protein is essential for plant growth enhancement phenomena.

  6. Image enhancement filters significantly improve reading performance for low vision observers

    NASA Technical Reports Server (NTRS)

    Lawton, T. B.

    1992-01-01

    As people age, so do their photoreceptors; many photoreceptors in central vision stop functioning when a person reaches their late sixties or early seventies. Low vision observers with losses in central vision, those with age-related maculopathies, were studied. Low vision observers no longer see high spatial frequencies, being unable to resolve fine edge detail. We developed image enhancement filters to compensate for the low vision observer's losses in contrast sensitivity to intermediate and high spatial frequencies. The filters work by boosting the amplitude of the less visible intermediate spatial frequencies. The lower spatial frequencies. These image enhancement filters not only reduce the magnification needed for reading by up to 70 percent, but they also increase the observer's reading speed by 2-4 times. A summary of this research is presented.

  7. Significant Enhancement of H2 Formation in Disk Galaxies under Strong Ram Pressure

    NASA Astrophysics Data System (ADS)

    Henderson, Benjamin; Bekki, Kenji

    2016-05-01

    We show for the first time that H2 formation on dust grains can be enhanced in disk galaxies under strong ram pressure (RP). We numerically investigate how the time evolution of H i and H2 components in disk galaxies orbiting a group/cluster of galaxies can be influenced by the hydrodynamical interaction between the gaseous components of the galaxies and the hot intracluster medium. We find that compression of H i caused by RP increases H2 formation in disk galaxies before RP rapidly strips H i, cutting off the fuel supply and causing a drop in H2 density. We also find that the level of this H2 formation enhancement in a disk galaxy under RP depends on the mass of its host cluster dark matter halo, the initial positions and velocities of the disk galaxy, and the disk inclination angle with respect to the orbital plane. We demonstrate that dust growth is a key factor in the evolution of the H i and H2 mass in disk galaxies under strong RP. We discuss how the correlation between H2 fractions and surface gas densities of disk galaxies evolves with time in the galaxies under RP. We also discuss whether galaxy-wide star formation rates (SFRs) in cluster disk galaxies can be enhanced by RP if the SFRs depend on H2 densities.

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

    SciTech Connect

    Zhang, Shukui; Poelker, Matthew; Stutzman, Marcy L.; Chen, Yiqiao; Moy, Aaron

    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.

  9. Enhanced silver nanoparticle synthesis by optimization of nitrate reductase activity.

    PubMed

    Vaidyanathan, Ramanathan; Gopalram, Shubaash; Kalishwaralal, Kalimuthu; Deepak, Venkataraman; Pandian, Sureshbabu Ram Kumar; Gurunathan, Sangiliyandi

    2010-01-01

    Nanostructure materials are attracting a great deal of attention because of their potential for achieving specific processes and selectivity, especially in biological and pharmaceutical applications. The generation of silver nanoparticles using optimized nitrate reductase for the reduction of Ag(+) with the retention of enzymatic activity in the complex is being reported. This report involves the optimization of enzyme activity to bring about enhanced nanoparticle synthesis. Response surface methodology and central composite rotary design (CCRD) were employed to optimize a fermentation medium for the production of nitrate reductase by Bacillus licheniformis at pH 8. The four variables involved in the study of nitrate reductase were Glucose, Peptone, Yeast extract and KNO(3). Glucose had a significant effect on nitrate reductase production. The optimized medium containing (%) Glucose: 1.5, Peptone: 1, Yeast extract: 0.35 and KNO(3): 0.35 resulted in a nitrate reductase activity of 452.206 U/ml which is same as that of the central level. The medium A (showing least nitrate reductase activity) and the medium B (showing maximum nitrate reductase activity) were compared for the synthesis. Spectrophotometric analysis revealed that the particles exhibited a peak at 431 nm and the A(431) for the medium B was 2-fold greater than that of the medium A. The particles were also characterized using TEM. The particles synthesized using the optimized enzyme activity ranged from 10 to 80 nm and therefore can be extended to various medicinal applications.

  10. Enhanced biological activity of carotenoids stabilized by phenyl groups.

    PubMed

    You, Ji Suk; Jeon, Sunhwa; Byun, Youn Jung; Koo, Sangho; Choi, Shin Sik

    2015-06-15

    Carotenoids are lipid soluble food ingredients with multifunction including antioxidant and anticancer activities. However, carotenoids are destructively oxidized upon reaction with radicals resulting in toxic effects on biological systems. Two synthetic carotenoids (BAS and BTS) containing the aromatic phenyl groups with a para-substituent (OMe and Me, respectively) at C-13 and C-13' position were prepared in order to overcome a structural instability of carotenoid. Both BAS and BTS exerted stronger radical scavenging activity than β-carotene in DPPH and ABTS assays. In particular, BTS significantly reduced in vivo ROS (reactive oxygen species) levels and improved body growth and reproduction of Caenorhabditiselegans. BTS has a great potential for the advanced and modified carotenoid material with stability leading to enhanced bioavailability.

  11. Porous carbon nitride nanosheets for enhanced photocatalytic activities

    NASA Astrophysics Data System (ADS)

    Hong, Jindui; Yin, Shengming; Pan, Yunxiang; Han, Jianyu; Zhou, Tianhua; Xu, Rong

    2014-11-01

    Porous carbon nitride nanosheets (PCNs) have been prepared for the first time by a simple liquid exfoliation method via probe sonication. These mesoporous nanosheets of around 5 nm in thickness combine several advantages including high surface area, enhanced light absorption and excellent water dispersity. It can be used as a versatile support for co-catalyst loading for photocatalytic dye degradation and water reduction. With 3.8 wt% Co3O4 loaded, PCNs can achieve more efficient photocatalytic degradation of Rhodamine B, compared with non-porous C3N4 nanosheets (CNs), bulk porous C3N4 (PCN) and bulk nonporous C3N4 (CN). With 1.0 wt% Pt loaded, CNs and PCN exhibit 7-8 times enhancement in H2 evolution than CN. Remarkably, PCNs with both porous and nanosheet-like features achieve 26 times higher activity in H2 evolution than CN. These significant improvements in photocatalytic activities can be attributed to the high surface area as well as better electron mobility of the two-dimensional nanostructure.Porous carbon nitride nanosheets (PCNs) have been prepared for the first time by a simple liquid exfoliation method via probe sonication. These mesoporous nanosheets of around 5 nm in thickness combine several advantages including high surface area, enhanced light absorption and excellent water dispersity. It can be used as a versatile support for co-catalyst loading for photocatalytic dye degradation and water reduction. With 3.8 wt% Co3O4 loaded, PCNs can achieve more efficient photocatalytic degradation of Rhodamine B, compared with non-porous C3N4 nanosheets (CNs), bulk porous C3N4 (PCN) and bulk nonporous C3N4 (CN). With 1.0 wt% Pt loaded, CNs and PCN exhibit 7-8 times enhancement in H2 evolution than CN. Remarkably, PCNs with both porous and nanosheet-like features achieve 26 times higher activity in H2 evolution than CN. These significant improvements in photocatalytic activities can be attributed to the high surface area as well as better electron mobility of

  12. Trends in space activities in 2014: The significance of the space activities of governments

    NASA Astrophysics Data System (ADS)

    Paikowsky, Deganit; Baram, Gil; Ben-Israel, Isaac

    2016-01-01

    This article addresses the principal events of 2014 in the field of space activities, and extrapolates from them the primary trends that can be identified in governmental space activities. In 2014, global space activities centered on two vectors. The first was geopolitical, and the second relates to the matrix between increasing commercial space activities and traditional governmental space activities. In light of these two vectors, the article outlines and analyzes trends of space exploration, human spaceflights, industry and technology, cooperation versus self-reliance, and space security and sustainability. It also reviews the space activities of the leading space-faring nations.

  13. Parthenolide enhances dacarbazine activity against melanoma cells.

    PubMed

    Koprowska, Kamila; Hartman, Mariusz L; Sztiller-Sikorska, Malgorzata; Czyz, Malgorzata E

    2013-09-01

    Dacarbazine induces a clinical response only in 15% of melanoma patients. New treatment strategies may involve combinations of drugs with different modes of action to target the tumor heterogeneity. We aimed to determine whether the combined treatment of heterogeneous melanoma cell populations in vitro with the alkylating agent dacarbazine and the nuclear factor-κB inhibitor parthenolide could be more effective than either drug alone. A panel of melanoma cell lines, including highly heterogeneous populations derived from surgical specimens, was treated with dacarbazine and parthenolide. The effect of drugs on the viable cell number was examined using an acid phosphatase activity assay, and the combination effect was determined by median-effect analysis. Cell death and cell-cycle arrest were assessed by flow cytometry. Gene expression was measured by real-time PCR and changes in the protein levels were evaluated by western blotting. Secretion of vascular endothelial growth factor and interleukin-8 was determined using an enzyme-linked immunosorbent assay. The self-renewing capacity was assessed using a clonogenic assay. Dacarbazine was less effective in heterogeneous melanoma populations than in the A375 cell line. Parthenolide and dacarbazine synergistically reduced the viable cell numbers. Both drugs induced cell-cycle arrest and apoptotic cell death. Importantly, parthenolide abrogated the baseline and dacarbazine-induced vascular endothelial growth factor secretion from melanoma cells in heterogeneous populations, whereas interleukin-8 secretion was not significantly affected by either drug. Parthenolide eradicated melanoma cells with self-renewing capacity also in cultures simultaneously treated with dacarbazine. The combination of parthenolide and dacarbazine might be considered as a new therapeutic modality against metastatic melanoma.

  14. Enhanced Gamma Oscillatory Activity in Rats with Chronic Inflammatory Pain

    PubMed Central

    Wang, Jing; Wang, Jing; Xing, Guo-Gang; Li, Xiaoli; Wan, You

    2016-01-01

    It has been reported that oscillatory gamma activity participates in brief acute pain and tonic ongoing pain. It is of great interest to determine whether the gamma activity is involved in chronic pain since chronic pain is a more severe pathological condition characterized by pain persistency. To investigate the oscillatory gamma activity in chronic pain, in the present study, we recorded spontaneous electrocorticogram (ECoG) signals during chronic pain development in rats with chronic inflammatory pain induced by monoarthritis. Power spectrum analysis of ECoG data showed that gamma power increased significantly at the late stage of chronic inflammatory pain. The increased gamma activity occurred mainly at electrodes over primary somatosensory cortices. In rats with chronic pain, the gamma power was positively correlated with the hyperalgesia measured by laser energy that elicited hindpaw withdrawal response. Furthermore, an increased coupling between the amplitude of gamma power and the phase of theta oscillations was observed in chronic inflammatory pain condition. These results indicate an enhanced spontaneous gamma activity in chronic pain and suggest a potential biomarker for the severity of chronic pain. PMID:27847461

  15. Discrete elements within the SV40 enhancer region display different cell-specific enhancer activities.

    PubMed Central

    Ondek, B; Shepard, A; Herr, W

    1987-01-01

    The SV40 enhancer contains three genetically defined elements, called A, B and C, that can functionally compensate for one another. By using short, synthetic DNA oligonucleotides, we show that each of these elements can act autonomously as an enhancer when present as multiple tandem copies. Analysis of a progressive series of B element oligomers shows a single element is ineffective as an enhancer and that the activity of two or more elements increases with copy number. Assay in five different cell lines of two separate enhancers containing six tandem copies of either the B or C element shows that these elements possess different cell-specific activities. Parallel oligomer enhancer constructs containing closely spaced double point mutations display no enhancer activity in any of the cell lines tested, indicating that these elements represent single units of enhancer function. These elements contain either a 'core' or 'octamer' consensus sequence but these consensus sequences alone are not sufficient for enhancer activity. The different cell-specific activities of the B and C elements are consistent with functional interactions with different trans-acting factors. We discuss how tandem duplication of such dissimilar elements, as in the wild-type SV40 72-bp repeats, can serve to expand the conditions under which an enhancer can function. Images Fig. 2. Fig. 3. Fig. 4. PMID:3036487

  16. Significantly enhanced giant Rashba splitting in a thin film of binary alloy

    NASA Astrophysics Data System (ADS)

    Tang, Shu-Jung; Chen, Wei-Chuan; Chang, Tay-Rong; Tsai, Sun-Ting; Kuo, Je-Ming; Yamamoto, Sh.; Cheng, Cheng-Maw; Tsuei, Ku-Ding; Yaji, Koichiro; Lin, Hsin; Jeng, Horng-Tay; Mou, Chung-Yu; Matsuda, Iwao

    Dirac cones in a 2D environment have attracted much attention not only because of the massless Dirac fermions but also due to their capability to lock the spin direction with the momentum. Here we demonstrate that the Rashba effect within a single layer of a binary alloy composed of heavy atoms, Pb and Au, can be driven by and even tweaked with the adjacent top and bottom layers to yield cones-like structures and further enhance the Rashba coupling strength. Two cones are observed at the surface zone center Γ with giant Rashba parameters 1.53 and 4.45 eVÅ an anisotropic giant Rashba splitting at the surface zone boundary M has a great value, 6.26 eVÅ, inferring the critical role of p- dhybridization between Pb and Au. Our results reveal not only an interesting natural phenomenon but also a feasible method of tweaking the Rashba effect of a 2D system.

  17. Hydrostatic pressure: A very effective approach to significantly enhance critical current density in granular iron pnictide superconductors

    PubMed Central

    Shabbir, Babar; Wang, Xiaolin; Ghorbani, S. R.; Shekhar, Chandra; Dou, Shixue; Srivastava, O. N.

    2015-01-01

    Pressure is well known to significantly raise the superconducting transition temperature, Tc, in both iron pnictides and cuprate based superconductors. Little work has been done, however, on how pressure can affect the flux pinning and critical current density in the Fe-based superconductors. Here, we propose to use hydrostatic pressure to significantly enhance flux pinning and Tc in polycrystalline pnictide bulks. We have chosen Sr4V2O6Fe2As2 polycrystalline samples as a case study. We demonstrate that the hydrostatic pressure up to 1.2 GPa can not only significantly increase Tc from 15 K (underdoped) to 22 K, but also significantly enhance the irreversibility field, Hirr, by a factor of 4 at 7 K, as well as the critical current density, Jc, by up to 30 times at both low and high fields. It was found that pressure can induce more point defects, which are mainly responsible for the Jc enhancement. Our findings provide an effective method to significantly enhance Tc, Jc, Hirr, and the upper critical field, Hc2, for other families of Fe-based superconductors in the forms of wires/tapes, films, and single crystal and polycrystalline bulks. PMID:25645351

  18. Significant enhancement of photoreactivity of graphitic carbon nitride catalysts under acidic conditions and the underlying H(+)-mediated mechanism.

    PubMed

    Zhang, Xue-Song; Tian, Ke; Hu, Jian-Yang; Jiang, Hong

    2015-12-01

    Graphitic carbon nitride (g-C3N4) is an emerging photocatalyst for organic pollutants degradation owing to its excellent stability and metal-free property. In this study, the photocatalytic activity of acidified g-C3N4 (ag-C3N4) was systematically investigated using rhodamine B (rhB) as a model organic pollutant. The results showed the photoreactivity of ag-C3N4 is significantly enhanced with the decrease of pH values. The apparent rate constant (kapp) of rhB degradation over ag-C3N4 is 11.59×10(-3)min(-1) at pH7.0 and it increases to 103.50×10(-3)min(-1) at pH3.0 under visible light. A series of analyses demonstrate that the photodegradation mechanism is a combination of a H(+)-promoted generation of OH and elevation of the redox potential of conduct band of C3N4. The change of surface properties of C3N4 caused by pH variation also affects the degradation of some zwitterionic compounds by changing the adsorption orientation of pollutants. The revealed mechanism of visible light-C3N4-rhB system is meaningful to broaden the usage of C3N4 to the photodegradation of other organic pollutants.

  19. MEETING REPORT: OMG Technical Committee Meeting in Orlando, FL, sees significant enhancement to CORBA

    NASA Astrophysics Data System (ADS)

    1998-06-01

    The Object Management Group (OMG) Platform Technology Committee (PTC) ratified its support for a new asynchronous messaging service for CORBA at OMG's recent Technical Committee Meeting in Orlando, FL. The meeting, held from 8 - 12 June, saw the PTC send the Messaging Service out for a final vote among the OMG membership. The Messaging Service, which will integrate Message Oriented Middleware (MOM) with CORBA, will give CORBA a true asynchronous messaging capability - something of great interest to users and developers. Formal adoption of the specification will most likely occur by the end of the year. The Messaging Service The Messaging Service, when adopted, will be the world's first standard for Message Oriented Middleware and will give CORBA a true asynchronous messaging capability. Asynchronous messaging allows developers to build simpler, richer client environments. With asynchronous messaging there is less need for multi-threaded clients because the Asynchronous Method Invocation is non-blocking, meaning the client thread can continue work while the application waits for a reply. David Curtis, Director of Platform Technology for OMG, said: `This messaging service is one of the more valuable additions to CORBA. It enhances CORBA's existing asynchronous messaging capabilities which is a feature of many popular message oriented middleware products. This service will allow better integration between ORBs and MOM products. This enhanced messaging capability will only make CORBA more valuable for builders of distributed object systems.' The Messaging Service is one of sixteen technologies currently being worked on by the PTC. Additionally, seventeen Revision Task Forces (RTFs) are working on keeping OMG specifications up to date. The purpose of these Revision Task Forces is to take input from the implementors of OMG specifications and clarify or make necessary changes based on the implementor's input. The RTFs also ensure that the specifications remain up to date

  20. Enormous enhancement of electric field in active gold nanoshells

    NASA Astrophysics Data System (ADS)

    Jiang, Shu-Min; Wu, Da-Jian; Wu, Xue-Wei; Liu, Xiao-Jun

    2014-04-01

    The electric field enhancement properties of an active gold nanoshell with gain material inside have been investigated by using Mie theory. As the gain coefficient of the inner core increases to a critical value, a super-resonance appears in the active gold nanoshell, and enormous enhancements of the electric fields can be found near the surface of the particle. With increasing shell thickness, the critical value of the gain coefficient for the super-resonance of the active gold nanoshell first decreases and then increases, and the corresponding surface enhanced Raman scattering (SERS) enhancement factor (G factor) also first increases and then decreases. The optimized active gold nanoshell can be obtained with an extremely high SERS G factor of the order of 1019-1020. Such an optimized active gold nanoshell possesses a high-efficiency SERS effect and may be useful for single-molecule detection.

  1. Significantly enhanced giant Rashba splitting in a thin film of binary alloy

    NASA Astrophysics Data System (ADS)

    Chen, Wei-Chuan; Chang, Tay-Rong; Tsai, Sun-Ting; Yamamoto, S.; Kuo, Je-Ming; Cheng, Cheng-Maw; Tsuei, Ku-Ding; Yaji, Koichiro; Lin, Hsin; Jeng, H.-T.; Mou, Chung-Yu; Matsuda, Iwao; Tang, S.-J.

    2015-08-01

    Dirac cones in a two-dimensional environment have attracted much attention not only because of the massless Dirac fermions but also due to their capability to lock the spin direction with the momentum. Here we demonstrate that the Rashba effect within a single layer of a binary alloy composed of heavy atoms, Pb and Au, can be driven by and even tweaked with the adjacent top and bottom layers to yield cone-like structures and further enhance the Rashba coupling strength. Two cones are observed at the surface zone center \\bar{Γ } with giant Rashba parameters 1.53 and 4.45 eVÅ an anisotropic giant Rashba splitting at the surface zone boundary \\bar{M} has a great value, 6.26 eVÅ, inferring the critical role of p-d hybridization between Pb and Au. Our results reveal not only an interesting natural phenomenon but also a feasible method of tweaking the Rashba effect of a two-dimensional system.

  2. Computational Identification of Active Enhancers in Model Organisms

    PubMed Central

    Wang, Chengqi; Zhang, Michael Q.; Zhang, Zhihua

    2013-01-01

    As a class of cis-regulatory elements, enhancers were first identified as the genomic regions that are able to markedly increase the transcription of genes nearly 30 years ago. Enhancers can regulate gene expression in a cell-type specific and developmental stage specific manner. Although experimental technologies have been developed to identify enhancers genome-wide, the design principle of the regulatory elements and the way they rewire the transcriptional regulatory network tempo-spatially are far from clear. At present, developing predictive methods for enhancers, particularly for the cell-type specific activity of enhancers, is central to computational biology. In this review, we survey the current computational approaches for active enhancer prediction and discuss future directions. PMID:23685394

  3. SIMPLE MACHINE PERFUSION SIGNIFICANTLY ENHANCES HEPATOCYTE YIELDS OF ISCHEMIC AND FRESH RAT LIVERS.

    PubMed

    Izamis, Maria-Louisa; Calhoun, Candice; Uygun, Basak E; Guzzardi, Maria Angela; Price, Gavrielle; Luitje, Martha; Saeidi, Nima; Yarmush, Martin L; Uygun, Korkut

    2013-01-01

    The scarcity of viable hepatocytes is a significant bottleneck in cell transplantation, drug discovery, toxicology, tissue engineering, and bioartificial assist devices, where trillions of high-functioning hepatocytes are needed annually. We took the novel approach of using machine perfusion to maximize cell recovery, specifically from uncontrolled cardiac death donors, the largest source of disqualified donor organs. In a rat model, we developed a simple 3 hour room temperature (20±2°C) machine perfusion protocol to treat non-premedicated livers exposed to 1 hour of warm (34°C) ischemia. Treated ischemic livers were compared to fresh, fresh-treated and untreated ischemic livers using viable hepatocyte yields and in vitro performance as quantitative endpoints. Perfusion treatment resulted in both a 25-fold increase in viable hepatocytes from ischemic livers, and a 40% increase from fresh livers. While cell morphology and function in suspension and plate cultures of untreated warm ischemic cells was significantly impaired, treated warm ischemic cells were indistinguishable from fresh hepatocytes. Further, a strong linear correlation between tissue ATP and cell yield enabled accurate evaluation of the extent of perfusion recovery. Maximal recovery of warm ischemic liver ATP content appears to be correlated with optimal flow through the microvasculature. These data demonstrate that the inclusion of a simple perfusion-preconditioning step can significantly increase the efficiency of functional hepatocyte yields and the number of donor livers that can be gainfully utilized.

  4. Simple Machine Perfusion Significantly Enhances Hepatocyte Yields of Ischemic and Fresh Rat Livers

    PubMed Central

    Izamis, Maria-Louisa; Calhoun, Candice; Uygun, Basak E.; Guzzardi, Maria Angela; Price, Gavrielle; Luitje, Martha; Saeidi, Nima; Yarmush, Martin L.; Uygun, Korkut

    2013-01-01

    The scarcity of viable hepatocytes is a significant bottleneck in cell transplantation, drug discovery, toxicology, tissue engineering, and bioartificial assist devices, where trillions of high-functioning hepatocytes are needed annually. We took the novel approach of using machine perfusion to maximize cell recovery, specifically from uncontrolled cardiac death donors, the largest source of disqualified donor organs. In a rat model, we developed a simple 3-h room temperature (20 ± 2°C) machine perfusion protocol to treat nonpremedicated livers exposed to 1 h of warm (34°C) ischemia. Treated ischemic livers were compared to fresh, fresh-treated, and untreated ischemic livers using viable hepatocyte yields and in vitro performance as quantitative endpoints. Perfusion treatment resulted in both a 25-fold increase in viable hepatocytes from ischemic livers and a 40% increase from fresh livers. While cell morphology and function in suspension and plate cultures of untreated warm ischemic cells was significantly impaired, treated warm ischemic cells were indistinguishable from fresh hepatocytes. Furthermore, a strong linear correlation between tissue ATP and cell yield enabled accurate evaluation of the extent of perfusion recovery. Maximal recovery of warm ischemic liver ATP content appears to be correlated with optimal flow through the microvasculature. These data demonstrate that the inclusion of a simple perfusion-preconditioning step can significantly increase the efficiency of functional hepatocyte yields and the number of donor livers that can be gainfully utilized. PMID:25431743

  5. Resveratrol Enhances Antitumor Activity of TRAIL in Prostate Cancer Xenografts through Activation of FOXO Transcription Factor

    PubMed Central

    Ganapathy, Suthakar; Chen, Qinghe; Singh, Karan P.; Shankar, Sharmila; Srivastava, Rakesh K.

    2010-01-01

    Background Resveratrol (3, 4′, 5 tri-hydroxystilbene), a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer. Methodology/Principal Findings Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining) and inducing apoptosis (TUNEL staining). The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27/K IP1, and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells) and markers of metastasis (MMP-2 and MMP-9). The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity. Conclusions/Significance These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer. PMID:21209944

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

    SciTech Connect

    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. ODV mobility enhancement using active height control

    NASA Astrophysics Data System (ADS)

    Rich, Shayne C.; Wood, Carl G.; Keller, Jared

    2000-07-01

    To enhance the mobility of the USU T-class of vehicles, the T3 vehicle has been developed that incorporates Z-axis motion of the drive wheel modules. Moving the wheels up and down provides the ability to pitch and roll the vehicle chassis and move the vehicle center of gravity to change the force distribution on the individual drive wheels. The omni- directional capability of the vehicle provides the capability to align the vehicle with the slope gradient that maximizes the vehicle stability. This paper shows that by pitching the vehicle into the slope, that the uphill traction limit of the vehicle can be increased by about 10 degree(s). Future research efforts concerning stair climbing, step negotiation, and obstacle field navigation are also discussed.

  8. Design of New Antibacterial Enhancers Based on AcrB’s Structure and the Evaluation of Their Antibacterial Enhancement Activity

    PubMed Central

    Song, Yi; Qin, Rongxin; Pan, Xichun; Ouyang, Qin; Liu, Tianyu; Zhai, Zhaoxia; Chen, Yingchun; Li, Bin; Zhou, Hong

    2016-01-01

    Previously, artesunate (AS) and dihydroartemisinine 7 (DHA7) were found to have antibacterial enhancement activity against Escherichia coli via inhibition of the efflux pump AcrB. However, they were only effective against E. coli standard strains. This study aimed to develop effective antibacterial enhancers based on the previous work. Our results demonstrate that 86 new antibacterial enhancers were designed via 3D-SAR and molecular docking. Among them, DHA27 had the best antibacterial enhancement activity. It could potentiate the antibacterial effects of ampicillin against not only E. coli standard strain but also clinical strains, and of β-lactam antibiotics, not non-β-lactamantibiotics. DHA27 could increase the accumulation of daunomycin and nile red within E. coli ATCC 35218, but did not increase the bacterial membrane permeability. DHA27 reduced acrB’s mRNA expression of E. coli ATCC 35218 in a dose-dependent manner, and its antibacterial enhancement activity is related to the degree of acrB mRNA expression in E. coli clinical strains. The polypeptides from AcrB were obtained via molecular docking assay; the pre-incubated polypeptides could inhibit the activity of DHA27. Importantly, DHA27 had no cytotoxicity on cell proliferation. In conclusion, among newly designed antibacterial enhancers, DHA27 had favorable physical and pharmacological properties with no significant cytotoxicity at effective concentrations, and might serve as a potential efflux pump inhibitor in the future. PMID:27869748

  9. Is Enhanced Physical Activity Possible Using Active Videogames?

    PubMed

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-06-01

    Our research indicated that 10-12-year-old children receiving two active Wii(™) (Nintendo(®); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  10. Enhancing Engagement through Active Student Response

    ERIC Educational Resources Information Center

    Tincani, Matt; Twyman, Janet S.

    2016-01-01

    Student engagement is critical to academic success. High-Active Student Response (ASR) teaching techniques are an effective way to improve student engagement and are an important component of evidence-based practice. High-ASR teaching strategies accompany important assumptions: (1) ASR is an alterable variable; (2) teachers can increase ASR in…

  11. Writing Composition Activities to Enhance Reading Comprehension.

    ERIC Educational Resources Information Center

    Gold, Janet T.

    A program of written composition based on reading comprehension can help students gain greater in-depth understanding of reading materials. Once the reading comprehension skill has been clearly defined for the class, the writing activity can provide clarification by allowing for analysis of the definition through written manipulation of language.…

  12. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    SciTech Connect

    Zhang, Yu; Duan, Junxin; Tang, Lan; Wu, Wenping

    2015-06-09

    Provided are isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. Also provided are nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

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

    PubMed

    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.

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

    PubMed

    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.

  15. Active Tails Enhance Arboreal Acrobatics in Geckos

    DTIC Science & Technology

    2008-03-18

    SI Movie 6). Discovering that active tails allow arboreal acrobatics in geckos opens the door for future studies of the tail’s neurome- chanical...declare no conflict of interest. This article is a PNAS Direct Submission. Freely available online through the PNAS open access option. *Present...ranging from 2.5 to 8.0 ms1. We mounted transparent Plexiglas sidewalls around the opening of the wind tunnel. This prevented geckos from maneuvering

  16. Is enhanced physical activity possible using active videogames?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our research indicated that 10– to 12-year-old children receiving two active Wii (TM)(Nintendo (R); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase phys...

  17. Protect and enhance: Lowi's juridical democracy and the prevention of significant deterioration of air quality

    SciTech Connect

    Meiburg, A.S.

    1986-01-01

    The capture of Federal regulatory agencies by the groups they were supposed to be regulating has been a topic of concern in the traditional literature of public administration. In his influential book The End of Liberalism, Professor Theordore Lowi suggested that capture resulted in part from vauge delegations of authority of Congress to regulatory agencies. Lowi argued that democracy would be better served if Congress were more specific in drafting laws, if agencies made greater use of formal rulemaking in implementing them, and if the courts rejected statutes which contained excessively vague delegations of authority - a remedy which he labeled juridicial democracy. This dissertation examines Lowi's theory in light of the experience of Congress and the Environmental Protection Agency (EPA) with the requirements of the Clean Air Act to prevent the significant deterioration of air quality in areas where air was already relatively clean. The history of the program to develop and carry out these requirements, known as PSD, is described in detail from its inception in the late 1960's through EPA's final regulations in 1980. Special attention is given to the actions taken by EPA after environmental groups successfully used the courts to force EPA to develop a PSD program in 1974, how Congress responded by amending the Clean Air Act in 1977, and the difficulties these amendments and subsequent additional court reviews caused for EPA.

  18. Activity and Imagined Activity Can Enhance Young Children's Reading Comprehension

    ERIC Educational Resources Information Center

    Glenberg, Arthur M.; Gutierrez, Tiana; Levin, Joel R.; Japuntich, Sandra; Kaschak, Michael P.

    2004-01-01

    The Indexical Hypothesis suggests a new method for enhancing children's reading comprehension. Young readers may not consistently "index," or map, words to the objects the words represent. Consequently, these readers fail to derive much meaning from the text. The instructional method involves manipulating toy objects referred to in the…

  19. Chemically modified RNA activated matrices enhance bone regeneration.

    PubMed

    Elangovan, Satheesh; Khorsand, Behnoush; Do, Anh-Vu; Hong, Liu; Dewerth, Alexander; Kormann, Michael; Ross, Ryan D; Sumner, D Rick; Allamargot, Chantal; Salem, Aliasger K

    2015-11-28

    There exists a dire need for improved therapeutics to achieve predictable bone regeneration. Gene therapy using non-viral vectors that are safe and efficient at transfecting target cells is a promising approach to overcoming the drawbacks of protein delivery of growth factors. Here, we investigated the transfection efficiency, cytotoxicity, osteogenic potential and in vivo bone regenerative capacity of chemically modified ribonucleic acid (cmRNA) (encoding BMP-2) complexed with polyethylenimine (PEI) and made comparisons with PEI complexed with conventional plasmid DNA (encoding BMP-2). The polyplexes were fabricated at an amine (N) to phosphate (P) ratio of 10 and characterized for transfection efficiency using human bone marrow stromal cells (BMSCs). The osteogenic potential of BMSCs treated with these polyplexes was validated by determining the expression of bone-specific genes, osteocalcin and alkaline phosphatase as well as through the detection of bone matrix deposition. Using a calvarial bone defect model in rats, it was shown that PEI-cmRNA (encoding BMP-2)-activated matrices promoted significantly enhanced bone regeneration compared to PEI-plasmid DNA (BMP-2)-activated matrices. Our proof of concept study suggests that scaffolds loaded with non-viral vectors harboring cmRNA encoding osteogenic proteins may be a powerful tool for stimulating bone regeneration with significant potential for clinical translation.

  20. Anaerobic incubation conditions enhance pyrazinamide activity against Mycobacterium tuberculosis.

    PubMed

    Wade, Mary Margaret; Zhang, Ying

    2004-08-01

    Pyrazinamide (PZA) is an unconventional front line tuberculosis drug characterized by high in vivo sterilizing activity, but poor in vitro activity. This disparity in PZA activity may reflect differences between the in vivo tissue environment and in vitro culture conditions. This study examined the effect of anaerobic conditions, which exist in granulomatous lesions in vivo, on PZA activity in vitro. Low oxygen enhanced the activity of PZA against Mycobacterium tuberculosis, with anaerobic conditions resulting in greater enhancement than microaerobic conditions. ATPase and respiratory chain enzyme inhibitors enhanced PZA activity under normal atmospheric conditions, but not under anaerobic conditions. Furthermore, the inhibitors did not enhance isoniazid or rifampicin activity. Nitrate as an alternative electron acceptor antagonized PZA activity under anaerobic conditions. These findings provide further support for a proposed mechanism of action of PZA in which the active form of PZA (pyrazinoic acid) depletes the membrane energy reserve. They also provide another explanation for the higher sterilizing activity of PZA within in vivo lesions with low oxygen than under in vitro drug susceptibility testing conditions with ambient oxygen.

  1. Doxycycline exerted neuroprotective activity by enhancing the activation of neuropeptide GPCR PAC1.

    PubMed

    Yu, Rongjie; Zheng, Lijun; Cui, Yue; Zhang, Huahua; Ye, Heng

    2016-04-01

    Doxycycline has significant neuroprotective effect with anti-inflammatory and anti-apoptotic activity. We found for the first time that doxycycline specially promoted the proliferation of Chinese hamster ovary (CHO) cells with high expression of neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) preferring G protein-coupled receptor (GPCR), PACAP receptor 1(PAC1) and induced the internalization of PAC1 tagged with yellow fluorescent protein (YFP) indicating doxycycline interacted with PAC1. The homology modeling of PAC1 and molecular docking of doxycycline with PAC1 showed the theoretical binding of doxycycline to PAC1 at the site where PACAP(30-37) recognized. The competition binding assay and PAC1 site-specific mutation of Asp116, which formed two hydrogen bonds with Dox, confirmed the binding of doxycycline to PAC1 imitating PACAP(30-37). Doxycycline (100 ng/mL) significantly promoted the proliferative activities of vasoactive intestinal polypeptide (VIP) and oligopeptide HSDGIF responsible for the activation of PAC1 in PAC1-CHO cells, indicating that doxycycline facilitated the binding and the activation of PAC1 imitating PACAP(28-38). In Neuro2a cells with endogenous expression of PAC1 and its ligands, doxycycline not only promoted the proliferation of Neuro2a cells but also protected the cells from scopolamine induced apoptosis, which was inhibited by cAMP-PKA signal pathway inhibitor H-89, PAC1 shRNA or PACAP antagonist PACAP(6-38). The in vivo study showed long-term treatment with doxycycline (100ug/kg) had significant effect against scopolamine induced amnesia, and the synergetic anti-apoptotic, anti-oxidative and neuroprotective effect of doxycycline with VIP was more efficient than doxycycline alone or VIP alone, indicating doxycycline enhanced the activation of PAC1 in vivo effectively. Furthermore, doxycycline analogue minocycline also had similar theoretically binding site on PAC1 to doxycycline and displayed corresponding

  2. Failure of Immune Sera to Enhance Significantly Phagocytosis of Staphylococus aureus: Nonspecific Adsorption of Phagocytosis-Promoting Factors.

    PubMed

    Shayegani, M

    1970-12-01

    Serum from rabbits immunized with either heat-killed or live nonencapsulated Staphylococcus aureus failed further to enhance phagocytosis and intracellular killing of the homologous organism by either normal rabbit polymorphonuclear leukocytes or monocytes, when compared with normal rabbit serum. These immune sera did, however, show an increase in agglutinating and precipitating antibody level. Adsorption of normal human serum with some gram-positive and gram-negative bacteria, yeast, and some inert particles significantly reduced the phagocytosis-promoting factors of the serum. It would seem, then, that nonencapsulated S. aureus differs from other pathogenic bacteria in that the humoral antibacterial factors promoting its phagocytosis and intracellular killing are not significantly enhanced by infection or immunization.

  3. Goniothalamin enhances the ATPase activity of the molecular chaperone Hsp90 but inhibits its chaperone activity.

    PubMed

    Yokoyama, Yuhei; Ohtaki, Aguru; Jantan, Ibrahim; Yohda, Masafumi; Nakamoto, Hitoshi

    2015-03-01

    Hsp90 is an ATP-dependent molecular chaperone that is involved in important cellular pathways such as signal transduction pathways. It is a potential cancer drug target because it plays a critical role for stabilization and activation of oncoproteins. Thus, small molecule compounds that control the Hsp90 function are useful to elucidate potential lead compounds against cancer. We studied effect of a naturally occurring styryl-lactone goniothalamin on the activity of Hsp90. Although many drugs targeting Hsp90 inhibit the ATPase activity of Hsp90, goniothalamin enhanced rather than inhibited the ATPase activity of a cyanobacterial Hsp90 (HtpG) and a yeast Hsp90. It increased both K(m) and k(cat) of the Hsp90s. Domain competition assays and tryptophan fluorescence measurements with various truncated derivatives of HtpG indicated that goniothalamin binds to the N-terminal domain of HtpG. Goniothalamin did not influence on the interaction of HtpG with a non-native protein or the anti-aggregation activity of HtpG significantly. However, it inhibited the activity of HtpG that assists refolding of a non-native protein in cooperation with the Hsp70 chaperone system. This is the first report to show that a small molecule that binds to the N-terminal domain of Hsp90 activates its ATPase activity, while inhibiting the chaperone function of Hsp90.

  4. The Idefix enhancer-blocking insulator also harbors barrier activity.

    PubMed

    Brasset, E; Hermant, C; Jensen, S; Vaury, C

    2010-01-15

    Chromatin insulators are cis-regulatory sequences participating in the regulation of gene expression. Their presence within the genome is associated with two main functions. One of them is an enhancer-blocking function that blocks enhancer-promoter communication when the insulator is located in between. The second is a boundary or barrier function that insulates independent units of transcription. This latter is observed when two insulators flanking a gene and its regulatory sequences block the regulatory influences of surrounding chromatin. Some years ago, we reported the presence of an insulator within the retrotransposon Idefix from Drosophila melanogaster. This insulator displays an enhancer-blocking activity toward an enhancer located within a second retrotransposon called ZAM. Here, we show that this insulator is not specific to the ZAM enhancer but has the capacity to interfere in the communication established between a broad range of cis-regulatory enhancer and a promoter. Furthermore, we show that, if it is placed on both sides of a transgene, this insulator acts as a barrier able to isolate the transgene from its repressive or enhancing environment. Thus, the Idefix insulator carries both an enhancer-blocking and a barrier activity. According to these properties, the Idefix insulator might prove to be a useful tool to isolate artificial transgenes from positive or negative influences from their integration sites.

  5. Environmental Education Activities to Enhance Decision-Making.

    ERIC Educational Resources Information Center

    Yambert, Paul A.; And Others

    This document contains a set of 10 activities that teachers may use with students (ages 10 to adult) to enhance environmental knowledge and environmentally responsible behavior. Sample worksheets are included when applicable. The activities focus on: renewable and nonrenewable resources; recycling; population growth; wildlife; recycling in a…

  6. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.

    PubMed

    Northcott, Paul A; Lee, Catherine; Zichner, Thomas; Stütz, Adrian M; Erkek, Serap; Kawauchi, Daisuke; Shih, David J H; Hovestadt, Volker; Zapatka, Marc; Sturm, Dominik; Jones, David T W; Kool, Marcel; Remke, Marc; Cavalli, Florence M G; Zuyderduyn, Scott; Bader, Gary D; VandenBerg, Scott; Esparza, Lourdes Adriana; Ryzhova, Marina; Wang, Wei; Wittmann, Andrea; Stark, Sebastian; Sieber, Laura; Seker-Cin, Huriye; Linke, Linda; Kratochwil, Fabian; Jäger, Natalie; Buchhalter, Ivo; Imbusch, Charles D; Zipprich, Gideon; Raeder, Benjamin; Schmidt, Sabine; Diessl, Nicolle; Wolf, Stephan; Wiemann, Stefan; Brors, Benedikt; Lawerenz, Chris; Eils, Jürgen; Warnatz, Hans-Jörg; Risch, Thomas; Yaspo, Marie-Laure; Weber, Ursula D; Bartholomae, Cynthia C; von Kalle, Christof; Turányi, Eszter; Hauser, Peter; Sanden, Emma; Darabi, Anna; Siesjö, Peter; Sterba, Jaroslav; Zitterbart, Karel; Sumerauer, David; van Sluis, Peter; Versteeg, Rogier; Volckmann, Richard; Koster, Jan; Schuhmann, Martin U; Ebinger, Martin; Grimes, H Leighton; Robinson, Giles W; Gajjar, Amar; Mynarek, Martin; von Hoff, Katja; Rutkowski, Stefan; Pietsch, Torsten; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Eils, Roland; Gilbertson, Richard J; Korshunov, Andrey; Taylor, Michael D; Lichter, Peter; Korbel, Jan O; Wechsler-Reya, Robert J; Pfister, Stefan M

    2014-07-24

    Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.

  7. Caffeine enhances micturition through neuronal activation in micturition centers.

    PubMed

    Cho, Young-Sam; Ko, Il-Gyu; Kim, Sung-Eun; Hwan, Lakkyong; Shin, Mal-Soon; Kim, Chang-Ju; Kim, Sang-Hoon; Jin, Jun-Jang; Chung, Jun-Young; Kim, Khae-Hawn

    2014-12-01

    Caffeine may promote incontinence through its diuretic effect, particularly in individuals with underlying detrusor overactivity, in addition to increasing muscle contraction of the bladder smooth muscle. Caffeine may also affect bladder function via central micturition centers, including the medial preoptic area, ventrolateral periaqueductal gray, and pontine micturition center. However, the biochemical mechanisms of caffeine in central micturition centers affecting bladder function remain unclear. In the present study, the effects of caffeine on the central micturition reflex were investigated by measuring the degree of neuronal activation, and by quantifying nerve growth factor (NGF) expression in rats. Following caffeine administration for 14 days, a urodynamic study was performed to assess the changes to bladder function. Subsequently, immunohistochemical staining to identify the expression of c‑Fos and NGF in the central micturition areas was performed. Ingestion of caffeine increased bladder smooth muscle contraction pressure and time as determined by cystometry. Expression levels of c‑Fos and NGF in all central micturition areas were significantly increased following the administration of caffeine. The effects on contraction pressure and time were the most potent and expression levels of c‑Fos and NGF were greatest at the lowest dose of caffeine. These results suggest that caffeine facilitates bladder instability through enhancing neuronal activation in the central micturition areas.

  8. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion.

    PubMed

    Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W; Liu, Yan; Walter, Nils G; Yan, Hao

    2016-02-10

    Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology.

  9. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion

    PubMed Central

    Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W.; Liu, Yan; Walter, Nils G.; Yan, Hao

    2016-01-01

    Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology. PMID:26861509

  10. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion

    NASA Astrophysics Data System (ADS)

    Zhao, Zhao; Fu, Jinglin; Dhakal, Soma; Johnson-Buck, Alexander; Liu, Minghui; Zhang, Ting; Woodbury, Neal W.; Liu, Yan; Walter, Nils G.; Yan, Hao

    2016-02-01

    Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology.

  11. Enhanced Multistatic Active Sonar via Innovative Signal Processing

    DTIC Science & Technology

    2015-09-30

    Grove, CA, November, 2014. [in press, refereed]. C . Gianelli, L. Xu, and J. Li, " Active Sonar Systems in the Presence of Strong Direct Blast", Oceans...3. DATES COVERED (From - To) Oct. 01, 2014-Sept. 30, 2015 4. TITLE AND SUBTITLE Enhanced Multistatic Active Sonar via Innovative Signal... active sonar (CAS) in the presence of strong direct blast is studied for the Doppler-tolerant linear frequency modulation waveform. A receiver design

  12. Enhanced Multistatic Active Sonar via Innovative Signal Processing

    DTIC Science & Technology

    2014-09-30

    DATES COVERED (From - To) Oct. 01. 2013-Sept. 30, 2014 4. TITLE AND SUBTITLE Enhanced Multistatic Active Sonar via Innovative Signal Processing 5a...DISTRIBUTION AVAILABILITY STATEMENT Approved for Public Release; Distribution is Unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Pulsed active sonar ...PAS) and continuous active sonar (CAS) in the presence of strong direct blast are studied for the Doppler-tolerant linear frequency modulation

  13. Forecast of enhanced activity of eta-Aquariids in 2013

    NASA Astrophysics Data System (ADS)

    Sato, M.; Watanabe, J.

    2014-07-01

    We tried to simulate distributions for Eta-Aquariids (ETA) of dust trails from 1P/Halley, we found out that some dust trails formed by meteoroids ejected in -1197 and -910 would approach the Earth in 2013. It means that the enhancement of eta-Aquariids would be expected. Actually, the enhanced activity of eta-Aquariids was observed in 2013. Its peak time corresponded with the time when the dust trails approached the Earth based on our simulation. Therefore, it was sure that the enhancement was caused by these dust trails.

  14. Enhancing antioxidant activity and antiproliferation of wheat bran through steam flash explosion.

    PubMed

    Chen, Yongsheng; Zhang, Ruiting; Liu, Chong; Zheng, Xueling; Liu, Benguo

    2016-07-01

    The effect of steam flash explosion (SFE), a green processing technology, on the phenolic composition, antioxidant activity and antiproliferation to HepG2 of wheat bran was investigated. Moderate SFE treatment significantly enhanced the total soluble phenolic content of wheat bran. After SFE pretreatment, the free and conjugated ferulic acid content in the wheat bran were significantly increased. Antioxidant activities of SFE treated wheat bran were higher than those untreated wheat bran. The cellular antioxidant and antiproliferative activities of SFE treated wheat bran were also significantly ameliorated. It was suggested that SFE pretreatment could be applied to release the bound phenolic compounds and enhance the antioxidant activities and antiproliferative activities of wheat bran.

  15. STATs Shape the Active Enhancer Landscape of T Cell Populations

    PubMed Central

    Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Sun, Hong-wei; Sartorelli, Vittorio; Kanno, Yuka; O’Shea, John J.

    2012-01-01

    SUMMARY Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. While enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4+ T cells as a model of differentiation, mapping the acquisition of cell-type-specific enhancer elements in T-helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the acquisition of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. PMID:23178119

  16. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan.

    PubMed

    Hubbard-Turner, Tricia; Wikstrom, Erik A; Guderian, Sophie; Turner, Michael J

    2015-09-01

    We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J) were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL) group, the transected anterior talofibular ligament (ATFL)/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse's lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011). Daily duration was different between the three running groups (p = 0.048). The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046) while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028) compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019) and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005). The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately. Key pointsA single ankle significantly decreased physical activity levels in mice across the lifespan.Decreased physical activity could significantly negatively impact overall health if not modified

  17. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

    PubMed Central

    Hubbard-Turner, Tricia; Wikstrom, Erik A.; Guderian, Sophie; Turner, Michael J.

    2015-01-01

    We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J) were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL) group, the transected anterior talofibular ligament (ATFL)/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011). Daily duration was different between the three running groups (p = 0.048). The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046) while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028) compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019) and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005). The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately. Key points A single ankle significantly decreased physical activity levels in mice across the lifespan. Decreased physical activity could significantly negatively impact overall health if not

  18. The glucagon-like peptide 1 receptor agonist enhances intrinsic peroxisome proliferator-activated receptor γ activity in endothelial cells

    SciTech Connect

    Onuma, Hirohisa; Inukai, Kouichi Kitahara, Atsuko; Moriya, Rie; Nishida, Susumu; Tanaka, Toshiaki; Katsuta, Hidenori; Takahashi, Kazuto; Sumitani, Yoshikazu; Hosaka, Toshio; Ishida, Hitoshi

    2014-08-22

    Highlights: • PPARγ activation was involved in the GLP-1-mediated anti-inflammatory action. • Exendin-4 enhanced endogenous PPARγ transcriptional activity in HUVECs. • H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement. • The anti-inflammatory effects of GLP-1 may be explained by PPARγ activation. - Abstract: Recent studies have suggested glucagon-like peptide-1 (GLP-1) signaling to exert anti-inflammatory effects on endothelial cells, although the precise underlying mechanism remains to be elucidated. In the present study, we investigated whether PPARγ activation is involved in the GLP-1-mediated anti-inflammatory action on endothelial cells. When we treated HUVEC cells with 0.2 ng/ml exendin-4, a GLP-1 receptor agonist, endogenous PPARγ transcriptional activity was significantly elevated, by approximately 20%, as compared with control cells. The maximum PPARγ activity enhancing effect of exendin-4 was observed 12 h after the initiation of incubation with exendin-4. As H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement, the signaling downstream from GLP-1 cross-talk must have been involved in PPARγ activation. In conclusion, our results suggest that GLP-1 has the potential to induce PPARγ activity, partially explaining the anti-inflammatory effects of GLP-1 on endothelial cells. Cross-talk between GLP-1 signaling and PPARγ activation would have major impacts on treatments for patients at high risk for cardiovascular disease.

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

    PubMed

    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.

  20. Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

    ERIC Educational Resources Information Center

    Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

    2011-01-01

    Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

  1. Subjective Significance Shapes Arousal Effects on Modified Stroop Task Performance: A Duality of Activation Mechanisms Account

    PubMed Central

    Imbir, Kamil K.

    2016-01-01

    Activation mechanisms such as arousal are known to be responsible for slowdown observed in the Emotional Stroop and modified Stroop tasks. Using the duality of mind perspective, we may conclude that both ways of processing information (automatic or controlled) should have their own mechanisms of activation, namely, arousal for an experiential mind, and subjective significance for a rational mind. To investigate the consequences of both, factorial manipulation was prepared. Other factors that influence Stroop task processing such as valence, concreteness, frequency, and word length were controlled. Subjective significance was expected to influence arousal effects. In the first study, the task was to name the color of font for activation charged words. In the second study, activation charged words were, at the same time, combined with an incongruent condition of the classical Stroop task around a fixation point. The task was to indicate the font color for color-meaning words. In both studies, subjective significance was found to shape the arousal impact on performance in terms of the slowdown reduction for words charged with subjective significance. PMID:26869974

  2. Chemical modification of capuramycins to enhance antibacterial activity

    PubMed Central

    Bogatcheva, Elena; Dubuisson, Tia; Protopopova, Marina; Einck, Leo; Nacy, Carol A.; Reddy, Venkata M.

    2011-01-01

    Objectives To extend capuramycin spectrum of activity beyond mycobacteria and improve intracellular drug activity. Methods Three capuramycin analogues (SQ997, SQ922 and SQ641) were conjugated with different natural and unnatural amino acids or decanoic acid (DEC) through an ester bond at one or more available hydroxyl groups. In vitro activity of the modified compounds was determined against Mycobacterium spp. and representative Gram-positive and Gram-negative bacteria. Intracellular activity was evaluated in J774A.1 mouse macrophages infected with Mycobacterium tuberculosis (H37Rv). Results Acylation of SQ997 and SQ641 with amino undecanoic acid (AUA) improved in vitro activity against most of the bacteria tested. Conjugation of SQ922 with DEC, but not AUA, improved its activity against Gram-positive bacteria. In the presence of efflux pump inhibitor phenylalanine arginine β-naphthyl amide, MICs of SQ997-AUA, SQ641-AUA and SQ922-DEC compounds improved even further against drug-susceptible and drug-resistant Staphylococcus aureus. In Gram-negative bacteria, EDTA-mediated permeabilization caused 4- to 16-fold enhancement of the activity of AUA-conjugated SQ997, SQ922 and SQ641. Conjugation of all three capuramycin analogues with AUA improved intracellular killing of H37Rv in murine macrophages. Conclusions Conjugation of capuramycin analogues with AUA or DEC enhanced in vitro activity, extended the spectrum of activity in Gram-positive bacteria and increased intracellular activity against H37Rv. PMID:21186194

  3. alpha-MSH enhances activity-based anorexia.

    PubMed

    Hillebrand, Jacquelien J G; Kas, Martien J H; Adan, Roger A H

    2005-10-01

    Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa (AN). In ABA, scheduled feeding in combination with voluntary access to running wheels, results in hyperactivity, hypophagia, body weight loss and activation of the HPA axis. Since stimulation of the melanocortin (MC) system has similar effects, this system is a candidate system involved in ABA. Here it is shown that chronic alpha-MSH treatment enhances ABA by increasing running wheel activity (RWA), decreasing food intake and increasing HPA axis activation.

  4. Active DNA demethylation at enhancers during the vertebrate phylotypic period.

    PubMed

    Bogdanović, Ozren; Smits, Arne H; de la Calle Mustienes, Elisa; Tena, Juan J; Ford, Ethan; Williams, Ruth; Senanayake, Upeka; Schultz, Matthew D; Hontelez, Saartje; van Kruijsbergen, Ila; Rayon, Teresa; Gnerlich, Felix; Carell, Thomas; Veenstra, Gert Jan C; Manzanares, Miguel; Sauka-Spengler, Tatjana; Ecker, Joseph R; Vermeulen, Michiel; Gómez-Skarmeta, José Luis; Lister, Ryan

    2016-04-01

    The vertebrate body plan and organs are shaped during a conserved embryonic phase called the phylotypic stage. However, the mechanisms that guide the epigenome through this transition and their evolutionary conservation remain elusive. Here we report widespread DNA demethylation of enhancers during the phylotypic period in zebrafish, Xenopus tropicalis and mouse. These enhancers are linked to developmental genes that display coordinated transcriptional and epigenomic changes in the diverse vertebrates during embryogenesis. Binding of Tet proteins to (hydroxy)methylated DNA and enrichment of 5-hydroxymethylcytosine in these regions implicated active DNA demethylation in this process. Furthermore, loss of function of Tet1, Tet2 and Tet3 in zebrafish reduced chromatin accessibility and increased methylation levels specifically at these enhancers, indicative of DNA methylation being an upstream regulator of phylotypic enhancer function. Overall, our study highlights a regulatory module associated with the most conserved phase of vertebrate embryogenesis and suggests an ancient developmental role for Tet dioxygenases.

  5. Immunoglobulin octanucleotide: independent activity and selective interaction with enhancers

    SciTech Connect

    Parslow, T.G.; Jones, S.D.; Bond, B.; Yamamoto, K.R.

    1987-03-20

    The thymidine kinase (tk) promoter of herpes simplex virus includes an octanucleotide sequence motif (ATTTGCAT) that is also an essential component of immunoglobulin kappa gene promoters. In the absence of an enhancer, tk promoter derivatives that contain this element support a higher rate of transcription than those that lack it. The action of the kappa enhancer augments that of the octanucleotide in B lymphoid cells; when both elements are present, tk promoter activity is increased by more than an order of magnitude. In contrast, the presence of the octanucleotide in this promoter markedly reduces its response to a nonimmunoglobulin enhancer. These results suggest that the octanucleotide may mediate a selective interaction among promoters and enhancers.

  6. Enhanced oxidation resistance of active nanostructures via dynamic size effect

    NASA Astrophysics Data System (ADS)

    Liu, Yun; Yang, Fan; Zhang, Yi; Xiao, Jianping; Yu, Liang; Liu, Qingfei; Ning, Yanxiao; Zhou, Zhiwen; Chen, Hao; Huang, Wugen; Liu, Ping; Bao, Xinhe

    2017-02-01

    A major challenge limiting the practical applications of nanomaterials is that the activities of nanostructures (NSs) increase with reduced size, often sacrificing their stability in the chemical environment. Under oxidative conditions, NSs with smaller sizes and higher defect densities are commonly expected to oxidize more easily, since high-concentration defects can facilitate oxidation by enhancing the reactivity with O2 and providing a fast channel for oxygen incorporation. Here, using FeO NSs as an example, we show to the contrary, that reducing the size of active NSs can drastically increase their oxidation resistance. A maximum oxidation resistance is found for FeO NSs with dimensions below 3.2 nm. Rather than being determined by the structure or electronic properties of active sites, the enhanced oxidation resistance originates from the size-dependent structural dynamics of FeO NSs in O2. We find this dynamic size effect to govern the chemical properties of active NSs.

  7. Significantly enhanced high-frequency permeability for composites with amorphous-membrane-fillers prepared using an infiltration method

    NASA Astrophysics Data System (ADS)

    Li, Z. W.; Yang, Z. H.

    2016-03-01

    Amorphous-membrane-filler composites have been fabricated using an infiltration method. The composites are able to significantly increase the permeability by 200%, as compared to general amorphous flake composites. SEM and magnetic measurement show that the amorphous flakes in membrane are in-plane arrangement. A model, which considers the effect of flake arrangement on demagnetizing factor Nd and permeability, is proposed. The effect of the arrangement of flakes is equivalent to an effective Nd, which is equal to 1/3 and zero for random and complete in-plane arrangements, respectively. Due to in-plane arrangement of amorphous flakes, the decreased Nd leads to significantly enhanced permeability for the amorphous-membrane-filler composites, based on the Maxwell-Garret mixing law.

  8. Eugenol nanocapsule for enhanced therapeutic activity against periodontal infections.

    PubMed

    Pramod, Kannissery; Aji Alex, M R; Singh, Manisha; Dang, Shweta; Ansari, Shahid H; Ali, Javed

    2016-01-01

    Eugenol is a godsend to dental care due to its analgesic, local anesthetic, and anti-inflammatory and antibacterial effects. The aim of the present research work was to prepare, characterize and evaluate eugenol-loaded nanocapsules (NCs) against periodontal infections. Eugenol-loaded polycaprolactone (PCL) NCs were prepared by solvent displacement method. The nanometric size of the prepared NCs was confirmed by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The in vitro drug release was found to follow a biphasic pattern and followed Michaelis-Menten like model. The percentage cell viability values near to 100 in the cell viability assay indicated that the NCs are not cytotoxic. In the in vivo studies, the eugenol NC group displayed significant difference in the continuity of epithelium of the interdental papilla in comparison to the untreated, pure eugenol and placebo groups. The in vivo performance of the eugenol-loaded NCs using ligature-induced periodontitis model in rats indicated that eugenol-loaded NCs could prevent septal bone resorption in periodontitis. On the basis of our research findings it could be concluded that eugenol-loaded PCL NCs could serve as a novel colloidal drug delivery system for enhanced therapeutic activity of eugenol in the treatment of periodontal infections.

  9. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    SciTech Connect

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2016-08-09

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  10. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    SciTech Connect

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2014-09-30

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  11. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    SciTech Connect

    Zhang, Yu; Duan, Junxin; Tang, Lan; Wu, Wenping

    2016-06-14

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  12. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Zhang, Yu; Duan, Junxin; Tang, Lan; Wu, Wenping

    2016-11-22

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  13. Brg1 modulates enhancer activation in mesoderm lineage commitment

    SciTech Connect

    Alexander, Jeffrey M.; Hota, Swetansu K.; He, Daniel; Thomas, Sean; Ho, Lena; Pennacchio, Len A.; Bruneau, B. G.

    2015-03-26

    The interplay between different levels of gene regulation in modulating developmental transcriptional programs, such as histone modifications and chromatin remodeling, is not well understood. Here, we show that the chromatin remodeling factor Brg1 is required for enhancer activation in mesoderm induction. In an embryonic stem cell-based directed differentiation assay, the absence of Brg1 results in a failure of cardiomyocyte differentiation and broad deregulation of lineage-specific gene expression during mesoderm induction. We find that Brg1 co-localizes with H3K27ac at distal enhancers and is required for robust H3K27 acetylation at distal enhancers that are activated during mesoderm induction. Brg1 is also required to maintain Polycomb-mediated repression of non-mesodermal developmental regulators, suggesting cooperativity between Brg1 and Polycomb complexes. Thus, Brg1 is essential for modulating active and repressive chromatin states during mesoderm lineage commitment, in particular the activation of developmentally important enhancers. In conclusion, these findings demonstrate interplay between chromatin remodeling complexes and histone modifications that, together, ensure robust and broad gene regulation during crucial lineage commitment decisions.

  14. Brg1 modulates enhancer activation in mesoderm lineage commitment

    DOE PAGES

    Alexander, Jeffrey M.; Hota, Swetansu K.; He, Daniel; ...

    2015-03-26

    The interplay between different levels of gene regulation in modulating developmental transcriptional programs, such as histone modifications and chromatin remodeling, is not well understood. Here, we show that the chromatin remodeling factor Brg1 is required for enhancer activation in mesoderm induction. In an embryonic stem cell-based directed differentiation assay, the absence of Brg1 results in a failure of cardiomyocyte differentiation and broad deregulation of lineage-specific gene expression during mesoderm induction. We find that Brg1 co-localizes with H3K27ac at distal enhancers and is required for robust H3K27 acetylation at distal enhancers that are activated during mesoderm induction. Brg1 is also requiredmore » to maintain Polycomb-mediated repression of non-mesodermal developmental regulators, suggesting cooperativity between Brg1 and Polycomb complexes. Thus, Brg1 is essential for modulating active and repressive chromatin states during mesoderm lineage commitment, in particular the activation of developmentally important enhancers. In conclusion, these findings demonstrate interplay between chromatin remodeling complexes and histone modifications that, together, ensure robust and broad gene regulation during crucial lineage commitment decisions.« less

  15. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Maiyuran, Suchindra; Kramer, Randall; Harris, Paul

    2014-10-21

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  16. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    SciTech Connect

    Schnorr, Kirk; Kramer, Randall

    2016-04-05

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  17. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Dotson, William D.; Greenier, Jennifer; Ding, Hanshu

    2007-09-18

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated nucleic acids encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the nucleic acids as well as methods for producing and using the polypeptides.

  18. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Lopez de Leon, Alfredo; Ding, Hanshu; Brown, Kimberly

    2011-10-25

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  19. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Schnorr, Kirk; Kramer, Randall

    2016-08-09

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  20. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Tang, Lan; Liu, Ye; Duan, Junxin; Zhang, Yu; Jorgensen, Christian Isak; Kramer, Randall

    2013-04-16

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  1. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Duan, Junxin; Tang, Lan; Liu, Ye; Wu, Wenping; Quinlan, Jason; Kramer, Randall

    2013-06-18

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  2. Polypeptide from a cellulolytic fungus having cellulolytic enhancing activity

    SciTech Connect

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2008-04-22

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  3. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    SciTech Connect

    Lopez de Leon, Alfredo; Ding, Hanshu; Brown, Kimberly

    2012-06-26

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  4. Enhancing the Lives of Nursing Home Patients through Reading Activities.

    ERIC Educational Resources Information Center

    Lovelace, Terry

    This study investigated the use of reading activities in the enhancement of the lives of nursing-home patients. A special reading group was led by a reading specialist in weekly sessions. Patients voluntarily attended the one-hour sessions and read short selections supplied by the reading specialist. Patients ranged in age from 54 to 91. The…

  5. Enhanced gamma-ray activity from the Crab nebula

    NASA Astrophysics Data System (ADS)

    Buehler, R.; Ciprini, S.

    2016-01-01

    Preliminary LAT analysis indicates enhanced gamma-ray activity from the Crab nebula. The daily-averaged gamma-ray emission (E > 100 MeV) from the direction of the Crab Nebula has surpassed 4.0 x 10^-6 ph cm^-2 s^-1 five times in the last 12 days.

  6. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    SciTech Connect

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2012-10-16

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  7. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    DOEpatents

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2010-06-22

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  8. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding the same

    DOEpatents

    Tang, Lan; Liu, Ye; Duan, Junxin; Zhang, Yu; Jorgensen, Christian Isak; Kramer, Randall

    2013-12-24

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  9. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Maiyuran, Suchindra; Kramer, Randall; Harris, Paul

    2013-10-29

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  10. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Dotson, William D.; Greenier, Jennifer; Ding, Hanshu

    2009-05-19

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated nucleic acids encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the nucleic acids as well as methods for producing and using the polypeptides.

  11. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding the same

    DOEpatents

    Duan, Junxin; Schnorr, Kirk Matthew; Wu, Wenping

    2013-11-19

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  12. Enhanced anti-cancer and antimicrobial activities of curcumin nanoparticles.

    PubMed

    Adahoun, Mo'ath Ahmad; Al-Akhras, Mohammed-Ali Hassan; Jaafar, Mohamad Suhaimi; Bououdina, Mohamed

    2017-02-01

    Background Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has demonstrated that these polyphenols play an important role in the maintenance of health and prevention of diseases, in addition to its therapeutic benefits such as anti-tumor, anti-inflammatory, and anti-oxidant activities. Materials and methods This study is devoted to the enhancement of the solubility and bioavailability of curcumin nanoparticles prepared by a process based on a wet-milling technique and then examine in vitro against prostate cancer cell line 3 (PC3), human embryonic kidney cell line (HEK), human erythrocytes (red blood cells (RBCs)), and against fourth different bacterial strains two gram-positive (Micrococcus luteus ATCC 9341, Staphylococcus aureus ATCC 29213), two gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853). Results The cell viability curve, the half maximal inhibitory concentration (IC50), and the minimum bactericidal concentration (MBC) were evaluated. Nanocurcumin displayed significant activity against cancer cell line (PC3) and low toxicity against normal cells (HEK) compared with parent curcumin in favor of PC3 (P < 0.05). In addition, it was found that the efficiency of toxicity for nanocurcumin against PC3 (E% = 59.66%) was much better than HEK (E% = 36.07%) compared with parent curcumin. The results also demonstrate that, although nanocurcumin has a little more ability to lays RBCs than parent curcumin after incubated 60 min, but the hemolysis % remained very low and there was no significant difference between hemolysis % of nanocurcumin and parent curcumin (P > 0.05). On the other hand, the results demonstrate that, the MBCs of nanocurcumin were lower than curcumin for all different bacterial strains. Moreover, the selected gram-positive bacteria had higher sensitivity than the selected gram-negative bacteria for both

  13. Are secular correlations between sunspots, geomagnetic activity, and global temperature significant?

    USGS Publications Warehouse

    Love, J.J.; Mursula, K.; Tsai, V.C.; Perkins, D.M.

    2011-01-01

    Recent studies have led to speculation that solar-terrestrial interaction, measured by sunspot number and geomagnetic activity, has played an important role in global temperature change over the past century or so. We treat this possibility as an hypothesis for testing. We examine the statistical significance of cross-correlations between sunspot number, geomagnetic activity, and global surface temperature for the years 1868-2008, solar cycles 11-23. The data contain substantial autocorrelation and nonstationarity, properties that are incompatible with standard measures of cross-correlational significance, but which can be largely removed by averaging over solar cycles and first-difference detrending. Treated data show an expected statistically- significant correlation between sunspot number and geomagnetic activity, Pearson p < 10-4, but correlations between global temperature and sunspot number (geomagnetic activity) are not significant, p = 0.9954, (p = 0.8171). In other words, straightforward analysis does not support widely-cited suggestions that these data record a prominent role for solar-terrestrial interaction in global climate change. With respect to the sunspot-number, geomagnetic-activity, and global-temperature data, three alternative hypotheses remain difficult to reject: (1) the role of solar-terrestrial interaction in recent climate change is contained wholly in long-term trends and not in any shorter-term secular variation, or, (2) an anthropogenic signal is hiding correlation between solar-terrestrial variables and global temperature, or, (3) the null hypothesis, recent climate change has not been influenced by solar-terrestrial interaction. ?? 2011 by the American Geophysical Union.

  14. Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma.

    PubMed

    Hillengass, Jens; Ritsch, Judith; Merz, Maximilian; Wagner, Barbara; Kunz, Christina; Hielscher, Thomas; Laue, Hendrik; Bäuerle, Tobias; Zechmann, Christian M; Ho, Anthony D; Schlemmer, Heinz-Peter; Goldschmidt, Hartmut; Moehler, Thomas M; Delorme, Stefan

    2016-07-01

    This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE-MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE-MRI of the lumbar spine. Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut-off point of 0·89 arbitrary units had a 2-year progression rate into symptomatic disease of 80%. In conclusion, DCE-MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS.

  15. Dramatic enhancement of enzymatic activity in organic solvents by lyoprotectants

    SciTech Connect

    Dabulis, K.; Klibanov, A.M. )

    1993-03-05

    When seven different hydrolytic enzymes (four proteases and three lipases) were lyophilized from aqueous solution containing a ligand, N-Ac-L-Phe-NH[sub 2], their catalytic activity in anhydrous solvents was far greater (one to two orders of magnitude) than that of the enzymes lyophilized without the ligand. This ligand-induced activation was expressed regardless of whether the substrate employed in organic solvents structurally resembled the ligand. Furthermore, nonligand lyoprotectants [sorbitol, other sugars, and poly(ethylene glycol)] also dramatically enhanced enzymatic activity in anhydrous solvents when present in enzyme aqueous solution prior to lyophilization. The effects of the ligand and of the lyoprotectants were nonadditive, suggesting the same mechanism of action. Excipient-activated and nonactivated enzymes exhibited identical activities in water. Also, addition of the excipients directly to suspensions of nonactivated enzymes in organic solvents had no appreciable effect on catalytic activity. These observations indicate that the mechanism of the excipient-induced activation is based on the ability of the excipients to alleviate reversible denaturation of enzymes upon lyophilization. Activity enhancement induced by the excipients is displayed even after their removal by washing enzymes with anhydrous solvents. Subtilisin Carlsberg, lyophilized with sorbitol, was found to be a much more efficient practical catalyst than its regular' counterpart.

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

    PubMed

    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.

  17. Allosteric activation of midazolam CYP3A5 hydroxylase activity by icotinib - Enhancement by ketoconazole.

    PubMed

    Zhuang, XiaoMei; Zhang, TianHong; Yue, SiJia; Wang, Juan; Luo, Huan; Zhang, YunXia; Li, Zheng; Che, JinJing; Yang, HaiYing; Li, Hua; Zhu, MingShe; Lu, Chuang

    2016-12-01

    Icotinib (ICO), a novel small molecule and a tyrosine kinase inhibitor, was developed and approved recently in China for non-small cell lung cancer. During screening for CYP inhibition potential in human liver microsomes (HLM), heterotropic activation toward CYP3A5 was revealed. Activation by icotinib was observed with CYP3A-mediated midazolam hydroxylase activity in HLM (∼40% over the baseline) or recombinant human CYP3A5 (rhCYP3A5) (∼70% over the baseline), but not in the other major CYPs including rhCYP3A4. When co-incubated with selective CYP3A4 inhibitor CYP3cide or monoclonal human CYP3A4 inhibitory antibody in HLM, the activation was extended to ∼60%, suggesting CYP3A5 might be the isozyme involved. Further, the relative activation was enhanced to ∼270% in rhCYP3A5 in the presence of ketoconazole. The activation was substrate and pathway dependent and observed only in the formation of 1'-OH-midazolam, and not 4-OH-midazolam, 6β-OH-testosterone, or oxidized nifedipine. The activation requires the presence of cytochrome b5 and it is only observed in the liver microsomes of dogs, monkeys, and humans, but not in rats and mice. Kinetic analyses of 1'-OH-midazolam formation showed that ICO increased the Vmax values in HLM and rhCYP3A5 with no significant changes in Km values. By adding CYP3cide with ICO to the incubation, the Vmax values increased 2-fold over the CYP3cide control. Addition of ketoconazole with ICO alone or ICO plus CYP3cide resulted in an increase in Vmax values and decrease in Km values compared to their controls. This phenomenon may be attributed to a new mechanism of CYP3A5 heterotropic activation, which warrants further investigation.

  18. Tobramycin variants with enhanced ribosome-targeting activity

    PubMed Central

    Fosso, Marina Y.; Zhu, Hongkun; Green, Keith D.

    2015-01-01

    With the increased evolution of aminoglycoside (AG)-resistant bacterial strains, the need to develop AGs with (i) enhanced antimicrobial activity, (ii) the ability to evade resistance mechanisms, and (iii) the capability of targeting the ribosome with higher efficiency, is more and more pressing. The chemical derivatization of the naturally occurring tobramycin (TOB) by attachment of 37 different thioethers groups at the 6″-position led to the identification of generally poorer substrates of TOB-targeting AG-modifying enzymes (AMEs). Thirteen of these displayed better antibacterial activity than the parental TOB while retaining ribosome-targeting specificity. Analysis of these compounds in vitro shed light on the mechanism by which they act and revealed three with clearly enhanced ribosome-targeting activity. PMID:26033429

  19. Molecular and functional significance of Ca2+-activated Cl− channels in pulmonary arterial smooth muscle

    PubMed Central

    Forrest, Abigail S.; Ayon, Ramon J.; Wiwchar, Michael; Angermann, Jeff E.; Pritchard, Harry A. T.; Singer, Cherie A.; Valencik, Maria L.; Britton, Fiona; Greenwood, Iain A.

    2015-01-01

    Abstract Increased peripheral resistance of small distal pulmonary arteries is a hallmark signature of pulmonary hypertension (PH) and is believed to be the consequence of enhanced vasoconstriction to agonists, thickening of the arterial wall due to remodeling, and increased thrombosis. The elevation in arterial tone in PH is attributable, at least in part, to smooth muscle cells of PH patients being more depolarized and displaying higher intracellular Ca2+ levels than cells from normal subjects. It is now clear that downregulation of voltage-dependent K+ channels (e.g., Kv1.5) and increased expression and activity of voltage-dependent (Cav1.2) and voltage-independent (e.g., canonical and vanilloid transient receptor potential [TRPC and TRPV]) Ca2+ channels play an important role in the functional remodeling of pulmonary arteries in PH. This review focuses on an anion-permeable channel that is now considered a novel excitatory mechanism in the systemic and pulmonary circulations. It is permeable to Cl− and is activated by a rise in intracellular Ca2+ concentration (Ca2+-activated Cl− channel, or CaCC). The first section outlines the biophysical and pharmacological properties of the channel and ends with a description of the molecular candidate genes postulated to encode for CaCCs, with particular emphasis on the bestrophin and the newly discovered TMEM16 and anoctamin families of genes. The second section provides a review of the various sources of Ca2+ activating CaCCs, which include stimulation by mobilization from intracellular Ca2+ stores and Ca2+ entry through voltage-dependent and voltage-independent Ca2+ channels. The third and final section summarizes recent findings that suggest a potentially important role for CaCCs and the gene TMEM16A in PH. PMID:26064450

  20. Liposomes encapsulating Aloe vera leaf gel extract significantly enhance proliferation and collagen synthesis in human skin cell lines.

    PubMed

    Takahashi, Makoto; Kitamoto, Dai; Asikin, Yonathan; Takara, Kensaku; Wada, Koji

    2009-01-01

    Aloe vela leaf gel extract (AGE) are widely used as cosmetic and pharmaceutical ingredients because of its versatile skin care properties. In order to enhance the bioavailability of AGE, liposomes encapsulating AGE were prepared and examined for their interfacial and biochemical properties. The liposomes prepared from a soybean lecithin (SLP-WHITE, 1.0 wt%) by the Bangham method gave relatively a good trapping efficiency up to the AGE concentration of 0.5 wt%. The stable liposomes were then prepared from 1.0 wt% of SLP-WHITE and different concentrations of AGE by the mechanochemical method using a homogenizer and microfluidizer. The liposomes obtained from 0.25 wt% of AGE were confirmed to be small unilamellar vesicles with a diameter of less than 200 nm, and remained well dispersed for at least two weeks. The obtained liposomes encapsulating AGE were further examined for the effects on proliferation and type I collagen synthesis in normal human neonatal skin fibroblasts, NB1RGB cells. Liposomal AGE clearly showed higher proliferation rate than that of AGE alone. In addition, compared to the control, liposomal AGE significantly increased the collagen synthesis by 23%, while AGE alone showed a small effect. Liposomal AGE was also assayed for the effect on proliferation in normal human epidermal keratinocytes, NHEK(F) cells. Interestingly, liposomal AGE fractions containing 4 and 20 microg/mL of the extract considerably increased the proliferation rate by 77% and 101%, respectively. In contrast, AGE alone fractions containing 4 and 20 microg/mL of the extract increased the rate by 41% and 60%, respectively. Accordingly, the bioavailability and skin care properties of AGE will be significantly enhanced by liposome encapsulation, and the present liposomal AGE should have a great potential as an effective skin care formulation.

  1. Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites.

    PubMed

    Blevins-Primeau, Andrea S; Sun, Dongxiao; Chen, Gang; Sharma, Arun K; Gallagher, Carla J; Amin, Shantu; Lazarus, Philip

    2009-03-01

    Tamoxifen (TAM) is a selective estrogen receptor modulator widely used in the prevention and treatment of breast cancer. A major mode of metabolism of the major active metabolites of TAM, 4-OH-TAM and endoxifen, is by glucuronidation via the UDP-glucuronosyltransferase (UGT) family of enzymes. To examine whether polymorphisms in the UGT enzymes responsible for the glucuronidation of active TAM metabolites play an important role in interindividual differences in TAM metabolism, cell lines overexpressing wild-type or variant UGTs were examined for their activities against TAM metabolites in vitro. For variants of active extrahepatic UGTs, the UGT1A8(173Ala/277Tyr) variant exhibited no detectable glucuronidation activity against the trans isomers of either 4-OH-TAM or endoxifen. Little or no difference in TAM glucuronidating activity was observed for the UGT1A8(173Gly/277Cys) or UGT1A10(139Lys) variants compared with their wild-type counterparts. For active hepatic UGTs, the UGT2B7(268Tyr) variant exhibited significant (P < 0.01) 2- and 5-fold decreases in activity against the trans isomers of 4-OH-TAM and endoxifen, respectively, compared with wild-type UGT2B7(268His). In studies of 111 human liver microsomal specimens, the rate of O-glucuronidation against trans-4-OH-TAM and trans-endoxifen was 28% (P < 0.001) and 27% (P = 0.002) lower, respectively, in individuals homozygous for the UGT2B7 Tyr(268)Tyr genotype compared with subjects with the UGT2B7 His(268)His genotype, with a significant (P < 0.01) trend of decreasing activity against both substrates with increasing numbers of the UGT2B7(268His) allele. These results suggest that functional polymorphisms in TAM-metabolizing UGTs, including UGT2B7 and potentially UGT1A8, may be important in interindividual variability in TAM metabolism and response to TAM therapy.

  2. Cu Nanowires with Clean Surfaces: Synthesis and Enhanced Electrocatalytic Activity.

    PubMed

    Liu, Xinmei; Sui, Yongming; Yang, Xinyi; Wei, Yingjin; Zou, Bo

    2016-10-12

    Low activity and high cost of electrocatalysts are the major challenge for the commercialization of the direct fuel cells (DFCs) and biofuel cells. In this work, we demonstrate the desirable "clean surfaces" effect of Cu nanocrystals in electrocatalysis. By a new reaction route of Cu2O nanospheres (Cu2O NSs), Cu nanowires (Cu NWs) with high purity and "clean surfaces" are first obtained under mild conditions. Benefiting from the path directing effects and abundant (100) facets, the as-prepared Cu NWs exhibit a lower overpotential to achieve the methanol electro-oxidation reaction (MOR) than that of analogous Cu nanoparticles (Cu NPs). Moreover, the "clean surfaces" provide more available active sites for the efficient transfer of electrons, enabling the Cu NWs to show their enhanced electrocatalytic activity. In the MOR, forward peak current density for the surface-cleaned Cu NWs is 2839 μA cm(-2), which is ca. 6.45-fold higher than that of the Cu NWs with residual capping molecules on their surface. The "clean surfaces" effect can also be extended to the glucose electro-oxidation reaction (GOR), and the enhancement in specific surface area activity for the Cu NWs is 11.3-fold. This work enhances the electrocatalytic performance of Cu nanocrystals without the need for additional noble metals, which opens up new avenues for utilizing non-noble metals in the DFC or biofuel cell applications.

  3. Acute moderate exercise enhances compensatory brain activation in older adults.

    PubMed

    Hyodo, Kazuki; Dan, Ippeita; Suwabe, Kazuya; Kyutoku, Yasushi; Yamada, Yuhki; Akahori, Mitsuya; Byun, Kyeongho; Kato, Morimasa; Soya, Hideaki

    2012-11-01

    A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation.

  4. Gramicidin D enhances the antibacterial activity of fluoride.

    PubMed

    Nelson, James W; Zhou, Zhiyuan; Breaker, Ronald R

    2014-07-01

    Fluoride is a toxic anion found in many natural environments. One of the major bacterial defenses against fluoride is the cell envelope, which limits passage of the membrane-impermeant fluoride anion. Accordingly, compounds that enhance the permeability of bacterial membranes to fluoride should also enhance fluoride toxicity. In this study, we demonstrate that the pore-forming antibiotic gramicidin D increases fluoride uptake in Bacillus subtilis and that the antibacterial activity of this compound is potentiated by fluoride. Polymyxin B, another membrane-targeting antibiotic with a different mechanism of action, shows no such improvement. These results, along with previous findings, indicate that certain compounds that destabilize bacterial cell envelopes can enhance the toxicity of fluoride.

  5. Chk1 inhibition significantly potentiates activity of nucleoside analogs in TP53-mutated B-lymphoid cells

    PubMed Central

    Zemanova, Jana; Hylse, Ondrej; Collakova, Jana; Vesely, Pavel; Oltova, Alexandra; Borsky, Marek; Zaprazna, Kristina; Kasparkova, Marie; Janovska, Pavlina; Verner, Jan; Kohoutek, Jiri; Dzimkova, Marta; Bryja, Vitezslav; Jaskova, Zuzana; Brychtova, Yvona; Paruch, Kamil; Trbusek, Martin

    2016-01-01

    Treatment options for TP53-mutated lymphoid tumors are very limited. In experimental models, TP53-mutated lymphomas were sensitive to direct inhibition of checkpoint kinase 1 (Chk1), a pivotal regulator of replication. We initially tested the potential of the highly specific Chk1 inhibitor SCH900776 to synergize with nucleoside analogs (NAs) fludarabine, cytarabine and gemcitabine in cell lines derived from B-cell malignancies. In p53-proficient NALM-6 cells, SCH900776 added to NAs enhanced signaling towards Chk1 (pSer317/pSer345), effectively blocked Chk1 activation (Ser296 autophosphorylation), increased replication stress (p53 and γ-H2AX accumulation) and temporarily potentiated apoptosis. In p53-defective MEC-1 cell line representing adverse chronic lymphocytic leukemia (CLL), Chk1 inhibition together with NAs led to enhanced and sustained replication stress and significantly potentiated apoptosis. Altogether, among 17 tested cell lines SCH900776 sensitized four of them to all three NAs. Focusing further on MEC-1 and co-treatment of SCH900776 with fludarabine, we disclosed chromosome pulverization in cells undergoing aberrant mitoses. SCH900776 also increased the effect of fludarabine in a proportion of primary CLL samples treated with pro-proliferative stimuli, including those with TP53 disruption. Finally, we observed a fludarabine potentiation by SCH900776 in a T-cell leukemia 1 (TCL1)-driven mouse model of CLL. Collectively, we have substantiated the significant potential of Chk1 inhibition in B-lymphoid cells. PMID:27556692

  6. Efficient thermal image segmentation through integration of nonlinear enhancement with unsupervised active contour model

    NASA Astrophysics Data System (ADS)

    Albalooshi, Fatema A.; Krieger, Evan; Sidike, Paheding; Asari, Vijayan K.

    2015-03-01

    Thermal images are exploited in many areas of pattern recognition applications. Infrared thermal image segmentation can be used for object detection by extracting regions of abnormal temperatures. However, the lack of texture and color information, low signal-to-noise ratio, and blurring effect of thermal images make segmenting infrared heat patterns a challenging task. Furthermore, many segmentation methods that are used in visible imagery may not be suitable for segmenting thermal imagery mainly due to their dissimilar intensity distributions. Thus, a new method is proposed to improve the performance of image segmentation in thermal imagery. The proposed scheme efficiently utilizes nonlinear intensity enhancement technique and Unsupervised Active Contour Models (UACM). The nonlinear intensity enhancement improves visual quality by combining dynamic range compression and contrast enhancement, while the UACM incorporates active contour evolutional function and neural networks. The algorithm is tested on segmenting different objects in thermal images and it is observed that the nonlinear enhancement has significantly improved the segmentation performance.

  7. Biological significance of nuclear localization of mitogen-activated protein kinase Pmk1 in fission yeast.

    PubMed

    Sánchez-Mir, Laura; Franco, Alejandro; Madrid, Marisa; Vicente-Soler, Jero; Villar-Tajadura, M Antonia; Soto, Teresa; Pérez, Pilar; Gacto, Mariano; Cansado, José

    2012-07-27

    Mitogen-activated protein kinase (MAPK) signaling pathways play a fundamental role in the response of eukaryotic cells to environmental changes. Also, much evidence shows that the stimulus-dependent nuclear targeting of this class of regulatory kinases is crucial for adequate regulation of distinct cellular events. In the fission yeast Schizosaccharomyces pombe, the cell integrity MAPK pathway, whose central element is the MAPK Pmk1, regulates multiple processes such as cell wall integrity, vacuole fusion, cytokinesis, and ionic homeostasis. In non-stressed cells Pmk1 is constitutively localized in both cytoplasm and nucleus, and its localization pattern appears unaffected by its activation status or in response to stress, thus questioning the biological significance of the presence of this MAPK into the nucleus. We have addressed this issue by characterizing mutants expressing Pmk1 versions excluded from the cell nucleus and anchored to the plasma membrane in different genetic backgrounds. Although nuclear Pmk1 partially regulates cell wall integrity at a transcriptional level, membrane-tethered Pmk1 performs many of the biological functions assigned to wild type MAPK like regulation of chloride homeostasis, vacuole fusion, and cellular separation. However, we found that down-regulation of nuclear Pmk1 by MAPK phosphatases induced by the stress activated protein kinase pathway is important for the fine modulation of extranuclear Pmk1 activity. These results highlight the importance of the control of MAPK activity at subcellular level.

  8. Biological Significance of Nuclear Localization of Mitogen-activated Protein Kinase Pmk1 in Fission Yeast*

    PubMed Central

    Sánchez-Mir, Laura; Franco, Alejandro; Madrid, Marisa; Vicente-Soler, Jero; Villar-Tajadura, M. Antonia; Soto, Teresa; Pérez, Pilar; Gacto, Mariano; Cansado, José

    2012-01-01

    Mitogen-activated protein kinase (MAPK) signaling pathways play a fundamental role in the response of eukaryotic cells to environmental changes. Also, much evidence shows that the stimulus-dependent nuclear targeting of this class of regulatory kinases is crucial for adequate regulation of distinct cellular events. In the fission yeast Schizosaccharomyces pombe, the cell integrity MAPK pathway, whose central element is the MAPK Pmk1, regulates multiple processes such as cell wall integrity, vacuole fusion, cytokinesis, and ionic homeostasis. In non-stressed cells Pmk1 is constitutively localized in both cytoplasm and nucleus, and its localization pattern appears unaffected by its activation status or in response to stress, thus questioning the biological significance of the presence of this MAPK into the nucleus. We have addressed this issue by characterizing mutants expressing Pmk1 versions excluded from the cell nucleus and anchored to the plasma membrane in different genetic backgrounds. Although nuclear Pmk1 partially regulates cell wall integrity at a transcriptional level, membrane-tethered Pmk1 performs many of the biological functions assigned to wild type MAPK like regulation of chloride homeostasis, vacuole fusion, and cellular separation. However, we found that down-regulation of nuclear Pmk1 by MAPK phosphatases induced by the stress activated protein kinase pathway is important for the fine modulation of extranuclear Pmk1 activity. These results highlight the importance of the control of MAPK activity at subcellular level. PMID:22685296

  9. Enhancing learning in geosciences and water engineering via lab activities

    NASA Astrophysics Data System (ADS)

    Valyrakis, Manousos; Cheng, Ming

    2016-04-01

    This study focuses on the utilisation of lab based activities to enhance the learning experience of engineering students studying Water Engineering and Geosciences. In particular, the use of modern highly visual and tangible presentation techniques within an appropriate laboratory based space are used to introduce undergraduate students to advanced engineering concepts. A specific lab activity, namely "Flood-City", is presented as a case study to enhance the active engagement rate, improve the learning experience of the students and better achieve the intended learning objectives of the course within a broad context of the engineering and geosciences curriculum. Such activities, have been used over the last few years from the Water Engineering group @ Glasgow, with success for outreach purposes (e.g. Glasgow Science Festival and demos at the Glasgow Science Centre and Kelvingrove museum). The activity involves a specific setup of the demonstration flume in a sand-box configuration, with elements and activities designed so as to gamely the overall learning activity. Social media platforms can also be used effectively to the same goals, particularly in cases were the students already engage in these online media. To assess the effectiveness of this activity a purpose designed questionnaire is offered to the students. Specifically, the questionnaire covers several aspects that may affect student learning, performance and satisfaction, such as students' motivation, factors to effective learning (also assessed by follow-up quizzes), and methods of communication and assessment. The results, analysed to assess the effectiveness of the learning activity as the students perceive it, offer a promising potential for the use of such activities in outreach and learning.

  10. Clinicopathologic and Prognostic Significance of Transducin-Like Enhancer of Split 1 Protein Expression in Invasive Breast Cancer

    PubMed Central

    Lee, Ji-Hye; Bae, Sang Byung; Oh, Mee-Hye; Cho, Hyun Deuk; Jang, Si-Hyong; Hong, Soon Auck; Cho, Junhun; Kim, Sung Yong; Han, Sun Wook; Lee, Jong Eun; Kim, Han Jo

    2017-01-01

    Purpose Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. We investigated the prognostic significance of TLE1 protein expression in breast cancers by using immunohistochemistry and explored the relationship of TLE1 with clinicopathological parameters. Methods Immunohistochemistry was performed on 456 cases of breast cancer tiled on tissue microarrays. The relationship between TLE1 expression in normal breast specimens and ductal carcinoma in situ (DCIS) was also analyzed. Results TLE1 was highly expressed in 57 of 456 (12.5%) carcinoma samples. TLE1 was more frequently expressed in DCIS and invasive breast cancers than in normal breast tissue (p=0.002). High expression of TLE1 significantly correlated with negative lymph node (LN) metastasis (p=0.007), high histologic grade (p<0.001), estrogen receptor negativity (p<0.001), progesterone receptor negativity (p<0.001), human epidermal growth factor receptor 2 (HER2) positivity (p<0.001), and high Ki-67 proliferation index (p<0.001). Based on intrinsic subtypes, high TLE1 expression was strongly associated with HER2+ and triple-negative breast cancers (TNBC) (p<0.001). Survival analysis demonstrated no significant association between TLE1 expression and disease-free survival (DFS) (p=0.167) or overall survival (OS) (p=0.286). In subgroup analyses, no correlation was found between TLE1 expression and DFS or OS according to LN status or intrinsic subtype. Conclusion High TLE1 expression is significantly associated with the HER2+ and TNBC subtypes. This is the first study documenting immunohistochemical expression of TLE1 in invasive breast cancer and its association with clinicopathological parameters, prognosis, and intrinsic subtype. PMID:28382094

  11. THE ENHANCEMENT OF MACROPHAGE BACTERIOSTASIS BY PRODUCTS OF ACTIVATED LYMPHOCYTES

    PubMed Central

    Fowles, Robert E.; Fajardo, Ileana M.; Leibowitch, Jacques L.; David, John R.

    1973-01-01

    It was reported previously that the incubation of normal guinea pig macrophages with partially purified products of activated lymphocytes resulted in altered macrophage function including increased cell adherence to culture vessels, spreading, phagocytosis, and glucose carbon-1 oxidation. Studies reported here demonstrate that such macrophages also exhibit enhanced bacteriostasis. Lymphocytes were stimulated with concanavalin A, the culture supernatant was chromatographed over Sephadex G-100 and the fraction of mol wt 25,000–55,000, rich in lymphocyte mediators, was cultured with normal guinea pig macrophages for 1–3 days. Macrophages incubated with fractions from unstimulated lymphocyte cultures served as controls. The resulting macrophage monolayers were infected with Listeria monocytogenes. Macrophages incubated with mediator-rich fractions exhibited 2- to 10-fold enhanced bacteriostasis compared to controls. Further studies indicate that this enhancement was attributable to intrinsic changes in the macrophages and not simply a consequence of the number of macrophages on the monolayers. The studies support the concept that macrophage bacteriostasis can be enhanced by lymphocyte mediators. However, macrophages, which have been preincubated directly with sensitive lymphocytes and antigen exhibit even greater bacteriostasis and sometimes bactericidal capacity, suggesting that either a labile lymphocyte factor or direct lymphocyte macrophage interaction may also be involved in bactericidal activity. PMID:4200649

  12. Quercetin phospholipid complex significantly protects against oxidative injury in ARPE-19 cells associated with activation of Nrf2 pathway.

    PubMed

    Xu, Xin-Rong; Yu, Hai-Tao; Yang, Yan; Hang, Li; Yang, Xue-Wen; Ding, Shu-Hua

    2016-01-05

    Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27μg/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400μM. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200μM. In addition, quercetin-PC at 200μM significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200μM failed to do so. Molecular examinations revealed that quercetin-PC at 200μM significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense.

  13. Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance

    PubMed Central

    Alam, Md. Fazle; Laskar, Amaj Ahmed; Maryam, Lubna

    2016-01-01

    Cruciferous vegetables contain the bio-active compound sulforaphane (SF) which has been reported to protect individuals against various diseases by a number of mechanisms, including activation of the phase II detoxification enzymes. In this study, we show that the extracts of five cruciferous vegetables that we commonly consume and SF activate human salivary aldehyde dehydrogenase (hsALDH), which is a very important detoxifying enzyme in the mouth. Maximum activation was observed at 1 μg/ml of cabbage extract with 2.6 fold increase in the activity. There was a ~1.9 fold increase in the activity of hsALDH at SF concentration of ≥ 100 nM. The concentration of SF at half the maximum response (EC50 value) was determined to be 52 ± 2 nM. There was an increase in the Vmax and a decrease in the Km of the enzyme in the presence of SF. Hence, SF interacts with the enzyme and increases its affinity for the substrate. UV absorbance, fluorescence and CD studies revealed that SF binds to hsALDH and does not disrupt its native structure. SF binds with the enzyme with a binding constant of 1.23 x 107 M-1. There is one binding site on hsALDH for SF, and the thermodynamic parameters indicate the formation of a spontaneous strong complex between the two. Molecular docking analysis depicted that SF fits into the active site of ALDH3A1, and facilitates the catalytic mechanism of the enzyme. SF being an antioxidant, is very likely to protect the catalytic Cys 243 residue from oxidation, which leads to the increase in the catalytic efficiency and hence the activation of the enzyme. Further, hsALDH which is virtually inactive towards acetaldehyde exhibited significant activity towards it in the presence of SF. It is therefore very likely that consumption of large quantities of cruciferous vegetables or SF supplements, through their activating effect on hsALDH can protect individuals who are alcohol intolerant against acetaldehyde toxicity and also lower the risk of oral cancer

  14. Volcanic activity before and after large tectonic earthquakes: Observations and statistical significance

    NASA Astrophysics Data System (ADS)

    Eggert, Silke; Walter, Thomas R.

    2009-06-01

    The study of volcanic triggering and interaction with the tectonic surroundings has received special attention in recent years, using both direct field observations and historical descriptions of eruptions and earthquake activity. Repeated reports of clustered eruptions and earthquakes may imply that interaction is important in some subregions. However, the subregions likely to suffer such clusters have not been systematically identified, and the processes responsible for the observed interaction remain unclear. We first review previous works about the clustered occurrence of eruptions and earthquakes, and describe selected events. We further elaborate available databases and confirm a statistically significant relationship between volcanic eruptions and earthquakes on the global scale. Moreover, our study implies that closed volcanic systems in particular tend to be activated in association with a tectonic earthquake trigger. We then perform a statistical study at the subregional level, showing that certain subregions are especially predisposed to concurrent eruption-earthquake sequences, whereas such clustering is statistically less significant in other subregions. Based on this study, we argue that individual and selected observations may bias the perceptible weight of coupling. The activity at volcanoes located in the predisposed subregions (e.g., Japan, Indonesia, Melanesia), however, often unexpectedly changes in association with either an imminent or a past earthquake.

  15. The temporal structures and functional significance of scale-free brain activity

    PubMed Central

    He, Biyu J.; Zempel, John M.; Snyder, Abraham Z.; Raichle, Marcus E.

    2010-01-01

    SUMMARY Scale-free dynamics, with a power spectrum following P ∝ f-β, are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with β being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349

  16. ENHANCED BIODEGRADATION OF IOPROMIDE AND TRIMETHOPRIM IN NITRIFYING ACTIVATED SLUDGE

    EPA Science Inventory

    Iopromide and trimethoprim are frequently detected pharmaceuticals in effluents of wastewater treatment plants and in surface waters due to their persistence and high usage. Laboratory scale experiments showed that a significantly higher removal rate in nutrifying activated sludg...

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

    PubMed

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

    2016-11-11

    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 <4%) and linolenic acid (a decrease from ~35% to <10%). These changes result in oils that are superior on multiple levels: they are healthier, more oxidatively stable and better suited for production of certain commercial chemicals, including biofuels. As expected, A. thaliana T2 and T3 generation seeds exhibiting these types of altered fatty acid profiles were homozygous for disrupted FAD2 alleles. In the allohexaploid, Camelina, guide RNAs were designed that simultaneously targeted all three homoeologous FAD2 genes. This strategy that significantly 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.

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

    PubMed

    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.

  19. The Crowded Sea: Incorporating Multiple Marine Activities in Conservation Plans Can Significantly Alter Spatial Priorities

    PubMed Central

    Mazor, Tessa; Possingham, Hugh P.; Edelist, Dori; Brokovich, Eran; Kark, Salit

    2014-01-01

    Successful implementation of marine conservation plans is largely inhibited by inadequate consideration of the broader social and economic context within which conservation operates. Marine waters and their biodiversity are shared by a host of stakeholders, such as commercial fishers, recreational users and offshore developers. Hence, to improve implementation success of conservation plans, we must incorporate other marine activities while explicitly examining trade-offs that may be required. In this study, we test how the inclusion of multiple marine activities can shape conservation plans. We used the entire Mediterranean territorial waters of Israel as a case study to compare four planning scenarios with increasing levels of complexity, where additional zones, threats and activities were added (e.g., commercial fisheries, hydrocarbon exploration interests, aquaculture, and shipping lanes). We applied the marine zoning decision support tool Marxan to each planning scenario and tested a) the ability of each scenario to reach biodiversity targets, b) the change in opportunity cost and c) the alteration of spatial conservation priorities. We found that by including increasing numbers of marine activities and zones in the planning process, greater compromises are required to reach conservation objectives. Complex plans with more activities incurred greater opportunity cost and did not reach biodiversity targets as easily as simplified plans with less marine activities. We discovered that including hydrocarbon data in the planning process significantly alters spatial priorities. For the territorial waters of Israel we found that in order to protect at least 10% of the range of 166 marine biodiversity features there would be a loss of ∼15% of annual commercial fishery revenue and ∼5% of prospective hydrocarbon revenue. This case study follows an illustrated framework for adopting a transparent systematic process to balance biodiversity goals and economic

  20. Surfaces of Fluorinated Pyridinium Block Copolymers with Enhanced Antibacterial Activity

    SciTech Connect

    Krishnan,S.; Ward, R.; Hexemer, A.; Sohn, K.; Lee, K.; Angert, E.; Fischer, D.; Kramer, E.; Ober, C.

    2006-01-01

    Polystyrene-b-poly(4-vinylpyridine) copolymers were quaternized with 1-bromohexane and 6-perfluorooctyl-1-bromohexane. Surfaces prepared from these polymers were characterized by contact angle measurements, near-edge X-ray absorption fine structure spectroscopy and X-ray photoelectron spectroscopy. The fluorinated pyridinium surfaces showed enhanced antibacterial activity compared to their nonfluorinated counterparts. Even a polymer with a relatively low molecular weight pyridinium block showed high antimicrobial activity. The bactericidal effect was found to be related to the molecular composition and organization in the top 2-3 nm of the surface and increased with increasing hydrophilicity and pyridinium concentration of the surface.

  1. Enhanced antiviral activity of acyclovir loaded into nanoparticles.

    PubMed

    Cavalli, Roberta; Donalisio, Manuela; Bisazza, Agnese; Civra, Andrea; Ranucci, Elisabetta; Ferruti, Paolo; Lembo, David

    2012-01-01

    The activity of antivirals can be enhanced by their incorporation in nanoparticulate delivery systems. Peculiar polymeric nanoparticles, based on a β-cyclodextrin-poly(4-acryloylmorpholine) monoconjugate (β-CD-PACM), are proposed as acyclovir carriers. The experimental procedure necessary to obtain the acyclovir-loaded nanoparticles using the solvent displacement preparation method will be described in this chapter. Fluorescent labeled nanoparticles are prepared using the same method for cellular trafficking studies. The biocompatibility assays necessary to obtain safe nanoparticles are reported. Section 4 of this chapter describes the assessment of the antiviral activity of the acyclovir-loaded nanoparticles.

  2. Enhancing the Effectiveness of Significant Event Analysis: Exploring Personal Impact and Applying Systems Thinking in Primary Care

    PubMed Central

    McNaughton, Elaine; Bruce, David; Holly, Deirdre; Forrest, Eleanor; Macleod, Marion; Kennedy, Susan; Power, Ailsa; Toppin, Denis; Black, Irene; Pooley, Janet; Taylor, Audrey; Swanson, Vivien; Kelly, Moya; Ferguson, Julie; Stirling, Suzanne; Wakeling, Judy; Inglis, Angela; McKay, John; Sargeant, Joan

    2016-01-01

    Introduction: Significant event analysis (SEA) is well established in many primary care settings but can be poorly implemented. Reasons include the emotional impact on clinicians and limited knowledge of systems thinking in establishing why events happen and formulating improvements. To enhance SEA effectiveness, we developed and tested “guiding tools” based on human factors principles. Methods: Mixed-methods development of guiding tools (Personal Booklet—to help with emotional demands and apply a human factors analysis at the individual level; Desk Pad—to guide a team-based systems analysis; and a written Report Format) by a multiprofessional “expert” group and testing with Scottish primary care practitioners who submitted completed enhanced SEA reports. Evaluation data were collected through questionnaire, telephone interviews, and thematic analysis of SEA reports. Results: Overall, 149/240 care practitioners tested the guiding tools and submitted completed SEA reports (62.1%). Reported understanding of how to undertake SEA improved postintervention (P < .001), while most agreed that the Personal Booklet was practical (88/123, 71.5%) and relevant to dealing with related emotions (93/123, 75.6%). The Desk Pad tool helped focus the SEA on systems issues (85/123, 69.1%), while most found the Report Format clear (94/123, 76.4%) and would recommend it (88/123, 71.5%). Most SEA reports adopted a systems approach to analyses (125/149, 83.9%), care improvement (74/149, 49.7), or planned actions (42/149, 28.2%). Discussion: Applying human factors principles to SEA potentially enables care teams to gain a systems-based understanding of why things go wrong, which may help with related emotional demands and with more effective learning and improvement. PMID:27583996

  3. Neural activity associated with enhanced facial attractiveness by cosmetics use.

    PubMed

    Ueno, Aya; Ito, Ayahito; Kawasaki, Iori; Kawachi, Yousuke; Yoshida, Kazuki; Murakami, Yui; Sakai, Shinya; Iijima, Toshio; Matsue, Yoshihiko; Fujii, Toshikatsu

    2014-04-30

    Previous psychological studies have shown that make-up enhances facial attractiveness. Although neuroimaging evidence indicates that the orbitofrontal cortex (OFC) shows greater activity for faces of attractive people than for those of unattractive people, there is no direct evidence that the OFC also shows greater activity for the face of an individual wearing make-up than for the same face without make-up. Using functional magnetic resonance imaging (fMRI), we investigated neural activity while subjects viewed 144 photographs of the same faces with and without make-up (48 with make-up, 48 without make-up, and 48 scrambled photographs) and assigned these faces an attractiveness rating. The behavioral data showed that the faces with make-up were rated as more attractive than those without make-up. The imaging data revealed that the left OFC and the right hippocampus showed greater activity for faces with make-up than for those without make-up. Furthermore, the activities of the right anterior cingulate cortex, left hippocampus, and left OFC increased with increasing facial attractiveness resulting from cosmetics use. These results provide direct evidence of the neural underpinnings of cosmetically enhanced facial attractiveness.

  4. The DNA polymerase activity of Saccharomyces cerevisiae Rev1 is biologically significant.

    PubMed

    Wiltrout, Mary Ellen; Walker, Graham C

    2011-01-01

    A cell's ability to tolerate DNA damage is directly connected to the human development of diseases and cancer. To better understand the processes underlying mutagenesis, we studied the cell's reliance on the potentially error-prone translesion synthesis (TLS), and an error-free, template-switching pathway in Saccharomyces cerevisiae. The primary proteins mediating S. cerevisiae TLS are three DNA polymerases (Pols): Rev1, Pol ζ (Rev3/7), and Pol η (Rad30), all with human homologs. Rev1's noncatalytic role in recruiting other DNA polymerases is known to be important for TLS. However, the biological significance of Rev1's unusual conserved DNA polymerase activity, which inserts dC, is much less well understood. Here, we demonstrate that inactivating Rev1's DNA polymerase function sensitizes cells to both chronic and acute exposure to 4-nitroquinoline-1-oxide (4-NQO) but not to UV or cisplatin. Full Rev1-dependent resistance to 4-NQO, however, also requires the additional Rev1 functions. When error-free tolerance is disrupted through deletion of MMS2, Rev1's catalytic activity is more vital for 4-NQO resistance, possibly explaining why the biological significance of Rev1's catalytic activity has been elusive. In the presence or absence of Mms2-dependent error-free tolerance, the catalytic dead strain of Rev1 exhibits a lower 4-NQO-induced mutation frequency than wild type. Furthermore, Pol ζ, but not Pol η, also contributes to 4-NQO resistance. These results show that Rev1's catalytic activity is important in vivo when the cell has to cope with specific DNA lesions, such as N(2)-dG.

  5. Significant correlation between refractive index and activity of mitochondria: single mitochondrion study.

    PubMed

    Haseda, Keisuke; Kanematsu, Keita; Noguchi, Keiichi; Saito, Hiromu; Umeda, Norihiro; Ohta, Yoshihiro

    2015-03-01

    Measurements of refractive indices (RIs) of intracellular components can provide useful information on the structure and function of cells. The present study reports, for the first time, determination of the RI of an isolated mitochondrion in isotonic solution using retardation-modulated differential interference contrast microscopy. The value was 1.41 ± 0.01, indicating that mitochondria are densely packed with molecules having high RIs. Further, the RIs of each mitochondrion were significantly correlated with the mitochondrial membrane potential, an index of mitochondrial activity. These results will provide useful information on the structures and functions of cells based on the intracellular distribution of RIs.

  6. Anticancer and enhanced antimicrobial activity of biosynthesizd silver nanoparticles against clinical pathogens

    NASA Astrophysics Data System (ADS)

    Rajeshkumar, Shanmugam; Malarkodi, Chelladurai; Vanaja, Mahendran; Annadurai, Gurusamy

    2016-07-01

    The present investigation shows the biosynthesis of eco-friendly silver nanoparticles using culture supernatant of Enterococcus sp. and study the effect of enhanced antimicrobial activity, anticancer activity against pathogenic bacteria, fungi and cancer cell lines. Silver nanoparticles was synthesized by adding 1 mM silver nitrate into the 100 ml of 24 h freshly prepared culture supernatant of Enterococcus sp. and were characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Transmission Electron Microscope (TEM), Selected Area Diffraction X-Ray (SAED), Energy Dispersive X Ray (EDX) and Fourier Transform Infra red Spectroscopy (FT-IR). The synthesized silver nanoparticles were impregnated with commercial antibiotics for evaluation of enhanced antimicrobial activity. Further these synthesized silver nanoparticles were assessed for its anticancer activity against cancer cell lines. In this study crystalline structured nanoparticles with spherical in the size ranges from 10 to 80 nm and it shows excellent enhanced antimicrobial activity than the commercial antibiotics. The in vitro assay of silver nanoparticles on anticancer have great potential to inhibit the cell viability. Amide linkages and carboxylate groups of proteins from Enterococcus sp. may bind with silver ions and convert into nanoparticles. The activities of commercial antibiotics were enhanced by coating silver nanoparticles shows significant improved antimicrobial activity. Silver nanoparticles have the great potential to inhibit the cell viability of liver cancer cells lines (HepG2) and lung cancer cell lines (A549).

  7. Enhancement of CA3 hippocampal network activity by activation of group II metabotropic glutamate receptors.

    PubMed

    Ster, Jeanne; Mateos, José María; Grewe, Benjamin Friedrich; Coiret, Guyllaume; Corti, Corrado; Corsi, Mauro; Helmchen, Fritjof; Gerber, Urs

    2011-06-14

    Impaired function or expression of group II metabotropic glutamate receptors (mGluRIIs) is observed in brain disorders such as schizophrenia. This class of receptor is thought to modulate activity of neuronal circuits primarily by inhibiting neurotransmitter release. Here, we characterize a postsynaptic excitatory response mediated by somato-dendritic mGluRIIs in hippocampal CA3 pyramidal cells and in stratum oriens interneurons. The specific mGluRII agonists DCG-IV or LCCG-1 induced an inward current blocked by the mGluRII antagonist LY341495. Experiments with transgenic mice revealed a significant reduction of the inward current in mGluR3(-/-) but not in mGluR2(-/-) mice. The excitatory response was associated with periods of synchronized activity at theta frequency. Furthermore, cholinergically induced network oscillations exhibited decreased frequency when mGluRIIs were blocked. Thus, our data indicate that hippocampal responses are modulated not only by presynaptic mGluRIIs that reduce glutamate release but also by postsynaptic mGluRIIs that depolarize neurons and enhance CA3 network activity.

  8. Particle-Cell Contact Enhances Antibacterial Activity of Silver Nanoparticles

    PubMed Central

    Bondarenko, Olesja; Ivask, Angela; Käkinen, Aleksandr; Kurvet, Imbi; Kahru, Anne

    2013-01-01

    Background It is generally accepted that antibacterial properties of Ag nanoparticles (AgNPs) are dictated by their dissolved fraction. However, dissolution-based concept alone does not fully explain the toxic potency of nanoparticulate silver compared to silver ions. Methodology/Principal Findings Herein, we demonstrated that the direct contact between bacterial cell and AgNPs' surface enhanced the toxicity of nanosilver. More specifically, cell-NP contact increased the cellular uptake of particle-associated Ag ions – the single and ultimate cause of toxicity. To prove that, we evaluated the toxicity of three different AgNPs (uncoated, PVP-coated and protein-coated) to six bacterial strains: Gram-negative Escherichia coli, Pseudomonas fluorescens, P. putida and P. aeruginosa and Gram-positive Bacillus subtilis and Staphylococcus aureus. While the toxicity of AgNO3 to these bacteria varied only slightly (the 4-h EC50 ranged from 0.3 to 1.2 mg Ag/l), the 4-h EC50 values of protein-coated AgNPs for various bacterial strains differed remarkably, from 0.35 to 46 mg Ag/l. By systematically comparing the intracellular and extracellular free Ag+ liberated from AgNPs, we demonstrated that not only extracellular dissolution in the bacterial test environment but also additional dissolution taking place at the particle-cell interface played an essential role in antibacterial action of AgNPs. The role of the NP-cell contact in dictating the antibacterial activity of Ag-NPs was additionally proven by the following observations: (i) separation of bacterial cells from AgNPs by particle-impermeable membrane (cut-off 20 kDa, ∼4 nm) significantly reduced the toxicity of AgNPs and (ii) P. aeruginosa cells which tended to attach onto AgNPs, exhibited the highest sensitivity to all forms of nanoparticulate Ag. Conclusions/Significance Our findings provide new insights into the mode of antibacterial action of nanosilver and explain some discrepancies in this field, showing that

  9. Aspects of igneous activity significant to a repository at Yucca Mountain, Nevada

    SciTech Connect

    Krier, D. J.; Perry, F. V.

    2004-01-01

    Location, timing, volume, and eruptive style of post-Miocene volcanoes have defined the volcanic hazard significant to a proposed high-level radioactive waste (HLW) and spent nuclear fuel (SNF) repository at Yucca Mountain, Nevada, as a low-probability, high-consequence event. Examination of eruptive centers in the region that may be analogueues to possible future volcanic activity at Yucca Mountain have aided in defining and evaluating the consequence scenarios for intrusion into and eruption above a repository. The probability of a future event intersecting a repository at Yucca Mountain has a mean value of 1.7 x 10{sup -8} per year. This probability comes from the Probabilistic Volcanic Hazard Assessment (PVHA) completed in 1996 and updated to reflect change in repository layout. Since that time, magnetic anomalies representing potential buried volcanic centers have been identified fiom magnetic surveys; however these potential buried centers only slightly increase the probability of an event intersecting the repository. The proposed repository will be located in its central portion of Yucca Mountain at approximately 300m depth. The process for assessing performance of a repository at Yucca Mountain has identified two scenarios for igneous activity that, although having a very low probability of occurrence, could have a significant consequence should an igneous event occur. Either a dike swarm intersecting repository drifts containing waste packages, or a volcanic eruption through the repository could result in release of radioactive material to the accessible environment. Ongoing investigations are assessing the mechanisms and significance of the consequence scenarios. Lathrop Wells Cone ({approx}80,000 yrs), a key analogue for estimating potential future volcanic activity, is the youngest surface expression of apparent waning basaltic volcanism in the region. Cone internal structure, lavas, and ash-fall tephra have been examined to estimate eruptive volume

  10. RSUME Enhances Glucocorticoid Receptor SUMOylation and Transcriptional Activity

    PubMed Central

    Druker, Jimena; Liberman, Ana C.; Antunica-Noguerol, María; Gerez, Juan; Paez-Pereda, Marcelo; Rein, Theo; Iñiguez-Lluhí, Jorge A.; Holsboer, Florian

    2013-01-01

    Glucocorticoid receptor (GR) activity is modulated by posttranslational modifications, including phosphorylation, ubiquitination, and SUMOylation. The GR has three SUMOylation sites: lysine 297 (K297) and K313 in the N-terminal domain (NTD) and K721 within the ligand-binding domain. SUMOylation of the NTD sites mediates the negative effect of the synergy control motifs of GR on promoters with closely spaced GR binding sites. There is scarce evidence on the role of SUMO conjugation to K721 and its impact on GR transcriptional activity. We have previously shown that RSUME (RWD-containing SUMOylation enhancer) increases protein SUMOylation. We now demonstrate that RSUME interacts with the GR and increases its SUMOylation. RSUME regulates GR transcriptional activity and the expression of its endogenous target genes, FKBP51 and S100P. RSUME uncovers a positive role for the third SUMOylation site, K721, on GR-mediated transcription, demonstrating that GR SUMOylation acts positively in the presence of a SUMOylation enhancer. Both mutation of K721 and small interfering RNA-mediated RSUME knockdown diminish GRIP1 coactivator activity. RSUME, whose expression is induced under stress conditions, is a key factor in heat shock-induced GR SUMOylation. These results show that inhibitory and stimulatory SUMO sites are present in the GR and at higher SUMOylation levels the stimulatory one becomes dominant. PMID:23508108

  11. Enhanced oxidation resistance of active nanostructures via dynamic size effect

    PubMed Central

    Liu, Yun; Yang, Fan; Zhang, Yi; Xiao, Jianping; Yu, Liang; Liu, Qingfei; Ning, Yanxiao; Zhou, Zhiwen; Chen, Hao; Huang, Wugen; Liu, Ping; Bao, Xinhe

    2017-01-01

    A major challenge limiting the practical applications of nanomaterials is that the activities of nanostructures (NSs) increase with reduced size, often sacrificing their stability in the chemical environment. Under oxidative conditions, NSs with smaller sizes and higher defect densities are commonly expected to oxidize more easily, since high-concentration defects can facilitate oxidation by enhancing the reactivity with O2 and providing a fast channel for oxygen incorporation. Here, using FeO NSs as an example, we show to the contrary, that reducing the size of active NSs can drastically increase their oxidation resistance. A maximum oxidation resistance is found for FeO NSs with dimensions below 3.2 nm. Rather than being determined by the structure or electronic properties of active sites, the enhanced oxidation resistance originates from the size-dependent structural dynamics of FeO NSs in O2. We find this dynamic size effect to govern the chemical properties of active NSs. PMID:28223687

  12. Shed syndecan-2 enhances tumorigenic activities of colon cancer cells

    PubMed Central

    Choi, Sojoong; Choi, Youngsil; Jun, Eunsung; Kim, In-San; Kim, Seong-Eun; Jung, Sung-Ae; Oh, Eok-Soo

    2015-01-01

    Because earlier studies showed the cell surface heparan sulfate proteoglycan, syndecan-2, sheds from colon cancer cells in culture, the functional roles of shed syndecan-2 were assessed. A non-cleavable mutant of syndecan-2 in which the Asn148-Leu149 residues were replaced with Asn148-Ile149, had decreased shedding, less cancer-associated activities of syndecan-2 in vitro, and less syndecan-2-mediated metastasis of mouse melanoma cells in vivo, suggesting the importance of shedding on syndecan-2-mediated pro-tumorigenic functions. Indeed, shed syndecan-2 from cancer-conditioned media and recombinant shed syndecan-2 enhanced cancer-associated activities, and depletion of shed syndecan-2 abolished these effects. Similarly, shed syndecan-2 was detected from sera of patients from advanced carcinoma (625.9 ng/ml) and promoted cancer-associated activities. Furthermore, a series of syndecan-2 deletion mutants showed that the tumorigenic activity of shed syndecan-2 resided in the C-terminus of the extracellular domain and a shed syndecan-2 synthetic peptide (16 residues) was sufficient to establish subcutaneous primary growth of HT29 colon cancer cells, pulmonary metastases (B16F10 cells), and primary intrasplenic tumor growth and liver metastases (4T1 cells). Taken together, these results demonstrate that shed syndecan-2 directly enhances colon cancer progression and may be a promising therapeutic target for controlling colon cancer development. PMID:25686828

  13. Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198.

    PubMed

    LaVallee, Theresa M; Burke, Patricia A; Swartz, Glenn M; Hamel, Ernest; Agoston, Gregory E; Shah, Jamshed; Suwandi, Lita; Hanson, Art D; Fogler, William E; Sidor, Carolyn F; Treston, Anthony M

    2008-06-01

    Clinical studies using the microtubule-targeting agent 2-methoxyestradiol (2ME2; Panzem) in cancer patients show that treatment is associated with clinical benefit, including prolonged stable disease, complete and partial responses, and an excellent safety profile. Studies have shown that 2ME2 is metabolized by conjugation at positions 3 and 17 and oxidation at position 17. To define structure-activity relationships for these positions of 2ME2 and to generate metabolically stable analogues with improved anti-tubulin properties, a series of analogues was generated and three lead analogues were selected, ENMD-1198, ENMD-1200, and ENMD-1237. These molecules showed improved metabolic stability with >65% remaining after 2-h incubation with hepatocytes. Pharmacokinetic studies showed that oral administration of the compounds resulted in increased plasma levels compared with 2ME2. All three analogues bind the colchicine binding site of tubulin, induce G(2)-M cell cycle arrest and apoptosis, and reduce hypoxia-inducible factor-1alpha levels. ENMD-1198 and ENMD-1200 showed improved in vitro antiproliferative activities. Significant reductions in tumor volumes compared with vehicle-treated mice were observed in an orthotopic breast carcinoma (MDA-MB-231) xenograft model following daily oral treatment with all compounds (ANOVA, P < 0.05). Significantly improved median survival time was observed with ENMD-1198 and ENMD-1237 (200 mg/kg/d) in a Lewis lung carcinoma metastatic model (P < 0.05). In both tumor models, the high-dose group of ENMD-1198 showed antitumor activity equivalent to that of cyclophosphamide. ENMD-1198 was selected as the lead molecule in this analogue series and is currently in a phase I clinical trial in patients with refractory solid tumors.

  14. Expression and biological significance of Ca2+-activated ion channels in human keratinocytes.

    PubMed

    Koegel, H; Alzheimer, C

    2001-01-01

    In whole-cell recordings from HaCaT keratinocytes, ATP, bradykinin, and histamine caused a biphasic change of the membrane potential consisting of an initial transient depolarization, followed by a pronounced and long-lasting hyperpolarization. Flash photolysis of caged IP3 mimicked the agonist-induced voltage response, suggesting that intracellular Ca2+ release and subsequent opening of Ca2+-activated ion channels serve as the common transduction mechanism. In contrast, cAMP- and PKC-dependent pathways were not involved in the electrophysiological effects of the extracellular signaling molecules. The depolarization was predominantly mediated by a DIDS- and niflumic acid-sensitive Cl- current, whereas a charybdotoxin- and clotrimazole-sensitive K+ current underlay the prominent hyperpolarization. Consistent with the electrophysiological data, RT-PCR showed that HaCaT keratinocytes express two types of Ca2+-activated Cl- channels, CaCC2 and CaCC3 (CLCA2), as well as the Ca2+-activated K+ channel hSK4. That the pronounced hSK4-mediated hyperpolarization bears significance on the growth and differentiation properties of keratinocytes is suggested by RNase protection assays showing that hSK4 mRNA expression is strongly down-regulated under conditions that allow keratinocyte differentiation. hSK4 might thus play a role in linking changes in membrane potential to the biological fate of keratinocytes.

  15. Activation of Big Grain1 significantly improves grain size by regulating auxin transport in rice.

    PubMed

    Liu, Linchuan; Tong, Hongning; Xiao, Yunhua; Che, Ronghui; Xu, Fan; Hu, Bin; Liang, Chengzhen; Chu, Jinfang; Li, Jiayang; Chu, Chengcai

    2015-09-01

    Grain size is one of the key factors determining grain yield. However, it remains largely unknown how grain size is regulated by developmental signals. Here, we report the identification and characterization of a dominant mutant big grain1 (Bg1-D) that shows an extra-large grain phenotype from our rice T-DNA insertion population. Overexpression of BG1 leads to significantly increased grain size, and the severe lines exhibit obviously perturbed gravitropism. In addition, the mutant has increased sensitivities to both auxin and N-1-naphthylphthalamic acid, an auxin transport inhibitor, whereas knockdown of BG1 results in decreased sensitivities and smaller grains. Moreover, BG1 is specifically induced by auxin treatment, preferentially expresses in the vascular tissue of culms and young panicles, and encodes a novel membrane-localized protein, strongly suggesting its role in regulating auxin transport. Consistent with this finding, the mutant has increased auxin basipetal transport and altered auxin distribution, whereas the knockdown plants have decreased auxin transport. Manipulation of BG1 in both rice and Arabidopsis can enhance plant biomass, seed weight, and yield. Taking these data together, we identify a novel positive regulator of auxin response and transport in a crop plant and demonstrate its role in regulating grain size, thus illuminating a new strategy to improve plant productivity.

  16. Subcortical evoked activity and motor enhancement in Parkinson's disease.

    PubMed

    Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Khan, Sadaquate; Javed, Shazia; Gill, Steven S; Ashkan, Keyoumars; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L; Aziz, Tipu; Brown, Peter

    2016-03-01

    Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of 'paradoxical kinesis' in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus - a key component of the reticular activating system - provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an 'energizing' influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease.

  17. Subcortical evoked activity and motor enhancement in Parkinson's disease

    PubMed Central

    Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Khan, Sadaquate; Javed, Shazia; Gill, Steven S.; Ashkan, Keyoumars; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L.; Aziz, Tipu; Brown, Peter

    2016-01-01

    Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of ‘paradoxical kinesis’ in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus – a key component of the reticular activating system – provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an ‘energizing’ influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease. PMID:26687971

  18. Boron Doping of Multiwalled Carbon Nanotubes Significantly Enhances Hole Extraction in Carbon-Based Perovskite Solar Cells.

    PubMed

    Zheng, Xiaoli; Chen, Haining; Li, Qiang; Yang, Yinglong; Wei, Zhanhua; Bai, Yang; Qiu, Yongcai; Zhou, Dan; Wong, Kam Sing; Yang, Shihe

    2017-03-15

    Compared to the conventional perovskite solar cells (PSCs) containing hole-transport materials (HTM), carbon materials based HTM-free PSCs (C-PSCs) have often suffered from inferior power conversion efficiencies (PCEs) arising at least partially from the inefficient hole extraction at the perovskite-carbon interface. Here, we show that boron (B) doping of multiwalled carbon nanotubes (B-MWNTs) electrodes are superior in enabling enhanced hole extraction and transport by increasing work function, carrier concentration, and conductivity of MWNTs. The C-PSCs prepared using the B-MWNTs as the counter electrodes to extract and transport hole carriers have achieved remarkably higher performances than that with the undoped MWNTs, with the resulting PCE being considerably improved from 10.70% (average of 9.58%) to 14.60% (average of 13.70%). Significantly, these cells show negligible hysteretic behavior. Moreover, by coating a thin layer of insulating aluminum oxide (Al2O3) on the mesoporous TiO2 film as a physical barrier to substantially reduce the charge losses, the PCE has been further pushed to 15.23% (average 14.20%). Finally, the impressive durability and stability of the prepared C-PSCs were also testified under various conditions, including long-term air exposure, heat treatment, and high humidity.

  19. Why Sn doping significantly enhances the dielectric properties of Ba(Ti1-xSnx)O3

    PubMed Central

    Shi, Tao; Xie, Lin; Gu, Lin; Zhu, Jing

    2015-01-01

    Through appropriate doping, the properties of BaTiO3-based ferroelectrics can be significantly enhanced. To determine the physical process induced by the doping of Sn atoms in Ba(Ti0.8Sn0.2)O3, we performed high-resolution scanning transmission electron microscopy experiments and observed that the regions with low Sn content formed polar nano regions (PNRs) embedded in the matrix in Ba(Ti0.8Sn0.2)O3. The interactions among Sn, Ti, Ba and O atoms were determined using first principles calculations. Based on the characteristics of the electronic structure and crystal lattice strain fields, the effects of doping with Sn were investigated. The Sn doping not only changed the electronic structure of the crystal but also increased the dielectric properties of the PNRs. Moreover, the Sn doping was also responsible for the diffuse phase transition of the Ba(Ti1-xSnx)O3 material. The effects mentioned in this paper are universal in lead-free ferroelectrics, and similar elements such as Sb, Mg, and Zr may have the same functions in other systems. Thus, these results provide guidance for the design of the doping process and new systems of ferroelectric or relaxor materials. PMID:25721479

  20. Significant fluorescence enhancement by supramolecular complex formation between berberine chloride and cucurbit(n=7)uril and its analytical application.

    PubMed

    Dong, Nan; Cheng, Li-na; Wang, Xiu-lin; Li, Qin; Dai, Chuan-yu; Tao, Zhu

    2011-05-15

    The supramolecular interaction of cucurbit(n=7)uril (Q[7]) with berberine chloride (BER) has been studied in aqueous solution at pH 2.0 and room temperature by spectro-fluorimetry. The association constant of the complex was 2.07 × 10(6) L mol(-1) calculated by using a nonlinear least squares method. (1)H NMR spectra confirmed that a 1:1 stable complex is formed between Q[7] and BER. This work proposes a possible interaction mode, in which the guest BER is incorporated inside the hydrophobic cavity of the host Q[7] via the isoquinoline ring part of the guest molecule. Based on a significant enhancement of the fluorescence intensity of this supramolecular complex, a spectrofluorimetric method with high sensitivity and selectivity has been developed for the determination of BER in aqueous solution in the presence of Q[7]. The linear range of the method was from 7.43 to 11.2 × 10(3) ng mL(-1)with the detection limit 4.2 ng mL(-1). There was no interference from the compounds normally used in tablets, serum or urine constituents. The proposed method was applied to the determination of BER in tablets, serum and urine samples with satisfactory results and good consistency with those obtained by the pharmacopoeia method. This shows that it has promising potential for therapeutic drug monitoring and pharmacokinetics and for clinical application.

  1. Mushroom bodies enhance initial motor activity in Drosophila.

    PubMed

    Serway, Christine N; Kaufman, Rebecca R; Strauss, Roland; de Belle, J Steven

    2009-01-01

    The central body (or central complex, CCX) and the mushroom bodies (MBs) are brain structures in most insect phyla that have been shown to influence aspects of locomotion. The CCX regulates motor coordination and enhances activity while MBs have, thus far, been shown to suppress motor activity levels measured over time intervals ranging from hours to weeks. In this report, we investigate MB involvement in motor behavior during the initial stages (15 minutes) of walking in Buridan's paradigm. We measured aspects of walking in flies that had MB lesions induced by mutations in six different genes and by chemical ablation. All tested flies were later examined histologically to assess MB neuroanatomy. Mutant strains with MB structural defects were generally less active in walking than wild-type flies. Most mutants in which MBs were also ablated with hydroxyurea (HU) showed additional activity decrements. Variation in measures of velocity and orientation to landmarks among wild-type and mutant flies was attributed to pleiotropy, rather than to MB lesions. We conclude that MBs upregulate activity during the initial stages of walking, but suppress activity thereafter. An MB influence on decision making has been shown in a wide range of complex behaviors. We suggest that MBs provide appropriate contextual information to motor output systems in the brain, indirectly fine tuning walking by modifying the quantity (i.e., activity) of behavior.

  2. ATP-enhanced peroxidase-like activity of gold nanoparticles.

    PubMed

    Shah, Juhi; Purohit, Rahul; Singh, Ragini; Karakoti, Ajay Singh; Singh, Sanjay

    2015-10-15

    Gold nanoparticles (AuNPs) are known to possess intrinsic biological peroxidase-like activity that has applications in development of numerous biosensors. The reactivity of the Au atoms at the surface of AuNPs is critical to the performance of such biosensors, yet little is known about the effect of biomolecules and ions on the peroxidase-like activity. In this work, the effect of ATP and other biologically relevant molecules and ions over peroxidase-like activity of AuNPs are described. Contrary to the expectation that nanoparticles exposed to biomolecules may lose the catalytic property, ATP and ADP addition enhanced the peroxidase-like activity of AuNPs. The catalytic activity was unaltered by the addition of free phosphate, sulphate and carbonate anions however, addition of ascorbic acid to the reaction mixture diminished the intrinsic peroxidase-like activity of AuNPs, even in the presence of ATP and ADP. In contrast to AuNPs, ATP did not synergize and improve the peroxidase activity of the natural peroxidase enzyme, horseradish peroxidase.

  3. Statins enhance peroxisome proliferator-activated receptor gamma coactivator-1alpha activity to regulate energy metabolism.

    PubMed

    Wang, Wenxian; Wong, Chi-Wai

    2010-03-01

    Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) serves as an inducible coactivator for a number of transcription factors to control energy metabolism. Insulin signaling through Akt kinase has been demonstrated to phosphorylate PGC-1alpha at serine 571 and downregulate its activity in the liver. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that reduce cholesterol synthesis in the liver. In this study, we found that statins reduced the active form of Akt and enhanced PGC-1alpha activity. Specifically, statins failed to activate an S571A mutant of PGC-1alpha. The activation of PGC-1alpha by statins selectively enhanced the expression of energy metabolizing enzymes and regulators including peroxisome proliferator-activated receptor alpha, acyl-CoA oxidase, carnitine palmitoyl transferase-1A, and pyruvate dehydrogenase kinase 4. Importantly, a constitutively active form of Akt partially reduced the statin-enhanced gene expression. Our study thus provides a plausible mechanistic explanation for the hypolipidemic effect of statin through elevating the rate of beta-oxidation and mitochondrial Kreb's cycle capacity to enhance fatty acid utilization while reducing the rate of glycolysis.

  4. Active Mediation of Plasmon Enhanced Localized Exciton Generation, Carrier Diffusion and Enhanced Photon Emission.

    PubMed

    Haq, Sharmin; Addamane, Sadhvikas; Kafle, Bijesh; Huang, Danhong; Balakrishnan, Ganesh; Habteyes, Terefe G

    2017-04-13

    Understanding the enhancement of charge carrier generation and their diffusion is imperative for improving the efficiency of optoelectronic devices particularly infrared photodetectors that are less developed than their visible counterpart. Here, using gold nanorods as model plasmonic systems, InAs quantum dots (QDs) embedded in an InGaAs quantum well as an emitter, and GaAs as an active mediator of surface plasmons for enhancing carrier generation and photon emission, the distance dependence of energy transfer and carrier diffusion have been investigated both experimentally and theoretically. Analysis of the QD emission enhancement as a function of distance reveals a Förster radius of 3.85 ± 0.15 nm, a near-field decay length of 4.8 ± 0.1 nm and an effective carrier diffusion length of 64.0 ± 3.0 nm. Theoretical study of the temporal-evolution of the electron-hole occupation number of the excited states of the QDs indicates that the emission enhancement trend is determined by the carrier diffusion and capture rates.

  5. A Smartphone Application Significantly Improved Diabetes Self-Care Activities with High User Satisfaction

    PubMed Central

    Kim, Yu Jin; Byun, Jong Kyu; Park, So Young; Hong, Soo Min; Chin, Sang Ouk; Chon, Suk; Oh, Seungjoon; Woo, Jeong-taek; Kim, Sung Woon; Kim, Young Seol

    2015-01-01

    Background We developed for the first time a smartphone application designed for diabetes self-management in Korea and registered a patent for the relevant algorithm. We also investigated the user satisfaction with the application and the change in diabetes related self-care activities after using the application. Methods We conducted a questionnaire survey on volunteers with diabetes who were using the application. Ninety subjects responded to the questionnaire between June 2012 and March 2013. A modified version of the Summary of Diabetes Self-Care Activities (SDSCA) was used in this study. Results The survey results exhibited a mean subject age of 44.0 years old, and males accounted for 78.9% of the subjects. Fifty percent of the subjects had diabetes for less than 3 years. The majority of respondents experienced positive changes in their clinical course after using the application (83.1%) and were satisfied with the structure and completeness of the application (86.7%). Additionally, the respondents' answers indicated that the application was easy to use (96.7%) and recommendable to others (97.7%) and that they would continue using the application to manage their diabetes (96.7%). After using the Diabetes Notepad application, diabetes related self-care activities assessed by SDSCA displayed statistically significant improvements (P<0.05), except for the number of days of drinking. Conclusion This smartphone-based application can be a useful tool leading to positive changes in diabetes related self-care activities and increase user satisfaction. PMID:26124991

  6. Reward anticipation enhances brain activation during response inhibition.

    PubMed

    Rosell-Negre, Patricia; Bustamante, Juan Carlos; Fuentes-Claramonte, Paola; Costumero, Víctor; Benabarre, Sergio; Barros-Loscertales, Alfonso

    2014-06-01

    The chance to achieve a reward starts up the required neurobehavioral mechanisms to adapt our thoughts and actions in order to accomplish our objective. However, reward does not equally reinforce everybody but depends on interindividual motivational dispositions. Thus, immediate reward contingencies can modulate the cognitive process required for goal achievement, while individual differences in personality can affect this modulation. We aimed to test the interaction between inhibition-related brain response and motivational processing in a stop signal task by reward anticipation and whether individual differences in sensitivity to reward (SR) modulate such interaction. We analyzed the cognitive-motivational interaction between the brain pattern activation of the regions involved in correct and incorrect response inhibition and the association between such brain activations and SR scores. We also analyzed the behavioral effects of reward on both reaction times for the "go" trials before and after correct and incorrect inhibition in order to test error prediction performance and postinhibition adjustment. Our results show enhanced activation during response inhibition under reward contingencies in frontal, parietal, and subcortical areas. Moreover, activation of the right insula and the left putamen positively correlates with the SR scores. Finally, the possibility of reward outcome affects not only response inhibition performance (e.g., reducing stop signal reaction time), but also error prediction performance and postinhibition adjustment. Therefore, reward contingencies improve behavioral performance and enhance brain activation during response inhibition, and SR is related to brain activation. Our results suggest the conditions and factors that subserve cognitive control strategies in cognitive motivational interactions during response inhibition.

  7. Understanding Interactions between Manganese Oxide and Gold That Lead to Enhanced Activity for Electrocatalytic Water Oxidation

    PubMed Central

    2015-01-01

    To develop active nonprecious metal-based electrocatalysts for the oxygen evolution reaction (OER), a limiting reaction in several emerging renewable energy technologies, a deeper understanding of the activity of the first row transition metal oxides is needed. Previous studies of these catalysts have reported conflicting results on the influence of noble metal supports on the OER activity of the transition metal oxides. Our study aims to clarify the interactions between a transition metal oxide catalyst and its metal support in turning over this reaction. To achieve this goal, we examine a catalytic system comprising nanoparticulate Au, a common electrocatalytic support, and nanoparticulate MnOx, a promising OER catalyst. We conclusively demonstrate that adding Au to MnOx significantly enhances OER activity relative to MnOx in the absence of Au, producing an order of magnitude higher turnover frequency (TOF) than the TOF of the best pure MnOx catalysts reported to date. We also provide evidence that it is a local rather than bulk interaction between Au and MnOx that leads to the observed enhancement in the OER activity. Engineering improvements in nonprecious metal-based catalysts by the addition of Au or other noble metals could still represent a scalable catalyst as even trace amounts of Au are shown to lead a significant enhancement in the OER activity of MnOx. PMID:24661269

  8. Phosphorous transient enhanced diffusion suppression and activation enhancement with cluster carbon co-implantation

    SciTech Connect

    Nakashima, Yoshiki; Hamamoto, Nariaki; Nagayama, Tsutomu; Koga, Yuji; Umisedo, Sei; Kawamura, Yasunori; Hashimoto, Masahiro; Onoda, Hiroshi

    2012-11-06

    Carbon co-implantation is well known as an effective method for suppressing boron/phosphorous transient enhanced diffusion (TED). Germanium pre-amorphization implantation (PAI) is usually applied prior to carbon co-implantation for suppressing channeling tail of dopants. In this study, cluster carbon was applied instead of the combination of germanium PAI and monomer carbon co-implantation prior to phosphorous implantation. Dependence of phosphorous activation and TED on amorphous layer thickness, carbon dose, carbon distribution and substrate temperature have been investigated. Cluster carbon implantation enables thick amorphous layer formation and TED suppression at the same time and low temperature implantation enhances the ability of amorphous layer formation so that shallow junction and low Rs can be achieved without Ge implantation.

  9. The association of phosphoinositide 3-kinase enhancer A with hepatic insulin receptor enhances its kinase activity.

    PubMed

    Chan, Chi Bun; Liu, Xia; He, Kunyan; Qi, Qi; Jung, Dae Y; Kim, Jason K; Ye, Keqiang

    2011-07-01

    Dysfunction of hepatic insulin receptor tyrosine kinase (IRTK) causes the development of type 2 diabetes. However, the molecular mechanism regulating IRTK activity in the liver remains poorly understood. Here, we show that phosphoinositide 3-kinase enhancer A (PIKE-A) is a new insulin-dependent enhancer of hepatic IRTK. Liver-specific Pike-knockout (LPKO) mice display glucose intolerance with impaired hepatic insulin sensitivity. Specifically, insulin-provoked phosphoinositide 3-kinase/Akt signalling is diminished in the liver of LPKO mice, leading to the failure of insulin-suppressed gluconeogenesis and hyperglycaemia. Thus, hepatic PIKE-A has a key role in mediating insulin signal transduction and regulating glucose homeostasis in the liver.

  10. [Lymphokine-activated killer cell adoptive immunotherapy for cancer treatment and its significance].

    PubMed

    Toge, T; Yamaguchi, Y

    1992-09-01

    New culture system, CDCS-T1, was developed for clinical conduction of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT). Advanced or recurrent cancer patients of digestive tract were treated with AIT with LAK cells generated by CDCS-T1 in combination with plasma exchange. Partial responses were shown in 10 to 20% of patients treated. Long survival was found in some responders, indicating the significance of LAK therapy for cancer treatment. AIT with LAK cell transfer was also conducted in patients with esophageal cancer as postoperative adjuvant therapy. Better restoration of postoperative depression of immunological parameters was found in patients with postoperative LAK cell transfer. It is suggested that postoperative LAK cell transfer is a good candidate for adjuvant immunotherapy for cancer treatment.

  11. Nanosilver based anionic linear globular dendrimer with a special significant antiretroviral activity.

    PubMed

    Ardestani, Mehdi Shafiee; Fordoei, Alireza Salehi; Abdoli, Asghar; Ahangari Cohan, Reza; Bahramali, Golnaz; Sadat, Seyed Mehdi; Siadat, Seyed Davar; Moloudian, Hamid; Nassiri Koopaei, Nasser; Bolhasani, Azam; Rahimi, Pooneh; Hekmat, Soheila; Davari, Mehdi; Aghasadeghi, Mohammad Reza

    2015-05-01

    HIV is commonly caused to a very complicated disease which has not any recognized vaccine, so designing and development of novel antiretroviral agents with specific application of nanomedicine is a globally interested research subject worldwide. In the current study, a novel structure of silver complexes with anionic linear globular dendrimer was synthesized, characterized and then assessed against HIV replication pathway in vitro as well. The results showed a very good yield of synthesis (up to 70%) for the nano-complex as well as a very potent significant (P < 0.05) antiretroviral activity with non-severe toxic effects in comparison with the Nevirapine as standard drug in positive control group. According to the present data, silver anionic linear globular dendrimers complex may have a promising future to inhibit replication of HIV viruse in clinical practice.

  12. Significant foreshock activities of M>7.5 earthquakes in the Kuril subduction zone

    NASA Astrophysics Data System (ADS)

    Harada, T.; Yokoi, S.; Satake, K.

    2014-12-01

    In the Kuril subduction zone, some M>7.5 earthquakes are accompanied by significant foreshock activities, providing a good opportunity to understand the characteristics of foreshocks for large interplate events such as occur along the Japan Trench and Nankai Trough etc. Some preliminary results from our examination of the foreshock sequences are as follows. Relocated foreshocks tend to migrate with time toward the trench axis. Foreshock distributions of the interplate earthquakes do not overlap with the large coseismic slips (asperities) of the mainshocks. Foreshocks of the 2007 northern Kuril outer-rise event, however, were distributed on the entire rupture area. Foreshock sequences seem to be limited in the regions where the background seismicity rates are relatively high. The foreshock activities were found in the examination of the space-time pattern of M>7 events along the northern Japan to Kuril trench since 1913 (e.g. Harada, Satake, and Ishibashi, 2011:AGU, 2012:AOGS). The large earthquakes preceded by active foreshock sequences are: the 2006 (M8.3), 2007 (M8.1) offshore Simushir earthquakes, the 1963 (M8.5), 1991 (M7.6), 1995 (M7.9) offshore Urup events, the 1978 (M7.8) offshore Iturup events, the 1969 (M8.2) offshore Shikotan event. In contrast, M>7.5 interplate earthquakes offshore Hokkaido (1952 (M8.1), 1973 (M7.8), 2003 (M8.1)) and intraslab earthquakes (1958 (M8.3), 1978 (M7.8), 1993 (M7.6), 1994 (M8.3)) had few or no foreshocks. In the examination of the active foreshocks, we relocated foreshocks by the Modified JHD method (Hurukawa, 1995), compared relocated foreshock areas with mainshock coseismic slip distributions estimated by the teleseismic body-wave inversion (Kikuchi and Kanamori, 2003), and examined the relation between active foreshock sequences and regional background seismicity. This study was supported by the MEXT's "New disaster mitigation research project on Mega thrust earthquakes around Nankai/Ryukyu subduction zones".

  13. Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.

    PubMed

    Lloyd, Steven A; Corkill, Beau; Bruster, Matthew C; Roberts, Rick L; Shanks, Ryan A

    2017-03-18

    Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity.

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

    PubMed

    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.

  15. Volcanic activity before and after large tectonic earthquakes: Observations and statistical significance

    NASA Astrophysics Data System (ADS)

    Eggert, S.; Walter, T. R.

    2009-04-01

    The study of volcanic triggering and coupling to the tectonic surroundings has received special attention in recent years, using both direct field observations and historical descriptions of eruptions and earthquake activity. Repeated reports of volcano-earthquake interactions in, e.g., Europe and Japan, may imply that clustered occurrence is important in some regions. However, the regions likely to suffer clustered eruption-earthquake activity have not been systematically identified, and the processes responsible for the observed interaction are debated. We first review previous works about the correlation of volcanic eruptions and earthquakes, and describe selected local clustered events. Following an overview of previous statistical studies, we further elaborate the databases of correlated eruptions and earthquakes from a global perspective. Since we can confirm a relationship between volcanic eruptions and earthquakes on the global scale, we then perform a statistical study on the regional level, showing that time and distance between events follow a linear relationship. In the time before an earthquake, a period of volcanic silence often occurs, whereas in the time after, an increase in volcanic activity is evident. Our statistical tests imply that certain regions are especially predisposed to concurrent eruption-earthquake pairs, e.g., Japan, whereas such pairing is statistically less significant in other regions, such as Europe. Based on this study, we argue that individual and selected observations may bias the perceptible weight of coupling. Volcanoes located in the predisposed regions (e.g., Japan, Indonesia, Melanesia), however, indeed often have unexpectedly changed in association with either an imminent or a past earthquake.

  16. Significance of Neuronal Cytochrome P450 Activity in Opioid-Mediated Stress-Induced Analgesia

    PubMed Central

    Hough, Lindsay B.; Nalwalk, Julia W.; Yang, Weizhu; Ding, Xinxin

    2014-01-01

    Stressful environmental changes can suppress nociceptive transmission, a phenomenon known as “stress-induced analgesia”. Depending on the stressor and the subject, opioid or non-opioid mechanisms are activated. Brain μ opioid receptors mediate analgesia evoked either by exogenous agents (e.g. morphine), or by the release of endogenous opioids following stressful procedures. Recent work with morphine and neuronal cytochrome P450 (P450)-deficient mice proposed a signal transduction role for P450 enzymes in μ analgesia. Since μ opioid receptors also mediate some forms of stress-induced analgesia, the present studies assessed the significance of brain P450 activity in opioid-mediated stress-induced analgesia. Two widely-used models of opioid stress-induced analgesia (restraint and warm water swim) were studied in both sexes of wild-type control and P450-deficient (Null) mice. In control mice, both stressors evoked moderate analgesic responses which were blocked by pretreatment with the opioid antagonist naltrexone, confirming the opioid nature of these responses. Consistent with literature, sex differences (control female > control male) were seen in swim-induced, but not restraint-induced, analgesia. Null mice showed differential responses to the two stress paradigms. As compared with control subjects, Null mice showed highly attenuated restraint-induced analgesia, showing a critical role for neuronal P450s in this response. However, warm water swim-induced analgesia was unchanged in Null vs. control mice. Additional control experiments confirmed the absence of morphine analgesia in Null mice. These results are the first to show that some forms of opioid-mediated stress-induced analgesia require brain neuronal P450 activity. PMID:25020125

  17. Villin severing activity enhances actin-based motility in vivo.

    PubMed

    Revenu, Céline; Courtois, Matthieu; Michelot, Alphée; Sykes, Cécile; Louvard, Daniel; Robine, Sylvie

    2007-03-01

    Villin, an actin-binding protein associated with the actin bundles that support microvilli, bundles, caps, nucleates, and severs actin in a calcium-dependant manner in vitro. We hypothesized that the severing activity of villin is responsible for its reported role in enhancing cell plasticity and motility. To test this hypothesis, we chose a loss of function strategy and introduced mutations in villin based on sequence comparison with CapG. By pyrene-actin assays, we demonstrate that this mutant has a strongly reduced severing activity, whereas nucleation and capping remain unaffected. The bundling activity and the morphogenic effects of villin in cells are also preserved in this mutant. We thus succeeded in dissociating the severing from the three other activities of villin. The contribution of villin severing to actin dynamics is analyzed in vivo through the actin-based movement of the intracellular bacteria Shigella flexneri in cells expressing villin and its severing variant. The severing mutations abolish the gain of velocity induced by villin. To further analyze this effect, we reconstituted an in vitro actin-based bead movement in which the usual capping protein is replaced by either the wild type or the severing mutant of villin. Confirming the in vivo results, villin-severing activity enhances the velocity of beads by more than two-fold and reduces the density of actin in the comets. We propose a model in which, by severing actin filaments and capping their barbed ends, villin increases the concentration of actin monomers available for polymerization, a mechanism that might be paralleled in vivo when an enterocyte undergoes an epithelio-mesenchymal transition.

  18. Villin Severing Activity Enhances Actin-based Motility In Vivo

    PubMed Central

    Revenu, Céline; Courtois, Matthieu; Michelot, Alphée; Sykes, Cécile; Louvard, Daniel

    2007-01-01

    Villin, an actin-binding protein associated with the actin bundles that support microvilli, bundles, caps, nucleates, and severs actin in a calcium-dependant manner in vitro. We hypothesized that the severing activity of villin is responsible for its reported role in enhancing cell plasticity and motility. To test this hypothesis, we chose a loss of function strategy and introduced mutations in villin based on sequence comparison with CapG. By pyrene-actin assays, we demonstrate that this mutant has a strongly reduced severing activity, whereas nucleation and capping remain unaffected. The bundling activity and the morphogenic effects of villin in cells are also preserved in this mutant. We thus succeeded in dissociating the severing from the three other activities of villin. The contribution of villin severing to actin dynamics is analyzed in vivo through the actin-based movement of the intracellular bacteria Shigella flexneri in cells expressing villin and its severing variant. The severing mutations abolish the gain of velocity induced by villin. To further analyze this effect, we reconstituted an in vitro actin-based bead movement in which the usual capping protein is replaced by either the wild type or the severing mutant of villin. Confirming the in vivo results, villin-severing activity enhances the velocity of beads by more than two-fold and reduces the density of actin in the comets. We propose a model in which, by severing actin filaments and capping their barbed ends, villin increases the concentration of actin monomers available for polymerization, a mechanism that might be paralleled in vivo when an enterocyte undergoes an epithelio-mesenchymal transition. PMID:17182858

  19. Effects of glucose on the performance of enhanced biological phosphorus removal activated sludge enriched with acetate.

    PubMed

    Gebremariam, Seyoum Yami; Beutel, Marc W; Christian, David; Hess, Thomas F

    2012-10-01

    The effects of glucose on enhanced biological phosphorus removal (EBPR) activated sludge enriched with acetate was investigated using sequencing batch reactors. A glucose/acetate mixture was serially added to the test reactor in ratios of 25/75%, 50/50%, and 75/25% and the EBPR activity was compared to the control reactor fed with 100% acetate. P removal increased at a statistically significant level to a near-complete in the test reactor when the mixture increased to 50/50%. However, EBPR deteriorated when the glucose/acetate mixture increased to 75/25% in the test reactor and when the control reactor abruptly switched to 100% glucose. These results, in contrast to the EBPR conventional wisdom, suggest that the addition of glucose at moderate levels in wastewaters does not impede and may enhance EBPR, and that glucose waste products should be explored as an economical sustainable alternative when COD enhancement of EBPR is needed.

  20. The Lipid Portion of Activated Platelet-Rich Plasma Significantly Contributes to Its Wound Healing Properties

    PubMed Central

    Hoeferlin, Lauren Alexis; Huynh, Quoc K.; Mietla, Jennifer A.; Sell, Scott A.; Tucker, Jason; Chalfant, Charles Edward; Wijesinghe, Dayanjan Shanaka

    2015-01-01

    Objective: Platelet-rich plasma (PRP) is a popular choice for the treatment of chronic wounds. Current dogma attributes these healing properties to the peptide growth factors of PRP. However, PRP is also rich in bioactive lipids whose contribution to healing has not been characterized and warrants investigation due to the protease-rich environment of chronic wounds. Approach: The lipid fraction of PRP was tested with respect to proliferation and migration of primary adult human dermal fibroblasts (HDFa)±exposure to chronic wound fluid (CWF). This fraction was also characterized via LC-MS/MS for bioactive lipids. A synthetic formulation of the bioactive lipid composition was developed and tested for the ability to overcome proliferative growth arrest induced by CWF. Results: The data demonstrate the ability of the lipid fraction of PRP to significantly enhance the migration and proliferation of HDFa, and to overcome the proliferative growth arrest induced by CWF. Furthermore, the synthetic lipid formulation generated following characterization of the PRP lipidome demonstrated a similar ability to overcome proliferative arrest of HDFa in the presence of CWF. Innovation: For the first time, we demonstrate the relevance of the lipid fraction of PRP toward the biology of wound healing. These studies open the possibility of altering the lipid profile of PRP via diet or exogenous pathway manipulation to obtain a better healing outcome. Conclusion: The lipid fraction of PRP is under investigated and yet relevant component in wound healing. The current study demonstrates the relevance of this fraction in wound healing by PRP. PMID:25713752

  1. Significant enhancement of compositional and superconducting homogeneity in Ti rather than Ta-doped Nb3Sn

    DOE PAGES

    Tarantini, C.; Sung, Z. -H.; Lee, P. J.; ...

    2016-01-25

    Nb3Sn wires are now very close to their final optimization but despite its classical nature, detailed understanding of the role of Ta and Ti doping in the A15 is not fully understood. Long thought to be essentially equivalent in their influence on Hc2, they were interchangeably applied. Here we show that Ti produces significantly more homogeneous chemical and superconducting properties. Despite Ta-doped samples having a slightly higher Tc onset in zero-field, they always have a wider Tc-distribution. In particular, whereas the Ta-doped A15 has a Tc-distribution extending from 18 down to 5-6 K (the lowest expected Tc for the binarymore » A15 phase), the Ti-doped samples have no A15 phase with Tc below ~12 K. The much narrower Tc distribution in the Ti-doped samples has a positive effect on their in-field Tc-distribution too, leading to an extrapolated μ0Hc2(0) 2 Tesla larger than the Ta-doped one. Ti-doping also appears to be very homogeneous even when the Sn content is reduced in order to inhibit breakdown of the diffusion barriers in very high Jc conductors. As a result, the enhanced homogeneity of the Ti-doped samples appears to result from its assistance of rapid diffusion of Sn into the filaments and by its incorporation into the A15 phase interchangeably with Sn on the Sn sites of the A15 phase.« less

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

    PubMed Central

    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

  3. Acellular Bone Marrow Extracts Significantly Enhance Engraftment Levels of Human Hematopoietic Stem Cells in Mouse Xeno-Transplantation Models

    PubMed Central

    Zibara, Kazem; Hamdan, Rima; Dib, Leila; Sindet-Pedersen, Steen; Kharfan-Dabaja, Mohamed; Bazarbachi, Ali; El-Sabban, Marwan

    2012-01-01

    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. PMID:22768336

  4. Active medulloblastoma enhancers reveal subgroup-specific cellular origins.

    PubMed

    Lin, Charles Y; Erkek, Serap; Tong, Yiai; Yin, Linlin; Federation, Alexander J; Zapatka, Marc; Haldipur, Parthiv; Kawauchi, Daisuke; Risch, Thomas; Warnatz, Hans-Jörg; Worst, Barbara C; Ju, Bensheng; Orr, Brent A; Zeid, Rhamy; Polaski, Donald R; Segura-Wang, Maia; Waszak, Sebastian M; Jones, David T W; Kool, Marcel; Hovestadt, Volker; Buchhalter, Ivo; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Gröschel, Stefan; Ryzhova, Marina; Korshunov, Andrey; Chen, Wenbiao; Chizhikov, Victor V; Millen, Kathleen J; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure; Eils, Roland; Lichter, Peter; Korbel, Jan O; Pfister, Stefan M; Bradner, James E; Northcott, Paul A

    2016-02-04

    Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Here, using H3K27ac and BRD4 chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-seq, that is responsible for subgroup divergence, and implicates candidate cells of origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins.

  5. Active medulloblastoma enhancers reveal subgroup-specific cellular origins

    PubMed Central

    Lin, Charles Y.; Erkek, Serap; Tong, Yiai; Yin, Linlin; Federation, Alexander J.; Zapatka, Marc; Haldipur, Parthiv; Kawauchi, Daisuke; Risch, Thomas; Warnatz, Hans-Jörg; Worst, Barbara C.; Ju, Bensheng; Orr, Brent A.; Zeid, Rhamy; Polaski, Donald R.; Segura-Wang, Maia; Waszak, Sebastian M.; Jones, David T.W.; Kool, Marcel; Hovestadt, Volker; Buchhalter, Ivo; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Gröschel, Stefan; Ryzhova, Marina; Korshunov, Andrey; Chen, Wenbiao; Chizhikov, Victor V.; Millen, Kathleen J.; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure; Eils, Roland; Lichter, Peter; Korbel, Jan O.; Pfister, Stefan M.; Bradner, James E.; Northcott, Paul A.

    2016-01-01

    Summary Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Using H3K27ac and BRD4 ChIP-Seq, coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-Seq, that are responsible for subgroup divergence and implicate candidate cells-of-origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins. PMID:26814967

  6. Stobadine pretreatment enhances glutathione peroxidase activity in the heart of irradiated mice.

    PubMed

    Kováciková, Z; Chorvatovicová, D; Ginter, E

    1997-05-01

    The effect of pretreatment with stobadine (a novel drug with cardioprotective properties) on the activity of glutathione peroxidase was studied in the heart of mice after Co60 irradiation. Exposure to 6.5 Gy caused significant decrease in the activity of the enzyme (p < 0.01). Treatment with stobadine (70.07 mg/kg) 1 or 2 h before irradiation resulted in activity enhancement in comparison with the nonpretreated irradiated group (p < 0.01). We conclude that the radical scavenging mechanism may be involved in the protection exerted by stobadine. The results are in agreement with those obtained by the micronucleus test.

  7. Psychopaths Show Enhanced Amygdala Activation during Fear Conditioning.

    PubMed

    Schultz, Douglas H; Balderston, Nicholas L; Baskin-Sommers, Arielle R; Larson, Christine L; Helmstetter, Fred J

    2016-01-01

    Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into "primary" and "secondary" psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional "fearlessness," while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC) for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths.

  8. Psychopaths Show Enhanced Amygdala Activation during Fear Conditioning

    PubMed Central

    Schultz, Douglas H.; Balderston, Nicholas L.; Baskin-Sommers, Arielle R.; Larson, Christine L.; Helmstetter, Fred J.

    2016-01-01

    Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into “primary” and “secondary” psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional “fearlessness,” while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC) for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths. PMID:27014154

  9. Significant bone microarchitecture impairment in premenopausal women with active celiac disease.

    PubMed

    Zanchetta, María Belén; Costa, Florencia; Longobardi, Vanesa; Longarini, Gabriela; Mazure, Roberto Martín; Moreno, María Laura; Vázquez, Horacio; Silveira, Fernando; Niveloni, Sonia; Smecuol, Edgardo; Temprano, María de la Paz; Hwang, Hui Jer; González, Andrea; Mauriño, Eduardo César; Bogado, Cesar; Zanchetta, Jose R; Bai, Julio César

    2015-07-01

    Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had

  10. Enhancement of activated sludge disintegration and dewaterability by Fenton process

    NASA Astrophysics Data System (ADS)

    Heng, G. C.; Isa, M. H.

    2016-06-01

    Municipal and industrial wastewater treatment plants produce large amounts of sludge. This excess sludge is an inevitable drawback inherent to the activated sludge process. In this study, the waste activated sludge was obtained from the campus wastewater treatment plant at Universiti Teknologi PETRONAS (UTP), Malaysia. Fenton pretreatment was optimized by using the response surface methodology (RSM) to study the effects of three operating conditions including the dosage of H2O2 (g H2O2/kg TS), the molar ratio of H2O2/Fe2+ and reaction time. The optimum operating variables to achieve MLVSS removal 65%, CST reduction 28%, sCOD 11000 mg/L and EPS 500 mg/L were: 1000 g H2O2/kg TS, H2O2/Fe2+ molar ratio 70 and reaction time 45 min. Fenton process was proved to be able to enhance the sludge disintegration and dewaterability.

  11. Enhanced photocatalytic activity of ZnO nanotetrapods

    NASA Astrophysics Data System (ADS)

    Wan, Q.; Wang, T. H.; Zhao, J. C.

    2005-08-01

    The photocatalytic characteristics of the tetrapod-branched ZnO nanostructures synthesized by thermal evaporation method are investigated. The fitting of absorbance maximum plot versus time indicates an exponential decay, suggesting the photodegradation of Rhodamine B catalyzed by the ZnO nanotetrapod is a pseudo first-order reaction. These results demonstrate that the photocatalytic activity of ZnO nanotetrapod is much better than that of P25 TiO2 and ZnO powders. The slow electron/hole recombine rate due to the abundant surface states, as well as the high surface-to-volume ratio will effectively enhance the photocatalytic activity of the ZnO nanotetrapod.

  12. Carbon Nanotube Materials for Substrate Enhanced Control of Catalytic Activity

    SciTech Connect

    Heben, M.; Dillon, A. C.; Engtrakul, C.; Lee, S.-H.; Kelley, R. D.; Kini, A. M.

    2007-05-01

    Carbon SWNTs are attractive materials for supporting electrocatalysts. The properties of SWNTs are highly tunable and controlled by the nanotube's circumferential periodicity and their surface chemistry. These unique characteristics suggest that architectures constructed from these types of carbon support materials would exhibit interesting and useful properties. Here, we expect that the structure of the carbon nanotube support will play a major role in stabilizing metal electrocatalysts under extreme operating conditions and suppress both catalyst and support degradation. Furthermore, the chemical modification of the carbon nanotube surfaces can be expected to alter the interface between the catalyst and support, thus, enhancing the activity and utilization of the electrocatalysts. We plan to incorporate discrete reaction sites into the carbon nanotube lattice to create intimate electrical contacts with the catalyst particles to increase the metal catalyst activity and utilization. The work involves materials synthesis, design of electrode architectures on the nanoscale, control of the electronic, ionic, and mass fluxes, and use of advanced optical spectroscopy techniques.

  13. Neuronal activity enhances tau propagation and tau pathology in vivo.

    PubMed

    Wu, Jessica W; Hussaini, S Abid; Bastille, Isle M; Rodriguez, Gustavo A; Mrejeru, Ana; Rilett, Kelly; Sanders, David W; Cook, Casey; Fu, Hongjun; Boonen, Rick A C M; Herman, Mathieu; Nahmani, Eden; Emrani, Sheina; Figueroa, Y Helen; Diamond, Marc I; Clelland, Catherine L; Wray, Selina; Duff, Karen E

    2016-08-01

    Tau protein can transfer between neurons transneuronally and trans-synaptically, which is thought to explain the progressive spread of tauopathy observed in the brain of patients with Alzheimer's disease. Here we show that physiological tau released from donor cells can transfer to recipient cells via the medium, suggesting that at least one mechanism by which tau can transfer is via the extracellular space. Neuronal activity has been shown to regulate tau secretion, but its effect on tau pathology is unknown. Using optogenetic and chemogenetic approaches, we found that increased neuronal activity stimulates the release of tau in vitro and enhances tau pathology in vivo. These data have implications for disease pathogenesis and therapeutic strategies for Alzheimer's disease and other tauopathies.

  14. Enhanced CCR5+/CCR3+ T helper cell ratio in patients with active cutaneous lupus erythematosus.

    PubMed

    Freutel, S; Gaffal, E; Zahn, S; Bieber, T; Tüting, T; Wenzel, J

    2011-10-01

    Cutaneous lupus erythematosus (CLE) is characterized by enhanced interferon α (IFNα) levels in serum and in tissue. Since IFNα promotes a Th1-biased immune response, we hypothesized that a Th1-associated chemokine receptor profile should be a typical finding in patients with active CLE. Therefore, peripheral blood mononuclear cells were isolated from patients with different CLE subsets (n = 15), healthy controls (n = 13) and patients under immunotherapy with IFNα (n = 7). T helper cells were analysed by flow cytometry for the expression of the chemokines receptor CCR5, indicative for Th1 cells, and of CCR3, indicating Th2. In addition, intracellular levels of the type I IFN-inducible MxA protein were measured. Patients with widespread active CLE skin lesions had a significantly increased expression of CCR5, whereas expression of CCR3 was decreased when compared with healthy controls. MxA expression was significantly enhanced in all investigated CLE subtypes, with the highest levels in patients with widespread skin lesions. The enhanced CCR5/CCR3 ratio closely correlated with the MxA levels in peripheral lymphocytes and with disease activity. Our analyses revealed that active CLE is associated with a systemic type I IFN effect that appears to induce a shift towards a Th1-associated chemokine receptor profile. The CCR5/CCR3 T-helper cell ratio might therefore represent an indirect marker for the disease activity in CLE.

  15. Carbamazepine enhances the activity of glutamate transporter type 3 via phosphatidylinositol 3-kinase.

    PubMed

    Lee, Gwanwoo; Huang, Yueming; Washington, Jacqueline M; Briggs, Nicole W; Zuo, Zhiyi

    2005-01-01

    Glutamate transporters (also called excitatory amino acid transporters, EAAT) participate in maintaining extracellular homeostasis of glutamate, a major excitatory neurotransmitter, and regulating glutamate neurotransmission. EAAT3, the major neuronal EAAT, may also regulate gamma-aminobutyric acid-mediated inhibitory neurotransmission. Dysfunction of EAAT3 has been shown to induce seizure in rats. We hypothesize that carbamazepine, a commonly used antiepileptic agent, enhances EAAT3 activity. We tested this hypothesis using oocytes artificially expressing EAAT3 and C6 rat glioma cells expressing endogenous EAAT3. In oocytes, carbamazepine dose-dependently enhanced EAAT3 activity. The EC50 of this carbamazepine effect was 12.2muM. The concentrations of carbamazepine to significantly enhance EAAT3 activity were within the therapeutic serum levels (17-51muM) of carbamazepine for the antiepileptic effect. Carbamazepine decreased the Km but did not change the maximal response of EAAT3 to glutamate. Carbamazepine-increased EAAT3 activity was inhibited by wortmannin or LY-294002, phosphatidylinositol 3-kinase (PI3K) inhibitors, but was not affected by staurosporine, chelerythrine or calphostin C, protein kinase C inhibitors. In C6 cells, carbamazepine also enhanced the endogenous EAAT3 activity. However, carbamazepine did not affect the activity of EAAT4 expressed in Cos7 cells. These results suggest that carbamazepine at clinically relevant concentrations specifically enhances the affinity of EAAT3 for glutamate to increase EAAT3 activity via a PI3K-dependent pathway. EAAT3 may be a therapeutic target for carbamazepine in the central nervous system.

  16. Silver enhances antibiotic activity against gram-negative bacteria.

    PubMed

    Morones-Ramirez, Jose Ruben; Winkler, Jonathan A; Spina, Catherine S; Collins, James J

    2013-06-19

    A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.

  17. Enhancing Academic Engagement in Knowledge Transfer Activity in the UK

    ERIC Educational Resources Information Center

    Francis-Smythe, Jan

    2008-01-01

    There has been an increasing call in the UK over the last decade for universities to become more entrepreneurial with a strengthening of university and industry/community links to contribute more significantly to the knowledge economy., and for UK higher education institutions (HEIs) to consider ways in which they can more actively engage in…

  18. Metallic MoO₂ cocatalyst significantly enhances visible-light photocatalytic hydrogen production over Mo₂/Zn₀.₅Cd₀.₅S heterojunction.

    PubMed

    Du, Hong; Xie, Xiao; Zhu, Qing; Lin, Ling; Jiang, Yi-Fan; Yang, Zheng-Kun; Zhou, Xiao; Xu, An-Wu

    2015-03-19

    As semiconductor-based nanoheterostructures play a decisive role in current electronics and optoelectronics, the introduction of active heterojunctions can afford new and improved capabilities that will enhance the conversion of solar energy into chemical energy. In this work, a novel metal/semiconductor MoO₂/Zn₀.₅Cd₀.₅S heterojunction has been designed and prepared to significantly enhance photocatalytic H₂ production efficiency. The photocatalytic activity of the as-prepared MoO₂/Zn₀.₅Cd₀.₅S for H₂ generation from water under visible-light irradiation (λ ≥ 420 nm) is measured. MoO₂/Zn₀.₅Cd₀.₅S hybrid nanoparticles have a higher photocatalytic activity than Zn₀.₅Cd₀.₅S even without the noble metal cocatalyst. The results show that the rate of H₂ evolution over annealed MoO₂/Zn₀.₅Cd₀.₅S is about 13 times higher than that of Zn₀.₅Cd₀.₅S alone, and 10 times higher than that of simply mixed MoO₂/Zn₀.₅Cd₀.₅S. Implying that the strong coupling at the interface of MoO₂ and Zn₀.₅Cd₀.₅S facilitates electron transfer from the conduction band of Zn₀.₅Cd₀.₅S to metallic MoO₂, thus promoting the separation of photogenerated electrons and holes. MoO₂ (2 wt%)/Zn₀.₅Cd₀.₅S heterostructured photocatalyst calcined at 673 K achieves the optimal overall activity for H₂ evolution. The introduction of metallic MoO₂ cocatalyst leads to a remarkable improvement in the photo current and photocatalytic H₂ production activity of Zn₀.₅Cd₀.₅S, and the content of MoO₂ in this catalyst has an important influence on the photocatalytic activity. It is shown that 2 wt% metallic MoO₂ loaded on Zn₀.₅Cd₀.₅S sample produces a maximum photocatalytic H₂ production rate of 252.4 μmol h(-1). The junctions formed between metallic MoO₂ and semiconductor Zn₀.₅Cd₀.₅S by calcination play a key role in high photocatalytic water splitting to produce H₂. Our study

  19. Treatment of activated carbon to enhance catalytic activity for reduction of nitric oxide with ammonia

    SciTech Connect

    Ku, B.J.; Rhee, H.K. . Dept. of Chemical Engineering); Lee, J.K.; Park, D. )

    1994-11-01

    Catalytic activity of activated carbon treated with various techniques was examined in a fixed bed reactor for the reduction of nitric oxide with ammonia at 150 C. Activated carbon derived from coconut shell impregnated with an aqueous solution of ammonium sulfate, further treated with sulfuric acid, dried at 120 C, and then heated in an inert gas stream at 400 C, showed the highest catalytic activity within the range of experimental conditions. The enhancement of catalytic activity of modified activated carbon could be attributed to the increase in the amount of oxygen function groups which increased the adsorption site for ammonia. Catalytic activity of activated carbons depended on the surface area and the oxygen content as well.

  20. Enhanced Cholinergic Activity Improves Cerebral Blood Flow during Orthostatic Stress

    PubMed Central

    Serrador, Jorge M.; Freeman, Roy

    2017-01-01

    Cerebral blood flow (CBF) and consequently orthostatic tolerance when upright depends on dilation of the cerebral vasculature in the face of reduced perfusion pressure associated with the hydrostatic gradient. However, it is still unclear if cholinergic activation plays a role in this dilation. To determine if enhancing central cholinergic activity with the centrally acting acetylcholinesterase inhibitor, physostigmine would increase CBF when upright compared to the peripherally acting acetylcholinesterase inhibitor, neostigmine, or saline. We performed a randomized double-blind dose-ranging study that took place over 3 days in a hospital-based research lab. Eight healthy controls (six women and two men, mean age, 26 years; range 21–33) were given infusions of physostigmine, neostigmine, or saline on three different days. Five-minute tilts were repeated at baseline (no infusion), Dose 1 (0.2 μg/kg/min physostigmine; 0.1 μg/kg/min neostigmine) and Dose 2 (0.6 μg/kg/min physostigmine or 0.3 μg/kg/min neostigmine), and placebo (0.9% NaCl). Cerebral blood velocity, beat-to-beat blood pressure, and end-tidal CO2 were continuously measured during tilts. Physostigmine (0.6 μg/kg/min) resulted in higher cerebral blood velocity during tilt (90.5 ± 1.5%) than the equivalent neostigmine (85.5 ± 2.6%) or saline (84.8 ± 1.7%) trials (P < 0.05). This increase occurred despite a greater postural hypocapnia, suggesting physostigmine had a direct vasodilatory effect on the cerebral vasculature. Cerebral hypoperfusion induced by repeated tilts was eliminated by infusion of physostigmine not neostigmine. In conclusion, this study provides the first evidence that enhancement of central, not peripheral, cholinergic activity attenuates the physiological decrease in CBF seen during upright tilt. These data support the need for further research to determine if enhancing central cholinergic activity may improve symptoms in patients with symptomatic

  1. Significant Enhancement of the Chiral Correlation Length in Nematic Liquid Crystals by Gold Nanoparticle Surfaces Featuring Axially Chiral Binaphthyl Ligands.

    PubMed

    Mori, Taizo; Sharma, Anshul; Hegmann, Torsten

    2016-01-26

    surface is diminished as the size of the particle is reduced. However, in comparison to the free ligands, per chiral molecule all tested gold nanoparticles induce helical distortions in a 10- to 50-fold larger number of liquid crystal host molecules surrounding each particle, indicating a significantly enhanced chiral correlation length. We propose that both the helicity and the chirality transfer efficiency of axially chiral binaphthyl derivatives can be controlled at metal nanoparticle surfaces by adjusting the particle size and curvature as well as the number and density of the chiral ligands to ultimately measure and tune the chiral correlation length.

  2. Enhancement of biological activities of nanostructured hydrophobic drug species

    NASA Astrophysics Data System (ADS)

    Han, Qiusen; Yang, Rong; Li, Jingying; Liang, Wei; Zhang, Ying; Dong, Mingdong; Besenbacher, Flemming; Wang, Chen

    2012-03-01

    We report a study of nanoribbons of quercetin, a phase I clinical trial anticancer drug, and their inhibitory effects on cancer cell proliferation. Novel quercetin nanoribbons have been prepared by atmospheric pressure physical vapor deposition (PVD). The nanostructures have been characterized by optical microscopy, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy, etc. Significantly enhanced solubility in PBS solution and increased drug release rate have been observed for quercetin nanoribbons in comparison to those of quercetin powder. The observed increase of inhibitory effects of quercetin nanoribbons on 4T1 cancel cell growth is correlated with an improvement in their solubility and drug release behavior.We report a study of nanoribbons of quercetin, a phase I clinical trial anticancer drug, and their inhibitory effects on cancer cell proliferation. Novel quercetin nanoribbons have been prepared by atmospheric pressure physical vapor deposition (PVD). The nanostructures have been characterized by optical microscopy, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy, etc. Significantly enhanced solubility in PBS solution and increased drug release rate have been observed for quercetin nanoribbons in comparison to those of quercetin powder. The observed increase of inhibitory effects of quercetin nanoribbons on 4T1 cancel cell growth is correlated with an improvement in their solubility and drug release behavior. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr12013e

  3. Seasonal activity of millipedes (Diplopoda)--their economic and medical significance.

    PubMed

    Kania, Grzegorz; Kłapeć, Teresa

    2012-01-01

    The millipede Brachydesmus superus Latzel, Polydesmus inconstans Latzel (Diplopoda: Polydesmida) and Kryphioiulus occultus C. L. Koch (Diplopoda: Julida) were collected from compost in gardens in Lublin, eastern Poland. Collections were made by using pitfall traps between April - September 2009 and 2010. Brachydesmus superus, Polydesmus inconstans and Kryphioiulus occultus play a significant role in composting of plant residues. Cylindroiulus caeruleocinctus Wood and Ommatoiulus sabulosus Linnaeus (Diplopoda: Julida) were collected manually in 2009-2011 in fallows and ruderals of Lublin and Kraków. C. caeruleocinctus and O. sabulosus caused considerable nuisance during mass occurrence and migration in human residences. The sex ratio has been determined for populations of C. caeruleocinctus, total sex ratio average 1:1.46. The number of females prevailed. Millipedes of the temperate climate have two peaks in the spring and autumn pattern of activity of the year. Both common species C. caeruleocinctus and O. sabulosus were analysed bacteriologically. The millipede Cylindroiulus caeruleocinctus transmits Citrobacter freundii, Pantoea agglomerans, Serratia marcescens, Raoultella planticola, Salmonella arizonae. The millipede Ommatoiulus sabulosus transmits Citrobacter freundii, Pantoea agglomerans, Raoultella planticola and Xanthomonas maltophila.

  4. Novel pyrazole derivatives as neutral CB₁ antagonists with significant activity towards food intake.

    PubMed

    Manca, Ilaria; Mastinu, Andrea; Olimpieri, Francesca; Falzoi, Matteo; Sani, Monica; Ruiu, Stefania; Loriga, Giovanni; Volonterio, Alessandro; Tambaro, Simone; Bottazzi, Mirko Emilio Heiner; Zanda, Matteo; Pinna, Gérard Aimè; Lazzari, Paolo

    2013-04-01

    In spite of rimonabant's withdrawal from the European market due to its adverse effects, interest in the development of drugs based on CB1 antagonists is revamping on the basis of the peculiar properties of this class of compounds. In particular, new strategies have been proposed for the treatment of obesity and/or related risk factors through CB1 antagonists, i.e. by the development of selectively peripherally acting agents or by the identification of neutral CB1 antagonists. New compounds based on the lead CB1 antagonist/inverse agonist rimonabant have been synthesized with focus on obtaining neutral CB1 antagonists. Amongst the new derivatives described in this paper, the mixture of the two enantiomers (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-(2-cyclohexyl-1-hydroxyethyl)-4-methyl-1H-pyrazole ((±)-5), and compound 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-[(Z)-2-cyclohexyl-1-fluorovinyl]-4-methyl-1H-pyrazole ((Z)-6), showed interesting pharmacological profiles. According to the preliminary pharmacological evaluation, these novel pyrazole derivatives showed in fact both neutral CB1 antagonism behaviour and significant in vivo activity towards food intake.

  5. Activated Protein C Enhances Human Keratinocyte Barrier Integrity via Sequential Activation of Epidermal Growth Factor Receptor and Tie2*

    PubMed Central

    Xue, Meilang; Chow, Shu-Oi; Dervish, Suat; Chan, Yee-Ka Agnes; Julovi, Sohel M.; Jackson, Christopher J.

    2011-01-01

    Keratinocytes play a critical role in maintaining epidermal barrier function. Activated protein C (APC), a natural anticoagulant with anti-inflammatory and endothelial barrier protective properties, significantly increased the barrier impedance of keratinocyte monolayers, measured by electric cell substrate impedance sensing and FITC-dextran flux. In response to APC, Tie2, a tyrosine kinase receptor, was rapidly activated within 30 min, and relocated to cell-cell contacts. APC also increased junction proteins zona occludens, claudin-1 and VE-cadherin. Inhibition of Tie2 by its peptide inhibitor or small interfering RNA abolished the barrier protective effect of APC. Interestingly, APC did not activate Tie2 through its major ligand, angiopoietin-1, but instead acted by binding to endothelial protein C receptor, cleaving protease-activated receptor-1 and transactivating EGF receptor. Furthermore, when activation of Akt, but not ERK, was inhibited, the barrier protective effect of APC on keratinocytes was abolished. Thus, APC activates Tie2, via a mechanism requiring, in sequential order, the receptors, endothelial protein C receptor, protease-activated receptor-1, and EGF receptor, which selectively enhances the PI3K/Akt signaling to enhance junctional complexes and reduce keratinocyte permeability. PMID:21173154

  6. Enhanced purity, activity and structural integrity of yeast ribosomes purified using a general chromatographic method.

    PubMed

    Leshin, Jonathan A; Rakauskaitė, Rasa; Dinman, Jonathan D; Meskauskas, Arturas

    2010-01-01

    One of the major challenges facing researchers working with eukaryotic ribosomes lies in their lability relative to their eubacterial and archael counterparts. In particular, lysis of cells and purification of eukaryotic ribosomes by conventional differential ultracentrifugation methods exposes them for long periods of time to a wide range of co-purifying proteases and nucleases, negatively impacting their structural integrity and functionality. A chromatographic method using a cysteine charged Sulfolink resin was adapted to address these problems. This fast and simple method significantly reduces co-purifying proteolytic and nucleolytic activities, producing good yields of highly biochemically active yeast ribosomes with fewer nicks in their rRNAs. In particular, the chromatographic purification protocol significantly improved the quality of ribosomes isolated from mutant cells. This method is likely applicable to mammalian ribosomes as well. The simplicity of the method, and the enhanced purity and activity of chromatographically purified ribosome represents a significant technical advancement for the study of eukaryotic ribosomes.

  7. Non-ionic surfactant vesicles simultaneously enhance antitumor activity and reduce the toxicity of cantharidin

    PubMed Central

    Han, Wei; Wang, Shengpeng; Liang, Rixin; Wang, Lan; Chen, Meiwan; Li, Hui; Wang, Yitao

    2013-01-01

    Objective The objective of the present study was to prepare cantharidin-entrapped non-ionic surfactant vesicles (CTD-NSVs) and evaluate their potential in enhancing the antitumor activities and reducing CTD’s toxicity. Methods and results CTD-NSVs were prepared by injection method. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry analysis showed that CTD-NSVs could significantly enhance in vitro toxicity against human breast cancer cell line MCF-7 and induce more significant cell-cycle arrest in G0/G1 phase. Moreover, Hoechst 33342 staining implicated that CTD-NSVs induced higher apoptotic rates in MCF-7 cells than free CTD solution. In vivo therapeutic efficacy was investigated in imprinting control region mice bearing mouse sarcoma S180. Mice treated with 1.0 mg/kg CTD-NSVs showed the most powerful antitumor activity, with an inhibition rate of 52.76%, which was significantly higher than that of cyclophosphamide (35 mg/kg, 40.23%) and the same concentration of free CTD (1.0 mg/kg, 31.05%). In addition, the acute toxicity and liver toxicity of CTD were also distinctly decreased via encapsulating into NSVs. Conclusion Our results revealed that NSVs could be a promising delivery system for enhancing the antitumor activity and simultaneously reducing the toxicity of CTD. PMID:23807847

  8. CNTF-Treated Astrocyte Conditioned Medium Enhances Large-Conductance Calcium-Activated Potassium Channel Activity in Rat Cortical Neurons.

    PubMed

    Sun, Meiqun; Liu, Hongli; Xu, Huanbai; Wang, Hongtao; Wang, Xiaojing

    2016-08-01

    Seizure activity is linked to astrocyte activation as well as dysfunctional cortical neuron excitability produced from changes in calcium-activated potassium (KCa) channel function. Ciliary neurotrophic factor-treated astrocyte conditioned medium (CNTF-ACM) can be used to investigate the peripheral effects of activated astrocytes upon cortical neurons. However, CNTF-ACM's effect upon KCa channel activity in cultured cortical neurons has not yet been investigated. Whole-cell patch clamp recordings were performed in rat cortical neurons to evaluate CNTF-ACM's effects upon charybdotoxin-sensitive large-conductance KCa (BK) channel currents and apamin-sensitive small-conductance KCa (SK) channel current. Biotinylation and RT-PCR were applied to assess CNTF-ACM's effects upon the protein and mRNA expression, respectively, of the SK channel subunits SK2 and SK3 and the BK channel subunits BKα1 and BKβ3. An anti-fibroblast growth factor-2 (FGF-2) monoclonal neutralizing antibody was used to assess the effects of the FGF-2 component of CNTF-ACM. CNTF-ACM significantly increased KCa channel current density, which was predominantly attributable to gains in BK channel activity (p < 0.05). CNTF-ACM produced a significant increase in BKα1 and BKβ3 expression (p < 0.05) but had no significant effect upon SK2 or SK3 expression (p > 0.05). Blocking FGF-2 produced significant reductions in KCa channel current density (p > 0.05) as well as BKα1 and BKβ3 expression in CNTF-ACM-treated neurons (p > 0.05). CNTF-ACM significantly enhances BK channel activity in rat cortical neurons and that FGF-2 is partially responsible for these effects. CNTF-induced astrocyte activation results in secretion of neuroactive factors which may affect neuronal excitability and resultant seizure activity in mammalian cortical neurons.

  9. Constitutive adipocyte mTORC1 activation enhances mitochondrial activity and reduces visceral adiposity in mice.

    PubMed

    Magdalon, Juliana; Chimin, Patricia; Belchior, Thiago; Neves, Rodrigo X; Vieira-Lara, Marcel A; Andrade, Maynara L; Farias, Talita S; Bolsoni-Lopes, Andressa; Paschoal, Vivian A; Yamashita, Alex S; Kowaltowski, Alicia J; Festuccia, William T

    2016-05-01

    Mechanistic target of rapamycin complex 1 (mTORC1) loss of function reduces adiposity whereas partial mTORC1 inhibition enhances fat deposition. Herein we evaluated how constitutive mTORC1 activation in adipocytes modulates adiposity in vivo. Mice with constitutive mTORC1 activation in adipocytes induced by tuberous sclerosis complex (Tsc)1 deletion and littermate controls were evaluated for body mass, energy expenditure, glucose and fatty acid metabolism, mitochondrial function, mRNA and protein contents. Adipocyte-specific Tsc1 deletion reduced visceral, but not subcutaneous, fat mass, as well as adipocyte number and diameter, phenotypes that were associated with increased lipolysis, UCP-1 content (browning) and mRNA levels of pro-browning transcriptional factors C/EBPβ and ERRα. Adipocyte Tsc1 deletion enhanced mitochondrial oxidative activity, fatty acid oxidation and the expression of PGC-1α and PPARα in both visceral and subcutaneous fat. In brown adipocytes, however, Tsc1 deletion did not affect UCP-1 content and basal respiration. Adipocyte Tsc1 deletion also reduced visceral adiposity and enhanced glucose tolerance, liver and muscle insulin signaling and adiponectin secretion in mice fed with purified low- or high-fat diet. In conclusion, adipocyte-specific Tsc1 deletion enhances mitochondrial activity, induces browning and reduces visceral adiposity in mice.

  10. Enhanced activities of organically bound tritium in biota samples.

    PubMed

    Svetlik, I; Fejgl, M; Malátová, I; Tomaskova, L

    2014-11-01

    A pilot study aimed on possible occurrence of elevated activity of non-exchangable organically bound tritium (NE-OBT) in biota was performed. The first results showed a significant surplus of NE-OBT activity in biota of the valley of Mohelno reservoir and Jihlava river. The liquid releases of HTO from the nuclear power plant Dukovany is the source of tritium in this area. This area can be a source of various types of natural samples for future studies of tritium pathways.

  11. Enhanced deacidification activity in Schizosaccharomyces pombe by genome shuffling.

    PubMed

    Ding, Su; Zhang, Ying; Zhang, Jing; Zeng, Wei; Yang, Ying; Guan, Jingxi; Pan, Lixia; Li, Wei

    2015-02-01

    A problem frequently occurring in making some kinds of wines, particularly Vitis quinquangularis Rehd wine, is the presence of malic acid at high concentrations, which is detrimental to the quality of wines. Thus, there is a need of the ways for effectively reducing the malic acid levels in wine. This study aimed to generate shuffled fusants of Schizosaccharomyces pombe with enhanced deacidification activity for reducing the excessive malic acid content in wine. Sz. pombe CGMCC 2.1628 was used as the original strain. The starting mutant population was generated by UV treatment. The mutants with higher deacidification activity were selected and subjected to recursive protoplast fusion. The resulting fusants were screened by using the indicator of malic acid concentration of fermentation supernatants on 96-well microtitre plates, measured with bromocresol green. After three rounds of genome shuffling, the best-performing fusant, named GS3-1, was obtained. Its deacidification activity (consumed 4.78 g/l malic acid within 10 days) was increased by 225.2% as compared to that of original strain. In the Vitis quinquangularis Rehd wine fermentation test, GS3-1 consumed 4.0 g/l malic acid during the whole cycle of fermentation, providing up to 185.7% improvement in malic acid consumption compared with that of the original strain. This study shows that GS3-1 has great potential for improving the quality of Vitis quinquangularis Rehd wine.

  12. Enhanced ionospheric plasma bubble generation in more active ITCZ

    NASA Astrophysics Data System (ADS)

    Li, Guozhu; Otsuka, Yuichi; Ning, Baiqi; Abdu, M. A.; Yamamoto, M.; Wan, Weixing; Liu, Libo; Abadi, Prayitno

    2016-03-01

    A close link between the atmospheric Intertropical Convergence Zone (ITCZ) and ionospheric plasma bubble has been proposed since the last century. But this relationship has often appeared to be less than convincing due to the simultaneous roles played by several other factors in shaping the global distribution of ionospheric bubbles. From simultaneous collaborative radar multibeam steering measurements at Kototabang (0.2°S, 100.3°E) and Sanya (18.4°N, 109.6°E), conducted during September-October of 2012 and 2013, we find that the total numbers of nights with bubble (i.e., occurrence rates) at the two closely located longitudes (Kototabang and Sanya) are comparable. But interestingly, the total number of nights with locally generated bubble (i.e., generation rate) over Kototabang is clearly more than that over Sanya. Further analysis reveals that a more active ITCZ is situated around the longitude of Kototabang. We surmise that the enhanced ionospheric bubble generation at Kototabang longitude could be caused by a higher gravity wave activity associated with the more active ITCZ.

  13. Fatty acid conjugation enhances the activities of antimicrobial peptides.

    PubMed

    Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun

    2013-04-01

    Antimicrobial peptides are small molecules that play a crucial role in innate immunity in multi-cellular organisms, and usually expressed and secreted constantly at basal levels to prevent infection, but local production can be augmented upon an infection. The clock is ticking as rising antibiotic abuse has led to the emergence of many drug resistance bacteria. Due to their broad spectrum antibiotic and antifungal activities as well as anti-viral and anti-tumor activities, efforts are being made to develop antimicrobial peptides into future microbial agents. This article describes some of the recent patents on antimicrobial peptides with fatty acid conjugation. Potency and selectivity of antimicrobial peptide can be modulated with fatty acid tails of variable length. Interaction between membranes and antimicrobial peptides was affected by fatty acid conjugation. At concentrations above the critical miscelle concentration (CMC), propensity of solution selfassembly hampered binding of the peptide to cell membranes. Overall, fatty acid conjugation has enhanced the activities of antimicrobial peptides, and occasionally it rendered inactive antimicrobial peptides to be bioactive. Antimicrobial peptides can not only be used as medicine but also as food additives.

  14. Enhancement of immunotoxin activity using chemical and biological reagents.

    PubMed Central

    Wu, M.

    1997-01-01

    One of the major discoveries of effective therapeutics is the use of targeted treatment, such as antibody-directed toxins, i.e. immunotoxins; however, this medicine delivery strategy is still at a developmental stage. A number of problems need to be resolved; one is their inefficacy when applied in vivo. Research has stimulated interest in this area through the use of chemical reagents and other moieties to increase the activity of immunotoxins. In this article, reagents that can potentiate the cytotoxicity of immunotoxins are reviewed and the mechanisms that increase activity of immunotoxins are discussed. Lysosomotropic amines, especially ammonium chloride and chloroquine, may raise the pH value of the lysosome in which the conjugates enter. Carboxylic ionophores, e.g. monensin, can influence Golgi vacuolation, which may facilitate the routing of conjugates, augmenting activity. Calcium channel antagonists may increase immunotoxin killing through morphological or other mechanisms that are not yet well understood. Viral particles and surface structure can enhance the cytotoxicity of conjugates, probably through the mechanism of disrupting endosomes. In addition, cytokines, beta-adrenergic blockers, immunosuppressive agents (cyclosporin A) and some antibiotics (daunorubicin) can be used to increase the effect of immunotoxins. PMID:9155057

  15. Efflux pumps of Mycobacterium tuberculosis play a significant role in antituberculosis activity of potential drug candidates.

    PubMed

    Balganesh, Meenakshi; Dinesh, Neela; Sharma, Sreevalli; Kuruppath, Sanjana; Nair, Anju V; Sharma, Umender

    2012-05-01

    Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. To understand these efflux mechanisms in Mycobacterium tuberculosis, we generated knockout (KO) mutants of four efflux pumps of the pathogen belonging to different classes. We measured the MICs and kill values of two different compound classes on the wild type (WT) and the efflux pump (EP) KO mutants in the presence and absence of the efflux inhibitors verapamil and l-phenylalanyl-l-arginyl-β-naphthylamide (PAβN). Among the pumps studied, the efflux pumps belonging to the ABC (ATP-binding cassette) class, encoded by Rv1218c, and the SMR (small multidrug resistance) class, encoded by Rv3065, appear to play important roles in mediating the efflux of different chemical classes and antibiotics. Efflux pumps encoded by Rv0849 and Rv1258c also mediate the efflux of these compounds, but to a lesser extent. Increased killing is observed in WT M. tuberculosis cells by these compounds in the presence of either verapamil or PAβN. The efflux pump KO mutants were more susceptible to these compounds in the presence of efflux inhibitors. We have shown that these four efflux pumps of M. tuberculosis play a vital role in mediating efflux of different chemical scaffolds. Inhibitors of one or several of these efflux pumps could have a significant impact in the treatment of tuberculosis. The identification and characterization of Rv0849, a new efflux pump belonging to the MFS (major facilitator superfamily) class, are reported.

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

    PubMed Central

    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. Slow-light-enhanced gain in active photonic crystal waveguides.

    PubMed

    Ek, Sara; Lunnemann, Per; Chen, Yaohui; Semenova, Elizaveta; Yvind, Kresten; Mork, Jesper

    2014-09-30

    Passive photonic crystals have been shown to exhibit a multitude of interesting phenomena, including slow-light propagation in line-defect waveguides. It was suggested that by incorporating an active material in the waveguide, slow light could be used to enhance the effective gain of the material, which would have interesting application prospects, for example enabling ultra-compact optical amplifiers for integration in photonic chips. Here we experimentally investigate the gain of a photonic crystal membrane structure with embedded quantum wells. We find that by solely changing the photonic crystal structural parameters, the maximum value of the gain coefficient can be increased compared with a ridge waveguide structure and at the same time the spectral position of the peak gain be controlled. The experimental results are in qualitative agreement with theory and show that gain values similar to those realized in state-of-the-art semiconductor optical amplifiers should be attainable in compact photonic integrated amplifiers.

  18. Autophagic machinery activated by dengue virus enhances virus replication

    SciTech Connect

    Lee, Y.-R.; Lei, H.-Y.; Liu, M.-T.; Wang, J.-R.; Chen, S.-H.; Jiang-Shieh, Y.-F.; Lin, Y.-S.; Yeh, T.-M.; Liu, C.-C.; Liu, H.-S.

    2008-05-10

    Autophagy is a cellular response against stresses which include the infection of viruses and bacteria. We unravel that Dengue virus-2 (DV2) can trigger autophagic process in various infected cell lines demonstrated by GFP-LC3 dot formation and increased LC3-II formation. Autophagosome formation was also observed under the transmission electron microscope. DV2-induced autophagy further enhances the titers of extracellular and intracellular viruses indicating that autophagy can promote viral replication in the infected cells. Moreover, our data show that ATG5 protein is required to execute DV2-induced autophagy. All together, we are the first to demonstrate that DV can activate autophagic machinery that is favorable for viral replication.

  19. Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells

    PubMed Central

    Pu, Yingying; Zhao, Zhilun; Li, Yingxing; Zou, Jin; Ma, Qi; Zhao, Yanna; Ke, Yuehua; Zhu, Yun; Chen, Huiyi; Baker, Matthew A.B.; Ge, Hao; Sun, Yujie; Xie, Xiaoliang Sunney; Bai, Fan

    2016-01-01

    Summary Natural variations in gene expression provide a mechanism for multiple phenotypes to arise in an isogenic bacterial population. In particular, a sub-group termed persisters show high tolerance to antibiotics. Previously, their formation has been attributed to cell dormancy. Here we demonstrate that bacterial persisters, under β-lactam antibiotic treatment, show less cytoplasmic drug accumulation as a result of enhanced efflux activity. Consistently, a number of multi-drug efflux genes, particularly the central component TolC, show higher expression in persisters. Time-lapse imaging and mutagenesis studies further establish a positive correlation between tolC expression and bacterial persistence. The key role of efflux systems, among multiple biological pathways involved in persister formation, indicates that persisters implement a positive defense against antibiotics prior to a passive defense via dormancy. Finally, efflux inhibitors and antibiotics together effectively attenuate persister formation, suggesting a combination strategy to target drug tolerance. PMID:27105118

  20. Active Tailoring of Lift Distribution to Enhance Cruise Performance

    NASA Technical Reports Server (NTRS)

    Flamm, Jeffrey D. (Technical Monitor); Pfeiffer, Neal J.; Christians, Joel G.

    2005-01-01

    During Phase I of this project, Raytheon Aircraft Company (RAC) has analytically and experimentally evaluated key components of a system that could be implemented for active tailoring of wing lift distribution using low-drag, trailing-edge modifications. Simple systems such as those studied by RAC could be used to enhance the cruise performance of a business jet configuration over a range of typical flight conditions. The trailing-edge modifications focus on simple, deployable mechanisms comprised of extendable small flap panels over portions of the span that could be used to subtly but positively optimize the lift and drag characteristics. The report includes results from low speed wind tunnel testing of the trailing-edge devices, descriptions of potential mechanisms for automation, and an assessment of the technology.

  1. Slow-light-enhanced gain in active photonic crystal waveguides

    NASA Astrophysics Data System (ADS)

    Ek, Sara; Lunnemann, Per; Chen, Yaohui; Semenova, Elizaveta; Yvind, Kresten; Mork, Jesper

    2014-09-01

    Passive photonic crystals have been shown to exhibit a multitude of interesting phenomena, including slow-light propagation in line-defect waveguides. It was suggested that by incorporating an active material in the waveguide, slow light could be used to enhance the effective gain of the material, which would have interesting application prospects, for example enabling ultra-compact optical amplifiers for integration in photonic chips. Here we experimentally investigate the gain of a photonic crystal membrane structure with embedded quantum wells. We find that by solely changing the photonic crystal structural parameters, the maximum value of the gain coefficient can be increased compared with a ridge waveguide structure and at the same time the spectral position of the peak gain be controlled. The experimental results are in qualitative agreement with theory and show that gain values similar to those realized in state-of-the-art semiconductor optical amplifiers should be attainable in compact photonic integrated amplifiers.

  2. Shh and ZRS enhancer colocalisation is specific to the zone of polarising activity

    PubMed Central

    Williamson, Iain; Lettice, Laura A.; Hill, Robert E.

    2016-01-01

    Limb-specific Shh expression is regulated by the (∼1 Mb distant) ZRS enhancer. In the mouse, limb bud-restricted spatiotemporal Shh expression occurs from ∼E10 to E11.5 at the distal posterior margin and is essential for correct autopod formation. Here, we have analysed the higher-order chromatin conformation of Shh in expressing and non-expressing tissues, both by fluorescence in situ hybridisation (FISH) and by chromosome conformation capture (5C). Conventional and super-resolution light microscopy identified significantly elevated frequencies of Shh/ZRS colocalisation only in the Shh-expressing regions of the limb bud, in a conformation consistent with enhancer-promoter loop formation. However, in all tissues and at all developmental stages analysed, Shh-ZRS spatial distances were still consistently shorter than those to a neural enhancer located between Shh and ZRS in the genome. 5C identified a topologically associating domain (TAD) over the Shh/ZRS genomic region and enriched interactions between Shh and ZRS throughout E11.5 embryos. Shh/ZRS colocalisation, therefore, correlates with the spatiotemporal domain of limb bud-specific Shh expression, but close Shh and ZRS proximity in the nucleus occurs regardless of whether the gene or enhancer is active. We suggest that this constrained chromatin configuration optimises the opportunity for the active enhancer to locate and instigate the expression of Shh. PMID:27402708

  3. Dengue virus infection-enhancing antibody activities against Indonesian strains in inhabitants of central Thailand.

    PubMed

    Yamanaka, Atsushi; Oddgun, Duangjai; Chantawat, Nantarat; Okabayashi, Tamaki; Ramasoota, Pongrama; Churrotin, Siti; Kotaki, Tomohiro; Kameoka, Masanori; Soegijanto, Soegeng; Konishi, Eiji

    2016-04-01

    Dengue virus (DENV) infection-enhancing antibodies are a hypothetic factor to increase the dengue disease severity. In this study, we investigated the enhancing antibodies against Indonesian strains of DENV-1-4 in 50 healthy inhabitants of central Thailand (Bangkok and Uthai Thani). Indonesia and Thailand have seen the highest dengue incidence in Southeast Asia. The infection history of each subject was estimated by comparing his/her neutralizing antibody titers against prototype DENV-1-4 strains. To resolve the difficulty in obtaining foreign live viruses for use as assay antigens, we used a recombinant system to prepare single-round infectious dengue viral particles based on viral sequence information. Irrespective of the previously infecting serotype(s), most serum samples showed significantly higher enhancement titers against Indonesian DENV-2 strains than against Thai DENV-2 strains, whereas the opposite effect was observed for the DENV-3 strains. Equivalent enhancing activities were observed against both DENV-1 and DENV-4. These results suggest that the genotype has an impact on enhancing antibody activities against DENV-2 and DENV-3, because the predominant circulating genotypes of each serotype differ between Indonesia and Thailand.

  4. Novel Cationic Lipids with Enhanced Gene Delivery and Antimicrobial Activity

    PubMed Central

    Fein, David E.; Bucki, Robert; Byfield, Fitzroy; Leszczynska, Katarzyna; Janmey, Paul A.

    2010-01-01

    Cationic lipids facilitate plasmid delivery, and some cationic sterol-based compounds have antimicrobial activity because of their amphiphilic character. These dual functions are relevant in the context of local ongoing infection during intrapulmonary gene transfer for cystic fibrosis. The transfection activities of two cationic lipids, dexamethasone spermine (DS) and disubstituted spermine (D2S), were tested as individual components and mixtures in bovine aortic endothelial cells and A549 cells. The results showed a 3- to 7-fold improvement in transgene expression for mixtures of DS with 20 to 40 mol% D2S. D2S and coformulations with DS, dioleoyl phosphatidylethanolamine, and DNA exhibited potent bactericidal activity against Escherichia coli MG1655, Bacillus subtilis, and Pseudomonas aeruginosa PAO1, which was maintained in bronchoalveolar lavage fluid. Complete bacterial killing was demonstrated at ∼5 μM, including gene delivery formulations, with 2 orders of magnitude higher tolerance before eukaryotic membrane disruption (erythrocyte hemolysis). D2S also exhibited lipopolysaccharide (LPS) scavenging activity resulting in significant inhibition of LPS-mediated activation of human neutrophils with 85 and 65% lower interleukin-8 released at 12 and 24 h, respectively. Mixtures of DS and D2S can improve transfection activity over common lipofection reagents, and D2S has strong antimicrobial action suited for the suppression of bacterial-mediated inflammation. PMID:20573781

  5. Reward Sensitivity Enhances Ventrolateral Prefrontal Cortex Activation during Free Choice

    PubMed Central

    Cho, Catherine; Smith, David V.; Delgado, Mauricio R.

    2016-01-01

    Expressing one's preference via choice can be rewarding, particularly when decisions are voluntarily made as opposed to being forced. An open question is whether engaging in choices involving rewards recruits distinct neural systems as a function of sensitivity to reward. Reward sensitivity is a trait partly influenced by the mesolimbic dopamine system, which can impact an individual's neural and behavioral response to reward cues. Here, we investigated how reward sensitivity contributes to neural activity associated with free and forced choices. Participants underwent a simple decision-making task, which presented free- or forced-choice trials in the scanner. Each trial presented two cues (i.e., points or information) that led to monetary reward at the end of the task. In free-choice trials, participants were offered the opportunity to choose between different reward cues (e.g., points vs. information), whereas forced-choice trials forced individuals to choose within a given reward cue (e.g., information vs. information, or points vs. points). We found enhanced ventrolateral prefrontal cortex (VLPFC) activation during free choice compared to forced choice in individuals with high reward sensitivity scores. Next, using the VLPFC as a seed, we conducted a PPI analysis to identify brain regions that enhance connectivity with the VLPFC during free choice. Our PPI analyses on free vs. forced choice revealed increased VLPFC connectivity with the posterior cingulate and precentral gyrus in reward sensitive individuals. These findings suggest reward sensitivity may recruit attentional control processes during free choice potentially supporting goal-directed behavior and action selection. PMID:27917106

  6. Significant difference in active metabolite levels of ginseng in humans consuming Asian or Western diet: The link with enteric microbiota.

    PubMed

    Wan, Jin-Yi; Wang, Chong-Zhi; Zhang, Qi-Hui; Liu, Zhi; Musch, Mark W; Bissonnette, Marc; Chang, Eugene B; Li, Ping; Qi, Lian-Wen; Yuan, Chun-Su

    2017-04-01

    After ingestion of ginseng, the bioavailability of its parent compounds is low and enteric microbiota plays an important role in parent compound biotransformation to their metabolites. Diet type can influence the enteric microbiota profile. When human subjects on different diets ingest ginseng, their different gut microbiota profiles may influence the metabolism of ginseng parent compounds. In this study, the effects of different diet type on gut microbiota metabolism of American ginseng saponins were investigated. We recruited six healthy adults who regularly consumed different diet types. These subjects received 7 days' oral American ginseng, and their biological samples were collected for LC-Q-TOF-MS analysis. We observed significant ginsenoside Rb1 (a major parent compound) and compound K (a major active metabolite) level differences in the samples from the subjects consuming different diets. Subjects on an Asian diet had much higher Rb1 levels but much lower compound K levels compared with those on a Western diet. Since compound K possesses much better cancer chemoprevention potential, our data suggested that consumers on a Western diet should obtain better cancer prevention effects with American ginseng intake compared with those on an Asian diet. Ginseng compound levels could be enhanced or reduced via gut microbiota manipulation for clinical utility.

  7. Enhancement of oxygen reduction reaction activities by Pt nanoclusters decorated on ordered mesoporous porphyrinic carbons

    SciTech Connect

    Sun-Mi Hwang; Choi, YongMan; Kim, Min Gyu; Sohn, Young-Jun; Cheon, Jae Yeong; Joo, Sang Hoon; Yim, Sung-Dae; Kuttiyiel, Kurian A.; Sasaki, Kotaro; Adzic, Radoslav R.; Park, Gu-Gon

    2016-03-08

    The high cost of Pt-based membrane electrode assemblies (MEAs) is a critical hurdle for the commercialization of polymer electrolyte fuel cells (PEFCs). Recently, non-precious metal-based catalysts (NPMCs) have demonstrated much enhanced activity but their oxygen reduction reaction (ORR) activity is still inferior to that of Pt-based catalysts resulting in a much thicker electrode in the MEA. For the reduction of mass transport and ohmic overpotential we adopted a new concept of catalyst that combines an ultra-low amount of Pt nanoclusters with metal–nitrogen (M–Nx) doped ordered mesoporous porphyrinic carbon (FeCo–OMPC(L)). The 5 wt% Pt/FeCo–OMPC(L) showed a 2-fold enhancement in activities compared to a higher loading of Pt. Our experimental results supported by first-principles calculations indicate that a trace amount of Pt nanoclusters on FeCo–OMPC(L) significantly enhances the ORR activity due to their electronic effect as well as geometric effect from the reduced active sites. Finally, in terms of fuel cell commercialization, this class of catalysts is a promising candidate due to the limited use of Pt in the MEA.

  8. Enhancement of oxygen reduction reaction activities by Pt nanoclusters decorated on ordered mesoporous porphyrinic carbons

    DOE PAGES

    Sun-Mi Hwang; Choi, YongMan; Kim, Min Gyu; ...

    2016-03-08

    The high cost of Pt-based membrane electrode assemblies (MEAs) is a critical hurdle for the commercialization of polymer electrolyte fuel cells (PEFCs). Recently, non-precious metal-based catalysts (NPMCs) have demonstrated much enhanced activity but their oxygen reduction reaction (ORR) activity is still inferior to that of Pt-based catalysts resulting in a much thicker electrode in the MEA. For the reduction of mass transport and ohmic overpotential we adopted a new concept of catalyst that combines an ultra-low amount of Pt nanoclusters with metal–nitrogen (M–Nx) doped ordered mesoporous porphyrinic carbon (FeCo–OMPC(L)). The 5 wt% Pt/FeCo–OMPC(L) showed a 2-fold enhancement in activities comparedmore » to a higher loading of Pt. Our experimental results supported by first-principles calculations indicate that a trace amount of Pt nanoclusters on FeCo–OMPC(L) significantly enhances the ORR activity due to their electronic effect as well as geometric effect from the reduced active sites. Finally, in terms of fuel cell commercialization, this class of catalysts is a promising candidate due to the limited use of Pt in the MEA.« less

  9. Enhanced capacitive properties of commercial activated carbon by re-activation in molten carbonates

    NASA Astrophysics Data System (ADS)

    Lu, Beihu; Xiao, Zuoan; Zhu, Hua; Xiao, Wei; Wu, Wenlong; Wang, Dihua

    2015-12-01

    Simple, affordable and green methods to improve capacitive properties of commercial activated carbon (AC) are intriguing since ACs possess a predominant role in the commercial supercapacitor market. Herein, we report a green reactivation of commercial ACs by soaking ACs in molten Na2CO3-K2CO3 (equal in mass ratios) at 850 °C combining the merits of both physical and chemical activation strategies. The mechanism of molten carbonate treatment and structure-capacitive activity correlations of the ACs are rationalized. Characterizations show that the molten carbonate treatment increases the electrical conductivity of AC without compromising its porosity and wettability of electrolytes. Electrochemical tests show the treated AC exhibited higher specific capacitance, enhanced high-rate capability and excellent cycle performance, promising its practical application in supercapacitors. The present study confirms that the molten carbonate reactivation is a green and effective method to enhance capacitive properties of ACs.

  10. Decreased activity and enhanced nuclear export of CCAAT-enhancer-binding protein beta during inhibition of adipogenesis by ceramide.

    PubMed Central

    Sprott, Kam M; Chumley, Michael J; Hanson, Janean M; Dobrowsky, Rick T

    2002-01-01

    To identify novel molecular mechanisms by which ceramide regulates cell differentiation, we examined its effect on adipogenesis of 3T3-L1 preadipocytes. Hormonal stimulation of 3T3-L1 preadipocytes induced formation of triacylglycerol-laden adipocytes over 7 days; in part, via the co-ordinated action of CCAAT-enhancer-binding proteins alpha, beta and delta (C/EBP-alpha, -beta and -delta) and peroxisome-proliferator-activated receptor gamma (PPARgamma). The addition of exogenous N-acetylsphingosine (C2-ceramide) or increasing endogenous ceramide levels inhibited the expression of C/EBPalpha and PPARgamma, and blocked adipocyte development. C2-ceramide did not decrease the cellular expression of C/EBPbeta, which is required for expression of C/EBPalpha and PPARgamma, but significantly blocked its transcriptional activity from a promoter construct after 24 h. The ceramide-induced decrease in the transcriptional activity of C/EBPbeta correlated with a strong decrease in its phosphorylation, DNA-binding ability and nuclear localization at 24 h. However, ceramide did not change the nuclear level of C/EBPbeta after a period of 4 or 16 h, suggesting that it was not affecting nuclear import. CRM1 (more recently named 'exportin-1') is a nuclear membrane protein that regulates protein export from the nucleus by binding to a specific nuclear export sequence. Leptomycin B is an inhibitor of CRM1/exportin-1, and reversed the ceramide-induced decrease in nuclear C/EBPbeta at 24 h. Taken together, these data support the hypothesis that ceramide may inhibit adipogenesis, at least in part, by enhancing dephosphorylation and premature nuclear export of C/EBPbeta at a time when its maximal transcriptional activity is required to drive adipogenesis. PMID:12071851

  11. Enhanced Estrogenic Activity of Soybean Isoflavones by Coadministration of Liuwei Dihuang Pills in Ovariectomized Rats.

    PubMed

    Xie, Baogang; Zhang, Shuohua; Liu, Jie; Zhan, Xuejun; Xie, Daze; Zhang, Zhirong

    2015-07-01

    Soybean isoflavones are beneficial for treating hormone-related diseases. Simultaneous consumption of soybean isoflavones and Liuwei Dihuang pills (LWPs) is effective for treating perimenopausal period syndrome. However, why the combination of isoflavones and LWPs is more effective than ingestion of each component alone remains unknown. Here, we show that enhanced estrogenic activities would appear when the ovariectomized rats were fed with a soybean diet in combination of LWPs treatment. Our further studies explored enhancements of Lactobacillus (19-fold) and Bifidobacterium (12-fold) contents in the intestine of rat and 1.84-fold higher intestinal β-glucosidase activity in LWPs treatment group compared with the control group. As a result, steady-state concentrations of genistein (1.20-fold), daidzein (1.36-fold), and equol (1.43-fold) in serum were significantly elevated in the combination group compared with the soybean alone group. The results present the first evidence of the mechanism of enhanced estrogenic activity of dietary soybean isoflavones in combination with LWPs. Our study indicates that alterations of gut bacteria after LWPs treatment play a key role in the enhanced estrogenic effect of dietary soybean, suggesting a direct relationship between dietary soybean, LWPs, and gut flora.

  12. Enhanced lysosomal activity by overexpressed aminopeptidase Y in Saccharomyces cerevisiae.

    PubMed

    Yoon, Jihee; Sekhon, Simranjeet Singh; Kim, Yang-Hoon; Min, Jiho

    2016-06-01

    Saccharomyces cerevisiae contains vacuoles corresponding to lysosomes in higher eukaryotes. Lysosomes are dynamic (not silent) organelles in which enzymes can be easily integrated or released when exposed to stressful conditions. Changes in lysosomal enzymes have been observed due to oxidative stress, resulting in an increased function of lysosomes. The protein profiles from H2O2- and NH4Cl-treated lysosomes showed different expression patterns, observed with two-dimensional gel electrophoresis. The aminopeptidase Y protein (APE3) that conspicuously enhanced antimicrobial activity than other proteins was selected for further studies. The S. cerevisiae APE3 gene was isolated and inserted into pYES2.0 expression vector. The GFP gene was inserted downstream to the APE3 gene for confirmation of APE3 targeting to lysosomes, and S. cerevisiae was transformed to pYES2::APE3::GFP. The APE3 did not enter in lysosomes and formed an inclusion body at 30 °C, but it inserted to lysosomes as shown by the merger of GFP with lysosomes at 28 °C. Antimicrobial activity of the cloned S. cerevisiae increased about 5 to 10 % against eight strains, compared to normal cells, and galactose induction is increased more two folds than that of normal cells. Therefore, S. cerevisiae was transformed to pYES2::APE3::GFP, accumulating a large amount of APE3, resulting in increased lysosomal activity. Increase in endogenous levels of lysosomes and their activity following genetic modification can lead to its use in applications such as antimicrobial agents and apoptosis-inducing materials for cancer cells, and consequently, it may also be possible to use the organelles for improving in vitro functions.

  13. Breadth and Intensity: Salient, Separable, and Developmentally Significant Dimensions of Structured Youth Activity Involvement

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda

    2009-01-01

    In recent years, an impressive volume of evidence has accumulated demonstrating that youth involvement in structured, organized activities (e.g. school sports, community clubs) may facilitate positive youth development. We present a theory-based framework for studying structured activity involvement (SAI) as a context for positive youth…

  14. Enhanced adsorption of quaternary amine using modified activated carbon.

    PubMed

    Prahas, Devarly; Wang, M J; Ismadji, Suryadi; Liu, J C

    2014-01-01

    This study examined different methodologies to modify activated carbon (AC) for the removal of quaternary amine, tetramethylammonium hydroxide (TMAH), from water. Commercial carbon (WAC) was treated by nitric acid oxidation (NA-WAC), silica impregnation (SM-WAC0.5), and oxygen plasma (P10-WAC), and their characteristics and adsorption capacity were compared. The Langmuir model fitted the equilibrium adsorption data well under different pH. The maximum adsorption capacity of WAC was 27.77 mg/g, while those of NA-WAC, SM-WAC 0.5, and P10-WAC were 37.46, 32.83 and 29.03 mg/g, respectively. Nitric acid oxidation was the most effective method for enhancing the adsorption capacity of TMAH. Higher pH was favorable for TMAH adsorption. Desorption study revealed that NA-WAC had no considerable reduction in performance even after five cycles of regeneration by 0.1 N hydrochloric acid. It was proposed that electrostatic interaction was the main mechanism of TMAH adsorption on activated carbon.

  15. Active screen plasma nitriding enhances cell attachment to polymer surfaces

    NASA Astrophysics Data System (ADS)

    Kaklamani, Georgia; Bowen, James; Mehrban, Nazia; Dong, Hanshan; Grover, Liam M.; Stamboulis, Artemis

    2013-05-01

    Active screen plasma nitriding (ASPN) is a well-established technique used for the surface modification of materials, the result of which is often a product with enhanced functional performance. Here we report the modification of the chemical and mechanical properties of ultra-high molecular weight poly(ethylene) (UHMWPE) using 80:20 (v/v) N2/H2 ASPN, followed by growth of 3T3 fibroblasts on the treated and untreated polymer surfaces. ASPN-treated UHMWPE showed extensive fibroblast attachment within 3 h of seeding, whereas fibroblasts did not successfully attach to untreated UHMWPE. Fibroblast-coated surfaces were maintained for up to 28 days, monitoring their metabolic activity and morphology throughout. The chemical properties of the ASPN-treated UHMWPE surface were studied using X-ray photoelectron spectroscopy, revealing the presence of Csbnd N, Cdbnd N, and Ctbnd N chemical bonds. The elastic modulus, surface topography, and adhesion properties of the ASPN-treated UHMWPE surface were studied over 28 days during sample storage under ambient conditions and during immersion in two commonly used cell culture media.

  16. Yeast Recombination Enhancer Is Stimulated by Transcription Activation

    PubMed Central

    Ercan, Sevinc; Reese, Joseph C.; Workman, Jerry L.; Simpson, Robert T.

    2005-01-01

    Saccharomyces cerevisiae mating type switching is a gene conversion event that exhibits donor preference. MATa cells choose HMLα for recombination, and MATα cells choose HMRa. Donor preference is controlled by the recombination enhancer (RE), located between HMLα and MATa on the left arm of chromosome III. A number of a-cell specific noncoding RNAs are transcribed from the RE locus. Mcm1 and Fkh1 regulate RE activity in a cells. Here we show that Mcm1 binding is required for both the transcription of the noncoding RNAs and Fkh1 binding. This requirement can be bypassed by inserting another promoter into the RE. Moreover, the insertion of this promoter increases donor preference and opens the chromatin structure around the conserved domains of RE. Additionally, we determined that the level of Fkh1 binding positively correlates with the level of donor preference. We conclude that the role of Mcm1 in RE is to open chromatin around the conserved domains and activate transcription; this facilitates Fkh1 binding and the level of this binding determines the level of donor preference. PMID:16135790

  17. Motor cortex plasticity induced by paired associative stimulation is enhanced in physically active individuals.

    PubMed

    Cirillo, John; Lavender, Andrew P; Ridding, Michael C; Semmler, John G

    2009-12-15

    Recent evidence indicates that regular physical activity enhances brain plasticity (i.e. the ability to reorganise neural connections) and improves neurocognitive function. However, the effect of regular physical activity on human motor cortex function is unknown. The purpose of this study was to examine motor cortex plasticity for a small hand muscle in highly active and sedentary individuals. Electromyographic recordings were obtained from the left abductor pollicis brevis (APB) muscle of 14 active and 14 sedentary subjects (aged 18-38 yrs). The extent of physical activity was assessed by questionnaire, where the physically active subjects performed >150 min per day moderate-to-vigorous aerobic activity on at least 5 days per week, whereas the sedentary group performed <20 min per day of physical activity on no more than 3 days per week. Transcranial magnetic stimulation (TMS) of the right hemisphere was used to assess changes in APB motor-evoked potentials (MEPs), input-output curve (IO curve), short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Neuroplastic changes were induced using paired-associative stimulation (PAS), which consisted of 90 paired stimuli (0.05 Hz for 30 min) of median nerve electrical stimulation at the wrist followed 25 ms later by TMS to the hand area of motor cortex. The IO curve slope was 35% steeper in individuals with increased physical activity (combined before and after PAS, P < 0.05), suggesting increased motor cortex excitability, although there was no difference in SICI or CSP between groups. PAS induced an increase in MEP amplitude in the physically active subjects (54% increase compared with before, P < 0.01), but no significant facilitation in the sedentary subjects. We conclude that participation in regular physical activity may offer global benefits to motor cortex function that enhances neuroplasticity, which could improve motor learning and neurorehabilitation in physically active individuals.

  18. The Significance of Turning Passive Into Active in Control Mastery Theory

    PubMed Central

    FOREMAN, STEVEN A.

    1996-01-01

    Turning passive into active was first described by Freud but was later given expanded importance by Weiss. This new conceptualization of turning passive into active as an interpersonal communication and test has made a major contribution to the clinical treatment of difficult patients. This article reviews "control mastery" theory and puts its notion of passive-into-active testing into perspective with regard to Freud’s original conception as well as other conceptions, such as identification with the aggressor and projective identification. Formulation and the treatment of patients are illustrated with clinical examples. PMID:22700271

  19. Investigation of effects of terpene skin penetration enhancers on stability and biological activity of lysozyme.

    PubMed

    Varman, Rahul M; Singh, Somnath

    2012-12-01

    The transport of proteins through skin can be facilitated potentially by using terpenes as chemical enhancers. However, we do not know about the effects of these enhancers on the stability and biological activity of proteins which is crucial for the development of safe and efficient formulations. Therefore, this project investigated the effects of terpene-based skin penetration enhancers which are reported as nontoxic to the skin (e.g., limonene, p-cymene, geraniol, farnesol, eugenol, menthol, terpineol, carveol, carvone, fenchone, and verbenone), on the conformational stability and biological activity of a model protein lysozyme. Terpene (5% v/v) was added to lysozyme solution and kept for 24 h (the time normally a transdermal patch remains) for investigating conformational stability profiles and biological activity. Fourier transform infrared spectrophotometer was used to analyze different secondary structures, e.g., α-helix, β-sheet, β-turn, and random coil. Conformational changes were also monitored by differential scanning calorimeter by determining midpoint transition temperature (Tm) and calorimetric enthalpy (ΔH). Biological activity of lysozyme was determined by measuring decrease in A (450) when it was added to a suspension of Micrococcus lysodeikticus. The results of this study indicate that terpenes 9, 10, and 11 (carvone, L-fenchone, and L-verbenone) decreased conformational stability and biological activity of lysozyme significantly (p < 0.05) less than other terpenes used in this study. It is concluded that smaller terpenes containing ketones with low lipophilicity (log K (ow) ∼2.00) would be optimal for preserving conformational stability and biological activity of lysozyme in a transdermal formulation containing terpene as permeation enhancer.

  20. Incorporating mobile nanospheres in the lumen of hybrid microcapsules for enhanced enzymatic activity.

    PubMed

    Shi, Jiafu; Zhang, Xiaoman; Zhang, Shaohua; Wang, Xiaoli; Jiang, Zhongyi

    2013-11-13

    Physical encapsulation of enzymes in microcapsules, as a mild, controllable method, has been widely utilized for enzyme immobilization. However, this method often suffers from the big mass transfer resistance from the capsule lumen. In this study, a novel biocatalysis system with enhanced catalytic activity is constructed through coencapsulating enzymes and nanospheres in the lumen of protamine/silica hybrid microcapsules, which are synthesized through the synergy of biomimetic silicification and layer-by-layer (LbL) assembly. When utilized as the host for catalase (CAT) encapsulation, the hybrid microcapsules maintain high mechanical stability, high enzyme loading, and low enzyme leaching. Particularly, because of the existence of mobile nanospheres, the mass transfer resistance in the microcapsules is significantly reduced because of the vigorous agitation, thus acquiring an enhanced catalytic activity. Our strategy may also find applications in drug delivery and biosensor fields.

  1. Arabidopsis TTG2 regulates TRY expression through enhancement of activator complex-triggered activation.

    PubMed

    Pesch, Martina; Dartan, Burcu; Birkenbihl, Rainer; Somssich, Imre E; Hülskamp, Martin

    2014-10-01

    Trichome patterning in Arabidopsis thaliana is regulated by a regulatory feedback loop of the trichome promoting factors TRANSPARENT TESTA GLABRA1 (TTG1), GLABRA3 (GL3)/ENHANCER OF GL3 (EGL3), and GL1 and a group of homologous R3MYB proteins that act as their inhibitors. Together, they regulate the temporal and spatial expression of GL2 and TTG2, which are considered to control trichome cell differentiation. In this work, we show that TTG2 is a specific activator of TRY (but not CPC or GL2). The WRKY protein TTG2 binds to W-boxes in a minimal promoter fragment of TRY, and these W-boxes are essential for rescue of the try mutant phenotype. We further show that TTG2 alone is not able to activate TRY expression, but rather drastically enhances the activation by TTG1 and GL3. As TTG2 physically interacts with TTG1 and because TTG2 can associate with GL3 through its interaction with TTG1, we propose that TTG2 enhances the activity of TTG1 and GL3 by forming a protein complex.

  2. Hydrogenation of Ferrimagnetic Graphene on a Co Surface: Significant Enhancement of Spin Moments by C-H Functionality.

    PubMed

    Kaul, Indu; Joshi, Niharika; Ballav, Nirmalya; Ghosh, Prasenjit

    2012-09-20

    Using ab initio density functional theory, we present a novel way of simultaneously enhancing the induced magnetic moment and opening up the band gap of a graphene sheet supported on ferromagnetic transition metal surface. Specifically, we have demonstrated that by simply hydrogenating graphene supported on ferromagnetic Co surface at saturation coverage, (i) there is a six-fold increase in the magnitude of the induced magnetic moment compared with the pristine graphene on the Co surface and (ii) for both the spin-up and the spin-down channels there is a band gap opening at the K-point of the Brillouin zone.

  3. Transport Activity of the Sodium Bicarbonate Cotransporter NBCe1 Is Enhanced by Different Isoforms of Carbonic Anhydrase

    PubMed Central

    Schueler, Christina; Becker, Holger M.; McKenna, Robert; Deitmer, Joachim W.

    2011-01-01

    Transport metabolons have been discussed between carbonic anhydrase II (CAII) and several membrane transporters. We have now studied different CA isoforms, expressed in Xenopus oocytes alone and together with the electrogenic sodium bicarbonate cotransporter 1 (NBCe1), to determine their catalytic activity and their ability to enhance NBCe1 transport activity. pH measurements in intact oocytes indicated similar activity of CAI, CAII and CAIII, while in vitro CAIII had no measurable activity and CAI only 30% of the activity of CAII. All three CA isoforms increased transport activity of NBCe1, as measured by the transport current and the rate of intracellular sodium rise in oocytes. Two CAII mutants, altered in their intramolecular proton pathway, CAII-H64A and CAII-Y7F, showed significant catalytic activity and also enhanced NBCe1 transport activity. The effect of CAI, CAII, and CAII mutants on NBCe1 activity could be reversed by blocking CA activity with ethoxyzolamide (EZA, 10 µM), while the effect of the less EZA-sensitive CAIII was not reversed. Our results indicate that different CA isoforms and mutants, even if they show little enzymatic activity in vitro, may display significant catalytic activity in intact cells, and that the ability of CA to enhance NBCe1 transport appears to depend primarily on its catalytic activity. PMID:22076132

  4. Enhancing human spermine synthase activity by engineered mutations.

    PubMed

    Zhang, Zhe; Zheng, Yueli; Petukh, Margo; Pegg, Anthony; Ikeguchi, Yoshihiko; Alexov, Emil

    2013-01-01

    Spermine synthase (SMS) is an enzyme which function is to convert spermidine into spermine. It was shown that gene defects resulting in amino acid changes of the wild type SMS cause Snyder-Robinson syndrome, which is a mild-to-moderate mental disability associated with osteoporosis, facial asymmetry, thin habitus, hypotonia, and a nonspecific movement disorder. These disease-causing missense mutations were demonstrated, both in silico and in vitro, to affect the wild type function of SMS by either destabilizing the SMS dimer/monomer or directly affecting the hydrogen bond network of the active site of SMS. In contrast to these studies, here we report an artificial engineering of a more efficient SMS variant by transferring sequence information from another organism. It is confirmed experimentally that the variant, bearing four amino acid substitutions, is catalytically more active than the wild type. The increased functionality is attributed to enhanced monomer stability, lowering the pKa of proton donor catalytic residue, optimized spatial distribution of the electrostatic potential around the SMS with respect to substrates, and increase of the frequency of mechanical vibration of the clefts presumed to be the gates toward the active sites. The study demonstrates that wild type SMS is not particularly evolutionarily optimized with respect to the reaction spermidine → spermine. Having in mind that currently there are no variations (non-synonymous single nucleotide polymorphism, nsSNP) detected in healthy individuals, it can be speculated that the human SMS function is precisely tuned toward its wild type and any deviation is unwanted and disease-causing.

  5. Polyphosphate Kinase from Activated Sludge Performing Enhanced Biological Phosphorus Removal†

    PubMed Central

    McMahon, Katherine D.; Dojka, Michael A.; Pace, Norman R.; Jenkins, David; Keasling, Jay D.

    2002-01-01

    A novel polyphosphate kinase (PPK) was retrieved from an uncultivated organism in activated sludge carrying out enhanced biological phosphorus removal (EBPR). Acetate-fed laboratory-scale sequencing batch reactors were used to maintain sludge with a high phosphorus content (approximately 11% of the biomass). PCR-based clone libraries of small subunit rRNA genes and fluorescent in situ hybridization (FISH) were used to verify that the sludge was enriched in Rhodocyclus-like β-Proteobacteria known to be associated with sludges carrying out EBPR. These organisms comprised approximately 80% of total bacteria in the sludge, as assessed by FISH. Degenerate PCR primers were designed to retrieve fragments of putative ppk genes from a pure culture of Rhodocyclus tenuis and from organisms in the sludge. Four novel ppk homologs were found in the sludge, and two of these (types I and II) shared a high degree of amino acid similarity with R. tenuis PPK (86 and 87% similarity, respectively). Dot blot analysis of total RNA extracted from sludge demonstrated that the Type I ppk mRNA was present, indicating that this gene is expressed during EBPR. Inverse PCR was used to obtain the full Type I sequence from sludge DNA, and a full-length PPK was cloned, overexpressed, and purified to near homogeneity. The purified PPK has a specific activity comparable to that of other PPKs, has a requirement for Mg2+, and does not appear to operate in reverse. PPK activity was found mainly in the particulate fraction of lysed sludge microorganisms. PMID:12324346

  6. Porous platinum mesoflowers with enhanced activity for methanol oxidation reaction

    SciTech Connect

    Zhuang Lina; Wang Wenjin; Hong Feng; Yang Shengchun; You Hongjun; Fang Jixiang; Ding Bingjun

    2012-07-15

    Porous Pt and Pt-Ag alloy mesoflowers (MFs) with about 2 {mu}m in diameter and high porosity were synthesized using Ag mesoflowers as sacrificial template by galvanic reaction. The silver content in Pt-Ag alloys can be facilely controlled by nitric acid treatment. And the pure Pt MFs can be obtained by selective removal of silver element from Pt{sub 72}Ag{sub 28} MFs electrochemically. Both Pt{sub 45}Ag{sub 55}, Pt{sub 72}Ag{sub 28} and pure Pt show a high catalytic performance in methanol oxidation reaction (MOR). Especially, pure Pt MFs exhibited a 2 to 3 times current density enhancement in MOR compared with the commercial used Pt black, which can be attributed to their porous nanostructure with 3-dimentional nature and small crystal sizes. - Graphical Abstract: The CVs of MOR on Pt (red) and Pt black (green) catalysts in 0.1 M HClO{sub 4} and 0.5 M CH{sub 3}OH for specific mass current. The insert shows the SEM images of two porous Pt MFs. Platinum mesoflowers (MFs) with about 2 {mu}m in diameter and high porosity were synthesised with Ag mesoflowers as sacrificial template by galvanic replacement. The porous Pt MFs exhibited a more than 3 times enhancement in electrocatalytic performance for methanol oxidation reaction compared the commercial used Pt black. Highlights: Black-Right-Pointing-Pointer Porous Pt and Pt-Ag mesoflowers (MFs) were synthesized using Ag MFs sacrifical template. Black-Right-Pointing-Pointer Pt MFs presents an improved catalytic activity in MOR compared with Pt black. Black-Right-Pointing-Pointer We provided a facile approach for the development of high performance Pt electrocatalysts for fuel cells.

  7. Significance of peroxisome proliferator-activated receptors in the cardiovascular system in health and disease.

    PubMed

    Robinson, Emma; Grieve, David J

    2009-06-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that belong to the nuclear receptor superfamily. Three isoforms of PPAR have been identified, alpha, delta and gamma, which play distinct roles in the regulation of key metabolic processes, such as glucose and lipid redistribution. PPARalpha is expressed predominantly in the liver, kidney and heart, and is primarily involved in fatty acid oxidation. PPARgamma is mainly associated with adipose tissue, where it controls adipocyte differentiation and insulin sensitivity. PPARdelta is abundantly and ubiquitously expressed, but as yet its function has not been clearly defined. Activators of PPARalpha (fibrates) and gamma (thiazolidinediones) have been used clinically for a number of years in the treatment of hyperlipidaemia and to improve insulin sensitivity in diabetes. More recently, PPAR activation has been found to confer additional benefits on endothelial function, inflammation and thrombosis, suggesting that PPAR agonists may be good candidates for the treatment of cardiovascular disease. In this regard, it has been demonstrated that PPAR activators are capable of reducing blood pressure and attenuating the development of atherosclerosis and cardiac hypertrophy. This review will provide a detailed discussion of the current understanding of basic PPAR physiology, with particular reference to the cardiovascular system. It will also examine the evidence supporting the involvement of the different PPAR isoforms in cardiovascular disease and discuss the current and potential future clinical applications of PPAR activators.

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

    PubMed Central

    Fujisawa, Naoaki; 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 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. PMID:26713153

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

    PubMed

    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.

  10. [Regulation of myostatin promoter activity by myocyte enhancer factor 2].

    PubMed

    Li, Jia; Deng, Jie; Zhang, Junlin; Cheng, De; Wang, Huayan

    2012-08-01

    Myostatin (Mstn) is a member of the transforming growth factor-beta superfamily that functions as a negative regulator of skeletal muscle growth and differentiation in mammals. The transcriptional regulation of Mstn is controlled by multiple genes including MEF2, which raise the importance of identifying the binding sites of MEF2 on myostatin promoter region and mechanisms underlying. In this study, we investigated the transcriptional regulation of MEF2 on porcine Mstn promoter activity in C2C12 cells. Sequence analysis of the 1 969 bp porcine Mstn promoter region revealed that it contained three potential MEF2 motifs. Using a serial deletion strategy, we tested the activity of several promoter fragments by luciferase assay. Overexpression of MEF2C, but not MEF2A increased Mstn promoter activity in all the promoter fragments with MEF2 motifs by two to six folds, in both C2C12 myoblasts and myotubes. When we transfected exogenous MEF2C, Mstn mRNA level was also upregulated in C2C12 cells, but the protein level was only significantly increased in myotubes. Thus, we propose that MEF2C could modulate and restrain myogenesis by Mstn activation and Mstn-dependent gene processing in porcine. Our research also provided potential targets and an effective molecule to regulate Mstn expression and gave a new way to explore the functional performance of Mstn.

  11. Significant role of climatic trends on hydrothermal activity Coso Hot Springs, California

    SciTech Connect

    Lofgren, B.E. )

    1990-05-01

    The hydrothermal features of Coso Hot Springs have attracted visitors for 130 yr and scientific investigators for two decades. In 1978, anticipating effects of major geothermal developments nearby, the Naval Weapons Center (NWC) initiated a comprehensive monitoring program at a dozen hydrothermal sites in the Coso Hot Springs area. Nine years of monitoring preceded power production in the nearby Coso geothermal field in July 1987. During this period, steam was rising from numerous vents and gently boiling mud pots. Local rainfall caused increased boiling activity in several mud pots, with some overflowing during wet periods. Then in August 1988, a year after geothermal power production began major changes in hot spring activity commenced. Small mud pots and steamers started to grow and coalesce. In March 1989, mud-pot activity became more violent. Many buried wells failed causing surface activity in other areas to diminish. During ensuing months, large mud cones developed and much of the steam and boiling water occurred in a few major pots. Because the abrupt changes in hydrothermal activity followed so closely after nearby geothermal production began, the obvious cause has been attributed to geothermal developments. Studies of NWC baseline monitoring data indicate, however, that no effects of geothermal developments have been felt in the hot springs area. Rainfall and barometric effects account for most of the fluctuations in records of the past decade. Early accounts and field evidence suggest similar changes have occurred in the past.

  12. Newly identified active faults in the Pollino seismic gap, southern Italy, and their seismotectonic significance

    NASA Astrophysics Data System (ADS)

    Brozzetti, Francesco; Cirillo, Daniele; de Nardis, Rita; Cardinali, Mauro; Lavecchia, Giusy; Orecchio, Barbara; Presti, Debora; Totaro, Cristina

    2017-01-01

    The following is a geological study of a Quaternary and active normal fault-system, which crops out in the Pollino area, a seismogenic sector of the Southern Apennines, Italy. From 2010 to 2014, this area was affected by long lasting seismic activity characterized by three major events which occurred in May 2012 (Mw 4.3), in October 2012 (Mw 5.2) and in June 2014 (Mw 4.0). The integration of structural-geological data with morpho-structural and remote sensing analyses, led to define the geometry, the kinematics, the cross-cutting relationships and the slip rates of the inferred active fault segments within and near the epicentral area. We reconstructed an asymmetric extensional pattern characterized by low-angle, E and NNE-dipping faults, and by antithetic, high-angle, SW- to WSW-dipping faults. The geometry of the faults at depth was constrained using high-resolution hypocenter distributions. The overall system fits well with the deformation field obtained from focal mechanisms and geodetic data. Comparing the fault pattern with the time-space evolution of the Pollino seismic activity, we identified the seismogenic sources in two, near-parallel, WSW-dipping faults, whose seismogenic potential were assessed. The peculiar perpendicular-to-fault-strike evolution of the seismic activity, is discussed in the frame of the reconstructed seismotectonic model.

  13. Enhanced adsorption of perfluorooctane sulfonate and perfluorooctanoate by bamboo-derived granular activated carbon.

    PubMed

    Deng, Shubo; Nie, Yao; Du, Ziwen; Huang, Qian; Meng, Pingping; Wang, Bin; Huang, Jun; Yu, Gang

    2015-01-23

    A bamboo-derived granular activated carbon with large pores was successfully prepared by KOH activation, and used to remove perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) from aqueous solution. The granular activated carbon prepared at the KOH/C mass ratio of 4 and activation temperature of 900°C had fast and high adsorption for PFOS and PFOA. Their adsorption equilibrium was achieved within 24h, which was attributed to their fast diffusion in the micron-sized pores of activated carbon. This granular activated carbon exhibited the maximum adsorbed amount of 2.32mmol/g for PFOS and 1.15mmol/g for PFOA at pH 5.0, much higher than other granular and powdered activated carbons reported. The activated carbon prepared under the severe activation condition contained many enlarged pores, favorable for the adsorption of PFOS and PFOA. In addition, the spent activated carbon was hardly regenerated in NaOH/NaCl solution, while the regeneration efficiency was significantly enhanced in hot water and methanol/ethanol solution, indicating that hydrophobic interaction was mainly responsible for the adsorption. The regeneration percent was up to 98% using 50% ethanol solution at 45°C.

  14. The evolution of magnetic activity on V711 Tauri and evidence for a significant facular contribution

    NASA Technical Reports Server (NTRS)

    Dorren, J. D.; Guinan, E. F.

    1990-01-01

    The nature of the long-term evolution of magnetic activity in the RS CVn binary V711 Tauri is investigated using the complete set of available archival IUE SWP low-dispersion spectra of V711 Tau for the period covering August 1978 - December 1984. An analysis of the spectra confirmed the pattern of a long-term smooth variation of chromospheric and transition region emission found previosly by Dorren et al. (1986). An explanation of the relationship between the different facets of the magnetic activity on V711 Tau is presented.

  15. Enhancement of photocatalytic and photoelectrocatalytic activity of Ag modified Mpg-C3N4 composites

    NASA Astrophysics Data System (ADS)

    He, Qiuchen; Zhou, Feng; Zhan, Su; Yang, Yifan; Liu, Yujun; Tian, Yu; Huang, Naibao

    2017-01-01

    In this study, mpg-C3N4/Ag composites of surface plasmon resonance structures were fabricated to improve the photocatalytic and photoelectrocatalytic activities of g-C3N4 via photo-assisted reduction method, which were characterized by XRD, EDS, XPS, FT-IR, FE-SEM, TEM, DRS and BET. The photocatalytic and photoelectrocatalytic activities were evaluated by the degradation of methylene blue (MB) and the oxygen reduction experiment under visible light. The results showed the photocatalytic and photoelectrocatalytic activities were dependent on the weight ratio of Ag and the optimum photocatalytic activity of mpg-C3N4/Ag at a weight ratio of 3% is almost 3 times as high as that of mpg-C3N4. Additionally, mpg-C3N4/Ag exhibited a significantly enhanced oxygen reduction performance under visible light. The limit current density was increased about 2 times by the modification of Ag nanoparticles, compared with that of pristine mpg-C3N4. Finally, based on the first principle, the enhancement mechanism of the photocatalytic and photoelectrocatalytic activities was discussed by the calculation on the band structure and density of states in the mpg-C3N4/Ag composites. The appropriate amount of Ag modification would cause the surface plasmon resonance effect, which improved the photocatalytic, photoelectrocatalytic, and oxygen reduction activities of mpg-C3N4.

  16. Aminoglycosylation Can Enhance the G-Quadruplex Binding Activity of Epigallocatechin

    PubMed Central

    Bai, Li-Ping; Ho, Hing-Man; Ma, Dik-Lung; Yang, Hui; Fu, Wai-Chung; Jiang, Zhi-Hong

    2013-01-01

    With the aim of enhancing G-quadruplex binding activity, two new glucosaminosides (16, 18) of penta-methylated epigallocatechin were synthesized by chemical glycosylation. Subsequent ESI-TOF-MS analysis demonstrated that these two glucosaminoside derivatives exhibit much stronger binding activity to human telomeric DNA and RNA G-quadruplexes than their parent structure (i.e., methylated EGC) (14) as well as natural epigallocatechin (EGC, 6). The DNA G-quadruplex binding activity of 16 and 18 is even more potent than strong G-quadruplex binder quercetin, which has a more planar structure. These two synthetic compounds also showed a higher binding strength to human telomeric RNA G-quadruplex than its DNA counterpart. Analysis of the structure-activity relationship revealed that the more basic compound, 16, has a higher binding capacity with DNA and RNA G-quadruplexes than its N-acetyl derivative, 18, suggesting the importance of the basicity of the aminoglycoside for G-quadruplex binding activity. Molecular docking simulation predicted that the aromatic ring of 16 π-stacks with the aromatic ring of guanine nucleotides, with the glucosamine moiety residing in the groove of G-quadruplex. This research indicates that glycosylation of natural products with aminosugar can significantly enhance their G-quadruplex binding activities, thus is an effective way to generate small molecules targeting G-quadruplexes in nucleic acids. In addition, this is the first report that green tea catechin can bind to nucleic acid G-quadruplex structures. PMID:23335983

  17. Evaluation of Skin Permeation and Analgesic Activity Effects of Carbopol Lornoxicam Topical Gels Containing Penetration Enhancer

    PubMed Central

    Al-Suwayeh, Saleh A.; Taha, Ehab I.; Al-Qahtani, Fahad M.; Ahmed, Mahrous O.; Badran, Mohamed M.

    2014-01-01

    The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC) and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl β-cyclodextrin (HP β-CD), beta-cyclodextrin (β-CD), Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8) showed the highest flux (14.31 μg/cm2/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP β-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo). This work shows that LOR can be formulated into carbopol gel in presence of PG and HP β-CD and may be promising in enhancing permeation. PMID:25045724

  18. The Measurement of Brain Electrical Activity and Its Significance to the Educator.

    ERIC Educational Resources Information Center

    Torello, Michael W.

    The article discusses the measurement of brain electrical activity and, in particular, the examination of electroencephalographic (EEG) data, as providing useful information in the diagnosis of dyslexia and other learning disabilities. Topographic imaging of EEG (TIE) is described as a procedure which provides functional data at comparatively low…

  19. Significant Centers of Tectonic Activity as Identified by Wrinkle Ridges for the Western Hemisphere of Mars

    NASA Technical Reports Server (NTRS)

    Anderson, R.C.; Haldemann, A. F. C.; Golombek, M. P.; Franklin, B. J.; Dohm, J. M.; Lias, J.

    2000-01-01

    The western hemisphere region of Mars has been the site of numerous scientific investigations regarding its tectonic evolution. For this region of Mars, the dominant tectonic region is the Tharsis province. Tharsis is characterized by an enormous system of radiating grabens and a circumferential system of wrinkle ridges. Past investigations of grabens associated with Tharsis have identified specific centers of tectonic activity. A recent structural analysis of the western hemisphere region of Mars which includes the Tharsis region, utilized 25,000 structures to determine the history of local and regional centers of tectonic activity based primarily on the spatial and temporal relationships of extensional features. This investigation revealed that Tharsis is more structurally complex (heterogeneous) than has been previously identified: it consists of numerous regional and local centers of tectonic activity (some are more dominant and/or more long lived than others). Here we use the same approach as Anderson et al. to determine whether the centers of tectonic activity that formed the extensional features also contributed to wrinkle ridge (compressional) formation.

  20. The Social and Economic Significance of Recreation Activities in the Marine Environment.

    ERIC Educational Resources Information Center

    Ditton, Robert B.

    Although the data obtained by an Outdoor Recreation Resources Review Commission in 1960 indicated that 44 percent of participants in outdoor recreation prefer water-based activities, the potential demand for recreation within the coastal zone is much greater than that study indicates, because the unfulfilled recreational demands of the urban…

  1. Enhanced Activities of Blood Thiamine Diphosphatase and Monophosphatase in Alzheimer's Disease

    PubMed Central

    Fei, Guoqiang; Jin, Lirong; Liu, Huimin; Wang, Zhiliang; Wang, Hui; Zhong, Chunjiu

    2017-01-01

    Background Thiamine metabolites and activities of thiamine-dependent enzymes are impaired in Alzheimer’s disease (AD). Objective To clarify the mechanism for the reduction of thiamine diphosphate (TDP), an active form of thiamine and critical coenzyme of glucose metabolism, in AD. Methods Forty-five AD patients clinically diagnosed and 38 age- and gender-matched control subjects without dementia were voluntarily recruited. The contents of blood TDP, thiamine monophosphate (TMP), and thiamine, as well as the activities of thiamine diphosphatase (TDPase), thiamine monophosphatase (TMPase), and thiamine pyrophosphokinase (TPK), were assayed by high performance liquid chromatography. Results Blood TDP contents of AD patients were significantly lower than those in control subjects (79.03 ± 23.24 vs. 127.60 ± 22.65 nmol/L, P<0.0001). Activities of TDPase and TMPase were significantly enhanced in AD patients than those in control subjects (TDPase: 1.24 ± 0.08 vs. 1.00 ± 0.04, P < 0.05; TMPase: 1.22 ± 0.04 vs. 1.00 ± 0.06, P < 0.01). TPK activity remained unchanged in AD as compared with that in control (0.93 ± 0.04 vs. 1.00 ± 0.04, P > 0.05). Blood TDP levels correlated negatively with TDPase activities (r = -0.2576, P = 0.0187) and positively with TPK activities (r = 0.2426, P = 0.0271) in all participants. Conclusion Enhanced TDPase and TMPase activities may contribute to the reduction of TDP level in AD patients. The results imply that an imbalance of phosphorylation-dephosphorylation related to thiamine and glucose metabolism may be a potential target for AD prevention and therapy. PMID:28060825

  2. Cu(2+) inhibits photosystem II activities but enhances photosystem I quantum yield of Microcystis aeruginosa.

    PubMed

    Deng, Chunnuan; Pan, Xiangliang; Wang, Shuzhi; Zhang, Daoyong

    2014-08-01

    Responses of photosystem I and II activities of Microcystis aeruginosa to various concentrations of Cu(2+) were simultaneously examined using a Dual-PAM-100 fluorometer. Cell growth and contents of chlorophyll a were significantly inhibited by Cu(2+). Photosystem II activity [Y(II)] and electron transport [rETRmax(II)] were significantly altered by Cu(2+). The quantum yield of photosystem II [Y(II)] decreased by 29 % at 100 μg L(-1) Cu(2+) compared to control. On the contrary, photosystem I was stable under Cu(2+) stress and showed an obvious increase of quantum yield [Y(I)] and electron transport [rETRmax(I)] due to activation of cyclic electron flow (CEF). Yield of cyclic electron flow [Y(CEF)] was enhanced by 17 % at 100 μg L(-1) Cu(2+) compared to control. The contribution of linear electron flow to photosystem I [Y(II)/Y(I)] decreased with increasing Cu(2+) concentration. Yield of cyclic electron flow [Y(CEF)] was negatively correlated with the maximal photosystem II photochemical efficiency (F v/F m). In summary, photosystem II was the major target sites of toxicity of Cu(2+), while photosystem I activity was enhanced under Cu(2+) stress.

  3. Activity Enhancement Based on the Chemical Equilibrium of Multiple-Subunit Nitrile Hydratase from Bordetella petrii.

    PubMed

    Liu, Yi; Liu, Ping; Lin, Lu; Zhao, Yueqin; Zhong, Wenjuan; Wu, Lunjie; Zhou, Zhemin; Sun, Weifeng

    2016-09-01

    The maturation mechanism of nitrile hydratase (NHase) of Pseudomonas putida NRRL-18668 was discovered and named as "self-subunit swapping." Since the NHase of Bordetella petrii DSM 12804 is similar to that of P. putida, the NHase maturation of B. petrii is proposed to be the same as that of P. putida. However, there is no further information on the application of NHase according to these findings. We successfully rapidly purified NHase and its activator through affinity his tag, and found that the cell extracts of NHase possessed multiple types of protein ingredients including α, β, α2β2, and α(P14K)2 who were in a state of chemical equilibrium. Furthermore, the activity was significantly enhanced through adding extra α(P14K)2 to the cell extracts of NHase according to the chemical equilibrium. Our findings are useful for the activity enhancement of multiple-subunit enzyme and for the first time significantly increased the NHase activity according to the chemical equilibrium.

  4. Enhancing Cancer Immunotherapy Via Activation of Innate Immunity.

    PubMed

    Goldberg, Jacob L; Sondel, Paul M

    2015-08-01

    Given recent technological advances and advances in our understanding of cancer, immunotherapy of cancer is being used with clear clinical benefit. The immunosuppression accompanying cancer itself, as well as with current cancer treatment with radiation or chemotherapy, impairs adaptive immune effectors to a greater extent than innate effector cells. In addition to being less suppressed, innate immune cells are capable of being enhanced via immune-stimulatory regimens. Most strategies being investigated to promote innate immune responses against cancer do not require complex, patient-specific, ex vivo cellular or molecular creation of therapeutic agents; thus they can, generally, be used as "off the shelf" therapeutics that could be administered by most cancer clinics. Successful applications of innate immunotherapy in the clinic have effectively targeted components of the innate immune response. Preclinical data demonstrate how initiation of innate immune responses can lead to subsequent adaptive long-term cancer immunity. We hypothesize that integration of innate immune activation strategies into combination therapies for cancer treatment will lead to more effective and long-term clinical benefit.

  5. Ultrasonically Enhanced Vancomycin Activity Against Staphylococcus epidermidis Biofilms In Vivo

    PubMed Central

    Carmen, J. C.; Roeder, B. L.; Nelson, J. L.; Beckstead, B. L.; Runyan, C. M.; Schaalje, G.B.; Robison, R. A.; Pitt, W. G.

    2006-01-01

    SUMMARY Infection of implanted medical devices by Gram-positive organisms such as Staphylococcus ssp. is a serious concern in the biomaterial community. In this research the application of low frequency ultrasound to enhance the activity of vancomycin against implanted Staphylococcus epidermidis biofilms was examined. Polyethylene disks covered with a biofilm of S. epidermidis were implanted subcutaneously in rabbits on both sides of their spine. The rabbits received systemic vancomycin for the duration of the experiment. Following 24 h of recovery, one disk was insonated for 24 or 48 h while the other was a control. Disks were removed and viable bacteria counted. At 24 h of insonation, there was no difference in viable counts between control and insonated biofilms, while at 48 h of insonation there were statistically fewer viable bacteria in the insonated biofilm. The S. epidermidis biofilms responded favorably to combinations of ultrasound and vancomycin, but longer treatment times are required for this Gram-positive organism than was observed previously for a Gram-negative species. PMID:15070512

  6. Enhancement of cloud-to-ground lightning activity over Taipei, Taiwan in relation to urbanization

    NASA Astrophysics Data System (ADS)

    Kar, S. K.; Liou, Y. A.

    2014-10-01

    Collecting the cloud-to-ground (CG) lightning flash data from Tai-Power Company of Taiwan, a long term study has been performed to investigate the enhancement of lightning activity in and around Taipei City, the largest metropolitan city of Taiwan, in relation to urbanization, for the period of 2005-2010. Results reveal that negative flash density is enhanced by approximately 64% while the positive flash density is enhanced by 48%, over and downwind of the city compared with other neighboring areas. On the other hand a decrease of nearly 24% in the percentage of positive flashes occurs over and downwind of Taipei compared to upwind values. We have also investigated the effect of urbanization on peak current of both polarities but no significant effect is noticed. Possible influence of urban particulate matter on the enhancement of CG lightning activity has been analyzed utilizing the annual averages of PM10 (particulate matter with aerodynamic diameter smaller than 10 μm) and SO2 (sulfur dioxide) concentrations data. Interesting results are found, indicating the higher concentrations of PM10 and SO2 contributes to the CG lightning enhancement. Both the concentrations exhibit a positive linear correlation with the percent change in CG flashes from the upwind to the urban area and from the upwind to the downwind area. However, the correlation coefficient for PM10 concentrations is comparatively much lower than SO2 concentrations. Positive correlations of 0.55 and 0.68 are found for the PM10 and SO2 concentrations, respectively, when compared separately with the percent change in CG flashes from the upwind to the downwind area, indicating the influence of aerosols on urban CG lightning enhancement. Hourly variation of lightning flashes show that the urban effects on CG lightning is prominent in the afternoon and early evening hours. The results obtained from the present analysis corroborate the results reported in the literature by other researchers.

  7. Using the Significant Learning Taxonomy and Active Learning to Improve Accounting Education

    ERIC Educational Resources Information Center

    Killian, Larita J.; Brandon, Christopher D.

    2009-01-01

    Like other members of the academy, accounting professors are challenged to improve student learning. We must help students move beyond the "bean counter" role and develop higher-level skills such as analysis, synthesis, and problem-solving. The Significant Learning Taxonomy was used as a template to improve learning in an introductory accounting…

  8. Culture, Leadership, and Activism: Translating Fink's Taxonomy of Significant Learning into Pedagogical Practice

    ERIC Educational Resources Information Center

    Jenkins, Toby S.

    2016-01-01

    Through the article, I share the theoretical foundations, structure, knowledge acquisition, and outcomes of a cultural leadership course. The process for course development integrates several theories and research methods into practice: L. Dee Fink's Taxonomy of Significant Learning, Feminist Theory, Critical Race Theory, and…

  9. Enhancing methane production from waste activated sludge using a novel indigenous iron activated peroxidation pre-treatment process.

    PubMed

    Zhou, Xu; Wang, Qilin; Jiang, Guangming

    2015-04-01

    Methane production from anaerobic digestion of waste activated sludge (WAS) is limited by the slow hydrolysis rate and/or poor methane potential of WAS. This study presents a novel pre-treatment strategy based on indigenous iron (in WAS) activated peroxidation to enhance methane production from WAS. Pre-treatment of WAS for 30 min at 50mg H2O2/g total solids (dry weight) and pH 2.0 (iron concentration in WAS was 7 mg/g TS) substantially enhanced WAS solubilization. Biochemical methane potential tests demonstrated that methane production was improved by 10% at a digestion time of 16d after incorporating the indigenous iron activated peroxidation pre-treatment. Model-based analysis indicated that indigenous iron activated peroxidation pre-treatment improved the methane potential by 13%, whereas the hydrolysis rate was not significantly affected. The economic analysis showed that the proposed pre-treatment method can save the cost by $112,000 per year in a treatment plant with a population equivalent of 300,000.

  10. Enhancing the capacity to facilitate physical activity in home-based child care settings.

    PubMed

    Naylor, Patti-Jean; Temple, Viviene A

    2013-01-01

    Healthy Opportunities for Preschoolers (HOP) is a physical activity and movement skill intervention that was developed to address the unique needs of home-based child care providers. The authors used a train-the-trainer approach to enhance local uptake and implementation of HOP and examined the impact on the trainers' (workshop leaders') perceived knowledge, confidence, and intention to implement community workshops and subsequently on the knowledge, confidence, and intentions of workshop participants. This study also assessed feasibility: reach, satisfaction, and facilitators and barriers to workshop implementation. Overall, 92% and 89.5% of the leaders were very or extremely satisfied with the workshop content and delivery, respectively. Training significantly increased their self-reported knowledge (p < .001) and confidence (p < .001). Subsequently, 73% of workshop participants (48 workshops, n = 321) took part in the evaluation; intention to use what they learned after the workshop was high (86%) and perceived knowledge, confidence, and attitude all increased significantly (p < .001). The HOP train-the-trainer approach was feasible and enhanced knowledge, confidence, and readiness to change among home-based child care providers. This approach should be considered as a component of an overall strategy to enhance the promotion of physical activity and movement skills in home-based child care settings.

  11. Constitutive nitric oxide synthase activation is a significant route for nitroglycerin-mediated vasodilation

    PubMed Central

    Bonini, Marcelo G.; Stadler, Krisztian; de Oliveira Silva, Sueli; Corbett, Jean; Dore, Michael; Petranka, John; Fernandes, Denise C.; Tanaka, Leonardo Y.; Duma, Danielle; Laurindo, Francisco R. M.; Mason, Ronald P.

    2008-01-01

    The physiological effects of nitroglycerin as a potent vasodilator have long been documented. However, the molecular mechanisms by which nitroglycerin exerts its biological functions are still a matter of intense debate. Enzymatic pathways converting nitroglycerin to vasoactive compounds have been identified, but none of them seems to fully account for the reported clinical observations. Here, we demonstrate that nitroglycerin triggers constitutive nitric oxide synthase (NOS) activation, which is a major source of NO responsible for low-dose (1–10 nM) nitroglycerin-induced vasorelaxation. Our studies in cell cultures, isolated vessels, and whole animals identified endothelial NOS activation as a fundamental requirement for nitroglycerin action at pharmacologically relevant concentrations in WT animals. PMID:18562300

  12. Activity enhances dopaminergic long-duration response in Parkinson disease

    PubMed Central

    Auinger, Peggy; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Mendis, Tilak

    2012-01-01

    Objective: We tested the hypothesis that dopamine-dependent motor learning mechanism underlies the long-duration response to levodopa in Parkinson disease (PD) based on our studies in a mouse model. By data-mining the motor task performance in dominant and nondominant hands of the subjects in a double-blind randomized trial of levodopa therapy, the effects of activity and dopamine therapy were examined. Methods: We data-mined the Earlier versus Later Levodopa Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed statistical analysis comparing the effects of levodopa and dominance of handedness over 42 weeks. Results: The mean change in finger-tapping counts from baseline before the initiation of therapy to predose at 9 weeks and 40 weeks increased more in the dominant compared to nondominant hand in levodopa-treated subjects in a dose-dependent fashion. There was no significant difference in dominant vs nondominant hands in the placebo group. The short-duration response assessed by the difference of postdose performance compared to predose performance at the same visit did not show any significant difference between dominant vs nondominant hands. Conclusions: Active use of the dominant hand and dopamine replacement therapy produces synergistic effect on long-lasting motor task performance during “off” medication state. Such effect was confined to dopamine-responsive symptoms and not seen in dopamine-resistant symptoms such as gait and balance. We propose that long-lasting motor learning facilitated by activity and dopamine is a form of disease modification that is often seen in trials of medications that have symptomatic effects. PMID:22459675

  13. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin.

    PubMed

    Li, Yuan; Xie, Yanming; Wang, Lianxin; Zhang, Yingying; Gu, Hao; Chai, Yan

    2016-01-01

    The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin's related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed.

  14. Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review

    PubMed Central

    Mishra, Ashish; Seth, Ankit; Maurya, Santosh Kumar

    2016-01-01

    Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area. PMID:27366356

  15. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin

    PubMed Central

    Xie, Yanming; Wang, Lianxin; Zhang, Yingying; Gu, Hao; Chai, Yan

    2016-01-01

    The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin's related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed. PMID:27069488

  16. Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review.

    PubMed

    Mishra, Ashish; Seth, Ankit; Maurya, Santosh Kumar

    2016-01-01

    Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area.

  17. Serotonin2c receptor constitutive activity: in vivo direct and indirect evidence and functional significance.

    PubMed

    Navailles, Sylvia; Lagière, Mélanie; Guthrie, Martin; De Deurwaerdère, Philippe

    2013-06-01

    Serotonin2c (5-HT2c) receptors are widely expressed in the central nervous system where they play a pivotal role in the regulation of neuronal network excitability. Along with this fundamental physiological function, 5-HT2c receptors are thought to be implicated in the pathophysiology of several neuropsychiatric disorders and have become a major pharmacological target for the development of improved treatments of these disorders. In the past decade, many studies have focused on the constitutive activity of 5-HT2c receptors and the therapeutic potential of drugs acting as inverse agonists. Although the constitutive activity of the 5-HT2c receptor has been clearly described in vitro, the transposition of this concept to living animals is often difficult to ascertain. Nevertheless, cumulating evidence has demonstrated the functional relevance of such property in regulating physiological systems in vivo both at the level of the central and peripheral nervous systems. The present review provides an update of the growing number of studies that show, by means of pharmacological tools, the participation of the constitutive activity of 5-HT2c receptors in the control of various biochemical and behavioural functions in vivo and emphasizes the functional organization of this constitutive control together with the phasic and tonic (involving the spontaneous release of 5-HT) modalities of the 5-HT2c receptor in the brain.

  18. Significantly enhanced production of acarbose in fed-batch fermentation with the addition of S-adenosylmethionine.

    PubMed

    Sun, Li-Hui; Li, Ming-Gang; Wang, Yuan-Shan; Zheng, Yu-Guo

    2012-06-01

    Acarbose, a pseudo-oligosaccharide, is widely used clinically in therapies for non-insulin-dependent diabetes. In the present study, S-adenosylmethionine (SAM) was added to selected media in order to investigate its effect on acarbose fermentation by Actinoplanes utahensis ZJB- 08196. Acarbose titer was seen to increase markedly when concentrations of SAM were added over a period of time. The effects of glucose and maltose on the production of acarbose were investigated in both batch and fed-batch fermentation. Optimal acarbose production was observed at relatively low glucose levels and high maltose levels. Based on these results, a further fed-batch experiment was designed so as to enhance the production of acarbose. Fed-batch fermentation was carried out at an initial glucose level of 10 g/l and an initial maltose level of 60 g/l. Then, 12 h post inoculation, 100 micromol/l SAM was added. In addition, 8 g/l of glucose was added every 24 h, and 20 g/l of maltose was added at 96 h. By way of this novel feeding strategy, the maximum titer of acarbose achieved was 6,113 mg/l at 192 h. To our knowledge, the production level of acarbose achieved in this study is the highest ever reported.

  19. Dissociated functional significance of decision-related activity in the primate dorsal stream

    PubMed Central

    Katz, Leor N.; Yates, Jacob L.; Pillow, Jonathan W.; Huk, Alexander C.

    2016-01-01

    During decision-making, neurons in multiple brain regions exhibit responses that are correlated with decisions1-6. However, it remains uncertain whether or not various forms of decision-related activity are causally related to decision-making7-9. Here we address this question by recording and reversibly inactivating the lateral intraparietal (LIP) and middle temporal (MT) areas of rhesus macaques performing a motion direction discrimination task. Neurons in area LIP exhibited firing rate patterns that directly resembled the evidence accumulation process posited to govern decision making2,10, with strong correlations between their response fluctuations and the animal's choices. Neurons in area MT, in contrast, exhibited weak correlations between their response fluctuations and animal choices, and had firing rate patterns consistent with their sensory role in motion encoding1. The behavioral impact of pharmacological inactivation of each area was inversely related to their degree of decision-related activity: while inactivation of neurons in MT profoundly impaired psychophysical performance, inactivation in LIP had no measurable impact on decision-making performance, despite having silenced the very clusters that exhibited strong decision-related activity. Although LIP inactivation did not impair psychophysical behavior, it did influence spatial selection and oculomotor metrics in a free-choice control task. The absence of an effect on perceptual decision-making was stable over trials and sessions, arguing against several forms of compensation, and was robust to changes in stimulus type and task geometry. Thus, decision-related signals in LIP do not appear to be necessary for computing perceptual decisions. Our findings highlight a dissociation between decision correlation and causation, showing that strong neuron-decision correlations may reflect secondary or epiphenomenal signals, and do not necessarily offer direct access to the neural computations underlying

  20. Caffeine-activated large-conductance plasma membrane cation channels in cardiac myocytes: characteristics and significance.

    PubMed

    Zhang, Yu-An; Tuft, Richard A; Lifshitz, Lawrence M; Fogarty, Kevin E; Singer, Joshua J; Zou, Hui

    2007-10-01

    Caffeine-activated, large-conductance, nonselective cation channels (LCCs) have been found in the plasma membrane of isolated cardiac myocytes in several species. However, little is known about the effects of opening these channels. To examine such effects and to further understand the caffeine-activation mechanism, we carried out studies using whole-cell patch-clamp techniques with freshly isolated cardiac myocytes from rats and mice. Unlike previous studies, thapsigargin was used so that both the effect of opening LCCs and the action of caffeine were independent of Ca(2+) release from intracellular stores. These Ca(2+)-permeable LCCs were found in a majority of the cells from atria and ventricles, with a conductance of approximately 370 pS in rat atria. Caffeine and all its direct metabolic products (theophylline, theobromine, and paraxanthine) activated the channel, while isocaffeine did not. Although they share some similarities with ryanodine receptors (RyRs, the openings of which give rise to Ca(2+) sparks), LCCs also showed some different characteristics. With simultaneous Ca(2+) imaging and current recording, the localized fluorescence increase due to Ca(2+) entry through a single opening of an LCC (SCCaFT) was detected. When membrane potential, instead of current, was recorded, SCCaFT-like fluorescence transients (indicating single LCC openings) were found to accompany membrane depolarizations. To our knowledge, this is the first report directly linking membrane potential changes to a single opening of an ion channel. Moreover, these events in cardiac cells suggest a possible additional mechanism by which caffeine and theophylline contribute to the generation of cardiac arrhythmias.

  1. Dissociated functional significance of decision-related activity in the primate dorsal stream.

    PubMed

    Katz, Leor N; Yates, Jacob L; Pillow, Jonathan W; Huk, Alexander C

    2016-07-14

    During decision making, neurons in multiple brain regions exhibit responses that are correlated with decisions. However, it remains uncertain whether or not various forms of decision-related activity are causally related to decision making. Here we address this question by recording and reversibly inactivating the lateral intraparietal (LIP) and middle temporal (MT) areas of rhesus macaques performing a motion direction discrimination task. Neurons in area LIP exhibited firing rate patterns that directly resembled the evidence accumulation process posited to govern decision making, with strong correlations between their response fluctuations and the animal's choices. Neurons in area MT, in contrast, exhibited weak correlations between their response fluctuations and choices, and had firing rate patterns consistent with their sensory role in motion encoding. The behavioural impact of pharmacological inactivation of each area was inversely related to their degree of decision-related activity: while inactivation of neurons in MT profoundly impaired psychophysical performance, inactivation in LIP had no measurable impact on decision-making performance, despite having silenced the very clusters that exhibited strong decision-related activity. Although LIP inactivation did not impair psychophysical behaviour, it did influence spatial selection and oculomotor metrics in a free-choice control task. The absence of an effect on perceptual decision making was stable over trials and sessions and was robust to changes in stimulus type and task geometry, arguing against several forms of compensation. Thus, decision-related signals in LIP do not appear to be critical for computing perceptual decisions, and may instead reflect secondary processes. Our findings highlight a dissociation between decision correlation and causation, showing that strong neuron-decision correlations do not necessarily offer direct access to the neural computations underlying decisions.

  2. UNESCO active learning approach in optics and photonics leads to significant change in Morocco

    NASA Astrophysics Data System (ADS)

    Berrada, K.; Channa, R.; Outzourhit, A.; Azizan, M.; Oueriagli, A.

    2014-07-01

    There are many difficulties in teaching science and technology in developing countries. Several different teaching strategies have to be applied in these cases. More specifically, for developing countries competencies in teaching science in the introductory classroom has attracted much attention. As a specific example we will consider the Moroccan system. In most developing countries everything is moving so slowly that the progress stays static for development. Also, any change needs time, effort and engagement. In our case we discovered that many teachers feel uncomfortable when introducing new teaching methods and evaluation in classes at introductory physics. However, the introduction of an Active Learning in our curricula showed difficulties that students have in understanding physics and especially concepts. Students were interested in having Active Learning courses much more than passive and traditional ones. Changing believes on physical phenomena and reality of the world students become more attractive and their way of thinking Science changed. The main philosophy of fostering modern hands-on learning techniques -adapted to local needs and availability of teaching resources- is elaborated. The Active Learning program provides the teachers with a conceptual evaluation instrument, drawn from relevant physics education research, giving teachers an important tool to measure student learning. We will try to describe the UNESCO Chair project in physics created in 2010 at Cadi Ayyad University since our first experience with UNESCO ALOP program. Many efforts have been done so far and the project helps now to develop more national and international collaborations between universities and Regional Academies of Education and Training. As a new result of these actions and according to our local needs, the translation of the ALOP program into Arabic is now available under the auspice of UNESCO and encouragement of international partners SPIE, ICTP, ICO and OSA.

  3. Enhanced excitatory synaptic network activity following transient group I metabotropic glutamate activation.

    PubMed

    Pan, Y-Z; Rutecki, P A

    2014-09-05

    Prolonged activation of group I metabotropic glutamate receptors (mGluRs) using the agonist (S)-3,5-dihydroxyphenylglycine (DHPG) produces long-lasting changes in the CA3 region of the hippocampal slice. Changes in CA3 pyramidal neuron excitability that follow DHPG exposure result in abnormal network activity manifest by epileptiform activity that consists of interictal and longer lasting ictal epileptiform discharges. In this study we evaluated changes in synaptic activity of CA3 neurons in rat hippocampal slices that occurred after exposure to DHPG. Whole-cell voltage-clamp recordings were made from visually identified CA3 neurons in control artificial cerebrospinal fluid at times greater than 1h after DHPG exposure. Compared to control slices, neurons from slices exposed to DHPG showed enhanced amplitude and frequency of spontaneously occurring excitatory postsynaptic currents (EPSCs) without a concurrent change in inhibitory postsynaptic current (IPSC) amplitude or frequency. Miniature EPSCs were not affected by DHPG exposure but mIPSCs occurred less frequently and were of reduced amplitude. IPSCs recorded in the presence of ionotropic glutamate receptor blockade occurred less frequently in neurons that had been exposed to DHPG. Monosynaptic-evoked IPSPs were also reduced in amplitude in neurons that had been exposed to DHPG. Taken together, these findings demonstrated an enhanced network excitability of the CA3 region and failure of compensatory synaptic inhibition. We propose that prolonged activation of group I mGluR that may occur under conditions of pathological glutamate release results in long-lasting changes in CA3 synaptic network activity and epileptiform activity driven by excessive synaptic excitation.

  4. Directed evolution of subtilisin E in Bacillus subtilis to enhance total activity in aqueous dimethylformamide.

    PubMed

    You, L; Arnold, F H

    1996-01-01

    Sequential rounds of error-prone PCR to introduce random mutations and screening of the resultant mutant libraries have been used to enhance the total catalytic activity of subtilisin E significantly in a non-natural environment, aqueous dimethylformamide (DMF). Seven DNA substitutions coding for three new amino acid substitutions were identified in a mutant isolated after two additional generations of directed evolution carried out on 10M subtilisin E, previously "evolved' to increase its specific activity in DMF. A Bacillus subtilis-Escherichia coli shuttle vector was developed in order to increase the size of the mutant library that could be established in B.subtilis and the stringency of the screening process was increased to reflect total as well as specific activity. This directed evolution approach has been extremely effective for improving enzyme activity in a non-natural environment: the resulting-evolved 13M subtilisin exhibits specific catalytic efficiency towards the hydrolysis of a peptide substrate succinyl-Ala-Ala-Pro-Phe-p-nitroanilide in 60% DMF solution that is three times that of the parent 10M and 471 times that of wild type subtilisin E. The total activity of the 13M culture supernatant is enhanced 16-fold over that of the parent 10M.

  5. Significance of conservative asparagine residues in the thermal hysteresis activity of carrot antifreeze protein.

    PubMed Central

    Zhang, Dang-Quan; Liu, Bing; Feng, Dong-Ru; He, Yan-Ming; Wang, Shu-Qi; Wang, Hong-Bin; Wang, Jin-Fa

    2004-01-01

    The approximately 24-amino-acid leucine-rich tandem repeat motif (PXXXXXLXXLXXLXLSXNXLXGXI) of carrot antifreeze protein comprises most of the processed protein and should contribute at least partly to the ice-binding site. Structural predictions using publicly available online sources indicated that the theoretical three-dimensional model of this plant protein includes a 10-loop beta-helix containing the approximately 24-amino-acid tandem repeat. This theoretical model indicated that conservative asparagine residues create putative ice-binding sites with surface complementarity to the 1010 prism plane of ice. We used site-specific mutagenesis to test the importance of these residues, and observed a distinct loss of thermal hysteresis activity when conservative asparagines were replaced with valine or glutamine, whereas a large increase in thermal hysteresis was observed when phenylalanine or threonine residues were replaced with asparagine, putatively resulting in the formation of an ice-binding site. These results confirmed that the ice-binding site of carrot antifreeze protein consists of conservative asparagine residues in each beta-loop. We also found that its thermal hysteresis activity is directly correlated with the length of its asparagine-rich binding site, and hence with the size of its ice-binding face. PMID:14531728

  6. A significant increase in both basal and maximal calcineurin activity in the rat pilocarpine model of status epilepticus.

    PubMed

    Kurz, J E; Sheets, D; Parsons, J T; Rana, A; Delorenzo, R J; Churn, S B

    2001-07-01

    This study focused on the effects of status epilepticus on the activity of calcineurin, a neuronally enriched, calcium-dependent phosphatase. Calcineurin is an important modulator of many neuronal processes, including learning and memory, induction of apoptosis, receptor function and neuronal excitability. Therefore, a status epilepticus-induced alteration of the activity of this important phosphatase would have significant physiological implications. Status epilepticus was induced by pilocarpine injection and allowed to continue for 60 min. Brain region homogenates were then assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant status epilepticus-dependent increase in both basal and Mn(2+)-dependent calcineurin activity was observed in homogenates isolated from the cortex and hippocampus, but not the cerebellum. This increase was resistant to 150 nM okadaic acid, but sensitive to 50 microM okadaic acid. The increase in basal activity was also resistant to 100 microM sodium orthovanadate. Both maximal dephosphorylation rate and substrate affinity were increased following status epilepticus. However, the increase in calcineurin activity was not found to be due to an increase in calcineurin enzyme levels. Finally, increase in calcineurin activity was found to be NMDA-receptor activation dependent. The data demonstrate that status epilepticus resulted in a significant increase in both basal and maximal calcineurin activity.

  7. Engineered Expression Vectors Significantly Enhanced the Production of 2-Keto-D-gluconic Acid by Gluconobacter oxidans.

    PubMed

    Shi, Yuan-yuan; Li, Ke-fei; Lin, Jin-ping; Yang, Sheng-li; Wei, Dong-zhi

    2015-06-10

    2-Keto-D-gluconic acid (2KGA), a precursor of the important food antioxidant erythorbic acid, can be produced by Gluconobacter oxidans. To genetically engineer G. oxidans for improved 2KGA production, six new expression vectors with increased copy numbers based on pBBR1MCS-5 were constructed via rational mutagenesis. The utility of the mutant vectors was demonstrated by the increased ga2dh mRNA abundance, enzyme activity, and 2KGA production when the ga2dh gene was overexpressed using these vectors. Among the obtained constructs, G. oxidans/pBBR-3510-ga2dh displayed the highest oxidative activity toward gluconic acid (GA). In a batch biotransformation process, the G. oxidans/pBBR-3510-ga2dh strain exhibited 2KGA productivity (0.63 g/g CWW/h) higher than that obtained using strain G. oxidans/pBBR-ga2dh (0.40 g/g CWW/h). When sufficient oxygen was supplied during the biotransformation, up to 480 g/L GA was exhausted in 45 h by the G. oxidans/pBBR-3510-ga2dh strain and approximately 486 g/L 2KGA was produced, generating the productivity of 0.54 g/g CWW/h.

  8. Activation of SIRT1 Attenuates Klotho Deficiency-Induced Arterial Stiffness and Hypertension by Enhancing AMP-Activated Protein Kinase Activity.

    PubMed

    Gao, Diansa; Zuo, Zhong; Tian, Jing; Ali, Quaisar; Lin, Yi; Lei, Han; Sun, Zhongjie

    2016-11-01

    Arterial stiffness is an independent risk factor for stroke and myocardial infarction. This study was designed to investigate the role of SIRT1, an important deacetylase, and its relationship with Klotho, a kidney-derived aging-suppressor protein, in the pathogenesis of arterial stiffness and hypertension. We found that the serum level of Klotho was decreased by ≈45% in patients with arterial stiffness and hypertension. Interestingly, Klotho haplodeficiency caused arterial stiffening and hypertension, as evidenced by significant increases in pulse wave velocity and blood pressure in Klotho-haplodeficient (KL(+/-)) mice. Notably, the expression and activity of SIRT1 were decreased significantly in aortic endothelial and smooth muscle cells in KL(+/-) mice, suggesting that Klotho deficiency downregulates SIRT1. Treatment with SRT1720 (15 mg/kg/d, IP), a specific SIRT1 activator, abolished Klotho deficiency-induced arterial stiffness and hypertension in KL(+/-) mice. Klotho deficiency was associated with significant decreases in activities of AMP-activated protein kinase α (AMPKα) and endothelial NO synthase (eNOS) in aortas, which were abolished by SRT1720. Furthermore, Klotho deficiency upregulated NADPH oxidase activity and superoxide production, increased collagen expression, and enhanced elastin fragmentation in the media of aortas. These Klotho deficiency-associated changes were blocked by SRT1720. In conclusion, this study provides the first evidence that Klotho deficiency downregulates SIRT1 activity in arterial endothelial and smooth muscle cells. Pharmacological activation of SIRT1 may be an effective therapeutic strategy for arterial stiffness and hypertension.

  9. Soil mulching significantly enhances yields and water and nitrogen use efficiencies of maize and wheat: a meta-analysis.

    PubMed

    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.

  10. Soil mulching significantly enhances yields and water and nitrogen use efficiencies of maize and wheat: a meta-analysis

    PubMed Central

    Qin, Wei; Hu, Chunsheng; Oenema, Oene

    2015-01-01

    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. PMID:26586114

  11. Soil mulching significantly enhances yields and water and nitrogen use efficiencies of maize and wheat: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Qin, Wei; Hu, Chunsheng; Oenema, Oene

    2015-11-01

    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.

  12. Novel activities of CYP11A1 and their potential physiological significance

    PubMed Central

    Slominski, Andrzej T.; Li, Wei; Kim, Tae-Kang; Semak, Igor; Wang, Jin; Zjawiony, Jordan K.; Tuckey, Robert C.

    2014-01-01

    CYP11A1, found only in vertebrates, catalyzes the first step of steroidogenesis where cholesterol is converted to pregnenolone. The purified enzyme, also converts desmosterol and plant sterols including campesterol and β-sitosterol, to pregnenolone. Studies, initially with purified enzyme, reveal that 7-dehydrocholesterol (7DHC), ergosterol, lumisterol 3, and vitamins D3 and D2 also serve as substrates for CYP11A1, with 7DHC being better and vitamins D3 and D2 being poorer substrates than cholesterol. Adrenal glands, placenta, and epidermal keratinocytes can also carry out these conversions and 7-dehydropregnenolone has been detected in the epidermis, adrenal glands, and serum, and 20-hydroxyvitamin D3 was detected in human serum and the epidermis. Thus, this metabolism does appear to occur in vivo, although its quantitative importance and physiological role remain to be established. CYP11A1 action on 7DHC in vivo is further supported by detection of Δ7steroids in Smith-Lemli-Opitz syndrome patients. The activity of CYP11A1 is affected by the structure of the substrate with sterols having steroidal or Δ7-steroidal structures undergoing side chain cleavage following hydroxylations at C22 and C20. In contrast, metabolism of vitamin D involves sequential hydroxylations that start at C20 but do not lead to cleavage. Molecular modeling using the crystal structure of CYP11A1 predicts that other intermediates of cholesterol synthesis could also serve as substrates for CYP11A1. Finally, CYP11A1-derived secosteroidal hydroxy-derivatives and Δ7steroids are biologically active when administered in vitro in a manner dependent on the structure of the compound and the lineage of the target cells, suggesting physiological roles for these metabolites. This article is part of a special issue entitled ‘SI: Steroid/Sterol signaling’. PMID:25448732

  13. Novel activities of CYP11A1 and their potential physiological significance.

    PubMed

    Slominski, Andrzej T; Li, Wei; Kim, Tae-Kang; Semak, Igor; Wang, Jin; Zjawiony, Jordan K; Tuckey, Robert C

    2015-07-01

    CYP11A1, found only in vertebrates, catalyzes the first step of steroidogenesis where cholesterol is converted to pregnenolone. The purified enzyme, also converts desmosterol and plant sterols including campesterol and β-sitosterol, to pregnenolone. Studies, initially with purified enzyme, reveal that 7-dehydrocholesterol (7DHC), ergosterol, lumisterol 3, and vitamins D3 and D2 also serve as substrates for CYP11A1, with 7DHC being better and vitamins D3 and D2 being poorer substrates than cholesterol. Adrenal glands, placenta, and epidermal keratinocytes can also carry out these conversions and 7-dehydropregnenolone has been detected in the epidermis, adrenal glands, and serum, and 20-hydroxyvitamin D3 was detected in human serum and the epidermis. Thus, this metabolism does appear to occur in vivo, although its quantitative importance and physiological role remain to be established. CYP11A1 action on 7DHC in vivo is further supported by detection of Δ(7)steroids in Smith-Lemli-Opitz syndrome patients. The activity of CYP11A1 is affected by the structure of the substrate with sterols having steroidal or Δ(7)-steroidal structures undergoing side chain cleavage following hydroxylations at C22 and C20. In contrast, metabolism of vitamin D involves sequential hydroxylations that start at C20 but do not lead to cleavage. Molecular modeling using the crystal structure of CYP11A1 predicts that other intermediates of cholesterol synthesis could also serve as substrates for CYP11A1. Finally, CYP11A1-derived secosteroidal hydroxy-derivatives and Δ(7)steroids are biologically active when administered in vitro in a manner dependent on the structure of the compound and the lineage of the target cells, suggesting physiological roles for these metabolites. This article is part of a special issue entitled 'SI: Steroid/Sterol signaling'.

  14. Does small-bodied salmon spawning activity enhance streambed mobility?

    NASA Astrophysics Data System (ADS)

    Hassan, Marwan A.; Tonina, Daniele; Buxton, Todd H.

    2015-09-01

    Female salmonids bury and lay their eggs in streambeds by digging a pit, which is then covered with sediment from a second pit that is dug immediately upstream. The spawning process alters streambed topography, winnows fine sediment, and mixes sediment in the active layer. The resulting egg nests (redds) contain coarser and looser sediments than those of unspawned streambed areas, and display a dune-like shape with an amplitude and length that vary with fish size, substrate conditions, and flow conditions. Redds increase local bed surface roughness (<10-1 channel width, W), but may reduce the size of macro bedforms by eroding reach-scale topography (100-101W). Research has suggested that spawning may increase flow resistance due to redd form drag, resulting in lower grain shear stress and less particle mobility. Spawning, also prevents streambed armoring by mixing surface and subsurface material, potentially increasing particle mobility. Here we use two-dimensional hydraulic modeling with detailed prespawning and postspawning bathymetries and field observations to test the effect of spawning by small-bodied salmonids on sediment transport. Our results show that topographical roughness from small salmon redds has negligible effects on shear stress at the reach-unit scale, and limited effects at the local scale. Conversely, results indicate sediment mixing reduces armoring and enhances sediment mobility, which increases potential bed load transport by subsequent floods. River restoration in fish-bearing streams should take into consideration the effects of redd excavation on channel stability. This is particularly important for streams that historically supported salmonids and are the focus of habitat restoration actions.

  15. [Flipped classroom as a strategy to enhance active learning].

    PubMed

    Wakabayashi, Noriyuki

    2015-03-01

    This paper reviews the introduction of a flipped class for fourth grade dentistry students, and analyzes the characteristics of the learning method. In fiscal 2013 and 2014, a series of ten three-hour units for removable partial prosthodontics were completed with the flipped class method; a lecture video of approximately 60 minutes was made by the teacher (author) and uploaded to the university's e-learning website one week before each class. Students were instructed to prepare for the class by watching the streaming video on their PC, tablet, or smartphone. In the flipped class, students were not given a lecture, but were asked to solve short questions displayed on screen, to make a short presentation about a part of the video lecture, and to discuss a critical question related to the main subject of the day. An additional team-based learning (TBL) session with individual and group answers was implemented. The average individual scores were considerably higher in the last two years, when the flipped method was implemented, than in the three previous years when conventional lectures were used. The following learning concepts were discussed: the role of the flipped method as an active learning strategy, the efficacy of lecture videos and short questions, students' participation in the class discussion, present-day value of the method, cooperation with TBL, the significance of active learning in relation with the students' learning ability, and the potential increase in the preparation time and workload for students.

  16. A more robust model of the biodiesel reaction, allowing identification of process conditions for significantly enhanced rate and water tolerance.

    PubMed

    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.

  17. Enhanced catalytic activity in strained chemically exfoliated WS₂ nanosheets for hydrogen evolution.

    PubMed

    Voiry, Damien; Yamaguchi, Hisato; Li, Junwen; Silva, Rafael; Alves, Diego C B; Fujita, Takeshi; Chen, Mingwei; Asefa, Tewodros; Shenoy, Vivek B; Eda, Goki; Chhowalla, Manish

    2013-09-01

    Efficient evolution of hydrogen through electrocatalysis at low overpotentials holds tremendous promise for clean energy. Hydrogen evolution can be easily achieved by electrolysis at large potentials that can be lowered with expensive platinum-based catalysts. Replacement of Pt with inexpensive, earth-abundant electrocatalysts would be significantly beneficial for clean and efficient hydrogen evolution. To this end, promising results have been reported using 2H (trigonal prismatic) XS₂ (where X  =  Mo or W) nanoparticles with a high concentration of metallic edges. The key challenges for XS₂ are increasing the number and catalytic activity of active sites. Here we report monolayered nanosheets of chemically exfoliated WS₂ as efficient catalysts for hydrogen evolution with very low overpotentials. Analyses indicate that the enhanced electrocatalytic activity of WS₂ is associated with the high concentration of the strained metallic 1T (octahedral) phase in the as-exfoliated nanosheets. Our results suggest that chemically exfoliated WS₂ nanosheets are interesting catalysts for hydrogen evolution.

  18. Enhancement of Neuromuscular Activity by Natural Specimens and Cultured Mycelia of Cordyceps sinensis in Mice

    PubMed Central

    Singh, K. P.; Meena, H. S.; Negi, P. S.

    2014-01-01

    The present study was aimed to evaluate the effect of natural specimen and laboratory cultured mycelia of Cordyceps sinensis on neuromuscular activity in mice. The powder of natural specimen and laboratory cultured Cordyceps sinensis was orally administered at the dose rate of 100, 300 and 500 mg/kg for 30 days. Natural specimen and in vitro propagated Cordyceps sinensis showed significant (P<0.05) enhancement in neuromuscular endurance and antidepressant activity at 300 and 500 mg/kg as compared to the control group. However, the fungus did not proved to be as effective as fluoxetine in exhibiting antidepressant action. Muscular endurance was determined on a Rota rod apparatus while antidepressant (mood elevating) activity was measured on a photoactometer in Swiss albino mice. The effects produced by both natural specimens and laboratory cultured Cordyceps sinensis were comparable and showed almost equal potency. PMID:25425763

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Effect of Evolvulus alsinoides Linn. on learning behavior and memory enhancement activity in rodents.

    PubMed

    Nahata, Alok; Patil, U K; Dixit, V K

    2010-04-01

    In the Ayurvedic system of medicine, the whole herb of 'Shankhpushpi' has been employed clinically for centuries for its memory potentiating, anxiolytic and tranquilizing properties. The present study was undertaken to investigate the effects of Evolvulus alsinoides (EA), considered as Shankhpushpi on learning and memory in rodents. Nootropic activity using Cook and Weidley's pole climbing apparatus, passive avoidance paradigms and active avoidance tests were used to test learning and memory. The ethanol extract of EA and its ethyl acetate and aqueous fractions were evaluated for their memory enhancing properties. Two doses (100 and 200 mg/kg p.o.) of the ethanol extract and ethyl acetate and aqueous fractions were administered in separate groups of animals. Both doses of all the extracts of EA significantly improved learning and memory in rats. Furthermore, these doses significantly reversed the amnesia induced by scopolamine (0.3 mg/kg i.p.). Nootropic activity was compared using piracetam as the standard. EA also exhibited potent memory enhancing effects in the step-down and shuttle-box avoidance paradigms.

  1. Effect of Convulvulus pluricaulis Choisy. on learning behaviour and memory enhancement activity in rodents.

    PubMed

    Nahata, Alok; Patil, U K; Dixit, V K

    2008-01-01

    The present study was undertaken to investigate the effects of Convulvulus pluricaulis (CP), considered as Shankhpushpi on learning and memory in rodents. Nootropic activity using Cook and Weidley's Pole Climbing Apparatus, passive avoidance paradigms and active avoidance tests were used to test learning and memory. The ethanolic extract of CP and its ethyl acetate and aqueous fractions were evaluated for their memory enhancing properties. Two doses (100 and 200 mg kg(-1) p.o.) of the ethanolic extract and ethyl acetate and aqueous fractions were administered in separate groups of animals. Both the doses of all the extracts of CP significantly improved learning and memory in rats. Furthermore, these doses significantly reversed the amnesia induced by scopolamine (0.3 mg kg(-1) i.p.). Nootropic activity was compared using piracetam as the standard. Moreover, CP has exhibited potent memory-enhancing effects in the step-down and shuttle-box avoidance paradigms. Further studies are necessitated to identify the exact mechanism of action.

  2. Enhanced complement activation is part of the unfavourable cardiovascular risk profile in South Asians

    PubMed Central

    Siezenga, M A; Chandie Shaw, P K; van der Geest, R N; Mollnes, T E; Daha, M R; Rabelink, T J; Berger, S P

    2009-01-01

    South Asian immigrants in western societies exhibit a high burden of diabetes and subsequent vascular complications. Diabetic vascular complications are associated with vascular inflammation. We hypothesize that enhanced complement activation is involved. Therefore, levels of complement C3 and SC5b-9 – the soluble end product of complement activation – in a group of 200 South Asians were compared with an age- and sex-matched control group of native Caucasians. In addition, the association between complement levels and albuminuria, an indicator of renal damage and a cardiovascular risk marker, was assessed in the diabetic South Asian group. Compared with native Caucasians, South Asians had significantly higher levels of both serum C3 and plasma SC5b-9, even when only non-diabetic South Asians were considered. Diabetic South Asians had significantly higher C3 levels compared with non-diabetic South Asians. In diabetic South Asians, higher levels of SC5b-9 were associated with an increased prevalence of albuminuria (odds ratio 5·4, 95% confidence interval 1·8–15·8). These results suggest that enhanced complement activation is part of the unfavourable cardiovascular risk profile in South Asians. PMID:19659775

  3. Adult acclimation to combined temperature and pH stressors significantly enhances reproductive outcomes compared to short-term exposures.

    PubMed

    Suckling, Coleen C; Clark, Melody S; Richard, Joelle; Morley, Simon A; Thorne, Michael A S; Harper, Elizabeth M; Peck, Lloyd S

    2015-05-01

    This study examined the effects of long-term culture under altered conditions on the Antarctic sea urchin, Sterechinus neumayeri. Sterechinus neumayeri was cultured under the combined environmental stressors of lowered pH (-0.3 and -0.5 pH units) and increased temperature (+2 °C) for 2 years. This time-scale covered two full reproductive cycles in this species and analyses included studies on both adult metabolism and larval development. Adults took at least 6-8 months to acclimate to the altered conditions, but beyond this, there was no detectable effect of temperature or pH. Animals were spawned after 6 and 17 months exposure to altered conditions, with markedly different outcomes. At 6 months, the percentage hatching and larval survival rates were greatest in the animals kept at 0 °C under current pH conditions, whilst those under lowered pH and +2 °C performed significantly less well. After 17 months, performance was not significantly different across treatments, including controls. However, under the altered conditions urchins produced larger eggs compared with control animals. These data show that under long-term culture adult S. neumayeri appear to acclimate their metabolic and reproductive physiology to the combined stressors of altered pH and increased temperature, with relatively little measureable effect. They also emphasize the importance of long-term studies in evaluating effects of altered pH, particularly in slow developing marine species with long gonad maturation times, as the effects of altered conditions cannot be accurately evaluated unless gonads have fully matured under the new conditions.

  4. Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure.

    PubMed

    Xu, Bo; Zheng, Hong; Patel, Kaushik P

    2012-04-15

    Previous studies have indicated that there is increased activation of the paraventricular nucleus (PVN) in rats with chronic heart failure (CHF); however, it is not clear if the preautonomic neurons within the PVN are specifically overactive. Also, it is not known if these neurons have altered responses to baroreceptor or osmotic challenges. Experiments were conducted in rats with CHF (6-8 wk after coronary artery ligation). Spontaneously active neurons were recorded in the PVN, of which 36% were antidromically activated from the rostral ventrolateral medulla (RVLM). The baseline discharge rate in RVLM-projecting PVN (PVN-RVLM) neurons from CHF rats was significantly greater than in sham-operated (sham) rats (6.0 ± 0.6 vs. 2.6 ± 0.3 spikes/s, P < 0.05). Picoinjection of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid significantly decreased the basal discharge of PVN-RVLM neurons by 80% in CHF rats compared with 37% in sham rats. Fifty-two percent of spontaneously active PVN-RVLM neurons responded to changes in the mean arterial pressure (MAP). The changes in discharge rate in PVN-RVLM neurons after a reduction in MAP (+52 ± 7% vs. +184 ± 61%) or an increase in MAP (-42 ± 8% vs. -71 ± 6%) were significantly attenuated in rats with CHF compared with sham rats. Most PVN-RVLM neurons (63%), including all barosensitive PVN-RVLM neurons, were excited by an internal carotid artery injection of hypertonic NaCl (2.1 osmol/l), whereas a smaller number (7%) were inhibited. The increase in discharge rate in PVN-RVLM neurons to hypertonic stimulation was significantly enhanced in rats with CHF compared with sham rats (134 ± 15% vs. 92 ± 13%). Taken together, these data suggest that PVN-RVLM neurons are more active under basal conditions and this overactivation is mediated by an enhanced glutamatergic tone in rats with CHF. Furthermore, this enhanced activation of PVN-RVLM neurons may contribute to the altered responses to

  5. Compositions comprising a polypeptide having cellulolytic enhancing activity and a bicycle compound and uses thereof

    DOEpatents

    Xu, Feng; Sweeney, Matthew; Quinlan, Jason

    2015-06-16

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a bicyclic compound. The present invention also relates to methods of using the compositions.

  6. Compositions comprising a polypeptide having cellulolytic enhancing activity and a bicyclic compound and uses thereof

    DOEpatents

    Quinlan, Jason; Xu, Feng; Sweeney, Matthew

    2016-10-04

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a bicyclic compound. The present invention also relates to methods of using the compositions.

  7. Compositions comprising a polypeptide having cellulolytic enhancing activity and a quinone compound and uses thereof

    DOEpatents

    Quinlan, Jason; Xu, Feng; Sweeney, Matthew

    2016-03-01

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a quinone compound. The present invention also relates to methods of using the compositions.

  8. Compositions comprising a polypeptide having cellulolytic enhancing activity and a heterocyclic compound and uses thereof

    DOEpatents

    Xu, Feng; Sweeney, Matthew; Quinlan, Jason

    2016-08-02

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a heterocyclic compound. The present invention also relates to methods of using the compositions.

  9. Compositions comprising a polypeptide having cellulolytic enhancing activity and a dioxy compound and uses thereof

    DOEpatents

    Sweeney, Matthew; Xu, Feng; Quinlan, Jason

    2016-07-19

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a dioxy compound. The present invention also relates to methods of using the compositions.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. On Stellar Activity Enhancement Due to Interactions with Extrasolar Giant Planets.

    PubMed

    Cuntz; Saar; Musielak

    2000-04-20

    We present a first attempt to identify and quantify possible interactions between recently discovered extrasolar giant planets (and brown dwarfs) and their host stars, resulting in activity enhancement in the stellar outer atmospheres. Many extrasolar planets have masses comparable to or larger than Jupiter and are within a distance of 0.5 AU, suggesting the possibility of their significant influence on stellar winds, coronae, and even chromospheres. Beyond the well-known rotational synchronization, the interactions include tidal effects (in which enhanced flows and turbulence in the tidal bulge lead to increased magnetoacoustic heating and dynamo action) and direct magnetic interaction between the stellar and planetary magnetic fields. We discuss relevant parameters for selected systems and give preliminary estimates of the relative interaction strengths.

  12. Performance Enhancement of a Full-Scale Vertical Tail Model Equipped with Active Flow Control

    NASA Technical Reports Server (NTRS)

    Whalen, Edward A.; Lacy, Douglas; Lin, John C.; Andino, Marlyn Y.; Washburn, Anthony E.; Graff, Emilio; Wygnanski, Israel J.

    2015-01-01

    This paper describes wind tunnel test results from a joint NASA/Boeing research effort to advance active flow control (AFC) technology to enhance aerodynamic efficiency. A full-scale Boeing 757 vertical tail model equipped with sweeping jet actuators was tested at the National Full-Scale Aerodynamics Complex (NFAC) 40- by 80-Foot Wind Tunnel (40x80) at NASA Ames Research Center. The model was tested at a nominal airspeed of 100 knots and across rudder deflections and sideslip angles that covered the vertical tail flight envelope. A successful demonstration of AFC-enhanced vertical tail technology was achieved. A 31- actuator configuration significantly increased side force (by greater than 20%) at a maximum rudder deflection of 30deg. The successful demonstration of this application has cleared the way for a flight demonstration on the Boeing 757 ecoDemonstrator in 2015.

  13. Senescence-induced loss in photosynthesis enhances cell wall beta-glucosidase activity.

    PubMed

    Mohapatra, Pranab Kishor; Patro, Lichita; Raval, Mukesh Kumar; Ramaswamy, Nemmara Krishnan; Biswal, Udaya Chand; Biswal, Basanti

    2010-03-01

    A link between senescence-induced decline in photosynthesis and activity of beta-glucosidase is examined in the leaves of Arabidopsis. The enzyme is purified and characterized. The molecular weight of the enzyme is 58 kDa. It shows maximum activity at pH 5.5 and at temperature of 50 degrees C. Photosynthetic measurements and activity of the enzyme are conducted at different developmental stages including senescence of leaves. Senescence causes a significant loss in total chlorophyll, stomatal conductance, rate of evaporation and in the ability of the leaves for carbon dioxide fixation. The process also brings about a decline in oxygen evolution, quantum yield of photosystem II (PS II) and quantum efficiency of PS II photochemistry of thylakoid membrane. The loss in photosynthesis is accompanied by a significant increase in the activity of the cell wall-bound beta-glucosidase that breaks down polysaccharides to soluble sugars. The loss in photosynthesis as a signal for the enhancement in the activity of the enzyme is confirmed from the observation that incubation of excised mature leaves in continuous dark or in light with a photosynthesis inhibitor 3-(3,4-dichlorophenyl)-1, 1-dimethylurea (DCMU) that leads to sugar starvation enhances the activity of the enzyme. The work suggests that in the background of photosynthetic decline, the polysaccharides bound to cell wall that remains intact even during late phase of senescence may be the last target of senescing leaves for a possible source of sugar for remobilization and completion of the energy-dependent senescence program.

  14. Ultraviolet A Enhances Cathepsin L Expression and Activity via JNK Pathway in Human Dermal Fibroblasts

    PubMed Central

    Xu, Qing-Fang; Zheng, Yue; Chen, Jian; Xu, Xin-Ya; Gong, Zi-Jian; Huang, Yun-Fen; Lu, Chun; Maibach, Howard I; Lai, Wei

    2016-01-01

    Background: Cathepsin L (CatL) is a cysteine protease with strong matrix degradation activity that contributes to photoaging. Mannose phosphate-independent sorting pathways mediate ultraviolet A (UVA)-induced alternate trafficking of CatL. Little is known about signaling pathways involved in the regulation of UVA-induced CatL expression and activity. This study aims to investigate whether a single UVA irradiation affects CatL expression and activity and whether mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) pathway is involved in the regulation of UVA-induced CatL expression and activity in human dermal fibroblasts (HDFs). Methods: Primary HDFs were exposed to UVA. Cell proliferation was determined by a cell counting kit. UVA-induced CatL production and activity were studied with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and fluorimetric assay in cell lysates collected on three consecutive days after irradiation. Time courses of UVA-activated JNK and p38MAPK signaling were examined by Western blotting. Effects of MAPK inhibitors and knockdown of Jun and Fos on UVA-induced CatL expression and activity were investigated by RT-PCR, Western blotting, and fluorimetric assay. Data were analyzed by one-way analysis of variance. Results: UVA significantly increased CatL gene expression, protein abundance, and enzymatic activity for three consecutive days after irradiation (F = 83.11, 56.14, and 71.19, respectively; all P < 0.05). Further investigation demonstrated phosphorylation of JNK and p38MAPK activated by UVA. Importantly, inactivation of JNK pathway significantly decreased UVA-induced CatL expression and activity, which were not affected by p38MAPK inhibition. Moreover, knockdown of Jun and Fos significantly attenuated basal and UVA-induced CatL expression and activity. Conclusions: UVA enhances CatL production and activity in HDFs, probably by activating JNK and downstreaming AP-1. These

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

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

    PubMed Central

    Wang, Guanyao; Huang, Xingyi; Jiang, Pingkai

    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 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. PMID:28225047

  18. Significant Correlation between TLR2 Agonist Activity and TNF-α Induction in J774.A1 Macrophage Cells by Different Medicinal Mushroom Products.

    PubMed

    Coy, Catherine; Standish, Leanna J; Bender, Geoff; Lu, Hailing

    2015-01-01

    In the US market, there is a variety of mushroom preparations available, even within the same species of mushroom. Nonetheless, little is known about whether species or the various extraction methods affect biological activity and potency of the immune modulatory activity of mushroom extracts. After discovering that protein-bound polysaccharide-K, a hot water extract from Trametes versicolor, was a potent Toll-like receptor (TLR)-2 agonist that stimulates both innate and adaptive immunity, this study was initiated to evaluate whether other medicinal mushroom products also have TLR2 agonist activity and immune-enhancing potential as measured by the induction of tumor necrosis factor (TNF)-α in J774.A1 murine macrophage cells. Furthermore, the products were divided by extraction method and species to determine whether these factors affect their immunomodulatory activity. The results showed that the majority (75%) of mushroom products tested had TLR2 agonist activity and that there was a significant correlation between TLR2 agonist activity and TNF-α induction potential in the mushroom products analyzed. In addition, the data demonstrated that hot water mushroom extracts are more potent than ground mushroom products in activating TLR2 and inducing TNF-α. These data provide evidence that extraction methods may affect the biological activity of mushroom products; thus, further studies are warranted to investigate the structural differences between various mushroom products.

  19. Extraction optimization and nanoencapsulation of jujube pulp and seed for enhancing antioxidant activity.

    PubMed

    Han, Hye Jung; Lee, Ji-Soo; Park, Sun-Ah; Ahn, Jun-Bae; Lee, Hyeon Gyu

    2015-06-01

    The aim of this study was to optimize extraction conditions for jujube pulp and seed in order to obtain maximum active ingredient yield and antioxidant activity, as well as to prepare chitosan nanoparticles loaded with jujube pulp and seed extracts for enhancing stability. The extraction conditions, i.e. temperature, time, and ethanol concentration, were optimized at the following respective values: 61.2 °C, 38 h, and 60.4% for pulp, and 58 °C, 34 h, and 59.2% for seed. The jujube nanoparticle size significantly increased with a higher chitosan/sodium tripolyphosphate ratio and extract concentration. Entrapment efficiency was greater than 80% regardless of preparation conditions. The stabilities of jujube pulp and seed extract in terms of total phenolic content and antioxidant activity were effectively enhanced by nanoencapsulation. In conclusion, jujube pulp and seed extracts prepared using optimal conditions could be useful as a natural functional food ingredient with antioxidant activity, and nanoencapsulation can be used to improve the stability of jujube extract. Therefore, these results could be used to promote the utilization of not only jujube pulp but also seed, by product.

  20. Enhancing physical activity adherence and well-being in multiple sclerosis: a randomised controlled trial.

    PubMed

    McAuley, E; Motl, R W; Morris, K S; Hu, L; Doerksen, S E; Elavsky, S; Konopack, J F

    2007-06-01

    Individuals with multiple sclerosis (MS) are more sedentary than the general population, increasing their propensity for reduced functional ability, mobility, and activities of daily living. Self-efficacy has been one of the most consistent determinants of physical activity across populations, including those with MS. However, no studies exist that have attempted to influence self-efficacy in MS patients, in an effort to improve physical activity participation. We conducted a three-month randomised, controlled trial (n=26), contrasting the effects of an efficacy-enhancement exercise condition and a control exercise condition on exercise adherence, well-being, and affective responses to exercise. Analyses indicated that individuals in the efficacy enhancement condition attended more exercise sessions, reported greater levels of well-being and exertion, and felt better following exercise than individuals in the standard care condition. Regardless of treatment condition, individuals with a stronger sense of exercise self-efficacy, who reported more enjoyment following the exercise sessions, demonstrated significantly greater adherence with the exercise program. We believe this to be the first empirical attempt to change physical activity behavior in persons with MS using a well-established theoretical framework to drive the intervention. Continued examination of self-efficacy as a determinant of behavior change in individuals with MS is needed.

  1. Graphene as conductive additives in binderless activated carbon electrodes for power enhancement of supercapacitor

    NASA Astrophysics Data System (ADS)

    Nor, N. S. M.; Deraman, M.; Suleman, M.; Norizam, M. D. M.; Basri, N. H.; Sazali, N. E. S.; Hamdan, E.; Hanappi, M. F. Y. M.; Tajuddin, N. S. M.; Othman, M. A. R.; Shamsudin, S. A.; Omar, R.

    2016-11-01

    Carbon based supercapacitor electrodes from composite of binderless activated carbon and graphene as a conductive additive were fabricated with various amount of graphene (0, 2, 4, 6, 8 and 10 wt%). Graphene was mixed in self-adhesive carbon grains produced from pre-carbonized powder derived from fibers of oil palm empty fruit bunches and converted into green monoliths (GMs). The GMs were carbonized (N2) and activated (CO2) to produce activated carbon monoliths (ACMs) electrodes. Porosity characterizations by nitrogen adsorption-desorption isotherm method shows that the pore characteristics of the ACMs are influenced by the graphene additive. The results of galvanostatic charge-discharge tests carried out on the supercapacitor cells fabricated using these electrodes shows that the addition of graphene additive (even in small amount) decreases the equivalent series resistance and enhances the specific power of the cells but significantly lowers the specific capacitance. The supercapacitor cell constructed with the electrode containing 4 wt % of graphene offers the maximum power (175 W kg-1) which corresponds to an improvement of 55%. These results demonstrate that the addition of graphene as conductive additive in activated carbon electrodes can enhance the specific power of the supercapacitor.

  2. Enhanced catalytic activity of solid and hollow platinum-cobalt nanoparticles towards reduction of 4-nitrophenol

    NASA Astrophysics Data System (ADS)

    Krajczewski, Jan; Kołątaj, Karol; Kudelski, Andrzej

    2016-12-01

    Previous investigations of hollow platinum nanoparticles have shown that such nanostructures are more active catalysts than their solid counterparts towards the following electrochemical reactions: reduction of oxygen, evolution of hydrogen, and oxidation of borohydride, methanol and formic acid. In this work we show that synthesised using standard galvanic replacement reaction (with Co templates) hollow platinum nanoparticles exhibit enhanced catalytic activity also towards reduction of 4-nitrophenol by sodium borohydride in water. Unlike in the case of procedures involving hollow platinum catalysts employed so far to carry out this reaction it is not necessary to couple analysed platinum nanoparticles to the surface of an electrode. Simplification of the analyzed reaction may eliminate same experimental errors. We found that the enhanced catalytic activity of hollow Pt nanoparticles is not only connected with generally observed larger surface area of hollow nanostructures, but is also due to the contamination of formed hollow nanostructures with cobalt, from which sacrificial templates used in the synthesis of hollow Pt nanostrustures have been formed. Because using sacrificial templates is a typical method of synthesis of hollow metal nanostructures, formed hollow nanoparticles are probably often contaminated, which may significantly influence their catalytic activity.

  3. Significantly Enhanced Energy Density in Nanocomposite Capacitors Combining the TiO2 Nanorod Array with Poly(vinylidene fluoride).

    PubMed

    Yao, Lingmin; Pan, Zhongbin; Liu, Shaohui; Zhai, Jiwei; Chen, Haydn H D

    2016-10-05

    A novel inorganic/polymer nanocomposite, using 1-dimensional TiO2 nanorod array as fillers (TNA) and poly(vinylidene fluoride) (PVDF) as matrix, has been successfully synthesized for the first time. A carefully designed process sequence includes several steps with the initial epitaxial growth of highly oriented TNA on the fluorine-doped tin oxide (FTO) conductive glass. Subsequently, PVDF is embedded into the nanorods by the spin-coating method followed by annealing and quenching processes. This novel structure with dispersive fillers demonstrates a successful compromise between the electric displacement and breakdown strength, resulting in a dramatic increase in the electric polarization which leads to a significant improvement on the energy density and discharge efficiency. The nanocomposites with various height ratios of fillers between the TNA and total film thickness were investigated by us. The results show that nanocomposite with 18% height ratio fillers obtains maximum increase in the energy density (10.62 J cm(-3)) at a lower applied electric field of 340 MV m(-1), and it also illustrates a higher efficiency (>85%) under the electric field less than 100 MV m(-1). Even when the electric field reached 340 MV m(-1), the efficiency of nanocomposites can still maintained at ∼70%. This energy density exceeds most of the previously reported TiO2-based nanocomposite values at such a breakdown strength, which provides another promising design for the next generation of dielectric nanocomposite material, by using the highly oriented nanorod array as fillers for the higher energy density capacitors. Additionally, the finite element simulation has been employed to analyze the distribution of electric fields and electric flux density to explore the inherent mechanism of the higher performance of the TNA/PVDF nanocomposites.

  4. Significance of an Active Volcanic Front in the Far Western Aleutian Arc

    NASA Astrophysics Data System (ADS)

    Yogodzinski, G. M.; Kelemen, P. B.; Hoernle, K.

    2015-12-01

    Discovery of a volcanic front west of Buldir Volcano, the western-most emergent Aleutian volcano, demonstrates that the surface expression of Aleutian volcanism falls below sea level just west of 175.9° E longitude, but is otherwise continuous from mainland Alaska to Kamchatka. The newly discovered sites of western Aleutian seafloor volcanism are the Ingenstrem Depression, a 60 km-long structural depression just west of Buldir, and an unnamed area 300 km further west, referred to as the Western Cones. These locations fall along a volcanic front that stretches from Buldir to Piip Seamount near the Komandorsky Islands. Western Aleutian seafloor volcanic rocks include large quantities of high-silica andesite and dacite, which define a highly calc-alkaline igneous series and carry trace element signatures that are unmistakably subduction-related. This indicates that subducting oceanic lithosphere is present beneath the westernmost Aleutian arc. The rarity of earthquakes below depths of 200 km indicates that the subducting plate is unusually hot. Some seafloor volcanoes are 6-8 km wide at the base, and so are as large as many emergent Aleutian volcanoes. The seafloor volcanoes are submerged in water depths >3000 m because they sit on oceanic lithosphere of the Bering Sea. The volcanic front is thus displaced to the north of the ridge of arc crust that underlies the western Aleutian Islands. This displacement, which developed since approximately 6 Ma when volcanism was last active on the islands, must be a consequence of oblique convergence in a system where the subducting plate and large blocks of arc crust are both moving primarily in an arc-parallel sense. The result is a hot-slab system where low subduction rates probably limit advection of hot mantle to the subarc, and produce a relatively cool and perhaps stagnant mantle wedge. The oceanic setting and highly oblique subduction geometry also severely limit rates of sediment subduction, so the volcanic rocks, which

  5. Enhanced Preliminary Assessment Report: Pontiac Storage Activity, Pontiac, Michigan

    DTIC Science & Technology

    1990-03-01

    objective of the enhanced PA was to assess the PSA’s present environmental status and the need for any further action required at the site prior to...of this erhanced PA is to assess the PSA’s present environmental status to determine the need for any further action. The enhanced PA involved...if any , of these materials contain asbestos. 3 o Spray-painting was formerly conducted in the maintenance area of Section C of the main facility. A

  6. Chromatin profiling of Drosophila CNS subpopulations identifies active transcriptional enhancers.

    PubMed

    Pearson, Joseph C; McKay, Daniel J; Lieb, Jason D; Crews, Stephen T

    2016-10-15

    One of the key issues in studying transcriptional regulation during development is how to employ genome-wide assays that reveals sites of open chromatin and transcription factor binding to efficiently identify biologically relevant genes and enhancers. Analysis of Drosophila CNS midline cell development provides a useful system for studying transcriptional regulation at the genomic level due to a large, well-characterized set of midline-expressed genes and in vivo validated enhancers. In this study, FAIRE-seq on FACS-purified midline cells was performed and the midline FAIRE data were compared with whole-embryo FAIRE data. We find that regions of the genome with a strong midline FAIRE peak and weak whole-embryo FAIRE peak overlap with known midline enhancers and provide a useful predictive tool for enhancer identification. In a complementary analysis, we compared a large dataset of fragments that drive midline expression in vivo with the FAIRE data. Midline enhancer fragments with a midline FAIRE peak tend to be near midline-expressed genes, whereas midline enhancers without a midline FAIRE peak were often distant from midline-expressed genes and unlikely to drive midline transcription in vivo.

  7. The vertical propagation and extent of stratospheric temperature and wind anomalies related to enhanced geomagnetic activity

    NASA Astrophysics Data System (ADS)

    Seppälä, A. M.; Baumgaertner, A. J.; Jöckel, P.; Clilverd, M.

    2010-12-01

    Model studies have suggested that Odd Nitrogen, NOx, created by Energetic Particle Precipitation (EPP) and the consequent ozone loss through catalytic loss cycles could have an effect on stratospheric and tropospheric (e.g. surface level) temperatures. These effects can potentially be comparable to the effects induced by the solar cycle at high latitudes. Significant mesospheric and stratospheric NOx enhancements have been observed during times of high solar activity (e.g. during Solar Proton Events). NOx can also be, through dynamics, transported from high altitudes (mesosphere-lower thermosphere), where it's created by EPP, down to the stratosphere. Once the NOx reaches the the stratosphere, ozone loss reactions involving NOx provide a link to the general stratospheric ozone balance. Surface temperature effects similar to those reported in the model studies were recently found in re-analysis meteorological data sets, but the mechanism connecting the high altitude NOx production to the surface level remained unclear. In this work, using meteorological re-analysis and operational data sets from the European Centre for Medium Range Weather Forecast and the UK Met Office from 1957 to 2009, we examine the vertical propagation and extent, particularly in the stratosphere, of temperature and wind anomalies related to enhanced geomagnetic activity (i.e. enhanced EPP into the atmosphere), to provide better understanding of the linking mechanism. Furthermore we discuss results from the atmospheric chemistry general circulation model ECHAM5/MESSy, which provides a more comprehensive view of the variation in atmospheric parameters as a result of varying EPP input.

  8. Computational Approaches for Mining GRO-Seq Data to Identify and Characterize Active Enhancers.

    PubMed

    Nagari, Anusha; Murakami, Shino; Malladi, Venkat S; Kraus, W Lee

    2017-01-01

    Transcriptional enhancers are DNA regulatory elements that are bound by transcription factors and act to positively regulate the expression of nearby or distally located target genes. Enhancers have many features that have been discovered using genomic analyses. Recent studies have shown that active enhancers recruit RNA polymerase II (Pol II) and are transcribed, producing enhancer RNAs (eRNAs). GRO-seq, a method for identifying the location and orientation of all actively transcribing RNA polymerases across the genome, is a powerful approach for monitoring nascent enhancer transcription. Furthermore, the unique pattern of enhancer transcription can be used to identify enhancers in the absence of any information about the underlying transcription factors. Here, we describe the computational approaches required to identify and analyze active enhancers using GRO-seq data, including data pre-processing, alignment, and transcript calling. In addition, we describe protocols and computational pipelines for mining GRO-seq data to identify active enhancers, as well as known transcription factor binding sites that are transcribed. Furthermore, we discuss approaches for integrating GRO-seq-based enhancer data with other genomic data, including target gene expression and function. Finally, we describe molecular biology assays that can be used to confirm and explore further the function of enhancers that have been identified using genomic assays. Together, these approaches should allow the user to identify and explore the features and biological functions of new cell type-specific enhancers.

  9. Enhanced leavening properties of baker's yeast by reducing sucrase activity in sweet dough.

    PubMed

    Zhang, Cui-Ying; Lin, Xue; Feng, Bing; Liu, Xiao-Er; Bai, Xiao-Wen; Xu, Jia; Pi, Li; Xiao, Dong-Guang

    2016-07-01

    Leavening ability in sweet dough is required for the commercial applications of baker's yeast. This property depends on many factors, such as glycolytic activity, sucrase activity, and osmotolerance. This study explored the importance of sucrase level on the leavening ability of baker's yeast in sweet dough. Furthermore, the baker's yeast strains with varying sucrase activities were constructed by deleting SUC2, which encodes sucrase or replacing the SUC2 promoter with the VPS8/TEF1 promoter. The results verify that the sucrase activity negatively affects the leavening ability of baker's yeast strains under high-sucrose conditions. Based on a certain level of osmotolerance, sucrase level plays a significant role in the fermentation performance of baker's yeast, and appropriate sucrase activity is an important determinant for the leavening property of baker's yeast in sweet dough. Therefore, modification on sucrase activity is an effective method for improving the leavening properties of baker's yeast in sweet dough. This finding provides guidance for the breeding of industrial baker's yeast strains for sweet dough leavening. The transformants BS1 with deleted SUC2 genetic background provided decreased sucrase activity (a decrease of 39.3 %) and exhibited enhanced leavening property (an increase of 12.4 %). Such a strain could be useful for industrial applications.

  10. Voriconazole Enhances the Osteogenic Activity of Human Osteoblasts In Vitro through a Fluoride-Independent Mechanism.

    PubMed

    Allen, Kahtonna C; Sanchez, Carlos J; Niece, Krista L; Wenke, Joseph C; Akers, Kevin S

    2015-12-01

    Periostitis, which is characterized by bony pain and diffuse periosteal ossification, has been increasingly reported with prolonged clinical use of voriconazole. While resolution of clinical symptoms following discontinuation of therapy suggests a causative role for voriconazole, the biological mechanisms contributing to voriconazole-induced periostitis are unknown. To elucidate potential mechanisms, we exposed human osteoblasts in vitro to voriconazole or fluconazole at 15 or 200 μg/ml (reflecting systemic or local administration, respectively), under nonosteogenic or osteogenic conditions, for 1, 3, or 7 days and evaluated the effects on cell proliferation (reflected by total cellular DNA) and osteogenic differentiation (reflected by alkaline phosphatase activity, calcium accumulation, and expression of genes involved in osteogenic differentiation). Release of free fluoride, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) was also measured in cell supernatants of osteoblasts exposed to triazoles, with an ion-selective electrode (for free fluoride) and enzyme-linked immunosorbent assays (ELISAs) (for VEGF and PDGF). Voriconazole but not fluconazole significantly enhanced the proliferation and differentiation of osteoblasts. In contrast to clinical observations, no increases in free fluoride levels were detected following exposure to either voriconazole or fluconazole; however, significant increases in the expression of VEGF and PDGF by osteoblasts were observed following exposure to voriconazole. Our results demonstrate that voriconazole can induce osteoblast proliferation and enhance osteogenic activity in vitro. Importantly, and in contrast to the previously proposed mechanism of fluoride-stimulated osteogenesis, our findings suggest that voriconazole-induced periostitis may also occur through fluoride-independent mechanisms that enhance the expression of cytokines that can augment osteoblastic activity.

  11. Apoferritin Nanoparticle: A Novel and Biocompatible Carrier for Enzyme Immobilization with Enhanced Activity and Stability

    SciTech Connect

    Zhang, Youyu; Tang, Zhiwen; Wang, Jun; Wu, Hong J.; Lin, Chiann Tso; Lin, Yuehe

    2011-11-01

    Apoferritin is a nanostructured material with a uniform size and spherical structure, and it has excellent bio-compatibility. In this work, we report the use of apoferritin as a novel and biocompatible carrier for stabilizing enzymes and their activities. We used glucose oxidase (GOx) as a model enzyme. GOx was immobilized on the surface of the apoferritin through a green synthetic approach taking advantage of bioaffinity binding between streptavidin and biotin. As a result, a glucose oxidase-biotin/streptavidin/biotin-apoferritin conjugate (Apo-GOx) was prepared using streptavidin as a bridge. The synthesized Apo-GOx was characterized with transmission electron microscopy, ultraviolet, and fluorescence spectroscopy. The activity and stability of GOx on the surface of the apoferritin were studied in different environments, such as temperature, chemicals, and pH, in comparison with the biotinylated GOx (B-GOx). The results showed that the activity of GOx on the apoferritin surface was significantly enhanced. The thermal and chemical stability of the GOx on the apoferritin was also greatly improved compared to free B-GOx in a solution. It was found that the activity of the GOx on the apoferritin only lost 30% in comparison to a 70% loss of free B-GOx after a 2 h incubation at 50oC. There was almost no decrease in activity for the GOx on the apoferritin as compared to an 80% activity decrease for free B-GOx after 30 min incubation in a 5 M urea solution. Glucose detection was used as a model application for the enzyme immobilization method developed in this work. The GOx immobilized apoferritin nanoparticles exhibited high sensitivity for glucose detection with a detection limit of 3 nM glucose. This work offers a novel approach for immobilizing enzymes with enhanced stability and activity, and this method may find a number of applications, such as in enzyme catalysis, DNA assays and immunoassays.

  12. Enhanced Correlation of SMART Active Flap Rotor Loads

    NASA Technical Reports Server (NTRS)

    Kottapalli, Sesi

    2011-01-01

    This is a follow-on study to a 2010 correlation effort. Measured data from the SMART rotor test in the NASA Ames 40- by 80- Foot Wind Tunnel are compared with CAMRAD II calculations. As background, during the wind tunnel test, unexpectedly high inboard loads were encountered, and it was hypothesized at that time that due to changes in the flexbeams over the years, the flexbeam properties used in the analysis needed updating. Boeing Mesa, recently updated these properties. This correlation study uses the updated flexbeam properties. Compared to earlier studies, the following two enhancements are implemented: i) the inboard loads (pitchcase and flexbeam loads) correlation is included for the first time (reliable prediction of the inboard loads is a prerequisite for any future anticipated flight-testing); ii) the number of blade modes is increased to better capture the flap dynamics and the pitchcase-flexbeam dynamics. Also, aerodynamically, both the rolled-up wake model and the more complex, multiple trailer wake model are used, with the latter slightly improving the blade chordwise moment correlation. This sensitivity to the wake model indicates that CFD is needed. Three high-speed experimental cases, one uncontrolled free flap case and two commanded flap cases, are considered. The two commanded flap cases include a 2o flap deflection at 5P case and a 0o flap deflection case. For the free flap case, selected modifications to the HH-06 section flap airfoil pitching moment table are implemented. For the commanded 2o flap case, the experimental flap variation is approximately matched by increasing the analytical flap hinge stiffness. This increased flap hinge stiffness is retained for the commanded 0o flap case also, which is treated as a free flap case, but with larger flap hinge stiffness. The change in the mid-span and outboard loads correlation due to the updating of the flexbeam properties is not significant. Increasing the number of blade modes results in an

  13. The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease.

    PubMed

    Rees, David C; Thein, Swee Lay; Osei, Anna; Drasar, Emma; Tewari, Sanjay; Hannemann, Anke; Gibson, John S

    2015-05-01

    HbSC disease is the second commonest form of sickle cell disease, with poorly understood pathophysiology and few treatments. We studied the role of K-Cl cotransport activity in determining clinical and laboratory features, and investigated its potential role as a biomarker. Samples were collected from 110 patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl cotransport activity was measured in the oxygenated (K-Cl cotransport(100)) and deoxygenated (K-Cl cotransport(0)) states, using radioactive tracer studies. K-Cl cotransport activity was high in HbSC and decreased significantly on deoxygenation. K-Cl cotransport activity correlated significantly and positively with the formation of sickle cells. On multiple regression analysis, K-Cl cotransport increased significantly and independently with increasing reticulocyte count and age. K-Cl cotransport activity was increased in patients who attended hospital with acute pain in 2011 compared to those who did not (K-Cl cotransport(100): mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport(0): mean 0.96 versus 0.68, P=0.037). On logistic regression only K-Cl cotransport was associated with hospital attendance. Increased K-Cl cotransport activity was associated with the presence of retinopathy, but this effect was confounded by age. This study links variability in a fundamental aspect of cellular pathology with a clinical outcome, suggesting that K-Cl cotransport is central to the pathology of HbSC disease. Increased K-Cl cotransport activity is associated with increasing age, which may be of pathophysiological significance. Effective inhibition of K-Cl cotransport activity is likely to be of therapeutic benefit.

  14. A significant increase in both basal and maximal calcineurin activity following fluid percussion injury in the rat.

    PubMed

    Kurz, Jonathan E; Parsons, J Travis; Rana, Aniruddha; Gibson, Cynthia J; Hamm, Robert J; Churn, Severn B

    2005-04-01

    Calcineurin, a neuronally enriched, calcium-stimulated phosphatase, is an important modulator of many neuronal processes, including several that are physiologically related to the pathology of traumatic brain injury. This study examined the effects of moderate, central fluid percussion injury on the activity of this important neuronal enzyme. Animals were sacrificed at several time-points postinjury and cortical, hippocampal, and cerebellar homogenates were assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant brain injury-dependent increase was observed in both hippocampal and cortical homogenates under both basal and maximally-stimulated reaction conditions. This increase persisted 2-3 weeks post-injury. Brain injury did not alter substrate affinity, but did induce a significant increase in the apparent maximal dephosphorylation rate. Unlike the other brain regions, no change in calcineurin activity was observed in the cerebellum following brain injury. No brain region tested displayed a significant change in calcineurin enzyme levels as determined by Western blot, demonstrating that increased enzyme synthesis was not responsible for the observed increase in activity. The data support the conclusion that fluid percussion injury results in increased calcineurin activity in the rat forebrain. This increased activity has broad physiological implications, possibly resulting in altered cellular excitability or a greater likelihood of neuronal cell death.

  15. Novel insights into enhanced dewaterability of waste activated sludge by Fe(II)-activated persulfate oxidation.

    PubMed

    Zhen, Guangyin; Lu, Xueqin; Li, Yuyou; Zhao, Youcai; Wang, Baoying; Song, Yu; Chai, Xiaoli; Niu, Dongjie; Cao, Xianyan

    2012-09-01

    The potential of Fe(II)-activated persulfate (S(2)O(8)(2-)) oxidation on enhancing the dewaterability of sludge flocs from 3-full scale wastewater treatment plants (WWTPs) were investigated. Normalized capillary suction time (CST) was applied to evaluate sludge dewaterability. Both extracellular polymeric substances (EPS) and metabolic activity of microorganisms were determined to explore the responsible mechanism. Fe(II)-S(2)O(8)(2-) oxidation effectively improved sludge dewaterability. The most important mechanisms were proposed to be the degradation of EPS incorporated in sludge flocs and rupture of microbial cells. Three-dimensional excitation-emission matrix (EEM) fluorescence spectroscopy confirmed that the powerful SO(4)(-) from Fe(II)-S(2)O(8)(2-) system destroyed the particular functional groups of fluorescing substances (i.e., aromatic protein-, tryptophan protein-, humic- and fulvic-like substances) in EPS and caused cleavage of linkages in the polymeric backbone and simultaneous destruction of microbial cells, resulting in the release of EPS-bound water, intracellular materials and water of hydration inside cells, and subsequent enhancement of dewaterability.

  16. Enhanced IPC by activation of pertussis toxin-sensitive and -insensitive G protein-coupled purinoceptors.

    PubMed

    Ninomiya, Hideki; Otani, Hajime; Lu, Kejie; Uchiyama, Takamichi; Kido, Masakuni; Imamura, Hiroji

    2002-05-01

    Extracellular ATP plays an important role in ischemic preconditioning (IPC) through the activation of P(2y) purinoceptors. This study examined whether ATP-stimulated P(2y) purinoceptors are coupled to pertussis toxin (PTX)-insensitive G protein and whether activation of this pathway enhances myocardial protection afforded by IPC. The rat was treated with PTX for 48 h, and the heart was then isolated and buffer perfused. The heart underwent IPC by three cycles of 5-min ischemia and 5-min reperfusion before 25 min of global ischemia. Isovolumic left ventricular function was measured, and functional recovery at 30 min after reperfusion was taken as an end point of myocardial protection. PTX pretreatment partially inhibited functional protection by IPC. Treatment with 100 microM 8-(p-sulfophenyl) theophylline (SPT) during IPC had no further effect on PTX-induced inhibition of functional protection by IPC, whereas suramin (300 microM) or reactive blue (RB) (10 microM) completely abolished myocardial protection in the preconditioned heart pretreated with PTX. Supplementation with adenosine (30 microM), ATP (30 microM), or UTP (50 microM) significantly enhanced IPC-induced functional protection, although preconditioning with these nucleotides without IPC had no protective effect. Adenosine-enhanced IPC was inhibited by pretreatment with PTX and SPT but not by suramin or RB, whereas ATP-enhanced IPC was inhibited by suramin or RB in combination with PTX pretreatment. On the other hand, UTP-enhanced IPC was not affected by PTX pretreatment but was inhibited by suramin or RB. Adenosine supplemented IPC without PTX pretreatment and ATP supplemented IPC with PTX pretreatment were not affected by nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (100 microM). Although the protein kinase C inhibitor Ro318425 (0.3 microM) or tyrosine kinase inhibitor genistein (50 microM) had no significant effect on the functional protection afforded by adenosine

  17. Enhanced exo-inulinase activity and stability by fusion of an inulin-binding module.

    PubMed

    Zhou, Shun-Hua; Liu, Yuan; Zhao, Yu-Juan; Chi, Zhe; Chi, Zhen-Ming; Liu, Guang-Lei

    2016-09-01

    In this study, an inulin-binding module from Bacillus macerans was successfully fused to an exo-inulinase from Kluyveromyces marxianus, creating a hybrid functional enzyme. The recombinant exo-inulinase (rINU), the hybrid enzyme (rINUIBM), and the recombinant inulin-binding module (rIBM) were, respectively, heterologously expressed and biochemically characterized. It was found that both the inulinase activity and the catalytic efficiency (k cat/K m(app)) of the rINUIBM were considerably higher than those of rINU. Though the rINU and the rINUIBM shared the same optimum pH of 4.5, the optimum temperature of the rINUIBM (60 °C) was 5 °C higher than that of the rINU. Notably, the fused IBM significantly enhanced both the pH stability and the thermostability of the rINUIBM, suggesting that the rINUIBM obtained would have more extensive potential applications. Furthermore, the fusion of the IBM could substantially improve the inulin-binding capability of the rINUIBM, which was consistent with the determination of the K m(app). This meant that the fused IBM could play a critical role in the recognition of polysaccharides and enhanced the hydrolase activity of the associated inulinase by increasing enzyme-substrate proximity. Besides, the extra supplement of the independent non-catalytic rIBM could also improve the inulinase activity of the rINU. However, this improvement was much better in case of the fusion. Consequently, the IBM could be designated as a multifunctional domain that was responsible for the activity enhancement, the stabilization, and the substrate binding of the rINUIBM. All these features obtained in this study make the rINUIBM become an attractive candidate for an efficient inulin hydrolysis.

  18. Response of ependymal progenitors to spinal cord injury or enhanced physical activity in adult rat.

    PubMed

    Cizkova, Dasa; Nagyova, Miriam; Slovinska, Lucia; Novotna, Ivana; Radonak, Jozef; Cizek, Milan; Mechirova, Eva; Tomori, Zoltan; Hlucilova, Jana; Motlik, Jan; Sulla, Igor; Vanicky, Ivo

    2009-09-01

    Ependymal cells (EC) in the spinal cord central canal (CC) are believed to be responsible for the postnatal neurogenesis following pathological or stimulatory conditions. In this study, we have analyzed the proliferation of the CC ependymal progenitors in adult rats processed to compression SCI or enhanced physical activity. To label dividing cells, a single daily injection of Bromo-deoxyuridine (BrdU) was administered over a 14-day-survival period. Systematic quantification of BrdU-positive ependymal progenitors was performed by using stereological principles of systematic, random sampling, and optical Dissector software. The number of proliferating BrdU-labeled EC increased gradually with the time of survival after both paradigms, spinal cord injury, or increased physical activity. In the spinal cord injury group, we have found 4.9-fold (4 days), 7.1-fold (7 days), 4.9-fold (10 days), and 5.6-fold (14 days) increase of proliferating EC in the rostro-caudal regions, 4 mm away from the epicenter. In the second group subjected to enhanced physical activity by running wheel, we have observed 2.1-2.6 fold increase of dividing EC in the thoracic spinal cord segments at 4 and 7 days, but no significant progression at 10-14 days. Nestin was rapidly induced in the ependymal cells of the CC by 2-4 days and expression decreased by 7-14 days post-injury. Double immunohistochemistry showed that dividing cells adjacent to CC expressed astrocytic (GFAP, S100beta) or nestin markers at 14 days. These data demonstrate that SCI or enhanced physical activity in adult rats induces an endogenous ependymal cell response leading to increased proliferation and differentiation primarily into macroglia or cells with nestin phenotype.

  19. Enhanced glycogen synthase kinase-3β activity mediates podocyte apoptosis under diabetic conditions.

    PubMed

    Paeng, Jisun; Chang, Jae Hyun; Lee, Sun Ha; Nam, Bo Young; Kang, Hye-Young; Kim, Seonghun; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2014-12-01

    Glycogen synthase kinase-3β (GSK-3β) is involved in the pathogenesis of various kidney diseases. This study was undertaken to examine the changes in GSK-3β activity in podocytes under diabetic conditions and to elucidate the functional role of GSK-3β in podocyte apoptosis. In vivo, 32 rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with 6-bromoindirubin-3'-oxime (BIO) for 3 months. In vitro, immortalized mouse podocytes were exposed to 5.6 mM glucose or 30 mM glucose (HG) with or without 10 μM BIO. Western blot analysis and TUNEL or Hoechst 33342 staining were performed to identify apoptosis. Urinary albumin excretion was significantly higher in DM rats, and this increase was significantly abrogated in DM rats by BIO treatment. The protein expression of Tyr216-phospho-GSK-3β was significantly increased in DM glomeruli and in cultured podocytes exposed to HG. Western blot analysis revealed that the protein expression of Bax and active fragments of caspase-3 were significantly increased, whereas phospho-Akt, β-catenin, and Bcl-2 protein expression were significantly decreased in DM glomeruli and HG-stimulated podocytes. Apoptosis, determined by TUNEL assay and Hoechst 33342 staining, was also significantly increased in podocytes under diabetic conditions. The changes in the expression of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG-stimulated podocytes were significantly ameliorated by BIO. These findings suggest that enhanced GSK-3β activity within podocytes under diabetic conditions is associated with podocyte loss in diabetic nephropathy.

  20. Enhanced Dopamine Transporter Activity in Middle-Aged Gdnf Heterozygous Mice

    PubMed Central

    Littrell, Ofelia M.; Pomerleau, Francois; Huettl, Peter; Surgener, Stewart; McGinty, Jacqueline F.; Middaugh, Lawrence D.; Granholm, Ann-Charlotte; Gerhardt, Greg A.; Boger, Heather A.

    2010-01-01

    Glial cell line-derived neurotrophic factor (GDNF) supports the viability of midbrain dopamine (DA) neurons that degenerate in Parkinson’s disease. Middle aged, 12-month-old, Gdnf heterozygous (Gdnf+/−) mice have diminished spontaneous locomotor activity and enhanced synaptosomal DA uptake compared to wildtype mice. In this study, dopamine transporter (DAT) function in middle-aged, 12-month-old Gdnf+/− mice was more thoroughly investigated using in vivo electrochemistry. Gdnf+/− mice injected with the DAT inhibitor, nomifensine, exhibited significantly more locomotor activity than wildtype mice. In vivo electrochemistry with carbon fiber microelectrodes demonstrated enhanced clearance of DA in the striatum of Gdnf+/− mice, suggesting greater surface expression of DAT than in wildtype littermates. Additionally, 12 month old Gdnf+/− mice expressed greater D2 receptor mRNA and protein in the striatum than wildtype mice. Neurochemical analyses of striatal tissue samples indicated significant reductions in DA and a faster DA metabolic rate in Gdnf+/− mice than in wildtype mice. Altogether, these data support an important role for GDNF in the regulation of uptake, synthesis, and metabolism of DA during aging. PMID:21144620

  1. Female Adolescents' Delinquent Activity: The Intersection of Bonds to Parents and Reputation Enhancement

    ERIC Educational Resources Information Center

    Kerpelman, Jennifer L.; Smith-Adcock, Sondra

    2005-01-01

    According to the reputation enhancement theory, social bonds influence adolescents' delinquent activity indirectly through the reputations they select. Findings from the current study of a school-based sample of female adolescents indicate that bonds to parents affect reputation enhancement beliefs, which, in turn, predict delinquent activity.…

  2. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models.

    PubMed

    Li, Zhimin; Qiu, Yushi; Personett, David; Huang, Peng; Edenfield, Brandy; Katz, Jason; Babusis, Darius; Tang, Yang; Shirely, Michael A; Moghaddam, Mehran F; Copland, John A; Tun, Han W

    2013-01-01

    Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS

  3. Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease.

    PubMed Central

    Rachmilewitz, D; Stamler, J S; Bachwich, D; Karmeli, F; Ackerman, Z; Podolsky, D K

    1995-01-01

    Recent studies have suggested that nitric oxide (NO.), the product of nitric oxide synthase in inflammatory cells, may play a part in tissue injury and inflammation through its oxidative metabolism. In this study the colonic generation of oxides of nitrogen (NOx) and nitric oxide synthase activity was determined in ulcerative colitis and Crohn's disease. Colonic biopsy specimens were obtained from inflammatory bowel disease patients and from normal controls. Mucosal explants were cultured in vitro for 24 hours and NOx generation was determined. Nitric oxide synthase activity was monitored by the conversion of [3H]-L-arginine to citrulline. Median NOx generation by inflamed colonic mucosa of patients with active ulcerative colitis and Crohn's colitis was 4.2- and 8.1-fold respectively higher than that by normal human colonic mucosa. In ulcerative colitis and Crohn's colitis nitric oxide synthase activity was 10.0- and 3.8-fold respectively higher than in normal subjects. Colonic NOx generation is significantly decreased by methylprednisolone and ketotifen. The decrease in NOx generation by cultured colonic mucosa induced by methylprednisolone suggests that NO synthase activity is induced during the culture and the steroid effect may contribute to its therapeutic effect. Enhanced colonic NOx generation by stimulated nitric oxide synthase activity in ulcerative colitis and Crohn's disease may contribute to tissue injury. PMID:7541008

  4. Carbohydrate in the mouth enhances activation of brain circuitry involved in motor performance and sensory perception.

    PubMed

    Turner, Clare E; Byblow, Winston D; Stinear, Cathy M; Gant, Nicholas

    2014-09-01

    The presence of carbohydrate in the human mouth has been associated with the facilitation of motor output and improvements in physical performance. Oral receptors have been identified as a potential mode of afferent transduction for this novel form of nutrient signalling that is distinct from taste. In the current study oral exposure to carbohydrate was combined with a motor task in a neuroimaging environment to identify areas of the brain involved in this phenomenon. A mouth-rinsing protocol was conducted whilst carbohydrate (CHO) and taste-matched placebo (PLA) solutions were delivered and recovered from the mouths of 10 healthy volunteers within a double-blind, counterbalanced design. This protocol eliminates post-oral factors and controls for the perceptual qualities of solutions. Functional magnetic resonance imaging of the brain was used to identify cortical areas responsive to oral carbohydrate during rest and activity phases of a hand-grip motor task. Mean blood-oxygen-level dependent signal change experienced in the contralateral primary sensorimotor cortex was larger for CHO compared with PLA during the motor task when contrasted with a control condition. Areas of activation associated with CHO exclusively were observed over the primary taste cortex and regions involved in visual perception. Regions in the limbic system associated with reward were also significantly more active with CHO. This is the first demonstration that oral carbohydrate signalling can increase activation within the primary sensorimotor cortex during physical activity and enhance activation of neural networks involved in sensory perception.

  5. Immortalized Parkinson's disease lymphocytes have enhanced mitochondrial respiratory activity

    PubMed Central

    Annesley, Sarah J.; Lay, Sui T.; De Piazza, Shawn W.; Sanislav, Oana; Hammersley, Eleanor; Allan, Claire Y.; Francione, Lisa M.; Bui, Minh Q.; Chen, Zhi-Ping; Ngoei, Kevin R. W.; Tassone, Flora; Kemp, Bruce E.; Storey, Elsdon; Evans, Andrew; Loesch, Danuta Z.

    2016-01-01

    ABSTRACT In combination with studies of post-mortem Parkinson's disease (PD) brains, pharmacological and genetic models of PD have suggested that two fundamental interacting cellular processes are impaired – proteostasis and mitochondrial respiration. We have re-examined the role of mitochondrial dysfunction in lymphoblasts isolated from individuals with idiopathic PD and an age-matched control group. As previously reported for various PD cell types, the production of reactive oxygen species (ROS) by PD lymphoblasts was significantly elevated. However, this was not due to an impairment of mitochondrial respiration, as is often assumed. Instead, basal mitochondrial respiration and ATP synthesis are dramatically elevated in PD lymphoblasts. The mitochondrial mass, genome copy number and membrane potential were unaltered, but the expression of indicative respiratory complex proteins was also elevated. This explains the increased oxygen consumption rates by each of the respiratory complexes in experimentally uncoupled mitochondria of iPD cells. However, it was not attributable to increased activity of the stress- and energy-sensing protein kinase AMPK, a regulator of mitochondrial biogenesis and activity. The respiratory differences between iPD and control cells were sufficiently dramatic as to provide a potentially sensitive and reliable biomarker of the disease state, unaffected by disease duration (time since diagnosis) or clinical severity. Lymphoblasts from control and PD individuals thus occupy two distinct, quasi-stable steady states; a ‘normal’ and a ‘hyperactive’ state characterized by two different metabolic rates. The apparent stability of the ‘hyperactive’ state in patient-derived lymphoblasts in the face of patient ageing, ongoing disease and mounting disease severity suggests an early, permanent switch to an alternative metabolic steady state. With its associated, elevated ROS production, the ‘hyperactive’ state might not cause pathology

  6. Albumin Enhances Caspofungin Activity against Aspergillus Species by Facilitating Drug Delivery to Germinating Hyphae.

    PubMed

    Ioannou, Petros; Andrianaki, Aggeliki; Akoumianaki, Tonia; Kyrmizi, Irene; Albert, Nathaniel; Perlin, David; Samonis, George; Kontoyiannis, Dimitrios P; Chamilos, Georgios

    2015-12-07

    The modest in vitro activity of echinocandins against Aspergillus implies that host-related factors augment the action of these antifungal agents in vivo. We found that, in contrast to the other antifungal agents (voriconazole, amphotericin B) tested, caspofungin exhibited a profound increase in activity against various Aspergillus species under conditions of cell culture growth, as evidenced by a ≥4-fold decrease in minimum effective concentrations (MECs) (P = 0. 0005). Importantly, the enhanced activity of caspofungin against Aspergillus spp. under cell culture conditions was strictly dependent on serum albumin and was not observed with the other two echinocandins, micafungin and anidulafungin. Of interest, fluorescently labeled albumin bound preferentially on the surface of germinating Aspergillus hyphae, and this interaction was further enhanced upon treatment with caspofungin. In addition, supplementation of cell culture medium with albumin resulted in a significant, 5-fold increase in association of fluorescently labeled caspofungin with Aspergillus hyphae (P < 0.0001). Collectively, we found a novel synergistic interaction between albumin and caspofungin, with albumin acting as a potential carrier molecule to facilitate antifungal drug delivery to Aspergillus hyphae.

  7. Impacts of membrane flux enhancers on activated sludge respiration and nutrient removal in MBRs.

    PubMed

    Iversen, Vera; Koseoglu, Hasan; Yigit, Nevzat O; Drews, Anja; Kitis, Mehmet; Lesjean, Boris; Kraume, Matthias

    2009-02-01

    This paper presents the findings of experimental investigations regarding the influence of 13 different flux enhancing chemicals (FeCl3, polyaluminium chloride, 2 chitosans, 5 synthetic polymers, 2 starches and 2 activated carbons) on respirometric characteristics and nitrification/denitrification performance of membrane bioreactor (MBR) mixed liquor. Flux enhancing chemicals are a promising method to reduce the detrimental effects of fouling phenomena via the modification of mixed liquor characteristics. However, potentially inhibiting effects of these chemicals on mixed liquor biological activity triggered the biokinetic studies (in jar tests) conducted in this work. The tested polyaluminium chloride (PACl) strongly impacted on nitrification (-16%) and denitrification rate (-43%). The biodegradable nature of chitosan was striking in endogenous and exogenous tests. Considering the relatively high costs of this chemical, an application for wastewater treatment does thus not seem to be advisable. Also, addition of one of the tested activated carbons strongly impacted on the oxygen uptake rate (-28%), nitrification (-90%) and denitrification rate (-43%), due to a decrease of pH. Results show that the changes in kLa values were mostly not significant, however, a decrease of 13% in oxygen transfer was found for sludge treated with PACl.

  8. Electrochemically prepared surface-enhanced Raman scattering-active silver substrates with improved stabilities

    NASA Astrophysics Data System (ADS)

    Yang, Kuang-Hsuan; Liu, Yu-Chuan; Yu, Chung-Chin; Chen, Bo-Chuen

    2011-01-01

    In this work, SiO 2 nanoparticles-modified surface-enhanced Raman scattering (SERS)-active silver substrates were prepared by electrochemical oxidation-reduction cycles (ORC) methods in 0.1 N HCl aqueous solutions containing 1 mM SiO 2 nanoparticles to improve their thermal stabilities and anti-aging abilities in SERS performances. Then these SERS-active substrates were further modified with different contents of SiO 2 nanoparticles to improve their corresponding SERS performances. Experimental results indicate that the operation temperature can be significantly raised from 125 to 175 °C based on this modified SERS-active Ag substrate. Also, the aging in SERS intensity is also depressed on this modified Ag substrate due to the contribution of SiO 2 nanoparticles. Moreover, the SERS enhancement capability on this modified Ag substrate is gradually raised from 25 °C to a maximum at 55 °C and monotonically decreased from 55 to 60 °C. This is a 10 °C delay as compared with the similar phenomenon observed on the unmodified Ag substrate.

  9. Visible-light-driven Bi 2 O 3 /WO 3 composites with enhanced photocatalytic activity

    DOE PAGES

    Adhikari, Shiba P.; Dean, Hunter; Hood, Zachary D.; ...

    2015-10-19

    Semiconductor heterojunctions (composites) have been shown to be effective photocatalytic materials to overcome the drawbacks of low photocatalytic efficiency that results from electron–hole recombination and narrow photo-response range. We prepared a novel visible-light-driven Bi2O3/WO3 composite photocatalyst by hydrothermal synthesis. The composite was characterized by scanning transmission electron microscopy (STEM), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), Brunauer–Emmett–Teller (BET) surface area, Raman spectroscopy, photoluminescence spectroscopy (PL) and electrochemical impedance spectroscopy (EIS) to better understand the structures, compositions, morphologies and optical properties. Bi2O3/WO3 heterojunction was found to exhibit significantly higher photocatalytic activity towards the decomposition of Rhodaminemore » B (RhB) and 4-nitroaniline (4-NA) under visible light irradiation compared to that of Bi2O3 and WO3. A tentative mechanism for the enhanced photocatalytic activity of the heterostructured composite is discussed based on observed activity, band position calculations, photoluminescence, and electrochemical impedance data. Our study provides a new strategy for the design of composite materials with enhanced visible light photocatalytic performance.« less

  10. Enhancement of UV-induced nucleotide excision repair activity upon forskolin treatment is cell growth-dependent

    PubMed Central

    Lee, Jeong-Min; Park, Jeong-Min; Kang, Tae-Hong

    2016-01-01

    Forskolin (FSK), an adenylyl cyclase activator, has recently been shown to enhance nucleotide excision repair (NER) upon UV exposure. However, our study revealed that this effect was detected in human skin epithelial ARPE19 cells only in growing cells, but not in non-cycling cells. When the cells were grown at low density (70% confluence), FSK was capable of stimulating cAMP responsive element binding (CREB) phosphorylation, a marker for FSK-stimulated PKA activation, and resulted in a significant increase of NER activity compared to control treatment. However, cells grown under 100% confluent conditions showed neither FSK-induced CREB phosphorylation nor the resulting NER enhancement. These findings indicate that cellular growth is critical for FSK-induced NER enhancement and suggest that cellular growth conditions should be considered as a variable while evaluating a reagent’s pharmacotherapeutic efficacy. [BMB Reports 2016; 49(10): 566-571] PMID:27470212

  11. Enhancement of UV-induced nucleotide excision repair activity upon forskolin treatment is cell growth-dependent.

    PubMed

    Lee, Jeong-Min; Park, Jeong-Min; Kang, Tae-Hong

    2016-10-01

    Forskolin (FSK), an adenylyl cyclase activator, has recently been shown to enhance nucleotide excision repair (NER) upon UV exposure. However, our study revealed that this effect was detected in human skin epithelial ARPE19 cells only in growing cells, but not in non-cycling cells. When the cells were grown at low density (70% confluence), FSK was capable of stimulating cAMP responsive element binding (CREB) phosphorylation, a marker for FSK-stimulated PKA activation, and resulted in a significant increase of NER activity compared to control treatment. However, cells grown under 100% confluent conditions showed neither FSK-induced CREB phosphorylation nor the resulting NER enhancement. These findings indicate that cellular growth is critical for FSK-induced NER enhancement and suggest that cellular growth conditions should be considered as a variable while evaluating a reagent's pharmacotherapeutic efficacy. [BMB Reports 2016; 49(10): 566-571].

  12. Focus on Freshman: Basic Instruction Programs Enhancing Physical Activity

    ERIC Educational Resources Information Center

    Curry, Jarred; Jenkins, Jayne M.; Weatherford, Jennifer

    2015-01-01

    Physical activity sharply decreases after different life stages, particularly high school graduation to beginning university education. The purpose of this study was to investigate the effect of a specifically designed university physical activity class, Exercise Planning for Freshman (EPF), on students' physical activity and group cohesion…

  13. Facile synthesis of polyaniline-modified CuS with enhanced adsorbtion and photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Wang, Xiufang; Chen, Shaohua; Shuai, Ying

    2016-10-01

    Novel hierarchical polyaniline-modified CuS (PANI-CuS) has been synthesized by simple assembling PANI on the surface of flower-like CuS spheres. The PANI modification enhances the adsorption properties of flower-like CuS. The prepared PANI-CuS composites exhibit higher visible-light-driven photocatalytic activities in degradation of rhodamine B (RhB) than that of neat CuS. The unusual photocatalytic activity could be attributed to the great adsorptivity of dyes, the extended photoresponse range, and the high migration efficiency of photoinduced electrons, which may effectively suppress the charge recombination. This work not only provides a simple strategy for fabricating highly efficient and stable CuS-based composites, but also proves that these unique structures are excellent platforms for significantly improving their visible- light-driven photoactivities, holding great promise for their applications in the field of purifying polluted water resources.

  14. Human Cytomegalovirus Infection Enhances NK Cell Activity In Vitro

    PubMed Central

    Tschan-Plessl, Astrid; Stern, Martin; Schmied, Laurent; Retière, Christelle; Hirsch, Hans H.; Garzoni, Christian; van Delden, Christian; Boggian, Katia; Mueller, Nicolas J.; Berger, Christoph; Villard, Jean; Manuel, Oriol; Meylan, Pascal; Terszowski, Grzegorz

    2016-01-01

    Background Occurring frequently after solid organ and hematopoietic stem cell transplantation, cytomegalovirus (CMV) replication remains a relevant cause of mortality and morbidity in affected patients. Despite these adverse effects, an increased alloreactivity of natural killer (NK) cells after CMV infection has been assumed, but the underlying physiopathological mechanisms have remained elusive. Methods We used serial analyses of NK cells before and after CMV infection in kidney transplant recipients as an in vivo model for CMV primary infection to explore the imprint of CMV infection using every patient as their own control: We analyzed NK cell phenotype and function in 47 CMV seronegative recipients of CMV seropositive kidney grafts, who developed CMV primary infection posttransplant. Seronegative recipients of seronegative kidney grafts served as controls. Results We observed a significant increase of NKG2C expressing NK cells after CMV infection (mean increase, 17.5%; 95% confidence interval [95% CI], 10.2-24.9, P < 0.001), whereas cluster of differentiation (CD)57 expressing cells decreased (mean decrease, 14.1%; 95% CI, 8.0-20.2; P < 0.001). Analysis of killer immunoglobulin-like receptor (KIR) expression showed an increase of cells expressing KIR2DL1 as their only inhibitory KIR in patients carrying the cognate ligand HLA-C2 (mean increase, 10.0%; 95% CI, 1.7-18.3; P = 0.018). In C2-negative individuals, KIR2DL1 expression decreased (mean decrease, 3.9%; 95% CI, 1.6-6.2; P = 0.001). As for activating KIR, there was no conclusive change pattern. Most importantly, we observed a significantly higher NK cell degranulation and IFNγ production in response to different target cells (target K562, CD107a: mean increase, 9.9%; 95% CI, 4.8-15.0; P < 0.001; IFNγ: mean increase, 6.6%; 95% CI, 1.6-11.1; P < 0.001; target MRC-5, CD107a: mean increase, 6.9%; 95% CI, 0.7-13.1; P = 0.03; IFNγ: mean increase, 4.8%; 95% CI, 1.7-7.8; P = 0.002). Conclusions We report

  15. Garden-like perovskite superstructures with enhanced photocatalytic activity.

    PubMed

    Ye, Meidan; Wang, Mengye; Zheng, Dajiang; Zhang, Nan; Lin, Changjian; Lin, Zhiqun

    2014-04-07

    By subjecting amorphous flower-like TiO2 to a facile hydrothermal synthesis in the presence of Sr(2+), garden-like perovskite SrTiO3 superstructures were achieved. The amorphous TiO2 was preformed using ZnO flowers as templates. Different three-dimensional SrTiO3 architectures were coexisted in the garden, including SrTiO3 flowers composed of several hollow sword-shaped petals, many sheet-shaped petals or numerous flake-shaped petals, and SrTiO3 grass consisting of a number of long blades. These SrTiO3 superstructures were simultaneously grown on fluorine-doped tin oxide (FTO) substrates. On the basis of a comprehensive study on the effects of growth time, temperature, initial concentrations of precursor, and pH, the formation of these various hierarchical architectures was attributed primarily to the dissolution of amorphous TiO2 and precipitation of perovskite crystals, followed by the Ostwald ripening process of perovskite nanocrystals and self-organization of perovskite building blocks. Interestingly, this approach can be readily extended to create other perovskite structures, including dendritic BaTiO3 and nest-like CaTiO3, as well as PbTiO3 transformed from plate-like pyrochlore Pb2Ti2O6 after post-thermal treatment. Garden-like SrTiO3 superstructures showed a superior photocatalytic performance when compared to other as-prepared semiconductors and perovskite materials (i.e., ZnO, TiO2, BaTiO3, CaTiO3 and PbTiO3), probably due to their intrinsic photocatalytic activity and special garden-like features with a coexistence of various structures that significantly facilitated the adsorption and diffusion of methyl blue (MB) molecules and oxygen species in the photochemical reaction of MB degradation.

  16. Influence of skin penetration enhancers on skin barrier function and skin protease activity.

    PubMed

    Mohammed, Diar; Hirata, Kazumasa; Hadgraft, Jonathan; Lane, Majella E

    2014-01-23

    In order to overcome the skin's excellent barrier function formulation scientists often employ skin penetration enhancers (SPEs) in topical and transdermal formulations. The effects of these compounds on skin health is still not well understood at the molecular level. The aim of the present work was to probe the effects of some common SPEs on desquamatory protease activity in healthy skin. The SPEs studied were isopropyl myristate (IPM), propylene glycol, (PG), propylene glycol laurate (PGL) and Transcutol™ (TC). Occluded infinite doses of each SPE were applied to human volunteers for 24 h. Transepidermal water loss (TEWL) measurements were taken before and after application of SPEs. Tape strips were collected from the treated sites to determine protein content and the activity of two desquamatory proteases kallikrein 5 (KLK5) and kallikrein 7 (KLK7). TEWL values were also measured after tape stripping. PG was found to elevate both TEWL values and KLK7 activity to a significant extent (p<0.05). No significant effects were observed for the other SPEs. The ability of PG to alter the skin barrier at the macroscopic level and the influence of the molecule on protease activity reported here may have implications for its use in topical formulations used for the management of impaired skin barrier function such as atopic eczema or psoriasis.

  17. GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity.

    PubMed

    Lin, Tzu-Chi; Chen, Syue-Ting; Huang, Min-Chuan; Huang, John; Hsu, Chia-Lang; Juan, Hsueh-Fen; Lin, Ho-Hsiung; Chen, Chi-Hau

    2017-03-28

    Ovarian cancer is the most lethal of the gynecologic malignancies. N-acetylgalactosaminyltransferase 6 (GALNT6), an enzyme that mediates the initial step of mucin type-O glycosylation, has been reported to regulate mammary carcinogenesis. However, the expression and role of GALNT6 in ovarian cancer are still unclear. Here we showed that high GALNT6 expression correlates with increased recurrence, lymph node metastasis, and chemoresistance in ovarian endometrioid and clear cell carcinomas; and higher GALNT6 levels are significantly associated with poorer patient survivals. GALNT6 knockdown with two independent siRNAs significantly suppressed viability, migration, and invasion of ovarian cancer cells. Using phospho-RTK array and Western blot analyses, we identified EGFR as a critical target of GALNT6. GALNT6 knockdown decreased phosphorylation of EGFR, whereas GALNT6 overexpression increased the phosphorylation. Lectin pull-down assays with Vicia villosa agglutinin (VVA) indicated that GALNT6 was able to modify O-glycans on EGFR. Moreover, the GALNT6-enhanced invasive behavior was significantly reversed by erlotinib, an EGFR inhibitor. Our results suggest that GALNT6 expression is associated with poor prognosis of ovarian cancer and enhances the aggressive behavior of ovarian cancer cells by regulating EGFR activity.

  18. Enhanced Locomotor Activity Is Required to Exert Dietary Restriction-Dependent Increase of Stress Resistance in Drosophila.

    PubMed

    Ghimire, Saurav; Kim, Man Su

    2015-01-01

    Dietary restriction (DR) is known to be one of the most effective interventions to increase stress resistance, yet the mechanisms remain elusive. One of the most obvious DR-induced changes in phenotype is an increase in locomotor activity. Although it is conceptually perceivable that nutritional scarcity should prompt enhanced foraging behavior to garner additional dietary resources, the significance of enhanced movement activity has not been associated with the DR-dependent increase of stress resistance. In this study, we confirmed that flies raised on DR exhibited enhanced locomotive activity and increased stress resistance. Excision of fly wings minimized the DR-induced increase in locomotive activity, which resulted in attenuation of the DR-dependent increase of stress resistance. The possibility that wing clipping counteracts the DR by coercing flies to have more intake was ruled out since it did not induce any weight gain. Rather it was found that elimination of reactive oxygen species (ROS) that is enhanced by DR-induced upregulation of expression of antioxidant genes was significantly reduced by wing clipping. Collectively, our data suggests that DR increased stress resistance by increasing the locomotor activity, which upregulated expression of protective genes including, but not limited to, ROS scavenger system.

  19. Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma.

    PubMed

    Lopes de Menezes, Daniel E; Denis-Mize, Kimberly; Tang, Yan; Ye, Helen; Kunich, John C; Garrett, Evelyn N; Peng, Jing; Cousens, Lawrence S; Gelb, Arnold B; Heise, Carla; Wilson, Susan E; Jallal, Bahija; Aukerman, Sharon L

    2007-01-01

    Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated. The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as evidenced by significant tumor regressions and increased time to tumor progression, compared with rIL-2 and rituximab single agents. In contrast, rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and showed an increased response when combined with rituximab. Using in vitro killing assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC. Antiproliferative and apoptotic tumor responses, along with an influx of immune effector cells, were observed by immunohistochemistry. Collectively, the data suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in part, through activation and trafficking of monocytes and natural killer cells to tumors. These data support the mechanistic and therapeutic rationale for combination of rIL-2 with rituximab in NHL clinical trials and for single-agent rIL-2 in rituximab-resistant NHL patients.

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

    PubMed

    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, p<0.05), and from 57.9±1.9 to 74.0±11.9% (FACS, p<0.05). Phosphorylation of activated MAPK signaling pathway, including extracellular signal-regulated kinase (ERK1/2), c-Jun NH2-terminal kinase (JNK) and p38 was also increased in antimycin A and daidzin 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.

  1. Galectin-3 protects keratinocytes from UVB-induced apoptosis by enhancing AKT activation and suppressing ERK activation

    PubMed Central

    Saegusa, Jun; Hsu, Daniel K.; Liu, Wei; Kuwabara, Ichiro; Kuwabara, Yasuko; Yu, Lan; Liu, Fu-Tong

    2009-01-01

    Keratinocytes undergo apoptosis in a variety of physiological and pathological conditions. Galectin-3 is a member of a family of β-galactoside-binding animal lectins expressed abundantly in keratinocytes and other epithelial cells. Here we have studied the regulatory role of galectin-3 in keratinocyte apoptosis by using cells from gene-targeted galectin-3 null (gal3−/−) mice. We showed that galectin-3 mRNA was transiently upregulated in ultraviolet-B (UVB)-irradiated wild-type keratinocytes. We found that gal3−/− keratinocytes were significantly more sensitive to apoptosis induced by UVB as well as various other stimuli, both in vitro and in vivo, than wild-type cells. Moreover, we demonstrated that increased apoptosis in gal3−/− keratinocytes was attributable to higher extracellular signal-regulated kinase (ERK) activation and lower AKT activation after UVB irradiation. We conclude that endogenous galectin-3 is an anti-apoptotic molecule in keratinocytes functioning by suppressing ERK activation and enhancing AKT activation and may play a role in the development of apoptosis-related skin diseases. PMID:18463681

  2. Tailoring micro-mesoporosity in activated carbon fibers to enhance SO₂ catalytic oxidation.

    PubMed

    Diez, Noel; Alvarez, Patricia; Granda, Marcos; Blanco, Clara; Gryglewicz, Grażyna; Wróbel-Iwaniec, Iwona; Sliwak, Agata; Machnikowski, Jacek; Menendez, Rosa

    2014-08-15

    Enhanced SO2 adsorption of activated carbon fibers is obtained by tailoring a specific micro-mesoporous structure in the fibers. This architecture is obtained via metal catalytic activation of the fibers with a novel precursor, cobalt naphthenate, which contrary to other precursors, also enhances spinnability and carbon fiber yield. In the SO2 oxidation, it is demonstrated that the combination of micropores and large mesopores is the main factor for an enhanced catalytic activity which is superior to that observed in other similar microporous activated carbon fibers. This provides an alternative way for the development of a new generation of catalytic material.

  3. GM-CSF Enhances Macrophage Glycolytic Activity In Vitro and Improves Detection of Inflammation In Vivo

    PubMed Central

    Singh, Parmanand; González-Ramos, Silvia; Mojena, Marina; Rosales-Mendoza, César Eduardo; Emami, Hamed; Swanson, Jeffrey; Morss, Alex; Fayad, Zahi A.; Rudd, James H.F.; Gelfand, Jeffrey; Paz-García, Marta; Martín-Sanz, Paloma; Boscá, Lisardo

    2016-01-01

    18F-FDG accumulates in glycolytically active tissues and is known to concentrate in tissues that are rich in activated macrophages. In this study, we tested the hypotheses that human granulocyte-macrophage colony-stimulating factor (GM-CSF), a clinically used cytokine, increases macrophage glycolysis and deoxyglucose uptake in vitro and acutely enhances 18F-FDG uptake within inflamed tissues such as atherosclerotic plaques in vivo. Methods: In vitro experiments were conducted on human macrophages whereby inflammatory activation and uptake of radiolabeled 2-deoxyglucose was assessed before and after GM-CSF exposure. In vivo studies were performed on mice and New Zealand White rabbits to assess the effect of GM-CSF on 18F-FDG uptake in normal versus inflamed arteries, using PET. Results: Incubation of human macrophages with GM-CSF resulted in increased glycolysis and increased 2-deoxyglucose uptake (P < 0.05). This effect was attenuated by neutralizing antibodies against tumor necrosis factor–α or after silencing or inhibition of 6-phosphofructo-2-kinase. In vivo, in mice and in rabbits, intravenous GM-CSF administration resulted in a 70% and 73% increase (P < 0.01 for both), respectively, in arterial 18F-FDG uptake in atherosclerotic animals but not in nonatherosclerotic controls. Histopathologic analysis demonstrated a significant correlation between in vivo 18F-FDG uptake and macrophage staining (R = 0.75, P < 0.01). Conclusion: GM-CSF substantially augments glycolytic flux in vitro (via a mechanism dependent on ubiquitous type 6-phosphofructo-2-kinase and tumor necrosis factor–α) and increases 18F-FDG uptake within inflamed atheroma in vivo. These findings demonstrate that GM-CSF can be used to enhance detection of inflammation. Further studies should explore the role of GM-CSF stimulation to enhance the detection of inflammatory foci in other disease states. PMID:27081166

  4. Facile synthesis of Ag–Cu{sub 2}O composites with enhanced photocatalytic activity

    SciTech Connect

    Yang, Jianbo; Li, Zhen; Zhao, Caixin; Wang, Yang; Liu, Xueqin

    2014-12-15

    Highlights: • Ag–Cu{sub 2}O nanocomposites were synthesized via awet-chemical precipitation route. • The growth temperature does not exceed 50 °C in any step of the synthesis. • Enhanced photocurrent of Ag–Cu{sub 2}O composites, compared to pure Cu{sub 2}O particles. • The photocatalytic property was studied upon simulated sunlight. • Enhanced photocatalytic property of Ag–Cu{sub 2}O composites, compared to pure Cu{sub 2}O particles. - Abstract: Silver–cuprous oxide (Ag–Cu{sub 2}O) microcomposites are successfully prepared by a facile low-cost solution method. The obtained materials were characterized by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), field emission scanning electron microscopy (FESEM), ultraviolet–visible (UV–vis) spectroscopy, X-ray photoelectron spectroscopy (XPS). Experiments demonstrated that the formation of Ag–Cu{sub 2}O microcomposites was significantly influenced by the concentration of AgNO{sub 3}, and with increasing the concentration of AgNO{sub 3}, the optical absorption of the composites becomes strong. The photocatalytic activity of the prepared Ag–Cu{sub 2}O composites was determined by measuring the degradation of methyl orange solution under visible light, to find out its potential application in waste water treatment. The results reveal that the photocurrent of the composite is about 4 times higher than that of pure Cu{sub 2}O and the visible light photocatalytic activity of the composite is enhanced greatly on degradation of methyl orange. The reason for improvement in photocatalytic activity of the Ag–Cu{sub 2}O composites was also discussed.

  5. Cooperative enhancement of deoxyribozyme activity by chemical modification and added cationic copolymer

    PubMed Central

    Saito, Ken; Shimada, Naohiko; Maruyama, Atushi

    2016-01-01

    Abstract Deoxyribozymes (DNAzymes) having RNA-cleaving activity have widely been explored as tools for therapeutic and diagnostic purposes. Both the chemical cleaving step and the turnover step should be improved for enhancing overall activity of DNAzymes. We have shown that cationic copolymer enhanced DNAzyme activity by increasing turnover efficacy. In this paper, effects of the copolymer on DNAzymes modified with locked nucleic acids (LNA) or 2′-O-methylated (2′-OMe) nucleic acids were studied. The copolymer increased activity of these chemically modified DNAzymes. More than 30-fold enhancement in multiple-turnover catalytic activity was observed with 2′-OMe-modified DNAzyme in the presence of the copolymer. DNAzyme catalytic activity was successfully enhanced by cooperation of the added copolymer and chemical modification of DNAzyme. PMID:27877894

  6. Crebinostat: a novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity.

    PubMed

    Fass, Daniel M; Reis, Surya A; Ghosh, Balaram; Hennig, Krista M; Joseph, Nadine F; Zhao, Wen-Ning; Nieland, Thomas J F; Guan, Ji-Song; Kuhnle, Chelsea E Groves; Tang, Weiping; Barker, Douglas D; Mazitschek, Ralph; Schreiber, Stuart L; Tsai, Li-Huei; Haggarty, Stephen J

    2013-01-01

    Long-term memory formation is known to be critically dependent upon de novo gene expression in the brain. As a consequence, pharmacological enhancement of the transcriptional processes mediating long-term memory formation provides a potential therapeutic strategy for cognitive disorders involving aberrant neuroplasticity. Here we focus on the identification and characterization of small molecule inhibitors of histone deacetylases (HDACs) as enhancers of CREB (cAMP response element-binding protein)-regulated transcription and modulators of chromatin-mediated neuroplasticity. Using a CREB reporter gene cell line, we screened a library of small molecules structurally related to known HDAC inhibitors leading to the identification of a probe we termed crebinostat that produced robust activation of CREB-mediated transcription. Further characterization of crebinostat revealed its potent inhibition of the deacetylase activity of recombinant class I HDACs 1, 2, 3, and class IIb HDAC6, with weaker inhibition of the class I HDAC8 and no significant inhibition of the class IIa HDACs 4, 5, 7, and 9. In cultured mouse primary neurons, crebinostat potently induced acetylation of both histone H3 and histone H4 as well as enhanced the expression of the CREB target gene Egr1 (early growth response 1). Using a hippocampus-dependent, contextual fear conditioning paradigm, mice systemically administered crebinostat for a ten day time period exhibited enhanced memory. To gain insight into the molecular mechanisms of memory enhancement by HDAC inhibitors, whole genome transcriptome profiling of cultured mouse primary neurons treated with crebinostat, combined with bioinformatic analyses of CREB-target genes, was performed revealing a highly connected protein-protein interaction network reflecting modules of genes important to synaptic structure and plasticity. Consistent with these findings, crebinostat treatment increased the density of synapsin-1 punctae along dendrites in cultured

  7. Synergistic Enhancement of Cellobiohydrolase Performance on Pretreated Corn Stover by Addition of Xylanase and Esterase Activities

    SciTech Connect

    Selig, M. J.; Knoshaug E. P.; Adney, W. S.; Himmel, M. E.; Decker, S. R.

    2007-11-01

    Significant increases in the depolymerization of corn stover cellulose by cellobiohydrolase I (Cel7A) from Trichoderma reesei were observed using small quantities of non-cellulolytic cell wall-degrading enzymes. Purified endoxylanase (XynA), ferulic acid esterase (FaeA), and acetyl xylan esterase (Axe1) all enhanced Cel7A performance on corn stover subjected to hot water pretreatment. In all cases, the addition of these activities improved the effectiveness of the enzymatic hydrolysis in terms of the quantity of cellulose converted per milligram of total protein. Improvement in cellobiose release by the addition of the non-cellulolytic enzymes ranged from a 13-84% increase over Cel7A alone. The most effective combinations included the addition of both XynA and Axe1, which synergistically enhance xylan conversions resulting in additional synergistic improvements in glucan conversion. Additionally, we note a direct relationship between enzymatic xylan removal in the presence of XynA and the enhancement of cellulose hydrolysis by Cel7A.

  8. Atomic Ordering Enhanced Electrocatalytic Activity of Nanoalloys for Oxygen Reduction Reaction

    SciTech Connect

    Loukrakpam, Rameshwori; Shan, Shiyao; Petkov, Valeri; Yang, Lefu; Luo, Jin; Zhong, Chuan-Jian

    2013-10-01

    For oxygen reduction reaction (ORR) over alloy electrocatalysts, the understanding of how the atomic arrangement of the metal species in the nanocatalysts is responsible for the catalytic enhancement is challenging for achieving better design and tailoring of nanoalloy catalysts. This paper reports results of an investigation of the atomic structures and the electrocatalytic activities of ternary and binary nanoalloys, aiming at revealing a fundamental insight into the unique atomic-scale structure-electrocatalytic activity relationship. PtIrCo catalyst and its binary counterparts (PtCo and PtIr) are chosen as a model system for this study. The effect of thermochemical treatment temperature on the atomic-scale structure of the catalysts was examined as a useful probe to the structure-activity correlation. The structural characterization of the binary and ternary nanoalloy catalysts was performed by combining surface sensitive techniques such as XPS and 3D atomic ordering sensitive techniques such as high-energy X-ray diffraction (HE-XRD) coupled to atomic pair distribution function (PDF) analysis (HE-XRD/PDFs) and computer simulations. The results show that the thermal treatment temperature tunes the nanoalloy’s atomic and chemical ordering in a different way depending on the chemical composition, leading to differences in the nanoalloy’s mass and specific activities. A unique structural tunability of the atomic ordering in a platinum-iridium-cobalt nanoalloy has been revealed for enhancing greatly the electrocatalytic activity toward oxygen reduction reaction, which has significant implication for rational design and nanoengineering of advanced catalysts for electrochemical energy conversion and storage.

  9. Novel Oxidatively Activated Agents Modify DNA and are Enhanced by Ercc1 Silencing

    PubMed Central

    Jones, Amy R.; Bell-Horwath, Tiffany R.; Li, Guorui; Rollmann, Stephanie M.; Merino, Edward J.

    2012-01-01

    chlorambucil, showed statistically significant enhanced toxicity in Drosophila with silenced Ercc1. In addition, 5-fluorouracil, which does not produce bulky lesions, showed no selective toxicity. An-Hq and An-Hq2 showed statistically significant toxicity in Drosophila with silenced Ercc1. Examination of cytotoxicity shows renal carcinoma cell lines as a target of these agents with a median IC50 of 1.8 μM. Taken together, this data shows that the designed oxidatively-activated agents form distinct, bulky DNA modifications that prove difficult for cancer cells possessing an elevated reactive oxygen species phenotype to overcome. The modification produced is relatively unique among anticancer agents. PMID:23051149

  10. High glucose enhances progression of cholangiocarcinoma cells via STAT3 activation.

    PubMed

    Saengboonmee, Charupong; Seubwai, Wunchana; Pairojkul, Chawalit; Wongkham, Sopit

    2016-01-08

    Epidemiological studies have indicated diabetes mellitus (DM) as a risk of cholangiocarcinoma (CCA), however, the effects and mechanisms of high glucose on progression of CCA remain unclear. This study reports for the first time of the enhancing effects of high glucose on aggressive phenotypes of CCA cells via STAT3 activation. CCA cells cultured in high glucose media exerted significantly higher rates of cell proliferation, adhesion, migration and invasion than those cultured in normal glucose. The phosphokinase array revealed STAT3 as the dominant signal activated in response to high glucose. Increased nuclear STAT3, p-STAT3 and its downstream target proteins, cyclin D1, vimentin and MMP2, were shown to be underling mechanisms of high glucose stimulation. The link of high glucose and STAT3 activation was confirmed in tumor tissues from CCA patients with DM that exhibited higher STAT3 activation than those without DM. Moreover, the levels of STAT3 activation were correlated with the levels of blood glucose. Finally, decreasing the level of glucose or using a STAT3 inhibitor could reduce the effects of high glucose. These findings suggest that controlling blood glucose or using a STAT3 inhibitor as an alternative approach may improve the therapeutic outcome of CCA patients with DM.

  11. Urease immobilized polymer hydrogel: Long-term stability and enhancement of enzymatic activity.

    PubMed

    Kutcherlapati, S N Raju; Yeole, Niranjan; Jana, Tushar

    2016-02-01

    A method has been developed in which an enzyme namely urease was immobilized inside hydrogel matrix to study the stability and enzymatic activity in room temperature (∼27-30°C). This urease coupled hydrogel (UCG) was obtained by amine-acid coupling reaction and this procedure is such that it ensured the wider opening of mobile flap of enzyme active site. A systematic comparison of urea-urease assay and the detailed kinetic data clearly revealed that the urease shows activity for more than a month when stored at ∼27-30°C in case of UCG whereas it becomes inactive in case of free urease (enzyme in buffer solution). The aqueous microenvironment inside the hydrogel, unusual morphological features and thermal behaviour were believed to be the reasons for unexpected behaviour. UCG displayed enzyme activity at basic pH and up to 60°C. UCG showed significant enhancement in activity against thermal degradation compared to free urease. In summary, this method is a suitable process to stabilize the biomacromolecules in standard room temperature for many practical uses.

  12. Transcriptional Regulation of Enhancers Active in Protodomains of the Developing Cerebral Cortex

    PubMed Central

    Pattabiraman, Kartik; Golonzhka, Olga; Lindtner, Susan; Nord, Alex S.; Taher, Leila; Hoch, Renee; Silberberg, Shanni N.; Zhang, Dongji; Chen, Bin; Zeng, HongKui; Pennacchio, Len; Puelles, Luis; Visel, Axel; Rubenstein, John L. R.

    2014-01-01

    SUMMARY Elucidating the genetic control of cerebral cortical (pallial) development is essential for understanding function, evolution, and disorders of the brain. Transcription factors (TFs) that embryonically regulate pallial regionalization are expressed in gradients, raising the question of how discrete domains are generated. We provide evidence that small enhancer elements active in protodomains integrate broad transcriptional information. CreERT2 and GFP expression from 14 different enhancer elements in stable transgenic mice allowed us to define the first comprehensive regional fate map of the pallium. We explored transcriptional mechanisms that control the activity of the enhancers using informatics, in vivo occupancy by TFs that regulate cortical patterning (CoupTFI, Pax6 and Pbx1), and analysis of enhancer activity in Pax6 mutants. Overall, the results provide novel insights into how broadly expressed patterning TFs regulate the activity of small enhancer elements that drive gene expression in pallial protodomains that fate map to distinct cortical regions. PMID:24814534

  13. Surfactant-activated lipase hybrid nanoflowers with enhanced enzymatic performance

    PubMed Central

    Cui, Jiandong; Zhao, Yamin; Liu, Ronglin; Zhong, Cheng; Jia, Shiru

    2016-01-01

    Increasing numbers of materials have been extensively used as platforms for enzyme immobilization to improve catalytic performance. However, activity of the most of the enzymes was declined after immobilization. Here, we develop a surfactant-activated lipase-inorganic flowerlike hybrid nanomaterials with rational design based on interfacial activation and self-assembly. The resulting surfactant-activated lipase-inorganic hybird nanoflower (activated hNF-lipase) exhibited 460% and 200% higher activity than native lipase and conventional lipase-inorganic hybird nanoflower (hNF-lipase). Furthermore, the activated hNF-lipase displayed good reusability due to its monodispersity and mechanical properties, and had excellent long-time stability. The superior catalytic performances were attributed to both the conformational modulation of surfactants and hierarchical structure of nanoflowers, which not only anchored lipases in an active form, but also decreased the enzyme-support negative interaction and mass-transfer limitations. This new biocatalytic system is promising to find widespread use in applications related to biomedicine, biosensor, and biodiesel. PMID:27297609

  14. Enhancing Learning Outcomes through Application Driven Activities in Marketing

    ERIC Educational Resources Information Center

    Stegemann, Nicole; Sutton-Brady, Catherine

    2013-01-01

    This paper introduces an activity used in class to allow students to apply previously acquired information to a hands-on task. As the authors have previously shown active learning is a way to effectively facilitate and improve students' learning outcomes. As a result to improve learning outcomes we have overtime developed a series of learning…

  15. Variation of antioxidative activity and growth enhancement of Brassicaceae induced by low-pressure oxygen plasma

    NASA Astrophysics Data System (ADS)

    Ono, Reoto; Hayashi, Nobuya

    2015-06-01

    The mechanism of growth enhancement induced by active oxygen species generated in an oxygen plasma is investigated. The plant growth enhancement induced by the active oxygen species would relate to an antioxidative activity, which is one of the biological responses. The amount of generated active oxygen species is varied by the oxygen gas pressure in a low-pressure RF glow discharge plasma. The antioxidative activity of sprouts of Brassicaceae induced by the oxygen plasma is maximized at pressures between 30 and 40 Pa, whereas the antioxidative activity becomes small at around 60 and 80 Pa. The pressure dependence of the antioxidative activity of sprout stems is opposite to that of the stem length of the sprouts. The growth enhancement would be induced by the increase in the concentration of active oxygen species in plants owing to the decrease in the amount of antioxidative substances.

  16. Garden-like perovskite superstructures with enhanced photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Ye, Meidan; Wang, Mengye; Zheng, Dajiang; Zhang, Nan; Lin, Changjian; Lin, Zhiqun

    2014-03-01

    By subjecting amorphous flower-like TiO2 to a facile hydrothermal synthesis in the presence of Sr2+, garden-like perovskite SrTiO3 superstructures were achieved. The amorphous TiO2 was preformed using ZnO flowers as templates. Different three-dimensional SrTiO3 architectures were coexisted in the garden, including SrTiO3 flowers composed of several hollow sword-shaped petals, many sheet-shaped petals or numerous flake-shaped petals, and SrTiO3 grass consisting of a number of long blades. These SrTiO3 superstructures were simultaneously grown on fluorine-doped tin oxide (FTO) substrates. On the basis of a comprehensive study on the effects of growth time, temperature, initial concentrations of precursor, and pH, the formation of these various hierarchical architectures was attributed primarily to the dissolution of amorphous TiO2 and precipitation of perovskite crystals, followed by the Ostwald ripening process of perovskite nanocrystals and self-organization of perovskite building blocks. Interestingly, this approach can be readily extended to create other perovskite structures, including dendritic BaTiO3 and nest-like CaTiO3, as well as PbTiO3 transformed from plate-like pyrochlore Pb2Ti2O6 after post-thermal treatment. Garden-like SrTiO3 superstructures showed a superior photocatalytic performance when compared to other as-prepared semiconductors and perovskite materials (i.e., ZnO, TiO2, BaTiO3, CaTiO3 and PbTiO3), probably due to their intrinsic photocatalytic activity and special garden-like features with a coexistence of various structures that significantly facilitated the adsorption and diffusion of methyl blue (MB) molecules and oxygen species in the photochemical reaction of MB degradation.By subjecting amorphous flower-like TiO2 to a facile hydrothermal synthesis in the presence of Sr2+, garden-like perovskite SrTiO3 superstructures were achieved. The amorphous TiO2 was preformed using ZnO flowers as templates. Different three-dimensional SrTiO3

  17. Enhanced gastric nitric oxide synthase activity in duodenal ulcer patients.

    PubMed Central

    Rachmilewitz, D; Karmeli, F; Eliakim, R; Stalnikowicz, R; Ackerman, Z; Amir, G; Stamler, J S

    1994-01-01

    Nitric oxide, the product of nitric oxide synthase in inflammatory cells, may have a role in tissue injury through its oxidative metabolism. Nitric oxide may have a role in the pathogenesis of duodenal ulcer and may be one of the mechanisms responsible for the association between gastric infection with Helicobacter pylori and peptic disease. In this study, calcium independent nitric oxide synthase activity was detected in human gastric mucosa suggesting expression of the inducible isoform. In 17 duodenal ulcer patients gastric antral and fundic nitric oxide synthase activity was found to be two and 1.5-fold respectively higher than its activity in the antrum and fundus of 14 normal subjects (p < 0.05). H pylori was detected in the antrum of 15 of 17 duodenal ulcer patients and only in 7 of 14 of the control subjects. Antral nitric oxide synthase activity in H pylori positive duodenal ulcer patients was twofold higher than in H pylori positive normal subjects (p < 0.05). In duodenal ulcer patients antral and fundic nitric oxide synthase activity resumed normal values after induction of ulcer healing with ranitidine. Eradication of H pylori did not further affect gastric nitric oxide synthase activity. These findings suggest that in duodenal ulcer patients stimulated gastric mucosal nitric oxide synthase activity, though independent of the H pylori state, may contribute to the pathogenesis of the disease. PMID:7525417

  18. Interfacial activity in alkaline flooding enhanced oil recovery

    SciTech Connect

    Chan, M.K.

    1981-01-01

    The ionization of long-chained organic acids in the crude oil to form soaps was shown to be primarily responsible for the lowering of oil-water interfacial tension at alkaline pH. These active acids can be concentrated by silica gel chromatography into a minor polar fraction. An equilibrium chemical model was proposed based on 2 competing reactions: the ionization of acids to form active anions, and the formation of undissociated soap between acid anions and sodium ions. It correlates the interfacial activity with the interfacial concentration of active acid anions which is expressed in terms of the concentrations of the chemical species in the system. The model successfully predicts the observed oil-alkaline solution interfacial phenomenon, including its dependence on pH, alkali and salt concentrations, type of acid present and type of soap formed. Flooding at different alkali concentrations to activate different acid species present in the crude was shown to give better recovery than flooding at a single high alkali concentration. Treating the crude oil with a dilute solution of mineral acids liberates additional free active acids and yields better interfacial activity during subsequent alkali contact.

  19. Cyclin C regulates adipogenesis by stimulating transcriptional activity of CCAAT/enhancer binding protein alpha.

    PubMed

    Song, Ziyi; Xiaoli, Alus M; Zhang, Quanwei; Zhang, Yi; Yang, Ellen S T; Wang, Sven; Chang, Rui; Zhang, Zhengdong D; Yang, Gongshe; Strich, Randy; Pessin, Jeffrey E; Yang, Fajun

    2017-03-28

    Brown adipose tissue (BAT) is important for maintaining energy homeostasis and adaptive thermogenesis in rodents and humans. As disorders arising from dysregulated energy metabolism, such as obesity and metabolic diseases, have increased, so has interest in the molecular mechanisms in adipocyte biology. Using a functional screen, we identified cyclin C (CycC), a conserved subunit of the Mediator complex, as a novel regulator for brown adipocyte formation. siRNA-mediated CycC knockdown (KD) in brown preadipocytes impaired the early transcriptional program of differentiation, and genetic knockout (KO) of CycC completely blocked the differentiation process. RNA-seq analyses of CycC-KD revealed a critical role of CycC in activating genes co-regulated by peroxisome proliferator activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα). Overexpression of PPARγ2 or addition of the PPARγ ligand rosiglitazone rescued the defects in CycC-KO brown preadipocytes, and efficiently activated the PPARγ-responsive promoters in both wild-type (WT) and CycC-KO cells, suggesting that CycC is not essential for PPARγ transcriptional activity. In contrast, CycC-KO significantly reduced C/EBPα-dependent gene expression. Unlike for PPARγ, overexpression of C/EBPα could not induce C/EBPα target gene expression in CycC-KO cells or rescue the CycC-KO defects in brown adipogenesis, suggesting that CycC is essential for C/EBPα-mediated gene activation. CycC physically interacted with C/EBPα and this interaction was required for C/EBPα transactivation domain activity. Consistent with the role of C/EBPα in white adipogenesis, CycC-KD also inhibited differentiation of 3T3-L1 cells into white adipocytes. Together, these data indicate that CycC activates adipogenesis by stimulating the transcriptional activity of C/EBPα.

  20. Antileishmanial effect of silver nanoparticles and their enhanced antiparasitic activity under ultraviolet light

    PubMed Central

    Allahverdiyev, Adil M; Abamor, Emrah Sefik; Bagirova, Malahat; Ustundag, Cem B; Kaya, Cengiz; Kaya, Figen; Rafailovich, Miriam

    2011-01-01

    Leishmaniasis is a protozoan vector-borne disease and is one of the biggest health problems of the world. Antileishmanial drugs have disadvantages such as toxicity and the recent development of resistance. One of the best-known mechanisms of the antibacterial effects of silver nanoparticles (Ag-NPs) is the production of reactive oxygen species to which Leishmania parasites are very sensitive. So far no information about the effects of Ag-NPs on Leishmania tropica parasites, the causative agent of leishmaniasis, exists in the literature. The aim of this study was to investigate the effects of Ag-NPs on biological parameters of L. tropica such as morphology, metabolic activity, proliferation, infectivity, and survival in host cells, in vitro. Consequently, parasite morphology and infectivity were impaired in comparison with the control. Also, enhanced effects of Ag-NPs were demonstrated on the morphology and infectivity of parasites under ultraviolet (UV) light. Ag-NPs demonstrated significant antileishmanial effects by inhibiting the proliferation and metabolic activity of promastigotes by 1.5- to threefold, respectively, in the dark, and 2- to 6.5-fold, respectively, under UV light. Of note, Ag-NPs inhibited the survival of amastigotes in host cells, and this effect was more significant in the presence of UV light. Thus, for the first time the antileishmanial effects of Ag-NPs on L. tropica parasites were demonstrated along with the enhanced antimicrobial activity of Ag-NPs under UV light. Determination of the antileishmanial effects of Ag-NPs is very important for the further development of new compounds containing nanoparticles in leishmaniasis treatment. PMID:22114501

  1. Interleukin-37 Enhances the Suppressive Activity of Naturally Occurring CD4+CD25+ Regulatory T Cells

    PubMed Central

    Wang, Da-Wei; Dong, Ning; Wu, Yao; Zhu, Xiao-Mei; Wang, Chun-Ting; Yao, Yong-Ming

    2016-01-01

    Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the suppression of autoimmunity and can control the immune-mediated pathology during the early phase of sepsis. Our previous data showed that silencing interleukin-37 (IL-37) in human CD4+CD25+ Tregs obviously reduced the suppressive activity of CD4+CD25+ Tregs. Here, we found that rhIL-37 stimulation markedly enhanced the suppressive activity of CD4+CD25+ Tregs isolated from naive C57BL/6 J mice in the absence or presence of lipopolysaccharide (LPS). Treatment with rhIL-37 could significantly upregulate the expression of cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and forkhead/winged helix transcription factor p3 (Foxp3) on CD4+CD25+ Tregs. Also, rhIL-37 stimulation promoted the production of transforming growth factor-β1 (TGF-β1) but not IL-10 in the supernatants of cultured CD4+CD25+ Tregs. Pretreated CD4+CD25+ Tregs with rhIL-37 in the presence or absence of LPS were cocultured with CD4+CD25− T cells, ratio of IL-4/interferon-γ in the supernatants obviously increased in IL-37-stimulated groups. In addition, early administration of IL-37 significantly improved the survival rate of septic mice induced by cecal ligation and puncture. Taken together, we concluded that rhIL-37 enhances the suppressive activity of CD4+CD25+ Tregs and might be a potential immunomodulator for the treatment of septic complications. PMID:27941849

  2. Nifedipine Treatment for Hypertension is Associated with Enhanced Lipolytic Activity and Accelerated Clearance of Postprandial Lipemia.

    PubMed

    Grosskopf, I; Shaish, A; Charach, G; Harats, D; Kamari, Y

    2016-04-01

    Hypertension, advanced age, postprandial hyperlipidemia, and insulin resistance are major risk factors for atherosclerosis. The calcium channel blocker nifedipine is reported to ameliorate insulin resistance possibly by activating PPARγ. This is expected to become accentuated in elderly individuals due to age-related insulin resistance. Insulin resistance modulates lipoprotein metabolism. Therefore, we reasoned that nifedipne offers the potential for improving postprandial lipemia in association with increasing age. We studied the effect of nifedipine on fasting lipids, postprandial lipemia, insulin sensitivity, and plasma lipolytic activity in 24 and 15 hypertensive subjects aged 70-75 years and 40-45 years, respectively. As expected, nifedipine significantly lowered systolic and diastolic blood pressure. Nifedipine decreased fasting triglyceride level (23%) and increased HDL-C (15%) in the elderly group. At baseline, postprandial triglyceride levels were remarkably elevated in elderly compared to younger patients (1 288±798 vs. 501±260 mg·dl(-1)·h, p<0.05), as was retinyl palmitate (surrogate marker for intestinally-derived cholesterol) in the chylomicrons (45.0±26.5 vs. 23.4±10.6 mg·l(-1)·h, p<0.05) and chylomicron remnant (15.2±5.4 vs. 11.7±4.7 mg·l(-1)·h, p<0.05) fractions. Importantly, while the level of chylomicron remnants in the group of younger subjects remained unchanged after treatment, nifedipine was associated with a significantly decreased chylomicron remnants retinyl palmitate in the elderly group, which dropped to levels, observed in younger subjects. This was accompanied by enhanced insulin sensitivity and augmented plasma lipolytic activity. The present work suggests that nifedipine has favorable metabolic effects that are beyond the known enhancement of insulin sensitivity. The improvement in postprandial lipidemia by nifedipine may add to its anti-atherogenic effects in hypertensive patients.

  3. Blood pressure lowering, fibrinolysis enhancing and antioxidant activities of cardamom (Elettaria cardamomum).

    PubMed

    Verma, S K; Jain, Vartika; Katewa, S S

    2009-12-01

    Elettaria cardamomum (L.) Maton. (Small cardamom) fruit powder was evaluated for its antihypertensive potential and its effect on some of the cardiovascular risk factors in individuals with stage 1 hypertension. Twenty, newly diagnosed individuals with primary hypertension of stage 1 were administered 3 g of cardamom powder in two divided doses for 12 weeks. Blood pressure was recorded initially and at 4 weeks interval for 3 months. Blood samples were also collected initially and at 4 weeks interval for estimation of lipid profile, fibrinogen and fibrinolysis. Total antioxidant status, however, was assessed initially and at the end of the study. Administration of 3 g cardamom powder significantly (p<0.001) decreased systolic, diastolic and mean blood pressure and significantly (p<0.05) increased fibrinolytic activity at the end of 12th week. Total antioxidant status was also significantly (p<0.05) increased by 90% at the end of 3 months. However, fibrinogen and lipid levels were not significantly altered. All study subjects experienced a feeling of well being without any side-effects. Thus, the present study demonstrates that small cardamom effectively reduces blood pressure, enhances fibrinolysis and improves antioxidant status, without significantly altering blood lipids and fibrinogen levels in stage 1 hypertensive individuals.

  4. Dual subcellular compartment delivery of doxorubicin to overcome drug resistant and enhance antitumor activity

    PubMed Central

    Song, Yan-feng; Liu, Dao-zhou; Cheng, Ying; Liu, Miao; Ye, Wei-liang; Zhang, Bang-le; Liu, Xin-you; Zhou, Si-yuan

    2015-01-01

    In order to overcome drug resistant and enhance antitumor activity of DOX, a new pH-sensitive micelle (DOX/DQA-DOX@DSPE-hyd-PEG-AA) was prepared to simultaneously deliver DOX to nucleus and mitochondria. Drug released from DOX/DQA-DOX@DSPE-hyd-PEG-AA showed a pH-dependent manner. DOX/DQA-DOX@DSPE-hyd-PEG-AA induced the depolarization of mitochondria and apoptosis in MDA-MB-231/ADR cells and A549 cells, which resulted in the high cytotoxicity of DOX/DQA-DOX@DSPE-hyd-PEG-AA against MDA-MB-231/ADR cells and A549 cells. Confocal microscopy confirmed that DOX/DQA-DOX@DSPE-hyd-PEG-AA simultaneously delivered DQA-DOX and DOX to the mitochondria and nucleus of tumor cell. After DOX/DQA-DOX@DSPE-hyd-PEG-AA was injected to the tumor-bearing nude mice by the tail vein, DOX was mainly found in tumor tissue. But DOX was widely distributed in the whole body after the administration of free DOX. Compared with free DOX, the same dose of DOX/DQA-DOX@DSPE-hyd-PEG-AA significantly inhibited the growth of DOX-resistant tumor in tumor-bearing mice without obvious systemic toxicity. Therefore, dual subcellular compartment delivery of DOX greatly enhanced the antitumor activity of DOX on DOX-resistant tumor. DOX/DQA-DOX@DSPE-hyd-PEG-AA has the potential in target therapy for DOX-resistant tumor. PMID:26530454

  5. Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation.