Comparison of carbon-sulfur and carbon-amine bond in therapeutic drug: 4β-S-aromatic heterocyclic podophyllum derivatives display antitumor activity

PubMed Central

Li, Jian-Long; Zhao, Wei; Zhou, Chen; Zhang, Ya-Xuan; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

2015-01-01

Herein is a first effort to systematically study the significance of carbon-sulfur (C-S) and carbon-amine (C-NH) bonds on the antitumor proliferation activity of podophyllum derivatives and their precise mechanism of apoptosis. Compared with the derivative modified by a C-NH bond, the derivative modified by a C-S bond exhibited superior antitumor activity, the inhibition activity of target proteins tubulin or Topo II, cell cycle arrest, and apoptosis induction. Antitumor mechanistic studies showed that the death receptor and the mitochondrial apoptotic pathways were simultaneously activated by the C-S bond modified aromatic heterocyclic podophyllum derivatives with a higher cellular uptake percentage of 60–90% and induction of a higher level of reactive oxygen species (ROS). Only the mitochondrial apoptotic pathway was activated by the C-NH bond modified aromatic heterocyclic podophyllum derivatives, with a lower cellular uptake percentage of 40–50%. This study provided insight into effects of the C-S and C-NH bond modification on the improvement of the antitumor activity of Podophyllum derivatives. PMID:26443888

Boosting heterosubtypic neutralization antibodies in recipients of 2009 pandemic H1N1 influenza vaccine.

PubMed

Qiu, Chao; Huang, Yang; Wang, Qian; Tian, Di; Zhang, Wanju; Hu, Yunwen; Yuan, Zhenghong; Zhang, Xiaoyan; Xu, Jianqing

2012-01-01

A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations.

Comparative Studies on Dyeability with Direct, Acid and Reactive Dyes after Chemical Modification of Jute with Mixed Amino Acids Obtained from Extract of Waste Soya Bean Seeds

NASA Astrophysics Data System (ADS)

Bhaumik, Nilendu Sekhar; Konar, Adwaita; Roy, Alok Nath; Samanta, Ashis Kumar

2017-12-01

Jute fabric was treated with mixed natural amino acids obtained from waste soya bean seed extract for chemical modification of jute for its cataionization and to enhance its dyeability with anionic dyes (like direct, reactive and acid dye) as well enabling soya modified jute for salt free dyeing with anionic reactive dyes maintaining its eco-friendliness. Colour interaction parameters including surface colour strength were assessed and compared for both bleached and soya-modified jute fabric for reactive dyeing and compared with direct and acid dye. Improvement in K/S value (surface colour strength) was observed for soya-modified jute even in absence of salt applied in dye bath for reactive dyes as well as for direct and acid dyes. In addition, reactive dye also shows good dyeability even in acid bath in salt free conditions. Colour fastness to wash was evaluated for bleached and soya-modified jute fabric after dyeing with direct, acid and reactive dyes are reported. Treatment of jute with soya-extracted mixed natural amino acids showed anchoring of some amino/aldemine groups on jute cellulosic polymer evidenced from Fourier Transform Infra-Red (FTIR) Spectroscopy. This amino or aldemine group incorporation in bleached jute causes its cationization and hence when dyed in acid bath for reactive dye (instead of conventional alkali bath) showed dye uptake for reactive dyes. Study of surface morphology by Scanning Electron Microscopy (SEM) of said soya-modified jute as compared to bleached jute was studied and reported.

Sorbents for the oxidation and removal of mercury

DOEpatents

Olson, Edwin S; Holmes, Michael J; Pavlish, John Henry

2013-08-20

A promoted activated carbon sorbent is described that is highly effective for the removal of mercury from flue gas streams. The sorbent comprises a new modified carbon form containing reactive forms of halogen and halides. Optional components may be added to increase reactivity and mercury capacity. These may be added directly with the sorbent, or to the flue gas to enhance sorbent performance and/or mercury capture. Mercury removal efficiencies obtained exceed conventional methods. The sorbent can be regenerated and reused. Sorbent treatment and preparation methods are also described. New methods for in-flight preparation, introduction, and control of the active sorbent into the mercury contaminated gas stream are described.

Sorbents for the oxidation and removal of mercury

DOEpatents

Olson, Edwin S [Grand Forks, ND; Holmes, Michael J [Thompson, ND; Pavlish, John H [East Grand Forks, MN

2008-10-14

A promoted activated carbon sorbent is described that is highly effective for the removal of mercury from flue gas streams. The sorbent comprises a new modified carbon form containing reactive forms of halogen and halides. Optional components may be added to increase reactivity and mercury capacity. These may be added directly with the sorbent, or to the flue gas to enhance sorbent performance and/or mercury capture. Mercury removal efficiencies obtained exceed conventional methods. The sorbent can be regenerated and reused. Sorbent treatment and preparation methods are also described. New methods for in-flight preparation, introduction, and control of the active sorbent into the mercury contaminated gas stream are described.

Sorbents for the oxidation and removal of mercury

DOEpatents

Olson, Edwin S [Grand Forks, ND; Holmes, Michael J [Thompson, ND; Pavlish, John H [East Grand Forks, MN

2012-05-01

A promoted activated carbon sorbent is described that is highly effective for the removal of mercury from flue gas streams. The sorbent comprises a new modified carbon form containing reactive forms of halogen and halides. Optional components may be added to increase reactivity and mercury capacity. These may be added directly with the sorbent, or to the flue gas to enhance sorbent performance and/or mercury capture. Mercury removal efficiencies obtained exceed conventional methods. The sorbent can be regenerated and reused. Sorbent treatment and preparation methods are also described. New methods for in-flight preparation, introduction, and control of the active sorbent into the mercury contaminated gas stream are described.

Sorbents for the oxidation and removal of mercury

DOEpatents

Olson, Edwin S.; Holmes, Michael J.; Pavlish, John Henry

2014-09-02

A promoted activated carbon sorbent is described that is highly effective for the removal of mercury from flue gas streams. The sorbent comprises a new modified carbon form containing reactive forms of halogen and halides. Optional components may be added to increase reactivity and mercury capacity. These may be added directly with the sorbent, or to the flue gas to enhance sorbent performance and/or mercury capture. Mercury removal efficiencies obtained exceed conventional methods. The sorbent can be regenerated and reused. Sorbent treatment and preparation methods are also described. New methods for in-flight preparation, introduction, and control of the active sorbent into the mercury contaminated gas stream are described.

Substitutions in PBP2b from β-Lactam-resistant Streptococcus pneumoniae Have Different Effects on Enzymatic Activity and Drug Reactivity*

PubMed Central

Calvez, Philippe; Breukink, Eefjan; Roper, David I.; Dib, Mélanie; Contreras-Martel, Carlos; Zapun, André

2017-01-01

Pneumococcus resists β-lactams by expressing variants of its target enzymes, the penicillin-binding proteins (PBPs), with many amino acid substitutions. Up to 10% of the sequence can be modified. These altered PBPs have a much reduced reactivity with the drugs but retain their physiological activity of cross-linking the peptidoglycan, the major constituent of the bacterial cell wall. However, because β-lactams are chemical and structural mimics of the natural substrate, resistance mediated by altered PBPs raises the following paradox: how PBPs that react poorly with the drugs maintain a sufficient level of activity with the physiological substrate. This question is addressed for the first time in this study, which compares the peptidoglycan cross-linking activity of PBP2b from susceptible and resistant strains with their inhibition by different β-lactams. Unexpectedly, the enzymatic activity of the variants did not correlate with their antibiotic reactivity. This finding indicates that some of the numerous amino acid substitutions were selected to restore a viable level of enzymatic activity by a compensatory molecular mechanism. PMID:28062575

Rheological properties of reactive extrusion modified waxy starch and waxy starch-polyacrylamide copolymer gels

USDA-ARS?s Scientific Manuscript database

The rheological properties of modified waxy starch and waxy starch-polyacrylamide graft copolymers prepared by reactive extrusion were investigated. Both materials can absorb huge amount of water and form gels. The modified waxy starch and waxy starch-polyacrylamide graft copolymer gels all exhibite...

Spatial proximity and sequence localization of the reactive sulfhydryls of porphobilinogen synthase.

PubMed Central

Markham, G. D.; Myers, C. B.; Harris, K. A.; Volin, M.; Jaffe, E. K.

1993-01-01

The zinc metalloenzyme porphobilinogen synthase (PBGS) contains several functionally important, but previously unidentified, reactive sulfhydryl groups. The enzyme has been modified with the reversible sulfhydryl-specific nitroxide spin label derivative of methyl methanethiosulfonate (MMTS), (1-oxyl-2,2,5,5-tetramethyl-delta 3-pyrroline-3-methyl)methanethiosulfonate (SL-MMTS) (Berliner, L. J., Grunwald, J., Hankovszky, H. O., & Hideg, K., 1982, Anal. Biochem. 119, 450-455). EPR spectra show that SL-MMTS labels three groups per PBGS subunit (24 per octamer), as does MMTS. EPR signals reflecting nitroxides of different mobilities are observed. Two of the three modified cysteines have been identified as Cys-119 and Cys-223 by sequencing peptides produced by an Asp-N protease digest of the modified protein. Because MMTS-reactive thiols have been implicated as ligands to the required Zn(II), EPR spectroscopy has been used to determine the spatial proximity of the modified cysteine residues. A forbidden (delta m = 2) EPR transition is observed indicating a through-space dipolar interaction between at least two of the nitroxides. The relative intensity of the forbidden and allowed transitions show that at least two of the unpaired electrons are within at most 7.6 A of each other. SL-MMTS-modified PBGS loses all Zn(II) and cannot catalyze product formation. The modified enzyme retains the ability to bind one of the two substrates at each active site. Binding of this substrate has no influence on the EPR spectral properties of the spin-labeled enzyme, or on the rate of release of the nitroxides when 2-mercaptoethanol is added.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8382991

Effect of active sensitization on the bronchopulmonary responses to tachykinins in the guinea pig. Modulation by peptidase inhibitors.

PubMed

Capaz, F R; Ruffié, C; Lefort, J; Manzini, S; Vargaftig, B B; Pretolani, M

1993-08-01

The i.v. administration of substance P (SP, 0.25-16 micrograms/kg) or of the selective metabolic stable NK-1 agonist, [Glp6,Pro9]SP-(6-11) (septide, 0.03-0.25 microgram) to atropine-treated guinea pigs or to isolated perfused lungs triggered a dose-dependent bronchoconstriction, which was enhanced in animals actively sensitized to ovalbumin. In vivo, bronchial hyper-responsiveness was restricted to SP and to septide, inasmuch as neurokinin A (0.06-1 microgram/kg)- or capsaicin (0.5-32 micrograms/kg)-induced bronchoconstriction were not modified. In contrast, isolated lungs from sensitized guinea pigs exhibited an increased bronchoconstriction also in response to capsaicin (0.01-10 micrograms), which was inhibited by atropine in the medium. Pretreatment of actively sensitized guinea pigs either with indomethacin plus mepyramine, the lipoxygenase inhibitor BW A4C or with the platelet-activating factor antagonist SR 27417, did not modify bronchial hyper-reactivity to SP. Captopril (5 mg/kg i.v.), but not thiorphan (0.8 mg/kg i.v.), increased the SP-induced bronchoconstriction in actively sensitized animals, whereas both inhibitors were equally effective in nonsensitized guinea pigs. Thiorphan, however, did not modify the in vivo response to septide. Our results demonstrate that guinea pigs sensitized to ovalbumin exhibit bronchial hyperreactivity to SP, but not to neurokinin A, as compared to nonsensitized animals, suggesting a decrease in the neutral endopeptidase activity in the airways brought by the immunization. However, the results obtained by using septide indicate that other mechanisms may be involved in the bronchial hyper-reactivity to SP.

Reactive power and voltage control strategy based on dynamic and adaptive segment for DG inverter

NASA Astrophysics Data System (ADS)

Zhai, Jianwei; Lin, Xiaoming; Zhang, Yongjun

2018-03-01

The inverter of distributed generation (DG) can support reactive power to help solve the problem of out-of-limit voltage in active distribution network (ADN). Therefore, a reactive voltage control strategy based on dynamic and adaptive segment for DG inverter is put forward to actively control voltage in this paper. The proposed strategy adjusts the segmented voltage threshold of Q(U) droop curve dynamically and adaptively according to the voltage of grid-connected point and the power direction of adjacent downstream line. And then the reactive power reference of DG inverter can be got through modified Q(U) control strategy. The reactive power of inverter is controlled to trace the reference value. The proposed control strategy can not only control the local voltage of grid-connected point but also help to maintain voltage within qualified range considering the terminal voltage of distribution feeder and the reactive support for adjacent downstream DG. The scheme using the proposed strategy is compared with the scheme without the reactive support of DG inverter and the scheme using the Q(U) control strategy with constant segmented voltage threshold. The simulation results suggest that the proposed method has a significant improvement on solving the problem of out-of-limit voltage, restraining voltage variation and improving voltage quality.

Adsorption of a reactive dye on chemically modified activated carbons--influence of pH.

PubMed

Orfão, J J M; Silva, A I M; Pereira, J C V; Barata, S A; Fonseca, I M; Faria, P C C; Pereira, M F R

2006-04-15

The surface chemistry of a commercial activated carbon with a slightly basic nature was modified by appropriate treatments in order to obtain two additional samples, respectively with acidic and basic properties, without changing its textural parameters significantly. Different techniques (N2 adsorption at 77 K, temperature programmed desorption, and determination of acidity, basicity, and pH at the point of zero charge) were used to characterize the adsorbents. Kinetic and equilibrium adsorption data of a selected textile reactive dye (Rifafix Red 3BN, C.I. reactive red 241) on the mentioned materials were obtained at the pH values of 2, 7, and 12. The kinetic curves are fitted using the second-order model. The respective rate constants seem to diminish progressively with the initial concentration for the more diluted solutions tested, reaching a constant value at higher concentrations, which depends on the experimental system under consideration (adsorbent and pH). In general, the Langmuir model provides the best fit for the equilibrium data. The different uptakes obtained are discussed in relation to the surface chemical properties of the adsorbents. It is shown that the adsorption of the reactive (anionic) dye on the basic sample (prepared by thermal treatment under H2 flow at 700 degrees C) is favored. This conclusion is explained on the basis of the dispersive and electrostatic interactions involved. Moreover, it is also shown that the optimal adsorption condition for all the activated carbons tested corresponds to solution pH values not higher than the pH(pzc) of the adsorbents, which may be interpreted by taking into account the electrostatic forces present.

ACTIVATION AND REACTIVITY OF NOVEL CALCIUM-BASED SORBENTS FOR DRY SO2 CONTROL IN BOILERS

EPA Science Inventory

Chemically modified calcium hydroxide (Ca(OH)2) sorbents developed in the U.S. Environmental Protection Agency's Air and Energy Engineering Research Laboratory (AEERL) for sulfur dioxide (SO2) control in utility boilers were tested in an electrically heated, bench-scale isotherma...

Investigations on dendrimer space reveal solid and liquid tumor growth-inhibition by original phosphorus-based dendrimers and the corresponding monomers and dendrons with ethacrynic acid motifs.

PubMed

El Brahmi, Nabil; Mignani, Serge M; Caron, Joachim; El Kazzouli, Saïd; Bousmina, Mosto M; Caminade, Anne-Marie; Cresteil, Thierry; Majoral, Jean-Pierre

2015-03-07

The well-known reactive diuretic ethacrynic acid (EA, Edecrin), with low antiproliferative activities, was chemically modified and grafted onto phosphorus dendrimers and the corresponding simple branched phosphorus dendron-like derivatives affording novel nanodevices showing moderate to strong antiproliferative activities against liquid and solid tumor cell lines, respectively.

Sorbents for the oxidation and removal of mercur

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olson, Edwin S.; Holmes, Michael J.; Pavlish, John Henry

A promoted activated carbon sorbent is described that is highly effective for the removal of mercury from flue gas streams. The sorbent comprises a new modified carbon form containing reactive forms of halogen and halides. Optional components may be added to increase reactivity and mercury capacity. These may be added directly with the sorbent, or to the flue gas to enhance sorbent performance and/or mercury capture. Mercury removal efficiencies obtained exceed conventional methods. The sorbent can be regenerated and reused. Sorbent treatment and preparation methods are also described. New methods for in-flight preparation, introduction, and control of the active sorbentmore » into the mercury contaminated gas stream are described.« less

Chromium and reactive element modified aluminide diffusion coatings on superalloys - Environmental testing

NASA Technical Reports Server (NTRS)

Bianco, Robert; Rapp, Robert A.; Smialek, James L.

1993-01-01

The high temperature performance of reactive element (RE)-doped and Cr/RE-modified aluminide diffusion coatings on commercial Ni-base alloy substrates was determined. In isothermal oxidation at 1100 C in air, RE-doped aluminide coatings on IN 713LC substrates formed a continuous slow-growing n-Al2O3 scale after 44 hrs of exposure. The coatings were protected by either an outer ridge Al2O3 scale with an inner compact Al2O3 scale rich in RE or by a continuous compact scale without any noticeable cracks or flaws. The cyclic oxidation behavior of Cr/RE-modified aluminide coatings on Rene 80 and IN 713LC alloys and of RE-doped aluminide coatings on IN 713LC alloys at 1100 C in static air was determined. Pack powder entrapment from the powder contacting (PC) process detracted significantly from the overall cyclic oxidation performance. Type I hot corrosion behavior of Cr/RE-modified aluminide coatings on Rene 80 and Mar-M247 alloy substrates at 900 C in a catalyzed 0.1 percent SO3/O3 gas mixture was determined. The modified coatings produced from the PC arrangement provided significantly better resistance to hot corrosion attack than commercial low-activity aluminide coatings produced by the above pack arrangement.

Non-Mendelian Female Sterility in DROSOPHILA MELANOGASTER: Influence of Aging and Thermic Treatments. III. Cumulative Effects Induced by These Factors

PubMed Central

Bucheton, Alain

1979-01-01

Crosses between various strains of Drosophila melanogaster may give rise to a female sterility of non-Mendelian determination. Reduced fertility is observed in females, known as SF females, bred from crosses between females of "reactive" strains and males of "inducer" strains. The reduced fertility of the SF females is the result of an interaction between an extrachromosomal property, the reactivity, and a chromosomal factor, I. The extrachromosomal property varies considerably in its ability to reduce fertility. The fertility reduction of the SF females corresponds to what is known as the reactivity level of their reactive mothers. Two nongenetic factors can modify the level of reactivity: aging and temperature. The action of aging is cumulative. When the flies of a reactive strain are submitted at each generation to the action of this factor, the level of reactivity of this strain is gradually modified. The modifications induced are reversible. Indeed, when such a modified strain is returned to standard breeding conditions, the reactivity returns progressively to its initial level. The effect of thermic treatments also seems to be cumulative and reversible. PMID:121289

Gone for 60 seconds: reactivation length determines motor memory degradation during reconsolidation.

PubMed

de Beukelaar, Toon T; Woolley, Daniel G; Wenderoth, Nicole

2014-10-01

When a stable memory is reactivated it becomes transiently labile and requires restabilization, a process known as reconsolidation. Animal studies have convincingly demonstrated that during reconsolidation memories are modifiable and can be erased when reactivation is followed by an interfering intervention. Few studies have been conducted in humans, however, and results are inconsistent regarding the extent to which a memory can be degraded. We used a motor sequence learning paradigm to show that the length of reactivation constitutes a crucial boundary condition determining whether human motor memories can be degraded. In our first experiment, we found that a short reactivation (less than 60 sec) renders the memory labile and susceptible to degradation through interference, while a longer reactivation does not. In our second experiment, we reproduce these results and show a significant linear relationship between the length of memory reactivation and the detrimental effect of the interfering task performed afterwards, i.e., the longer the reactivation, the smaller the memory loss due to interference. Our data suggest that reactivation via motor execution activates a time-dependent process that initially destabilizes the memory, which is then followed by restabilization during further practice.

Modifying Memory: Selectively Enhancing and Updating Personal Memories for a Museum Tour by Reactivating Them

PubMed Central

St. Jacques, Peggy L.; Schacter, Daniel L.

2013-01-01

Memory can be modified when reactivated, but little is known about how the properties and extent of reactivation can selectively affect subsequent memory. We developed a novel museum paradigm to directly investigate reactivation-induced plasticity for personal memories. Participants reactivated memories triggered by photos taken from a camera they wore during a museum tour and made relatedness judgments on novel photos taken from a different tour of the same museum. Subsequent recognition memory for events at the museum was better for memories that were highly reactivated (i.e., the retrieval cues during reactivation matched the encoding experience) than for memories that were reactivated at a lower level (i.e., the retrieval cues during reactivation mismatched the encoding experience), but reactivation also increased false recognition of photographs depicting stops that were not experienced during the museum tour. Reactivation thus enables memories to be selectively enhanced and distorted via updating, thereby supporting the dynamic and flexible nature of memory. PMID:23406611

Modifying Memory for a Museum Tour in Older Adults: Reactivation-Related Updating that Enhances and Distorts Memory is Reduced in Aging

PubMed Central

St Jacques, Peggy L.; Montgomery, Daniel; Schacter, Daniel L.

2015-01-01

Memory reactivation, the activation of a latent memory trace when we are reminded of a past experience, strengthens memory but can also contribute to distortions if new information present during reactivation is integrated with existing memory. In a previous study in young adults we found that the quality of memory reactivation, manipulated using the principle of encoding specificity and indexed by recollection ratings, modulated subsequent true and false memories for events experienced during a museum tour. Here, we examined age-related changes in the quality of memory reactivation on subsequent memory. Young and older adults reactivated memories for museum stops immediately followed by the presentation of a novel lure photo from an alternate tour version (i.e., reactivation plus new information). There was an increase in subsequent true memories for reactivated targets and for subsequent false memories for lures that followed reactivated targets, when compared to baseline target and lure photos. However, the influence of reactivation on subsequent memories was reduced in older adults. These data reveal that aging alters reactivation-related updating processes that allow memories to be strengthened and updated with new information-consequently reducing memory distortions in older compared to young adults. PMID:24993055

Modifying memory for a museum tour in older adults: Reactivation-related updating that enhances and distorts memory is reduced in ageing.

PubMed

St Jacques, Peggy L; Montgomery, Daniel; Schacter, Daniel L

2015-01-01

Memory reactivation, the activation of a latent memory trace when we are reminded of a past experience, strengthens memory but can also contribute to distortions if new information present during reactivation is integrated with existing memory. In a previous study in young adults we found that the quality of memory reactivation, manipulated using the principle of encoding specificity and indexed by recollection ratings, modulated subsequent true and false memories for events experienced during a museum tour. Here in this study, we examined age-related changes in the quality of memory reactivation on subsequent memory. Memories of museum stops in young and older adults were reactivated and then immediately followed by the presentation of a novel lure photo from an alternate tour version (i.e., reactivation plus new information). There was an increase in subsequent true memories for reactivated targets and for subsequent false memories for lures that followed reactivated targets, when compared to baseline target and lure photos. However, the influence of reactivation on subsequent memories was reduced in older adults. These data reveal that ageing alters reactivation-related updating processes that allow memories to be strengthened and updated with new information, consequently reducing memory distortions in older adults compared to young adults.

Medial compressible forefoot sole elements reduce ankle inversion in lateral SSC jumps.

PubMed

Fleischmann, Jana; Mornieux, Guillaume; Gehring, Dominic; Gollhofer, Albert

2013-06-01

Sideward movements are associated with high incidences of lateral ankle sprains. Special shoe constructions might be able to reduce these injuries during lateral movements. The purpose of this study was to investigate whether medial compressible forefoot sole elements can reduce ankle inversion in a reactive lateral movement, and to evaluate those elements' influence on neuromuscular and mechanical adjustments in lower extremities. Foot placement and frontal plane ankle joint kinematics and kinetics were analyzed by 3-dimensional motion analysis. Electromyographic data of triceps surae, peroneus longus, and tibialis anterior were collected. This modified shoe reduced ankle inversion in comparison with a shoe with a standard sole construction. No differences in ankle inversion moments were found. With the modified shoe, foot placement occurred more internally rotated, and muscle activity of the lateral shank muscles was reduced. Hence, lateral ankle joint stability during reactive sideward movements can be improved by these compressible elements, and therefore lower lateral shank muscle activity is required. As those elements limit inversion, the strategy to control inversion angles via a high external foot rotation does not need to be used.

Methods and apparatuses for reagent delivery, reactive barrier formation, and pest control

DOEpatents

Gilmore, Tyler [Pasco, WA; Kaplan, Daniel I [Aiken, SC; Last, George [Richland, WA

2002-07-09

A reagent delivery method includes positioning reagent delivery tubes in contact with soil. The tubes can include a wall that is permeable to a soil-modifying reagent. The method further includes supplying the reagent in the tubes, diffusing the reagent through the permeable wall and into the soil, and chemically modifying a selected component of the soil using the reagent. The tubes can be in subsurface contact with soil, including groundwater, and can be placed with directional drilling equipment independent of groundwater well casings. The soil-modifying reagent includes a variety of gases, liquids, colloids, and adsorbents that may be reactive or non-reactive with soil components. The method may be used inter alia to form reactive barriers, control pests, and enhance soil nutrients for microbes and plants.

Remediation of arsenic-contaminated groundwater using media-injected permeable reactive barriers with a modified montmorillonite: sand tank studies.

PubMed

Luo, Ximing; Liu, Haifei; Huang, Guoxin; Li, Ye; Zhao, Yan; Li, Xu

2016-01-01

A modified montmorillonite (MMT) was prepared using an acid activation-sodium activation-iron oxide coating method to improve the adsorption capacities of natural MMTs. For MMT, its interlamellar distance increased from 12.29 to 13.36 Å, and goethite (α-FeOOH) was intercalated into its clay layers. Two novel media-injected permeable reactive barrier (MI-PRB) configurations were proposed for removing arsenic from groundwater. Sand tank experiments were conducted to investigate the performance of the two MI-PRBs: Tank A was filled with quartz sand. Tank B was packed with quartz sand and zero-valent iron (ZVI) in series, and the MMT slurry was respectively injected into them to form reactive zones. The results showed that for tank A, total arsenic (TA) removal of 98.57% was attained within the first 60 mm and subsequently descended slowly to 88.84% at the outlet. For tank B, a similar spatial variation trend was observed in the quartz sand layer, and subsequently, TA removal increased to ≥99.80% in the ZVI layer. TA removal by MMT mainly depended on both surface adsorption and electrostatic adhesion. TA removal by ZVI mainly relied on coagulation/precipitation and adsorption during the iron corrosion. The two MI-PRBs are feasible alternatives for in situ remediation of groundwater with elevated As levels.

Oxidative Risk for Atherothrombotic Cardiovascular Disease

PubMed Central

Leopold, Jane A.; Loscalzo, Joseph

2009-01-01

In the vasculature, reactive oxidant species including reactive oxygen, nitrogen, or halogenating species, and thiyl, tyrosyl, or protein radicals, may oxidatively modify lipids and proteins with deleterious consequences for vascular function. These biologically active free radical and non-radical species may be produced by increased activation of oxidant-generating sources and/or decreased cellular antioxidant capacity. Once formed, these species may engage in reactions to yield more potent oxidants that promote transition of the homeostatic vascular phenotype to a pathobiological state that is permissive for atherothrombogenesis. This dysfunctional vasculature is characterized by lipid peroxidation and aberrant lipid deposition, inflammation, immune cell activation, platelet activation, thrombus formation, and disturbed hemodynamic flow. Each of these pathobiological states is associated with an increase in the vascular burden of free radical species-derived oxidation products and, thereby, implicates increased oxidant stress in the pathogenesis of atherothrombotic vascular disease. PMID:19751821

Noble metal-modified titania with visible-light activity for the decomposition of microorganisms

PubMed Central

Endo, Maya; Wei, Zhishun; Wang, Kunlei; Karabiyik, Baris; Yoshiiri, Kenta; Rokicka, Paulina; Ohtani, Bunsho

2018-01-01

Commercial titania photocatalysts were modified with silver and gold by photodeposition, and characterized by diffuse reflectance spectroscopy (DRS), X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and scanning transmission electron microscopy (STEM). It was found that silver co-existed in zero valent (core) and oxidized (shell) forms, whereas gold was mainly zero valent. The obtained noble metal-modified samples were examined with regard to antibacterial (Escherichia coli (E. coli)) and antifungal (Aspergillus niger (A. niger), Aspergillus melleus (A. melleus), Penicillium chrysogenum (P. chrysogenum), Candida albicans (C. albicans)) activity under visible-light irradiation and in the dark using disk diffusion, suspension, colony growth (“poisoned food”) and sporulation methods. It was found that silver-modified titania, besides remarkably high antibacterial activity (inhibition of bacterial proliferation), could also decompose bacterial cells under visible-light irradiation, possibly due to an enhanced generation of reactive oxygen species and the intrinsic properties of silver. Gold-modified samples were almost inactive against bacteria in the dark, whereas significant bactericidal effect under visible-light irradiation suggested that the mechanism of bacteria inactivation was initiated by plasmonic excitation of titania by localized surface plasmon resonance of gold. The antifungal activity tests showed efficient suppression of mycelium growth by bare titania, and suppression of mycotoxin generation and sporulation by gold-modified titania. Although, the growth of fungi was hardly inhibited through disc diffusion (inhibition zones around discs), it indicates that gold does not penetrate into the media, and thus, a good stability of plasmonic photocatalysts has been confirmed. In summary, it was found that silver-modified titania showed superior antibacterial activity, whereas gold-modified samples were very active against fungi, suggesting that bimetallic photocatalysts containing both gold and silver should exhibit excellent antimicrobial properties. PMID:29600144

A model of Martian surface chemistry

NASA Technical Reports Server (NTRS)

Oyama, V. I.; Berdahl, B. J.

1979-01-01

Alkaline earth and alkali metal superoxides and peroxides, gamma-Fe2O3 and carbon suboxide polymer, are proposed to be constituents of the Martian surface material. These reactive substances explain the water modified reactions and thermal behaviors of the Martian samples demonstrated by all of the Viking Biology Experiments. It is also proposed that the syntheses of these substances result mainly from electrical discharges between wind-mobilized particles at Martian pressures; plasmas are initiated and maintained by these discharges. Active species in the plasma either combine to form or react with inorganic surfaces to create the reactive constituents.

Restorative and synergistic efficacy of Kalpaamruthaa, a modified Siddha preparation, on an altered antioxidant status in adjuvant induced arthritic rat model.

PubMed

Mythilypriya, Rajendran; Shanthi, Palanivelu; Sachdanandam, Panchanatham

2007-07-20

Rheumatoid arthritis (RA) is a prevalent and debilitating disease that affects the joints. Infiltration of blood-derived cells in the affected joints upon activation generate reactive oxygen/nitrogen species, resulting in an oxidative stress. One approach to counteract this oxidative stress is the use of antioxidants as therapeutic agents. Kalpaamruthaa (KA), a modified indigenous Siddha preparation constituting Semecarpus anacardium nut milk extract (SA), Emblica officinalis (EO) and honey was evaluated for its synergistic antioxidant potential in adjuvant induced arthritic rats than sole SA treatment. Levels/activities of reactive oxygen species (ROS)/reactive nitrogen species (RNS), myeloperoxidase, lipid peroxide and enzymic and non-enzymic antioxidants were determined in control, arthritis induced, SA and KA treated (150 mg/kg b.wt.) animals. The levels/activities of ROS/RNS, myeloperoxidase and lipid peroxide were increased significantly (p<0.05) and the activities of enzymic and non-enzymic antioxidants were in turn decreased in arthritic rats, whereas these changes were reverted to near normal levels upon SA and KA treatment. KA showed an enhanced antioxidant potential than sole treatment of SA in adjuvant induced arthritic rats. KA via enhancing the antioxidant status in adjuvant induced arthritic rats than sole SA treatment proves to be an important therapeutic modality in the management of RA and thereby instituting the role of oxidative stress in the clinical manifestation of the disease RA. The profound antioxidant efficacy of KA than SA alone might be due to the synergistic action of the polyphenols such as flavonoids, tannins and other compounds such as vitamin C and hydroxycinnamates present in KA.

p300/CBP Histone Acetyltransferase Activity Is Required for Newly Acquired and Reactivated Fear Memories in the Lateral Amygdala

ERIC Educational Resources Information Center

Maddox, Stephanie A.; Watts, Casey S.; Schafe, Glenn E.

2013-01-01

Modifications in chromatin structure have been widely implicated in memory and cognition, most notably using hippocampal-dependent memory paradigms including object recognition, spatial memory, and contextual fear memory. Relatively little is known, however, about the role of chromatin-modifying enzymes in amygdala-dependent memory formation.…

Cannabis, tobacco, and caffeine use modify the blood pressure reactivity protection of ascorbic acid.

PubMed

Brody, Stuart; Preut, Ragnar

2002-07-01

Cannabis, caffeine, and tobacco use are associated with increased mesolimbic dopamine activity. Ascorbic acid (AA) modulates some dopaminergic agent effects, and was recently found to decrease systolic blood pressure (SBP) stress reactivity. To examine how AA SBP stress reactivity protection varies by use of these substances, data from an AA trial (Cetebe, 3000 mg/day for 14 days; N=108) were compared by substance use level regarding SBP reactivity to the anticipation and actual experience phases of a standardized psychological stressor (10 min of public speaking and arithmetic). Self-reported never users of cannabis, persons not currently smoking tobacco, and persons consuming three or more caffeine beverages daily all exhibited AA SBP stress reactivity protection to the actual stressor, but not during the anticipation phase. Conversely, self-reported ever cannabis users, current tobacco smokers, and persons consuming less than three caffeine beverages daily exhibited the AA SBP protection during the anticipation phase, but only the lower caffeine consumption group exhibited AA protection during both phases. Covariates (neuroticism, extraversion, and depression scores, age, sex, body mass index) were all nonsignificant. Results are discussed in terms of dopaminergic effects of these substances, modulation of catecholaminergic and endothelial activity, and AA support of coping styles.

Novel whole blood assay for phenotyping platelet reactivity in mice identifies ICAM-1 as a mediator of platelet-monocyte interaction

PubMed Central

Kirkby, Nicholas S.; Chan, Melissa V.; Finsterbusch, Michaela; Hogg, Nancy; Nourshargh, Sussan; Warner, Timothy D.

2015-01-01

Testing of platelet function is central to the cardiovascular phenotyping of genetically modified mice. Traditional platelet function tests have been developed primarily for testing human samples and the volumes required make them highly unsuitable for the testing of mouse platelets. This limits research in this area. To address this problem, we have developed a miniaturized whole blood aggregometry assay, based on a readily accessible 96-well plate format coupled with quantification of single platelet depletion by flow cytometric analysis. Using this approach, we observed a concentration-dependent loss of single platelets in blood exposed to arachidonic acid, collagen, U46619 or protease activated receptor 4 activating peptide. This loss was sensitive to well-established antiplatelet agents and genetic manipulation of platelet activation pathways. Observations were more deeply analyzed by flow cytometric imaging, confocal imaging, and measurement of platelet releasates. Phenotypic analysis of the reactivity of platelets taken from mice lacking intercellular adhesion molecule (ICAM)-1 identified a marked decrease in fibrinogen-dependent platelet-monocyte interactions, especially under inflammatory conditions. Such findings exemplify the value of screening platelet phenotypes of genetically modified mice and shed further light upon the roles and interactions of platelets in inflammation. PMID:26215112

ENHANCEMENT OF REACTIVITY IN SURFACTANT-MODIFIED SORBENTS FOR SULFUR DIOXIDE CONTROL

EPA Science Inventory

The paper discusses the enhancement of reactivity in surfactant-modified sorbents for S02 control. Injecting calcium-based sorbents into the post-flame zone of utility boilers can achieve S02 captures of 50-60% at a stoichiometry of 2. Calcium hydroxide-- Ca(OH)2--appears to be t...

ROLE OF CANOPY-SCALE PHOTOCHEMISTRY IN MODIFYING BIOGENIC-ATMOSPHERE EXCHANGE OF REACTIVE TERPENE SPECIES: RESULTS FROM THE CELTIC FIELD STUDY

EPA Science Inventory

A one-dimensional canopy model was used to quantify the impact of photochemistry in modifying biosphere-atmosphere exchange of trace gases. Canopy escape efficiencies, defined as the fraction of emission that escapes into the well-mixed boundary layer, were calculated for reactiv...

Modulation of Active Site Electronic Structure by the Protein Matrix to Control [NiFe] Hydrogenase Reactivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Dayle MA; Raugei, Simone; Squier, Thomas C.

2014-09-30

Control of the reactivity of the nickel center of the [NiFe] hydrogenase and other metalloproteins commonly involves outer coordination sphere ligands that act to modify the geometry and physical properties of the active site metal centers. We carried out a combined set of classical molecular dynamics and quantum/classical mechanics calculations to provide quantitative estimates of how dynamic fluctuations of the active site within the protein matrix modulate the electronic structure at the catalytic center. Specifically we focused on the dynamics of the inner and outer coordination spheres of the cysteinate-bound Ni–Fe cluster in the catalytically active Ni-C state. There aremore » correlated movements of the cysteinate ligands and the surrounding hydrogen-bonding network, which modulate the electron affinity at the active site and the proton affinity of a terminal cysteinate. On the basis of these findings, we hypothesize a coupling between protein dynamics and electron and proton transfer reactions critical to dihydrogen production.« less

Modulation of active site electronic structure by the protein matrix to control [NiFe] hydrogenase reactivity.

PubMed

Smith, Dayle M A; Raugei, Simone; Squier, Thomas C

2014-11-21

Control of the reactivity of the nickel center of the [NiFe] hydrogenase and other metalloproteins commonly involves outer coordination sphere ligands that act to modify the geometry and physical properties of the active site metal centers. We carried out a combined set of classical molecular dynamics and quantum/classical mechanics calculations to provide quantitative estimates of how dynamic fluctuations of the active site within the protein matrix modulate the electronic structure at the catalytic center. Specifically we focused on the dynamics of the inner and outer coordination spheres of the cysteinate-bound Ni-Fe cluster in the catalytically active Ni-C state. There are correlated movements of the cysteinate ligands and the surrounding hydrogen-bonding network, which modulate the electron affinity at the active site and the proton affinity of a terminal cysteinate. On the basis of these findings, we hypothesize a coupling between protein dynamics and electron and proton transfer reactions critical to dihydrogen production.

MicroRNA-155 Reinforces HIV Latency*

PubMed Central

Ruelas, Debbie S.; Chan, Jonathan K.; Oh, Eugene; Heidersbach, Amy J.; Hebbeler, Andrew M.; Chavez, Leonard; Verdin, Eric; Rape, Michael; Greene, Warner C.

2015-01-01

The presence of a small number of infected but transcriptionally dormant cells currently thwarts a cure for the more than 35 million individuals infected with HIV. Reactivation of these latently infected cells may result in three fates: 1) cell death due to a viral cytopathic effect, 2) cell death due to immune clearance, or 3) a retreat into latency. Uncovering the dynamics of HIV gene expression and silencing in the latent reservoir will be crucial for developing an HIV-1 cure. Here we identify and characterize an intracellular circuit involving TRIM32, an HIV activator, and miR-155, a microRNA that may promote a return to latency in these transiently activated reservoir cells. Notably, we demonstrate that TRIM32, an E3 ubiquitin ligase, promotes reactivation from latency by directly modifying IκBα, leading to a novel mechanism of NF-κB induction not involving IκB kinase activation. PMID:25873391

T cell reactivity with allergoids: influence of the type of APC.

PubMed

Kahlert, H; Grage-Griebenow, E; Stüwe, H T; Cromwell, O; Fiebig, H

2000-08-15

The use of allergoids for allergen-specific immunotherapy has been established for many years. The characteristic features of these chemically modified allergens are their strongly reduced IgE binding activity compared with the native form and the retained immunogenicity. T cell reactivity of chemically modified allergens is documented in animals, but in humans indirect evidence of reactivity has been concluded from the induction of allergen-specific IgG during immunotherapy. Direct evidence of T cell reactivity was obtained recently using isolated human T cells. To obtain further insight into the mechanism of action of allergoids, we compared the Ag-presenting capacity of different APC types, including DC and macrophages, generated from CD14+ precursor cells from the blood of grass pollen allergic subjects, autologous PBMC, and B cells. These APC were used in experiments together with Phl p 5-specific T cell clones under stimulation with grass pollen allergen extract, rPhl p 5b, and the respective allergoids. Using DC and macrophages, allergoids exhibited a pronounced and reproducible T cell-stimulating capacity. Responses were superior to those with PBMC, and isolated B cells failed to present allergoids. Considerable IL-12 production was observed only when using the DC for Ag presentation of both allergens and allergoids. The amount of IL-10 in supernatants was dependent on the phenotype of the respective T cell clone. High IL-10 production was associated with suppressed IL-12 production from the DC in most cases. In conclusion, the reactivity of Th cells with allergoids is dependent on the type of the APC.

An unconditioned stimulus retrieval extinction procedure to prevent the return of fear memory.

PubMed

Liu, Jianfeng; Zhao, Liyan; Xue, Yanxue; Shi, Jie; Suo, Lin; Luo, Yixiao; Chai, Baisheng; Yang, Chang; Fang, Qin; Zhang, Yan; Bao, Yanping; Pickens, Charles L; Lu, Lin

2014-12-01

Conditioned fear memories can be updated by extinction during reconsolidation, and this effect is specific to the reactivated conditioned stimulus (CS). However, a traumatic event can be associated with several cues, and each cue can potentially trigger recollection of the event. We introduced a technique to target all diverse cues associated with an aversive event that causes fear. In human experiments, 161 subjects underwent modified fear conditioning, in which they were exposed to an unconditioned stimulus (US) or unreinforced CS to reactivate the memory and then underwent extinction, spontaneous recovery, and reinstatement. In animal experiments, 343 rats underwent contextual fear conditioning under a similar protocol as that used in the human experiments. We also explored the molecular alterations after US reactivation in rats. Presentation of a lower intensity US before extinction disrupted the associations between the different CS and reactivated US in both humans and rats. This effect persisted for at least 6 months in humans and was selective to the reactivated US. This procedure was also effective for remote memories in both humans and rats. Compared with the CS, the US induced stronger endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptors 1 and 2 and stronger activation of protein kinase A, p70S6 kinase, and cyclic adenosine monophosphate response element binding protein in the dorsal hippocampus in rats. These findings demonstrate that a modified US retrieval extinction strategy may have a potential impact on therapeutic approaches to prevent the return of fear. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Memory Trace Reactivation and Behavioral Response during Retrieval Are Differentially Modulated by Amygdalar Glutamate Receptors Activity: Interaction between Amygdala and Insular Cortex

ERIC Educational Resources Information Center

Osorio-Gómez, Daniel; Guzmán-Ramos, Kioko; Bermúdez-Rattoni, Federico

2017-01-01

The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the…

Microscopic approaches to liquid nitromethane detonation properties.

PubMed

Hervouët, Anaïs; Desbiens, Nicolas; Bourasseau, Emeric; Maillet, Jean-Bernard

2008-04-24

In this paper, thermodynamic and chemical properties of nitromethane are investigated using microscopic simulations. The Hugoniot curve of the inert explosive is computed using Monte Carlo simulations with a modified version of the adaptative Erpenbeck equation of state and a recently developed intermolecular potential. Molecular dynamic simulations of nitromethane decomposition have been performed using a reactive potential, allowing the calculation of kinetic rate constants and activation energies. Finally, the Crussard curve of detonation products as well as thermodynamic properties at the Chapman-Jouguet (CJ) point are computed using reactive ensemble Monte Carlo simulations. Results are in good agreement with both thermochemical calculations and experimental measurements.

Severe disease exacerbations in patients with multiple sclerosis after discontinuing fingolimod.

PubMed

Członkowska, Anna; Smoliński, Łukasz; Litwin, Tomasz

Discontinuation of fingolimod in patients with multiple sclerosis (MS) can lead to disease reactivation. In this review, we describe cases of severe exacerbations in patients with MS following discontinuation of fingolimod, including three cases from our center. We consider potential mechanisms of disease reactivation after cessation of fingolimod, and the evidence supporting this rebound effect. We conclude that discontinuation of fingolimod results in the return of disease activity, which then leads to severe exacerbations (i.e., rebounds) in a clinically significant proportion of patients. Lastly, we consider disease-modifying treatment options for patients who discontinue fingolimod. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

Co-gasification of tire and biomass for enhancement of tire-char reactivity in CO2 gasification process.

PubMed

Lahijani, Pooya; Zainal, Zainal Alimuddin; Mohamed, Abdul Rahman; Mohammadi, Maedeh

2013-06-01

In this investigation, palm empty fruit bunch (EFB) and almond shell (AS) were implemented as two natural catalysts rich in alkali metals, especially potassium, to enhance the reactivity of tire-char through co-gasification process. Co-gasification experiments were conducted at several blending ratios using isothermal Thermogravimetric analysis (TGA) under CO2. The pronounced effect of inherent alkali content of biomass-chars on promoting the reactivity of tire-char was proven when acid-treated biomass-chars did not exert any catalytic effect on improving the reactivity of tire-char in co-gasification experiments. In kinetic studies of the co-gasified samples in chemically-controlled regime, modified random pore model (M-RPM) was adopted to describe the reactive behavior of the tire-char/biomass-char blends. By virtue of the catalytic effect of biomass, the activation energy for tire-char gasification was lowered from 250 kJ/mol in pure form 203 to 187 kJ/mol for AS-char and EFB-char co-gasified samples, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Peri-Procedural Platelet Reactivity in Percutaneous Coronary Intervention.

PubMed

Alexopoulos, Dimitrios; Xenogiannis, Iosif; Vlachakis, Panagiotis; Tantry, Udaya; Gurbel, Paul A

2018-06-04

Platelet activation and aggregation play a pivotal role in thrombotic complications occurring during percutaneous coronary intervention (PCI), and peri-PCI anti-platelet therapy represents a standard of care. High platelet reactivity prior to PCI has been correlated with an increased incidence of peri-procedural myonecrosis. Pre-PCI platelet reactivity predicts post-PCI platelet reactivity and has a prognostic impact on subsequent ischaemic and bleeding events, so as the platelet inhibition measured post-PCI. Many anti-platelet treatment strategies, including aspirin, glycoprotein IIb/IIIa inhibitors, P2Y 12 receptor blockers and vorapaxar, are being used in the routine clinical practice to modify platelet reactivity at each stage, e.g. pre-, during and post-PCI. Anti-platelet strategies with a 'stronger and faster' pharmacodynamic effect than clopidogrel have been mostly adopted in patients with acute coronary syndromes. However, several issues regarding the anti-platelet treatment such as benefits/risks of anti-platelet therapy pre-treatment and duration, and definite association between speed and potency of various anti-platelet agents and clinical outcomes remain controversial. We believe that a better understanding of peri-PCI platelet reactivity and its relations to outcomes may lead to the development of more effective and safe treatment strategies. Schattauer GmbH Stuttgart.

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.

PubMed

Lo Re, Marianna; Capobianco, Marco; Ragonese, Paolo; Realmuto, Sabrina; Malucchi, Simona; Berchialla, Paola; Salemi, Giuseppe; Bertolotto, Antonio

2015-12-01

Natalizumab (NTZ) discontinuation can be followed by multiple sclerosis (MS) disease reactivation. Currently no disease-modifying drug (DMD) has been shown to be able to abolish disease reactivation. The aims of the current study were: (1) to determine the frequency of MS reactivation after NTZ discontinuation; (2) to evaluate predictors of reactivation risk, and (3) to compare the effect of different treatments in reducing this risk. Data from 132 patients with MS followed-up for 2 years before NTZ treatment and 1 year after interruption were collected from two Italian MS centers and retrospectively evaluated. Overall, 72 of 132 patients (54.5%) had relapses after NTZ discontinuation and 60 of 125 patients (48%), who had magnetic resonance imaging, had radiological reactivation. Rebound was observed in 28 of 132 patients (21.2%). A higher number of relapses in the 2 years before NTZ treatment, a longer washout period, and a lower number NTZ infusions correlated with reactivation and rebound. Untreated patients (n = 37) had higher clinical and radiological activity and rebound in comparison to patients receiving DMDs. Moreover, a lower risk of relapses was found in patients treated with second-line therapies (NTZ and fingolimod) than in those treated with first-line therapies (interferon beta, glatiramer acetate, teriflunomide, azathioprine). Interestingly, no disease reactivation in off-label treatment (rituximab, autologous hematopoietic stem cell transplantation) was observed. NTZ discontinuation is a risk for MS reactivation and rebound. An alternative treatment should be promptly resumed mainly in patients with a previous very active disease course and with a shorter NTZ therapy. Second-line therapies demonstrate superiority in preventing relapses after NTZ discontinuation.

Neural correlates of reactive aggression in children with attention-deficit/hyperactivity disorder and comorbid disruptive behaviour disorders.

PubMed

Bubenzer-Busch, S; Herpertz-Dahlmann, B; Kuzmanovic, B; Gaber, T J; Helmbold, K; Ullisch, M G; Baurmann, D; Eickhoff, S B; Fink, G R; Zepf, F D

2016-04-01

Attention deficit hyperactivity disorder (ADHD) is often linked with impulsive and aggressive behaviour, indexed by high comorbidity rates between ADHD and disruptive behaviour disorders (DBD). The present study aimed to investigate underlying neural activity of reactive aggression in children with ADHD and comorbid DBD using functional neuroimaging techniques (fMRI). Eighteen boys with ADHD (age 9-14 years, 10 subjects with comorbid DBD) and 18 healthy controls were administered a modified fMRI-based version of the 'Point Subtraction Aggression Game' to elicit reactive aggressive behaviour. Trials consisted of an 'aggression phase' (punishment for a fictitious opponent) and an 'outcome phase' (presentation of the trial outcome). During the aggression phase, higher aggressive responses of control children were accompanied by higher activation of the ventral anterior cingulate cortex and the temporoparietal junction. Patients displayed inverted results. During the outcome phase, comparison between groups and conditions showed differential activation in the dorsal striatum and bilateral insular when subjects gained points. Losing points was accompanied by differential activation of regions belonging to the insula and the middle temporal sulcus. Data support the hypothesis that deficient inhibitory control mechanisms are related to increased impulsive aggressive behaviour in young people with ADHD and comorbid DBD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Functionalized poly(arylene ethers) as toughness modifiers for bismaleimides

NASA Technical Reports Server (NTRS)

Stenzenberger, H. D.; Roemer, W.; Hergenrother, P. M.; Jensen, B.; Breitigam, W.

1990-01-01

A family of novel, low molecular weight functionalized poly(arylene ether) resins has been investigated to ascertain its members' toughness-imparting contribution to neat bismaleimide (BMI) resin and BMI-matrix laminate composite properties. Attention is given to the contribution of the reactive poly(arylene ether)'s backbone chemistry to fracture toughness, as well as to the comparative influence of high and low molecular weight reactive poly(arylene ether) types on the modified BMI resin systems. The modified BMIs possess a polyphase morphology, with good adhesion between the thermoplastic nodules and the host thermoset systems.

Site-specific covalent modifications of human insulin by catechol estrogens: Reactivity and induced structural and functional changes

NASA Astrophysics Data System (ADS)

Ku, Ming-Chun; Fang, Chieh-Ming; Cheng, Juei-Tang; Liang, Huei-Chen; Wang, Tzu-Fan; Wu, Chih-Hsing; Chen, Chiao-Chen; Tai, Jung-Hsiang; Chen, Shu-Hui

2016-06-01

Proteins, covalently modified by catechol estrogens (CEs), were identified recently from the blood serum of diabetic patients and referred to as estrogenized proteins. Estrogenization of circulating insulin may occur and affect its molecular functioning. Here, the chemical reactivity of CEs towards specific amino acid residues of proteins and the structural and functional changes induced by the estrogenization of insulin were studied using cyclic voltammetry, liquid chromatography-mass spectrometry, circular dichroism spectroscopy, molecular modeling, and bioassays. Our results indicate that CEs, namely, 2- and 4-hydroxyl estrogens, were thermodynamically and kinetically more reactive than the catechol moiety. Upon co-incubation, intact insulin formed a substantial number of adducts with one or multiple CEs via covalent conjugation at its Cys 7 in the A or B chain, as well as at His10 or Lys29 in the B chain. Such conjugation was coupled with the cleavage of inter-chain disulfide linkages. Estrogenization on these sites may block the receptor-binding pockets of insulin. Insulin signaling and glucose uptake levels were lower in MCF-7 cells treated with modified insulin than in cells treated with native insulin. Taken together, our findings demonstrate that insulin molecules are susceptible to active estrogenization, and that such modification may alter the action of insulin.

The effect of Fe-Rh alloying on CO hydrogenation to C 2+ oxygenates

DOE PAGES

Palomino, Robert; Magee, Joseph W.; Llorca, Jordi; ...

2015-05-20

A combination of reactivity and structural studies using X-ray diffraction (XRD), pair distribution function (PDF), and transmission electron microscopy (TEM) was used to identify the active phases of Fe-modified Rh/TiO 2 catalysts for the synthesis of ethanol and other C 2+ oxygenates from CO hydrogenation. XRD and TEM confirm the existence of Fe–Rh alloys for catalyst with 1–7 wt% Fe and ~2 wt% Rh. Rietveld refinements show that FeRh alloy content increases with Fe loading up to ~4 wt%, beyond which segregation to metallic Fe becomes favored over alloy formation. Catalysts that contain Fe metal after reduction exhibit some carburizationmore » as evidenced by the formation of small amounts of Fe 3C during CO hydrogenation. Analysis of the total Fe content of the catalysts also suggests the presence of FeO x also increased under reaction conditions. Reactivity studies show that enhancement of ethanol selectivity with Fe loading is accompanied by a significant drop in CO conversion. Comparison of the XRD phase analyses with selectivity suggests that higher ethanol selectivity is correlated with the presence of Fe–Rh alloy phases. As a result, the interface between Fe and Rh serves to enhance the selectivity of ethanol, but suppresses the activity of the catalyst which is attributed to the blocking or modifying of Rh active sites.« less

Reactivity and Specificity of RNase T1, RNase A, and RNase H toward Oligonucleotides of RNA Containing 8-Oxo-7,8-dihydroguanosine.

PubMed

Herbert, Cassandra; Dzowo, Yannick Kokouvi; Urban, Anthony; Kiggins, Courtney N; Resendiz, Marino J E

2018-05-22

Understanding how oxidatively damaged RNA interacts with ribonucleases is important because of its proposed role in the development and progression of disease. Thus, understanding structural aspects of RNA containing lesions generated under oxidative stress, as well as its interactions with other biopolymers, is fundamental. We explored the reactivity of RNase A, RNase T 1 , and RNase H toward oligonucleotides of RNA containing 8-oxo-7,8-dihydroguanosine (8oxoG). This is the first example that addresses this relationship and will be useful for understanding (1) how these RNases can be used to characterize the structural impact that this lesion has on RNA and (2) how oxidatively modified RNA may be handled intracellularly. 8-OxoG was incorporated into 10-16-mers of RNA, and its reactivity with each ribonuclease was assessed via electrophoretic analyses, circular dichroism, and the use of other C8-purine-modified analogues (8-bromoguanosine, 8-methoxyguanosine, and 8-oxoadenosine). RNase T 1 does not recognize sites containing 8-oxoG, while RNase A recognizes and cleaves RNA at positions containing this lesion while differentiating if it is involved in H-bonding. The selectivity of RNase A followed the order C > 8-oxoG ≈ U. In addition, isothermal titration calorimetry showed that an 8-oxoG-C3'-methylphosphate derivative can inhibit RNase A activity. Cleavage patterns obtained from RNase H displayed changes in reactivity in a sequence- and concentration-dependent manner and displayed recognition at sites containing the modification in some cases. These data will aid in understanding how this modification affects reactivity with ribonucleases and will enable the characterization of global and local structural changes in oxidatively damaged RNA.

Synthesis and immobilization of Ag(0) nanoparticles on diazonium modified electrodes: SECM and cyclic voltammetry studies of the modified interfaces.

PubMed

Noël, Jean-Marc; Zigah, Dodzi; Simonet, Jacques; Hapiot, Philippe

2010-05-18

A versatile method was used to prepare modified surfaces on which metallic silver nanoparticles are immobilized on an organic layer. The preparation method takes advantage, on one hand, of the activated reactivity of some alkyl halides with Ag-Pd alloys to produce metallic silver nanoparticles and, on the other hand, of the facile production of an anchoring polyphenyl acetate layer by the electrografting of substituted diazonium salts on carbon surfaces. Transport properties inside such modified layers were investigated by cyclic voltammetry, scanning electrochemical microscopy (SECM) in feedback mode, and conducting AFM imaging for characterizing the presence and nature of the conducting pathways. The modification of the blocking properties of the surface (or its conductivity) was found to vary to a large extent on the solvents used for surface examination (H(2)O, CH(2)Cl(2), and DMF).

Scale-Invariant Forms of Conservation Equations in Reactive Fields and a Modified Hydro-Thermo-Diffusive Theory of Laminar Flames

NASA Technical Reports Server (NTRS)

Sohrab, Siavash H.; Piltch, Nancy (Technical Monitor)

2000-01-01

A scale-invariant model of statistical mechanics is applied to present invariant forms of mass, energy, linear, and angular momentum conservation equations in reactive fields. The resulting conservation equations at molecular-dynamic scale are solved by the method of large activation energy asymptotics to describe the hydro-thermo-diffusive structure of laminar premixed flames. The predicted temperature and velocity profiles are in agreement with the observations. Also, with realistic physico-chemical properties and chemical-kinetic parameters for a single-step overall combustion of stoichiometric methane-air premixed flame, the laminar flame propagation velocity of 42.1 cm/s is calculated in agreement with the experimental value.

Flavonoids: hemisynthesis, reactivity, characterization and free radical scavenging activity.

PubMed

Es-Safi, Nour-Eddine; Ghidouche, Souhila; Ducrot, Paul Henri

2007-09-26

Phenolic compounds form one of the main classes of secondary metabolites. They display a large range of structures and they are responsible for the major organoleptic characteristics of plant-derived-foods and beverages, particularly color and taste properties and they also contribute to the nutritional qualities of fruits and vegetables. Phenolic compounds are also highly unstable compounds which undergo numerous enzymatic and chemical reactions during postharvest food storage and processing thus adding to the complexity of plant polyphenol composition. Among these compounds flavonoids constitute one of the most ubiquitous groups of all plant phenolics. Owing to their importance in food organoleptic properties and in human health, a better understanding of their structures, their reactivity and chemical properties in addition to the mechanisms generating them appears essential to predict and control food quality. The purpose of this work is an overview of our findings concerning the hemisynthesis, the reactivity and the enzymatic oxidation of some flavonoids and shed light on the mechanisms involved in some of these processes and the structures of the resulting products. The free radical scavenging activity of some of the synthesized compounds is also presented and a structure-activity relationship is discussed. The first part of this review concerns the synthesis and structural characterization of modified monomeric flavanols. The use of these compounds as precursor for the preparation of natural and modified dimeric procyanidin derivatives was then explored through different coupling reactions. The full characterization of the synthesized compounds was achieved by concerted use of NMR and ESI-MS techniques. The free radical scavenging activity of some of the synthesized compounds was investigated. The second part of this review concerns the enzymatic oxidation of several flavonols by Trametes versicolor laccase. Most of the major oxidation products have been isolated as pure compounds and their structures unambiguously established through spectroscopic methods. Correlation between the structure of the oxidation product and the substitution pattern of the starting materials allows mechanistic features of this transformation to be elucidated.

Substoichiometric hydroxynonenylation of a single protein recapitulates whole-cell-stimulated antioxidant response.

PubMed

Parvez, Saba; Fu, Yuan; Li, Jiayang; Long, Marcus J C; Lin, Hong-Yu; Lee, Dustin K; Hu, Gene S; Aye, Yimon

2015-01-14

Lipid-derived electrophiles (LDEs) that can directly modify proteins have emerged as important small-molecule cues in cellular decision-making. However, because these diffusible LDEs can modify many targets [e.g., >700 cysteines are modified by the well-known LDE 4-hydroxynonenal (HNE)], establishing the functional consequences of LDE modification on individual targets remains devilishly difficult. Whether LDE modifications on a single protein are biologically sufficient to activate discrete redox signaling response downstream also remains untested. Herein, using T-REX (targetable reactive electrophiles and oxidants), an approach aimed at selectively flipping a single redox switch in cells at a precise time, we show that a modest level (∼34%) of HNEylation on a single target is sufficient to elicit the pharmaceutically important antioxidant response element (ARE) activation, and the resultant strength of ARE induction recapitulates that observed from whole-cell electrophilic perturbation. These data provide the first evidence that single-target LDE modifications are important individual events in mammalian physiology.

Acceptance lowers stress reactivity: Dismantling mindfulness training in a randomized controlled trial.

PubMed

Lindsay, Emily K; Young, Shinzen; Smyth, Joshua M; Brown, Kirk Warren; Creswell, J David

2018-01-01

Mindfulness interventions, which train practitioners to monitor their present-moment experience with a lens of acceptance, are known to buffer stress reactivity. Little is known about the active mechanisms driving these effects. We theorize that acceptance is a critical emotion regulation mechanism underlying mindfulness stress reduction effects. In this three-arm parallel trial, mindfulness components were dismantled into three structurally equivalent 15-lesson smartphone-based interventions: (1) training in both monitoring and acceptance (Monitor+Accept), (2) training in monitoring only (Monitor Only), or (3) active control training (Coping control). 153 stressed adults (mean age=32years; 67% female; 53% white, 21.5% black, 21.5% Asian, 4% other race) were randomly assigned to complete one of three interventions. After the intervention, cortisol, blood pressure, and subjective stress reactivity were assessed using a modified Trier Social Stress Test. As predicted, Monitor+Accept training reduced cortisol and systolic blood pressure reactivity compared to Monitor Only and control trainings. Participants in all three conditions reported moderate levels of subjective stress. This study provides the first experimental evidence that brief smartphone mindfulness training can impact stress biology, and that acceptance training drives these effects. We discuss implications for basic and applied research in contemplative science, emotion regulation, stress and coping, health, and clinical interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adsorption of dyes using different types of clay: a review

NASA Astrophysics Data System (ADS)

Adeyemo, Aderonke Ajibola; Adeoye, Idowu Olatunbosun; Bello, Olugbenga Solomon

2017-05-01

Increasing amount of dyes in the ecosystem particularly in wastewater has propelled the search for more efficient low-cost adsorbents. The effective use of the sorption properties (high surface area and surface chemistry, lack of toxicity and potential for ion exchange) of different clays as adsorbents for the removal of different type of dyes (basic, acidic, reactive) from water and wastewater as potential alternatives to activated carbons has recently received widespread attention because of the environmental-friendly nature of clay materials. Insights into the efficiencies of raw and modified/activated clay adsorbents and ways of improving their efficiencies to obtain better results are discussed. Acid-modified clay resulted in higher rate of dye adsorption and an increased surface area and porosity (49.05 mm2 and 53.4 %). Base-modified clay has lower adsorption capacities, while ZnCl2-modified clay had the least rate of adsorption with a surface area of 44.3 mm2 and porosity of 43.4 %. This review also explores the grey areas of the adsorption properties of the raw clays and the improved performance of activated/modified clay materials with particular reference to the effects of pH, temperature, initial dye concentration and adsorbent dosage on the adsorption capacities of the clays. Various challenges encountered in using clay materials are highlighted and a number of future prospects for the adsorbents are proposed.

Influence of the sulfur species reactivity on biofilm conformation during pyrite colonization by Acidithiobacillus thiooxidans.

PubMed

Lara, René H; García-Meza, J Viridiana; Cruz, Roel; Valdez-Pérez, Donato; González, Ignacio

2012-08-01

Massive pyrite (FeS₂) electrodes were potentiostatically modified by means of variable oxidation pulse to induce formation of diverse surface sulfur species (S(n)²⁻, S⁰). The evolution of reactivity of the resulting surfaces considers transition from passive (e.g., Fe(1-x )S₂) to active sulfur species (e.g., Fe(1-x )S(2-y ), S⁰). Selected modified pyrite surfaces were incubated with cells of sulfur-oxidizing Acidithiobacillus thiooxidans for 24 h in a specific culture medium (pH 2). Abiotic control experiments were also performed to compare chemical and biological oxidation. After incubation, the attached cells density and their exopolysaccharides were analyzed by confocal laser scanning microscopy (CLMS) and atomic force microscopy (AFM) on bio-oxidized surfaces; additionally, S(n)²⁻/S⁰ speciation was carried out on bio-oxidized and abiotic pyrite surfaces using Raman spectroscopy. Our results indicate an important correlation between the evolution of S(n)²⁻/S⁰ surface species ratio and biofilm formation. Hence, pyrite surfaces with mainly passive-sulfur species were less colonized by A. thiooxidans as compared to surfaces with active sulfur species. These results provide knowledge that may contribute to establishing interfacial conditions that enhance or delay metal sulfide (MS) dissolution, as a function of the biofilm formed by sulfur-oxidizing bacteria.

Effect of selected dimethylaminochalcones on some mitochondrial activities.

PubMed

Vašková, Janka; Reisch, Renáta; Vaško, Ladislav; Poškrobová, Martina; Kron, Ivan; Guzy, Juraj; Perjési, Pál

2013-05-01

Chalcones and their synthetic cyclic analogues have been shown to possess a full scale of biological activities in a variety of experimental systems. They were assessed to be mostly effective in defense against free radicals in the organism, but several compounds exhibited cytotoxic pro-oxidant activities. The respiratory response and antioxidant status in mitochondria were investigated upon addition of 4'-dimethylaminochalcone (1a) and its cyclic analogues, (E)-2-(4'-((CH3)2 N)-benzylidene)-1-indanone (1b), -1-tetralone (1c), and -1-benzosuberone (1d). Selected structures were able to change the respiratory response of mitochondria and showed an ability to modify mitochondrial metabolic and redox efficiency, though they did not indicate redox reactivity towards glutathione in adduct-free incubations. The results of the study indicate that -chalcone and -tetralone derivatives cause suppression of reactive oxygen species affecting mitochondrial respiration by mild uncoupling. In addition, (E)-2-(4'-((CH3)2 N)-indanone (1b), and to a greater extent, -benzosuberone (1d), showed pro-oxidant effects, which partially explain their cytotoxicity.

Quantum mechanical calculations suggest that lytic polysaccharide monooxygenases use a copper-oxyl, oxygen-rebound mechanism

PubMed Central

Kim, Seonah; Ståhlberg, Jerry; Sandgren, Mats; Paton, Robert S.; Beckham, Gregg T.

2014-01-01

Lytic polysaccharide monooxygenases (LPMOs) exhibit a mononuclear copper-containing active site and use dioxygen and a reducing agent to oxidatively cleave glycosidic linkages in polysaccharides. LPMOs represent a unique paradigm in carbohydrate turnover and exhibit synergy with hydrolytic enzymes in biomass depolymerization. To date, several features of copper binding to LPMOs have been elucidated, but the identity of the reactive oxygen species and the key steps in the oxidative mechanism have not been elucidated. Here, density functional theory calculations are used with an enzyme active site model to identify the reactive oxygen species and compare two hypothesized reaction pathways in LPMOs for hydrogen abstraction and polysaccharide hydroxylation; namely, a mechanism that employs a η1-superoxo intermediate, which abstracts a substrate hydrogen and a hydroperoxo species is responsible for substrate hydroxylation, and a mechanism wherein a copper-oxyl radical abstracts a hydrogen and subsequently hydroxylates the substrate via an oxygen-rebound mechanism. The results predict that oxygen binds end-on (η1) to copper, and that a copper-oxyl–mediated, oxygen-rebound mechanism is energetically preferred. The N-terminal histidine methylation is also examined, which is thought to modify the structure and reactivity of the enzyme. Density functional theory calculations suggest that this posttranslational modification has only a minor effect on the LPMO active site structure or reactivity for the examined steps. Overall, this study suggests the steps in the LPMO mechanism for oxidative cleavage of glycosidic bonds. PMID:24344312

12-Chloracetyl-PPD, a novel dammarane derivative, shows anti-cancer activity via delay the progression of cell cycle G2/M phase and reactive oxygen species-mediate cell apoptosis.

PubMed

Wang, Xu De; Sun, Yuan Yuan; Zhao, Chen; Qu, Fan Zhi; Zhao, Yu Qing

2017-03-05

(20R)-Dammarane-3β, 12β, 20, 25-tetrol (25-OH-PPD) is a ginsenoside isolated from Panax ginseng (C. A. Meyer). This compound exhibits anti-cancer activities on many human cancer cell lines. In this study, we investigated anti-cancer mechanisms of 12β-O-( L -Chloracetyl)-dammar-20(22)-ene-3β,25-diol(12-Chloracetyl-PPD), a modified 25-OH-PPD. We found that compound 12-Chloracetyl-PPD resulted in a concentration-dependent inhibition of viability in prostate, breast, and gastric cancer cells, without affecting the viability of normal cell (human gastric epithelial cell line-GES-1, hair follicle dermal papilla cell line-HHDPC and rat myocardial cell line-H9C2). In MDA-MB-435 and C4-2B cancer cells, 12-Chloracetyl-PPD induced G2/M cell cycle arrest, down-regulated mouse double minute 2 (MDM2) expression, up-regulated p53 expression, triggered apoptosis, and stimulated reactive oxygen species production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. Our results suggested that compound 12-Chloracetyl-PPD showed obvious anti-cancer activity based on delaying cell cycle arrest and inducing cell apoptosis by reactive oxygen species production, which supported development of 12-Chloracetyl-PPD as a potential agent for cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Fission control system for nuclear reactor

DOEpatents

Conley, G.H.; Estes, G.P.

Control system for nuclear reactor comprises a first set of reactivity modifying rods fixed in a reactor core with their upper ends stepped in height across the core, and a second set of reactivity modifying rods movable vertically within the reactor core and having their lower ends stepped to correspond with the stepped arrangement of the first set of rods, pairs of the rods of the first and second sets being in coaxial alignment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Usman, Yasir; Kim, Jinho; Muljadi, Eduard

Wake effects cause wind turbine generators (WTGs) within a wind power plant (WPP) to produce different levels of active power and subsequent reactive power capabilities. Further, the impedance between a WTG and the point of interconnection (POI)-which depends on the distance between them-impacts the WPP's reactive power injection capability at the POI. This paper proposes a voltage control scheme for a WPP based on the available reactive current of the doubly-fed induction generators (DFIGs) and its impacts on the POI to improve the reactive power injection capability of the WPP. In this paper, a design strategy for modifying the gainmore » of DFIG controller is suggested and the comprehensive properties of these control gains are investigated. In the proposed scheme, the WPP controller, which operates in a voltage control mode, sends the command signal to the DFIGs based on the voltage difference at the POI. The DFIG controllers, which operate in a voltage control mode, employ a proportional controller with a limiter. The gain of the proportional controller is adjusted depending on the available reactive current of the DFIG and the series impedance between the DFIG and the POI. The performance of the proposed scheme is validated for various disturbances such as a reactive load connection and grid fault using an EMTP-RV simulator. Furthermore, simulation results demonstrate that the proposed scheme promptly recovers the POI voltage by injecting more reactive power after a disturbance than the conventional scheme.« less

A Reactive Balance Rating Method that Correlates with Kinematics after Trip-Like Perturbations on a Treadmill and Fall Risk Among Residents of Older Adult Congregate Housing.

PubMed

Madigan, Michael L; Aviles, Jessica; Allin, Leigh J; Nussbaum, Maury A; Alexander, Neil B

2018-04-16

A growing number of studies are using modified treadmills to train reactive balance after trip-like perturbations that require multiple steps to recover balance. The goal of this study was thus to develop and validate a low-tech reactive balance rating method in the context of trip-like treadmill perturbations to facilitate the implementation of this training outside the research setting. Thirty-five residents of five senior congregate housing facilities participated in the study. Subjects completed a series of reactive balance tests on a modified treadmill from which the reactive balance rating was determined, along with a battery of standard clinical balance and mobility tests that predict fall risk. We investigated the strength of correlation between the reactive balance rating and reactive balance kinematics. We compared the strength of correlation between the reactive balance rating and clinical tests predictive of fall risk, with the strength of correlation between reactive balance kinematics and the same clinical tests. We also compared the reactive balance rating between subjects predicted to be at a high or low risk of falling. The reactive balance rating was correlated with reactive balance kinematics (Spearman's rho squared = .04 - .30), exhibited stronger correlations with clinical tests than most kinematic measures (Spearman's rho squared = .00 - .23), and was 42-60% lower among subjects predicted to be at a high risk for falling. The reactive balance rating method may provide a low-tech, valid measure of reactive balance kinematics, and an indicator of fall risk, after trip-like postural perturbations.

Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators

PubMed Central

Flierl, Ulrike; Nero, Tracy L.; Lim, Bock; Arthur, Jane F.; Yao, Yu; Jung, Stephanie M.; Gitz, Eelo; Pollitt, Alice Y.; Zaldivia, Maria T.K.; Jandrot-Perrus, Martine; Schäfer, Andreas; Nieswandt, Bernhard; Andrews, Robert K.; Parker, Michael W.; Gardiner, Elizabeth E.

2015-01-01

Nucleotide-based drug candidates such as antisense oligonucleotides, aptamers, immunoreceptor-activating nucleotides, or (anti)microRNAs hold great therapeutic promise for many human diseases. Phosphorothioate (PS) backbone modification of nucleotide-based drugs is common practice to protect these promising drug candidates from rapid degradation by plasma and intracellular nucleases. Effects of the changes in physicochemical properties associated with PS modification on platelets have not been elucidated so far. Here we report the unexpected binding of PS-modified oligonucleotides to platelets eliciting strong platelet activation, signaling, reactive oxygen species generation, adhesion, spreading, aggregation, and thrombus formation in vitro and in vivo. Mechanistically, the platelet-specific receptor glycoprotein VI (GPVI) mediates these platelet-activating effects. Notably, platelets from GPVI function–deficient patients do not exhibit binding of PS-modified oligonucleotides, and platelet activation is fully abolished. Our data demonstrate a novel, unexpected, PS backbone–dependent, platelet-activating effect of nucleotide-based drug candidates mediated by GPVI. This unforeseen effect should be considered in the ongoing development programs for the broad range of upcoming and promising DNA/RNA therapeutics. PMID:25646267

Study of zwitterionic sulfopropylbetaine containing reactive siloxanes for application in antibacterial materials.

PubMed

Chen, Shiguo; Chen, Shaojun; Jiang, Song; Mo, Yangmiao; Luo, Junxuan; Tang, Jiaoning; Ge, Zaochuan

2011-07-01

Antibacterial agents receive a great deal of attention around the world due to the interesting academic problems of how to combat bacteria and of the beneficial health, social and economic effects of successful agents. Scientists are actively developing new antibacterial agents for biomaterial applications. This paper reports the novel antibacterial agent siloxane sulfopropylbetaine (SSPB), which contains reactive alkoxysilane groups. The structure and properties of SSPB were systematically investigated, with the results showing that SSPB contains both quaternary ammonium compounds and reactive siloxane groups. SSPB has good antibacterial activity against both Escherichia coli (E. coli, 8099) and Staphylococcus aureus (S. aureus, ATCC 6538). The minimal inhibition concentration is 70 μmol/ml SSPB against both E. coli and S. aureus. In addition, the SSPB antibacterial agent can be used in both weak acid and weak alkaline environments, functioning within the wide pH range of 4.0-9.0. The SSPB-modified glass surface killed 99.96% of both S. aureus and E. coli organisms within 24 h. No significant decrease was observed in this antibacterial activity after 20 washes. Moreover, SSPB does not induce a skin reaction and is nontoxic to animals. Thus, SSPB is an ideal candidate for future applications as a safe, environmentally friendly antibacterial agent. Copyright © 2011 Elsevier B.V. All rights reserved.

Purification and complete amino acid sequence of a new type of sweet protein taste-modifying activity, curculin.

PubMed

Yamashita, H; Theerasilp, S; Aiuchi, T; Nakaya, K; Nakamura, Y; Kurihara, Y

1990-09-15

A new taste-modifying protein named curculin was extracted with 0.5 M NaCl from the fruits of Curculigo latifolia and purified by ammonium sulfate fractionation, CM-Sepharose ion-exchange chromatography, and gel filtration. Purified curculin thus obtained gave a single band having a Mr of 12,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of 8 M urea. The molecular weight determined by low-angle laser light scattering was 27,800. These results suggest that native curculin is a dimer of a 12,000-Da polypeptide. The complete amino acid sequence of curculin was determined by automatic Edman degradation. Curculin consists of 114 residues. Curculin itself elicits a sweet taste. After curculin, water elicits a sweet taste, and sour substances induce a stronger sense of sweetness. No protein with both sweet-tasting and taste-modifying activities has ever been found. There are five sets of tripeptides common to miraculin (a taste-modifying protein), six sets of tripeptides common to thaumatin (a sweet protein), and two sets of tripeptides common to monellin (a sweet protein). Anti-miraculin serum was not immunologically reactive with curculin. The mechanism of the taste-modifying action of curculin is discussed.

High-throughput identification of promiscuous inhibitors from screening libraries with the use of a thiol-containing fluorescent probe.

PubMed

McCallum, Megan M; Nandhikonda, Premchendar; Temmer, Jonathan J; Eyermann, Charles; Simeonov, Anton; Jadhav, Ajit; Yasgar, Adam; Maloney, David; Arnold, Alexander Leggy

2013-07-01

Testing small molecules for their ability to modify cysteine residues of proteins in the early stages of drug discovery is expected to accelerate our ability to develop more selective drugs with lesser side effects. In addition, this approach also enables the rapid evaluation of the mode of binding of new drug candidates with respect to thiol reactivity and metabolism by glutathione. Herein, we describe the development of a fluorescence-based high-throughput assay that allows the identification of thiol-reactive compounds. A thiol-containing fluorescent probe, MSTI, was synthesized and used to evaluate small molecules from the Library of Pharmacologically Active Compounds (LOPAC) collection of bioactive molecules. LOPAC compounds that are known to react with sulfur nucleophiles were identified with this assay, for example, irreversible protease inhibitors, nitric oxide-releasing compounds, and proton-pump inhibitors. The results confirm that both electrophilic and redox reactive compounds can be quickly identified in a high-throughput manner, enabling the assessment of screening libraries with respect to thiol-reactive compounds.

Comparison of several oximes on reactivation of soman-inhibited blood, brain and tissue cholinesterase activity in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shih, T.M.

1993-12-31

The ability of three oximes, HI-6, MMB-4 and ICD-467, to reactivate cholinesterase (ChE) inhibited by the organophosphorus compound soman was compared in blood (plasma and erythrocytes), brain regions (including spinal cord) and peripheral tissues of rats. Animals were intoxicated with soman (100 ttg/kg. SC; equivalent to 0.9 x LDs0 dose) and treated 1 min later with one of these oximes (100 or 200 ttmo1/kg, IM). Toxic sign scores and total tissue ChE activities were determined 30 min later. Soman markedly inhibited ChE activity in blood (93 - 96%), brain regions (ranging from 78% to 95%), and all peripheral tissues (rangingmore » from 48.9% to 99.8%) except liver (11.9%). In blood, treatment with HI-6 or ICD-467 resulted in significant reactivation of soman-inhibited ChE. in contrast, MMB-4 was completely ineffective. HI-6 and ICD-467 were equally effective at the high dose. At the low dose ICD-467 treatment resulted in significantly higher plasma ChE than Hl-6 treatment, whereas HI-6 treatment resulted in higher erythrocyte ChE than ICD-467 treatment. However, none of these three oximesreactivated or protected soman-inhibited ChE in the brain. In all peripheral tissues (except liver) studied, MMB-4 was not effective. 111-6 reactivated soman-inhibited ChE in all tis- sues except lung, heart, and skeletal muscle. ICD-467 was highly effective in reactivating ChE in all tissues and afforded a complete recovery of ChE to control levels in Intercostal muscle and salivary gland. Oxime treatments did not modify the toxic scores produced by soman.« less

One-Step Synthesis of Silver Nanoparticles on Polydopamine-Coated Sericin/Polyvinyl Alcohol Composite Films for Potential Antimicrobial Applications.

PubMed

Cai, Rui; Tao, Gang; He, Huawei; Song, Kai; Zuo, Hua; Jiang, Wenchao; Wang, Yejing

2017-04-30

Silk sericin has great potential as a biomaterial for biomedical applications due to its good hydrophilicity, reactivity, and biodegradability. To develop multifunctional sericin materials for potential antibacterial application, a one-step synthesis method for preparing silver nanoparticles (AgNPs) modified on polydopamine-coated sericin/polyvinyl alcohol (PVA) composite films was developed. Polydopamine (PDA) acted as both metal ion chelating and reducing agent to synthesize AgNPs in situ on the sericin/PVA composite film. Scanning electron microscopy and energy dispersive spectroscopy analysis revealed that polydopamine could effectively facilitate the high-density growth of AgNPs as a 3-D matrix. X-ray diffractometry studies suggested the synthesized AgNPs formed good face-centered cubic crystalline structures. Contact angle measurement and mechanical test indicated AgNPs modified PDA-sericin/PVA composite film had good hydrophilicity and mechanical property. The bacterial growth curve and inhibition zone assays showed the AgNPs modified PDA-sericin/PVA composite film had long-term antibacterial activities. This work develops a new method for the preparation of AgNPs modified PDA-sericin/PVA film with good hydrophilicity, mechanical performance and antibacterial activities for the potential antimicrobial application in biomedicine.

A Class of Reactive Acyl-CoA Species Reveals the Non-Enzymatic Origins of Protein Acylation

PubMed Central

Wagner, Gregory R.; Bhatt, Dhaval P.; O’Connell, Thomas M.; Thompson, J. Will; Dubois, Laura G.; Backos, Donald S.; Yang, Hao; Mitchell, Grant A.; Ilkayeva, Olga R.; Stevens, Robert D.; Grimsrud, Paul A.; Hirschey, Matthew D.

2017-01-01

SUMMARY The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that undergoes intramolecular catalysis to form reactive intermediates which non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized a protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine. Using quantitative proteomics, we compared the ‘acylomes’ of two reactive acyl-CoA species, namely HMG-CoA and glutaryl-CoA, which are generated in different pathways. We found proteins that are uniquely modified by each reactive metabolite, as well as common proteins and pathways. We identified the tricarboxylic acid cycle as a pathway commonly regulated by acylation, and validated malate dehydrogenase as a key target. These data uncover a fundamental relationship between reactive acyl-CoA species and proteins, and define a new regulatory paradigm in metabolism. PMID:28380375

Nicotinamide Cofactors Suppress Active-Site Labeling of Aldehyde Dehydrogenases.

PubMed

Stiti, Naim; Chandrasekar, Balakumaran; Strubl, Laura; Mohammed, Shabaz; Bartels, Dorothea; van der Hoorn, Renier A L

2016-06-17

Active site labeling by (re)activity-based probes is a powerful chemical proteomic tool to globally map active sites in native proteomes without using substrates. Active site labeling is usually taken as a readout for the active state of the enzyme because labeling reflects the availability and reactivity of active sites, which are hallmarks for enzyme activities. Here, we show that this relationship holds tightly, but we also reveal an important exception to this rule. Labeling of Arabidopsis ALDH3H1 with a chloroacetamide probe occurs at the catalytic Cys, and labeling is suppressed upon nitrosylation and oxidation, and upon treatment with other Cys modifiers. These experiments display a consistent and strong correlation between active site labeling and enzymatic activity. Surprisingly, however, labeling is suppressed by the cofactor NAD(+), and this property is shared with other members of the ALDH superfamily and also detected for unrelated GAPDH enzymes with an unrelated hydantoin-based probe in crude extracts of plant cell cultures. Suppression requires cofactor binding to its binding pocket. Labeling is also suppressed by ALDH modulators that bind at the substrate entrance tunnel, confirming that labeling occurs through the substrate-binding cavity. Our data indicate that cofactor binding adjusts the catalytic Cys into a conformation that reduces the reactivity toward chloroacetamide probes.

Photocatalysis of Modified Transition Metal Oxide Surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Batzill, Matthias

The goal of this project has been to establish a cause-effect relationship for photocatalytic activity variations of different structures of the same material; and furthermore gain fundamental understanding on modification of photocatalysts by compositional or surface modifications. The reasoning is that gaining atomic scale understanding of how surface and bulk modifications alter the photo reactivity will lead to design principles for next generation photocatalysts. As a prototypical photocatalyst the research focused on TiO 2 synthesized in well-defined single crystalline form to enable fundamental characterizations.We have obtained results in the following areas: (a) Preparation of epitaxial anatase TiO 2 samples bymore » pulsed laser deposition. (b) Comparison of hydrogen diffusion on different crystallographic surface. (c) Determining the stability of the TiO 2(011)-2x1 reconstruction upon interactions with adsorbates. (d) Characterization of adsorption and (thermal and photo) reaction of molecules with nitro-endgroups, (e) Exploring the possibility of modifying planar model photocatalyst surfaces with graphene to enable fundamental studies on reported enhanced photocatalytic activities of graphene modified transition metal oxides, (f) gained fundamental understanding on the role of crystallographic polymorphs of the same material for their photocatalytic activities.« less

Photo-switchable microbial fuel-cells.

PubMed

Schlesinger, Orr; Dandela, Rambabu; Bhagat, Ashok; Adepu, Raju; Meijler, Michael M; Xia, Lin; Alfonta, Lital

2018-05-01

Regulation of Bio-systems in a clean, simple, and efficient way is important for the design of smart bio-interfaces and bioelectronic devices. Light as a non-invasive mean to control the activity of a protein enables spatial and temporal control far superior to other chemical and physical methods. The ability to regulate the activity of a catalytic enzyme in a biofuel-cell reduces the waste of resources and energy and turns the fuel-cell into a smart and more efficient device for power generation. Here we present a microbial-fuel-cell based on a surface displayed, photo-switchable alcohol dehydrogenase. The enzyme was modified near the active site using non-canonical amino acids and a small photo-reactive molecule, which enables reversible control of enzymatic activity. Depending on the modification site, the enzyme exhibits reversible behavior upon irradiation with UV and visible light, in both biochemical, and electrochemical assays. The change observed in power output of a microbial fuel cell utilizing the modified enzyme was almost five-fold, between inactive and active states. © 2018 Wiley Periodicals, Inc.

Reduced in vitro T-cell responses induced by glutaraldehyde-modified allergen extracts are caused mainly by retarded internalization of dendritic cells

PubMed Central

Heydenreich, Bärbel; Bellinghausen, Iris; Lorenz, Steffen; Henmar, Helene; Strand, Dennis; Würtzen, Peter A; Saloga, Joachim

2012-01-01

Although allergen-specific immunotherapy is a clinically effective therapy for IgE-mediated allergic diseases, the risk of IgE-mediated adverse effects still exists. For this reason, chemically modified allergoids have been introduced, which may destroy IgE-binding sites while T-cell activation should be retained. The aim of the study was to analyse the differences between intact allergens and differently modified/aggregated allergoids concerning their internalization as well as T-cell and basophil activation. For this purpose human monocyte-derived immature dendritic cells (DC) were incubated with Phleum pratense or Betula verrucosa pollen extract or with the corresponding allergoids, modified with formaldehyde or glutaraldehyde. After an additional maturation process, the antigen-loaded mature DC were co-cultured with autologous CD4+ T cells. Allergenicity was tested by leukotriene release from basophils. In addition, the uptake of intact allergens and allergoids by immature DC was analysed. The proliferation of, as well as the interleukin-4 (IL-4), IL-10, IL-13 and interferon-γ production by, CD4+ T cells which had been stimulated with glutaraldehyde allergoid-treated DC was reduced compared with CD4+ T cells stimulated with intact allergen-treated or formaldehyde allergoid-treated DC. In line with this, glutaraldehyde-modified allergoids were more aggregated and were internalized more slowly. Furthermore, only the allergoids modified with glutaraldehyde induced a decreased leukotriene release by activated basophils. These findings suggest that IgE-reactive epitopes were destroyed more efficiently by modification with glutaraldehyde than with formaldehyde under the conditions chosen for these investigations. Glutaraldehyde-modified allergoids also displayed lower T-cell stimulatory capacity, which is mainly the result of greater modification/aggregation and diminished uptake by DC. PMID:22348538

Reduced in vitro T-cell responses induced by glutaraldehyde-modified allergen extracts are caused mainly by retarded internalization of dendritic cells.

PubMed

Heydenreich, Bärbel; Bellinghausen, Iris; Lorenz, Steffen; Henmar, Helene; Strand, Dennis; Würtzen, Peter A; Saloga, Joachim

2012-06-01

Although allergen-specific immunotherapy is a clinically effective therapy for IgE-mediated allergic diseases, the risk of IgE-mediated adverse effects still exists. For this reason, chemically modified allergoids have been introduced, which may destroy IgE-binding sites while T-cell activation should be retained. The aim of the study was to analyse the differences between intact allergens and differently modified/aggregated allergoids concerning their internalization as well as T-cell and basophil activation. For this purpose human monocyte-derived immature dendritic cells (DC) were incubated with Phleum pratense or Betula verrucosa pollen extract or with the corresponding allergoids, modified with formaldehyde or glutaraldehyde. After an additional maturation process, the antigen-loaded mature DC were co-cultured with autologous CD4(+) T cells. Allergenicity was tested by leukotriene release from basophils. In addition, the uptake of intact allergens and allergoids by immature DC was analysed. The proliferation of, as well as the interleukin-4 (IL-4), IL-10, IL-13 and interferon-γ production by, CD4(+) T cells which had been stimulated with glutaraldehyde allergoid-treated DC was reduced compared with CD4(+) T cells stimulated with intact allergen-treated or formaldehyde allergoid-treated DC. In line with this, glutaraldehyde-modified allergoids were more aggregated and were internalized more slowly. Furthermore, only the allergoids modified with glutaraldehyde induced a decreased leukotriene release by activated basophils. These findings suggest that IgE-reactive epitopes were destroyed more efficiently by modification with glutaraldehyde than with formaldehyde under the conditions chosen for these investigations. Glutaraldehyde-modified allergoids also displayed lower T-cell stimulatory capacity, which is mainly the result of greater modification/aggregation and diminished uptake by DC. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

Identification of Transglutaminase Reactive Residues in Human Osteopontin and Their Role in Polymerization

PubMed Central

Christensen, Brian; Zachariae, Elias D.; Scavenius, Carsten; Thybo, Morten; Callesen, Morten M.; Kløverpris, Søren; Oxvig, Claus; Enghild, Jan J.; Sørensen, Esben S.

2014-01-01

Osteopontin (OPN) is a highly posttranslationally modified protein present in several tissues where it is implicated in numerous physiological processes. OPN primarily exerts its functions through interaction with integrins via the Arg-Gly-Asp and Ser-Val-Val-Tyr-Gly-Leu-Arg sequences located in the N-terminal part of the protein. OPN can be polymerized by the cross-linking enzyme transglutaminase 2 (TG2), and polymerization has been shown to enhance the biological activity of OPN. However, little is known about the reactivity and location of the glutamine and lysine residues involved in the TG2-mediated modification of OPN. Here we show that TG2 catalyses the incorporation of 5-(Biotinamido)pentylamine at glutamines in both the N- and C-terminal parts of OPN, whereas TG2 primarily incorporated the glutamine-donor peptide biotinyl-TVQQEL-OH into the C-terminal part of OPN. By mass spectrometric analyses we identified Gln34, Gln42, Gln193 and Gln248 as the major TG2 reactive glutamines in OPN. The distribution of reactive Gln and Lys residues in OPN proved to be important, as the full-length protein but not the physiologically highly active integrin-binding N-terminal part of OPN were able to polymerize in a TG2-mediated reaction. Collectively, these data provide important new molecular knowledge about the mechanism of OPN polymerization. PMID:25419572

Modified Allergens for Immunotherapy.

PubMed

Satitsuksanoa, Pattraporn; Głobińska, Anna; Jansen, Kirstin; van de Veen, Willem; Akdis, Mübeccel

2018-02-16

During the past few decades, modified allergens have been developed for use in allergen-specific immunotherapy (AIT) with the aim to improve efficacy and reduce adverse effects. This review aims to provide an overview of the different types of modified allergens, their mechanism of action and their potential for improving AIT. In-depth research in the field of allergen modifications as well as the advance of recombinant DNA technology have paved the way for improved diagnosis and research on human allergic diseases. A wide range of structurally modified allergens has been generated including allergen peptides, chemically altered allergoids, adjuvant-coupled allergens, and nanoparticle-based allergy vaccines. These modified allergens show promise for the development of AIT regimens with improved safety and long-term efficacy. Certain modifications ensure reduced IgE reactivity and retained T cell reactivity, which facilities induction of immune tolerance to the allergen. To date, multiple clinical trials have been performed using modified allergens. Promising results were obtained for the modified cat, grass and birch pollen, and house dust mite allergens. The use of modified allergens holds promise for improving AIT efficacy and safety. There is however a need for larger clinical studies to reliably assess the added benefit for the patient of using modified allergens for AIT.

Comparison between the electrocatalytic properties of different metal ion phthalocyanines and porphyrins towards the oxidation of hydroxide.

PubMed

De Wael, Karolien; Adriaens, Annemie

2008-02-15

This work reports on the electrocatalytic oxidation of hydroxide using different central metal ion phthalocyanines and porphyrins immobilized on gold electrodes. The apparent electrocatalytic activity of cobalt phthalocyanine or porphyrin modified electrodes was found to be the greatest among the present series of metal ion macrocycles investigated. Copper and unmetallated phthalocyanine or porphyrin modified electrodes show no electrocatalytic behaviour towards hydroxide, such as bare gold. A possible mechanism for the enhanced reactivity of cobalt ion macrocycles towards the oxygen evolution is given. It is also stated that the electrocatalytic activity towards an adsorbate involves several aspects, such as the coordination state of the central metal ion, the nature of the ligand, the stability of the complexes, the number of d electrons, the energy of orbitals and the strength of the bonding between the central metal ion and the axial ligand.

Reactivity effects of moderator voids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahlfeld, C.E.; Pryor, R.J.

1975-01-01

Reactivity worths for large moderator voids similar to those produced by steaming in postulated reactor transients were measured in the Process Development Pile (PDP) reactor. The experimental results were compared to the computed void worths obtained from techniques currently used in routine safety analyses. Neutron energy spectrum measurements were used to verify a modified lattice pattern that correctly computed the measured spectrum, and consequently, improved macroscopic cross sections. In addition, a special two-dimensional transport calculation was performed to obtain an axially defined diffusion coefficient for the void region. The combination of the modified lattice calculations and the axial diffusion coefficientmore » yielded void reactivity worths which agreed very well with experiment. It was concluded that the computational modules available in the JOSHUA system (GLASS, GRIMHX) would yield accurate void reactivity worths in SLR--SRP safety analysis studies, provided the above mentioned modifications were made.« less

Modification of Keap1 Cysteine Residues by Sulforaphane

PubMed Central

Hu, Chenqi; Eggler, Aimee L.; Mesecar, Andrew D.; van Breemen, Richard B.

2011-01-01

Activation of the transcription factor NF-E2-related factor-2 (Nrf2) through modification of Kelch-like ECH-associated protein 1 (Keap1) cysteines, leading to up-regulation of the antioxidant response element (ARE), is an important mechanism of cellular defense against reactive oxygen species and xenobiotic electrophiles. Sulforaphane, occurring in cruciferous vegetables such as broccoli, is a potent natural ARE activator that functions by modifying Keap1 cysteine residues, but there are conflicting in vitro and in vivo data regarding which of these cysteine residues react. Although most biological data indicate that modification of C151 is essential for sulforaphane action, some recent studies using mass spectrometry have failed to identify C151 as a site of Keap1 sulforaphane reaction. We have reconciled these conflicting data using mass spectrometry with a revised sample preparation protocol and confirmed that C151 is indeed among the most readily modified cysteines of Keap1 by sulforaphane. Previous mass spectrometry-based studies used iodoacetamide during sample preparation to derivatize free cysteine sulfhydryl groups causing loss of sulforaphane from highly reactive and reversible cysteine residues on Keap1 including C151. By omitting iodoacetamide from the protocol and reducing sample preparation time, our mass spectrometry-based studies now confirm previous cell-based studies which showed that sulforaphane reacts with at least four cysteine residues of Keap1 including C151. PMID:21391649

The inhibition, reactivation and mechanism of VX-, sarin-, fluoro-VX and fluoro-sarin surrogates following their interaction with HuAChE and HuBuChE.

PubMed

Chao, Chih-Kai; Balasubramanian, Narayanaganesh; Gerdes, John M; Thompson, Charles M

2018-06-16

In this study, the mechanisms of HuAChE and HuBChE inhibition by Me-P(O) (OPNP) (OR) [PNP = p-nitrophenyl; R = CH 2 CH 3 , CH 2 CH 2 F, OCH(CH 3 ) 2 , OCH(CH 3 ) (CH 2 F)] representing surrogates and fluoro-surrogates of VX and sarin were studied by in vitro kinetics and mass spectrometry. The in vitro measures showed that the VX- and fluoro-VX surrogates were relatively strong inhibitors of HuAChE and HuBChE (k i  ∼ 10 5 -10 6  M -1 min -1 ) and underwent spontaneous and 2-PAM-mediated reactivation within 30 min. The sarin surrogates were weaker inhibitors of HuAChE and HuBChE (k i  ∼ 10 4 -10 5  M -1 min -1 ), and in general did not undergo spontaneous reactivation, although HuAChE adducts were partially reactivatable at 18 h using 2-PAM. The mechanism of HuAChE and HuBChE inhibition by the surrogates was determined by Q-TOF and MALDI-TOF mass spectral analyses. The surrogate-adducted proteins were trypsin digested and the active site-containing peptide bearing the OP-modified serine identified by Q-TOF as triply- and quadruply-charged ions representing the respective increase in mass of the attached OP moiety. Correspondingly, monoisotopic ions of the tryptic peptides representing the mass increase of the OP-adducted peptide was identified by MALDI-TOF. The mass spectrometry analyses validated the identity of the OP moiety attached to HuAChE or HuBChE as MeP(O) (OR)-O-serine peptides (loss of the PNP leaving group) via mechanisms consistent with those found with chemical warfare agents. MALDI-TOF MS analyses of the VX-modified peptides versus time showed a steady reduction in adduct versus parent peptide (reactivation), whereas the sarin-surrogate-modified peptides remained largely intact over the course of the experiment (24 h). Overall, the presence of a fluorine atom on the surrogate modestly altered the rate constants of inhibition and reactivation, however, the mechanism of inhibition (ejection of PNP group) did not change. Copyright © 2018. Published by Elsevier B.V.

Neural mechanisms of interference control in working memory: effects of interference expectancy and fluid intelligence.

PubMed

Burgess, Gregory C; Braver, Todd S

2010-09-20

A critical aspect of executive control is the ability to limit the adverse effects of interference. Previous studies have shown activation of left ventrolateral prefrontal cortex after the onset of interference, suggesting that interference may be resolved in a reactive manner. However, we suggest that interference control may also operate in a proactive manner to prevent effects of interference. The current study investigated the temporal dynamics of interference control by varying two factors - interference expectancy and fluid intelligence (gF) - that could influence whether interference control operates proactively versus reactively. A modified version of the recent negatives task was utilized. Interference expectancy was manipulated across task blocks by changing the proportion of recent negative (interference) trials versus recent positive (facilitation) trials. Furthermore, we explored whether gF affected the tendency to utilize specific interference control mechanisms. When interference expectancy was low, activity in lateral prefrontal cortex replicated prior results showing a reactive control pattern (i.e., interference-sensitivity during probe period). In contrast, when interference expectancy was high, bilateral prefrontal cortex activation was more indicative of proactive control mechanisms (interference-related effects prior to the probe period). Additional results suggested that the proactive control pattern was more evident in high gF individuals, whereas the reactive control pattern was more evident in low gF individuals. The results suggest the presence of two neural mechanisms of interference control, with the differential expression of these mechanisms modulated by both experimental (e.g., expectancy effects) and individual difference (e.g., gF) factors.

Quantitative Protein Sulfenic Acid Analysis Identifies Platelet Releasate-Induced Activation of Integrin β2 on Monocytes via NADPH Oxidase.

PubMed

Li, Ru; Klockenbusch, Cordula; Lin, Liwen; Jiang, Honghui; Lin, Shujun; Kast, Juergen

2016-12-02

Physiological stimuli such as thrombin, or pathological stimuli such as lysophosphatidic acid (LPA), activate platelets. The activated platelets bind to monocytes through P-selectin-PSGL-1 interactions but also release the contents of their granules, commonly called "platelet releasate". It is known that monocytes in contact with platelet releasate produce reactive oxygen species (ROS). Reversible cysteine oxidation by ROS is considered to be a potential regulator of protein function. In a previous study, we used THP-1 monocytic cells exposed to LPA- or thrombin-induced platelet releasate and a modified biotin switch assay to unravel the biological processes that are influenced by reversible cysteine oxidation. To gain a better understanding of the redox regulation of monocytes in atherosclerosis, we have now altered the modified biotin switch to selectively quantify protein sulfenic acid, a subpopulation of reversible cysteine oxidation. Using arsenite as reducing agent in the modified biotin switch assay, we were able to quantify 1161 proteins, in which more than 100 sulfenic acid sites were identified. Bioinformatics analysis of the quantified sulfenic acid sites highlighted the relevant, previously missed biological process of monocyte transendothelial migration, which included integrin β 2 . Flow cytometry validated the activation of LFA-1 (α L β 2 ) and Mac-1 (α M β 2 ), two subfamilies of integrin β 2 complexes, on human primary monocytes following platelet releasate treatment. The activation of LFA-1 was mediated by ROS from NADPH oxidase (NOX) activation. Production of ROS and activation of LFA-1 in human primary monocytes were independent of P-selectin-PSGL-1 interaction. Our results proved the modified biotin switch assay to be a powerful tool with the ability to reveal new regulatory mechanisms and identify new therapeutic targets.

Reactive modification of polyesters and their blends

NASA Astrophysics Data System (ADS)

Wan, Chen

2004-12-01

As part of a broader research effort to investigate the chemical modification of polyesters by reactive processing a low molecular weight (MW) unsaturated polyester (UP) and a higher MW saturated polyester, polyethylene terephthalate (PET), alone or blended with polypropylene (PP) were melt processed in a batch mixer and continuous twin screw extruders. Modification was monitored by on-line rheology and the products were characterized primarily by off-line rheology, morphology and thermal analysis. Efforts were made to establish processing/property relationships and provide an insight of the accompanying structural changes. The overall response of the reactively modified systems was found to be strongly dependent on the component characteristics, blend composition, type and concentrations of reactive additives and processing conditions. The work concluded that UP can be effectively modified through reactive melt processing. Its melt viscosity and MW can be increased through chemical reactions between organic peroxides (POX) and chain unsaturation or between MgO and carboxyl/hydroxyl end groups. Reactive blending of PP/UP blends through peroxide modification gave finer and more uniform morphology than unreacted blends and at a given PP/UP weight ratio more thermoplastic elastomers-like rheological behavior. This is due to the continuously decreasing viscosity ratio of PP/UP towards unity by the competing reactions between POX and the blend components and formation of PP-UP copolymers which serve as in-situ compatibilizers to promote better interfacial adhesion. Kinetics of the competing reactions were analyzed through a developed model. In addition to POX concentration and mixing efficiency, rheology and morphology of UP/PP bends were significantly affected by the addition of inorganic and organic coagents. Addition of coagents such as a difunctional maleimide, MgO and/or an anhydride functionalized PP during reactive blending offers effective means for tailoring the desired rheological and structural characteristics of the final products for potential applications such as low density extrusion foaming or compatibilization of immiscible polymer blends. Important modification conditions through coagents are identified and reaction mechanisms are proposed. A high MW saturated polyester, PET, can also be rheologically modified in extruders through low MW multifunctional anhydride and epoxy compounds by chain extension/branching. Several such modifiers were successfully screened in terms of their reactivity towards PET under controlled reactive extrusion conditions. A dianhydride with medium reactivity was then successfully used in a one-step reactive modification/extrusion foaming process to produce low density foams. A similar process was successfully used to produce small cell size foams from a four component system containing PET, PP and lesser amounts of a low molecular weight multifunctional epoxy compound and an acid functionalized polyolefin, the latter acting as compatibilizers.

Critical biological parameters modulate affinity as a determinant of function in T-cell receptor gene-modified T-cells.

PubMed

Spear, Timothy T; Wang, Yuan; Foley, Kendra C; Murray, David C; Scurti, Gina M; Simms, Patricia E; Garrett-Mayer, Elizabeth; Hellman, Lance M; Baker, Brian M; Nishimura, Michael I

2017-11-01

T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity. It is critical to re-evaluate the importance of other biophysical, structural, or cellular factors that drive the reactivity of TCR gene-modified T-cells. Using a model for altered antigen recognition, we determined how TCR-pMHC affinity influenced the reactivity of hepatitis C virus (HCV) TCR gene-modified T-cells against a panel of naturally occurring HCV peptides and HCV-expressing tumor targets. The impact of other factors, such as TCR-pMHC stabilization and signaling contributions by the CD8 co-receptor, as well as antigen and TCR density were also evaluated. We found that changes in TCR-pMHC affinity did not always predict or dictate IFNγ release or degranulation by TCR gene-modified T-cells, suggesting that less emphasis might need to be placed on TCR-pMHC affinity as a means of predicting or augmenting the therapeutic potential of TCR gene-modified T-cells used in ACT. A more complete understanding of antigen recognition by gene-modified T-cells and a more rational approach to improve the design and implementation of novel TCR-based immunotherapies is necessary to enhance efficacy and maximize safety in patients.

Identification of liver protein targets modified by tienilic acid metabolites using a two-dimensional Western blot-mass spectrometry approach

NASA Astrophysics Data System (ADS)

Methogo, Ruth Menque; Dansette, Patrick M.; Klarskov, Klaus

2007-12-01

A combined approach based on two-dimensional electrophoresis-immuno-blotting and nanoliquid chromatography coupled on-line with electrospray ionization mass spectrometry (nLC-MS/MS) was used to identify proteins modified by a reactive intermediate of tienilic acid (TA). Liver homogenates from rats exposed to TA were fractionated using ultra centrifugation; four fractions were obtained and subjected to 2D electrophoresis. Following transfer to PVDF membranes, modified proteins were visualized after India ink staining, using an anti-serum raised against TA and ECL detection. Immuno-reactive spots were localized on the PVDF membrane by superposition of the ECL image, protein spots of interest were excised, digested on the membrane with trypsin followed by nLC-MS/MS analysis and protein identification. A total of 15 proteins were identified as likely targets modified by a TA reactive metabolite. These include selenium binding protein 2, senescence marker protein SMP-30, adenosine kinase, Acy1 protein, adenosylhomocysteinase, capping protein (actin filament), protein disulfide isomerase, fumarylacetoacetase, arginase chain A, ketohexokinase, proteasome endopeptidase complex, triosephosphate isomerase, superoxide dismutase, dna-type molecular chaperone hsc73 and malate dehydrogenase.

Fragmentation and reactivity in collisions of protonated diglycine with chemically modified perfluorinated alkylthiolate-self-assembled monolayer surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barnes, George L.; Yang Li; Hase, William L.

2011-03-07

Direct dynamics simulations are reported for quantum mechanical (QM)/molecular mechanical (MM) trajectories of N-protonated diglycine (gly{sub 2}-H{sup +}) colliding with chemically modified perfluorinated octanethiolate self-assembled monolayer (SAM) surfaces. The RM1 semiempirical theory is used for the QM component of the trajectories. RM1 activation and reaction energies were compared with those determined from higher-level ab initio theories. Two chemical modifications are considered in which a head group (-COCl or -CHO) is substituted on the terminal carbon of a single chain of the SAM. These surfaces are designated as the COCl-SAM and CHO-SAM, respectively. Fragmentation, peptide reaction with the SAM, and covalentmore » linkage of the peptide or its fragments with the SAM surface are observed. Peptide fragmentation via concerted CH{sub 2}-CO bond breakage is the dominant pathway for both surfaces. HCl formation is the dominant species produced by reaction with the COCl-SAM, while for the CHO-SAM a concerted H-atom transfer from the CHO-SAM to the peptide combined with either a H-atom or radical transfer from the peptide to the surface to form singlet reaction products is the dominant pathway. A strong collision energy dependence is found for the probability of peptide fragmentation, its reactivity, and linkage with the SAM. Surface deposition, i.e., covalent linkage between the surface and the peptide, is compared to recent experimental observations of such bonding by Laskin and co-workers [Phys. Chem. Chem. Phys. 10, 1512 (2008)]. Qualitative differences in reactivity are seen between the COCl-SAM and CHO-SAM showing that chemical identity is important for surface reactivity. The probability of reactive surface deposition, which is most closely analogous to experimental observables, peaks at a value of around 20% for a collision energy of 50 eV.« less

Processing Mode Causally Influences Emotional Reactivity

PubMed Central

Watkins, Ed; Moberly, Nicholas J.; Moulds, Michelle L.

2008-01-01

Three studies are reported showing that emotional responses to stress can be modified by systematic prior practice in adopting particular processing modes. Participants were induced to think about positive and negative scenarios in a mode either characteristic of or inconsistent with the abstract-evaluative mind-set observed in depressive rumination, via explicit instructions (Experiments 1 and 2) and via implicit induction of interpretative biases (Experiment 3), before being exposed to a failure experience. In all three studies, participants trained into the mode antithetical to depressive rumination demonstrated less emotional reactivity following failure than participants trained into the mode consistent with depressive rumination. These findings provide evidence consistent with the hypothesis that processing mode modifies emotional reactivity and support the processing-mode theory of rumination. PMID:18540752

Enhancing the reactivity of gold: Nanostructured Au(111) adsorbs CO

DOE PAGES

Hoffmann, F. M.; Hrbek, J.; Ma, S.; ...

2015-12-02

Low-coordinated sites are surface defects whose presence can transform a surface of inert or noble metal such as Au into an active catalyst. We prepared gold surfaces modified by pits, starting with a well-ordered Au(111) surface; we then used microscopy (STM) for their structural characterization and CO spectroscopy (IRAS and NEXAFS) for probing reactivity of surface defects. In contrast to the Au(111) surface CO adsorbs readily on the pitted surfaces bonding to low-coordinated sites identified as step atoms forming {111} and {100} microfacets. Finally, pitted nanostructured surfaces can serve as interesting and easily prepared models of catalytic surfaces with definedmore » defects that offer an attractive alternative to vicinal surfaces or nanoparticles commonly employed in catalysis science.« less

Voltage control for a wind power plant based on the available reactive current of a DFIG and its impacts on the point of interconnection

DOE PAGES

Usman, Yasir; Kim, Jinho; Muljadi, Eduard; ...

2016-01-01

Wake effects cause wind turbine generators (WTGs) within a wind power plant (WPP) to produce different levels of active power and subsequent reactive power capabilities. Further, the impedance between a WTG and the point of interconnection (POI)-which depends on the distance between them-impacts the WPP's reactive power injection capability at the POI. This paper proposes a voltage control scheme for a WPP based on the available reactive current of the doubly-fed induction generators (DFIGs) and its impacts on the POI to improve the reactive power injection capability of the WPP. In this paper, a design strategy for modifying the gainmore » of DFIG controller is suggested and the comprehensive properties of these control gains are investigated. In the proposed scheme, the WPP controller, which operates in a voltage control mode, sends the command signal to the DFIGs based on the voltage difference at the POI. The DFIG controllers, which operate in a voltage control mode, employ a proportional controller with a limiter. The gain of the proportional controller is adjusted depending on the available reactive current of the DFIG and the series impedance between the DFIG and the POI. The performance of the proposed scheme is validated for various disturbances such as a reactive load connection and grid fault using an EMTP-RV simulator. Furthermore, simulation results demonstrate that the proposed scheme promptly recovers the POI voltage by injecting more reactive power after a disturbance than the conventional scheme.« less

Hoarding and emotional reactivity: the link between negative emotional reactions and hoarding symptomatology.

PubMed

Shaw, A M; Timpano, K R; Steketee, G; Tolin, D F; Frost, R O

2015-04-01

Hoarding disorder (HD) is characterized by difficulty discarding, clutter, and frequently excessive acquiring. Theories have pointed to intense negative emotional reactions (e.g., sadness) as one factor that may play a critical role in HD's etiology. Preliminary work with an analogue sample indicated that more intense negative emotions following emotional films were linked with greater hoarding symptoms. Symptom provocation imaging studies with HD patients have also found evidence for excessive activation in brain regions implicated in processing emotions. The current study utilized a sample with self-reported serious hoarding difficulties to examine how hoarding symptoms related to both general and hoarding-related emotional reactivity, taking into account the specificity of these relationships. We also examined how two cognitive factors, fear of decision-making and confidence in memory, modified this relationship. 628 participants with self-identified hoarding difficulties completed questionnaires about general emotional reactivity, depression, anxiety, decision-making, and confidence in memory. To assess hoarding-related emotional reactivity, participants reported their emotional reactions when imagining discarding various items. Heightened general emotional reactivity and more intense emotional reactions to imagined discarding were associated with both difficulty discarding and acquisition, but not clutter, controlling for age, gender, and co-occurring mood and anxiety symptoms. Fear of decision-making and confidence in memory interacted with general emotional reactivity to predict hoarding symptoms. These findings provide support for cognitive-behavioral models of hoarding. Experimental research should be conducted to discover whether emotional reactivity increases vulnerability for HD. Future work should also examine whether emotional reactivity should be targeted in interventions for hoarding. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hoarding and emotional reactivity: The link between negative emotional reactions and hoarding symptomatology

PubMed Central

Shaw, A.M.; Timpano, K.R.; Steketee, G.; Tolin, D. F.; Frost, R.O.

2015-01-01

Hoarding disorder (HD) is characterized by difficulty discarding, clutter, and frequently excessive acquiring. Theories have pointed to intense negative emotional reactions (e.g., sadness) as one factor that may play a critical role in HD’s etiology. Preliminary work with an analogue sample indicated that more intense negative emotions following emotional films were linked with greater hoarding symptoms. Symptom provocation imaging studies with HD patients have also found evidence for excessive activation in brain regions implicated in processing emotions. The current study utilized a sample with self-reported serious hoarding difficulties to examine how hoarding symptoms related to both general and hoarding-related emotional reactivity, taking into account the specificity of these relationships. We also examined how two cognitive factors, fear of decision-making and confidence in memory, modified this relationship. 628 participants with self-identified hoarding difficulties completed questionnaires about general emotional reactivity, depression, anxiety, decision-making, and confidence in memory. To assess hoarding-related emotional reactivity, participants reported their emotional reactions when imagining discarding various items. Heightened general emotional reactivity and more intense emotional reactions to imagined discarding were associated with both difficulty discarding and acquisition, but not clutter, controlling for age, gender, and co-occurring mood and anxiety symptoms. Fear of decision-making and confidence in memory interacted with general emotional reactivity to predict hoarding symptoms. These findings provide support for cognitive-behavioral models of hoarding. Experimental research should be conducted to discover whether emotional reactivity increases vulnerability for HD. Future work should also examine whether emotional reactivity should be targeted in interventions for hoarding. PMID:25732668

Development of modified flyash as a permeable reactive barrier medium for a former manufactured gas plant site, Northern Ireland

NASA Astrophysics Data System (ADS)

Doherty, R.; Phillips, D. H.; McGeough, K. L.; Walsh, K. P.; Kalin, R. M.

2006-05-01

A sequential biological permeable reactive barrier (PRB) was determined to be the best option for remediating groundwater that has become contaminated with a wide range of organic contaminants (i.e., benzene, toluene, ethylbenzene, xylene and polyaromatic hydrocarbons), heavy metals (i.e., lead and arsenic), and cyanide at a former manufactured gas plant after 150 years of operation in Portadown, Northern Ireland. The objective of this study was to develop a modified flyash that could be used in the initial cell within a sequential biological PRB to filter complex contaminated groundwater containing ammonium. Flyash modified with lime (CaOH) and alum was subjected to a series of batch tests which investigated the modified cation exchange capacity (CEC) and rate of removal of anions and cations from the solution. These tests showed that a high flyash composition medium (80%) could remove 8.65 mol of ammonium contaminant for every kilogram of medium. The modified CEC procedure ruled out the possibility of cation exchange as the major removal mechanism. The medium could also adsorb anions as well as cations (i.e., Pb and Cr), but not with the same capacity. The initial mechanism for Pb and Cr removal is probably precipitation. This is followed by sorption, which is possibly the only mechanism for the removal of dichromate anions. Scanning electron microscopic analysis revealed very small (<1 μm) cubic highly crystalline precipitates on the flyash, although this new crystalline zeolite growth did not occur rapidly enough to enable productive zeolite formation. Surface area measurements showed that biofilm growth on the medium could be a major factor in the comparative reduction of surface area between real and synthetic contaminant groundwaters. The modified flyash was found to be a highly sorptive granular material that did not inhibit microbiological activity, however, leaching tests revealed that the medium would fail as a long-term barrier material.

On the Inevitability of Aging: Essentialist Beliefs Moderate the Impact of Negative Age Stereotypes on Older Adults' Memory Performance and Physiological Reactivity.

PubMed

Weiss, David

2016-07-20

The goal of this research was to investigate how individual differences in essentialist beliefs about aging affect how older adults' respond to negative age stereotypes. Essentialist beliefs about aging (EBA) define the process of aging as fixed and inevitable rather than malleable and modifiable. Two experiments including older adults tested the hypothesis that EBA moderate the effect of negative age stereotypes on older adults' memory performance and physiological reactivity. In line with predictions, results of Experiment 1 (N = 79, 61-87 years) showed that for older adults with strong EBA, the activation of negative age stereotypes (vs neutral information) led to stereotype assimilation entailing a poorer memory performance. In contrast, for older adults with non-EBA, the activation of negative age stereotypes led to stereotype reactance entailing a better memory performance. Experiment 2 (N = 41; 65-92 years) replicated this pattern and also showed that older adults who endorsed rather than rejected EBA exhibited increased systolic blood pressure reactivity when negative age stereotypes were activated. The discussion focuses on pathways through which age stereotypes impact cognitive performance and health in later adulthood, as well as ways to stimulate positive plasticity by changing EBA. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Validation of Autonomic and Endocrine Reactivity to a Laboratory Stressor in Young Children

PubMed Central

Roos, Leslie E.; Giuliano, Ryan J.; Beauchamp, Kathryn G.; Gunnar, Megan; Amidon, Brigette; Fisher, Philip A.

2017-01-01

The validation of laboratory paradigms that reliably induce a stress response [including hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) activation], is critical for understanding how children’s stress-response systems support emotional and cognitive function. Early childhood research to date is markedly limited, given the difficulty in establishing paradigms that reliably induce a cortisol response. Furthermore, research to date has not included a control condition or examined concurrent ANS reactivity. We addressed these limitations by characterizing the extent to which a modified matching task stressor paradigm induces HPA and ANS activation, beyond a closely matched control condition. Modifications include an unfamiliar and unfriendly assessor to increase the stressful nature of the task. Results validate the matching task as a laboratory stressor, with significant differences in HPA and ANS responsivity between conditions. The Stressor group exhibited a cortisol increase post-stressor, while the Control group was stable over time. Children in both conditions exhibited reduced parasympathetic activity to the first-half of the task, but in the second-half, only children in the Stressor condition, who were experiencing exaggerated signals of failure, exhibited further parasympathetic decline. The Stressor condition induced higher sympathetic activity (versus Control) throughout the task, with exaggerated second-half differences. Within the Stressor condition, responsivity was convergent across systems, with greater cortisol reactivity correlated with the magnitude of parasympathetic withdrawal and sympathetic engagement. Future research employing the matching task will facilitate understanding the role of HPA and ANS function in development. PMID:28024268

Hydroxynonenal and uncoupling proteins: a model for protection against oxidative damage.

PubMed

Echtay, Karim S; Pakay, Julian L; Esteves, Telma C; Brand, Martin D

2005-01-01

In this mini review we summarize recent studies from our laboratory that show the involvement of superoxide and the lipid peroxidation product 4-hydroxynonenal in the regulation of mitochondrial uncoupling. Superoxide produced during mitochondrial respiration is a major cause of the cellular oxidative damage that may underlie degenerative diseases and ageing. Superoxide production is very sensitive to the magnitude of the mitochondrial protonmotive force, so can be strongly decreased by mild uncoupling. Superoxide is able to give rise to other reactive oxygen species, which elicit deleterious effects primarily by oxidizing intracellular components, including lipids, DNA and proteins. Superoxide-induced lipid peroxidation leads to the production of reactive aldehydes, including 4-hydroxynonenal. These aldehydic lipid peroxidation products are in turn able to modify proteins such as mitochondrial uncoupling proteins and the adenine nucleotide translocase, converting them into active proton transporters. This activation induces mild uncoupling and so diminishes mitochondrial superoxide production, hence protecting against disease and oxidative damage at the expense of energy production.

Mucosal reactive oxygen species decrease virulence by disrupting Campylobacter jejuni phosphotyrosine signaling

PubMed Central

Corcionivoschi, Nicolae; Alvarez, Luis A.; Sharp, Thomas H.; Strengert, Monika; Alemka, Abofu; Mantell, Judith; Verkade, Paul; Knaus, Ulla G.; Bourke, Billy

2013-01-01

Summary Reactive oxygen species (ROS) play key roles in mucosal defense, yet how they are induced and the consequences for pathogens are unclear. We report that ROS generated by epithelial NADPH oxidases (Nox1/Duox2) during Campylobacter jejuni infection impair bacterial capsule formation and virulence by altering bacterial signal transduction. Upon C. jejuni invasion, ROS released from the intestinal mucosa inhibit the bacterial phosphotyrosine network that is regulated by the outer membrane tyrosine kinase Cjtk (Cj1170/OMP50). ROS-mediated Cjtk inactivation results in an overall decrease in the phosphorylation of C. jejuni outer membrane / periplasmic proteins including UDP-GlcNAc/Glc 4-epimerase (Gne), an enzyme required for N-glycosylation and capsule formation. Cjtk positively regulates Gne by phosphorylating an active site tyrosine, while loss of Cjtk or ROS treatment inhibits Gne activity, causing altered polysaccharide synthesis. Thus, epithelial NADPH oxidases are an early antibacterial defense system in the intestinal mucosa that modifies virulence by disrupting bacterial signaling. PMID:22817987

Affective and cognitive reactivity to mood induction in chronic depression.

PubMed

Guhn, Anne; Sterzer, Philipp; Haack, Friderike H; Köhler, Stephan

2018-03-15

Chronic depression (CD) is strongly associated with childhood maltreatment, which has been proposed to lead to inefficient coping styles that are characterized by abnormal affective responsiveness and dysfunctional cognitive attitudes. However, while this notion forms an important basis for psychotherapeutic strategies in the treatment of CD, there is still little direct empirical evidence for a role of altered affective and cognitive reactivity in CD. The present study therefore experimentally investigated affective and cognitive reactivity to two forms of negative mood induction in CD patients versus a healthy control sample (HC). For the general mood induction procedure, a combination of sad pictures and sad music was used, while for individualized mood induction, negative mood was induced by individualized scripts with autobiographical content. Both experiments included n = 15 CD patients versus n = 15 HC, respectively. Interactions between affective or cognitive reactivity and group were analyzed by repeated measurements ANOVAs. General mood induction neither revealed affective nor cognitive reactivity in the patient group while the control group reported the expected decrease of positive affect [interaction (IA) affective reactivity x group: p = .011, cognitive reactivity x group: n.s.]. In contrast, individualized mood induction specifically increased affective reactivity (IA: p = .037) as well as the amount of dysfunctional cognitions in patients versus controls (IA: p = .014). The experiments were not balanced in a crossover design, causal conclusions are thus limited. Additionally, the differences to non-chronic forms of depression are still outstanding. The results suggest that in patients with CD, specific emotional activation through autobiographical memories is a key factor in dysfunctional coping styles. Psychotherapeutic interventions aimed at modifying affective and cognitive reactivity are thus of high relevance in the treatment of CD. Copyright © 2018 Elsevier B.V. All rights reserved.

Reactive Black 5 dye degradation using filters of smuggled cigarette modified with Fe3.

PubMed

Glugoski, Letícia Polli; de Jesus Cubas, Paloma; Fujiwara, Sérgio Toshio

2017-03-01

This study presents an attempt to solve two serious environmental problems: the generation of toxic effluents and solid waste disposal. The work proposes recycling cigarette filters with the purpose of degrading reactive dyes, which are used in the textile industry. Filters of smuggled cigarettes were recycled through Fe 3+ immobilization on their surface. The material obtained was characterized through Fourier transform infrared spectroscopy (FTIR), atomic absorption spectroscopy (AAS), scanning electron microscopy-energy-dispersive spectroscopy (SEM-EDS), and ultraviolet-visible spectroscopy (UV-vis). The factorial design revealed that the most suitable conditions for the degradation of Reactive Black 5 dye were obtained by using 1 g of material at pH 3.0 in a 100 mg L -1 hydrogen peroxide solution. The material showed excellent performance in the Reactive Black 5 dye degradation process; in 60 min, 99.09 % dye was removed. At pH 7.0, the dye degradation was 72.67 %, indicating that the material prepared can be used at pH values greater than 3.0 without the occurrence of hydrated Fe 3+ oxide precipitation. Furthermore, the material showed no loss of catalytic activity after three degradation studies.

Remediation of nitrate-contaminated groundwater by PRB-Electrokinetic integrated process.

PubMed

Ghaeminia, Mahdyar; Mokhtarani, Nader

2018-05-30

Activated carbon is used as a reactive media in Permeable Reactive Barrier (PRB) for the removal of inorganic contaminants such as nitrate from groundwater. Since removal rate by this media decreases by time and due to the high costs of excavation and replacement of new media, the usage of activated carbon as an adsorbent in PRB is limited. The present study aimed to solve this defect by integrating electrokinetic process and PRB, using in-situ regeneration of activated carbon. This research was carried out on a laboratory scale using synthetically contaminated water and modified activated carbon as a reactive media in PRB. The effects of pH, nitrate concentration, carbon to sand ratio, and also electric gradient on the performance of the process were evaluated, and optimal conditions were determined, to increase the system longevity. According to the results, by applying an electric gradient of 1.25 V cm -1 to the PRB alone process in optimum operating condition (135 mg L -1 initial nitrate concentration, flow rate of 2.3 L min -1 , pH = 6.8, and carbon to sand ratios of 1:1) the adsorbent capacity increased by 90%. Under these conditions, the integrated process could keep nitrate concentration in the effluent below the standard limit for about 111 h, while the PRB alone process could do the same job for about 59 h. Also, SEM analysis showed that by applying electrokinetic process, activated carbon was regenerated. Integration of electrokinetic process and PRB was also caused nitrate to transfer from activated carbon media into the soil layer above the system. This nitrate-rich soil has the potential for reuse in agricultural activities. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease

PubMed Central

Lauterbach, Edward C.; Fontenelle, Leonardo F.; Teixeira, Antonio L.

2012-01-01

Neuroprotective treatments in Parkinson's disease (PD) have remained elusive. Psychotropics are commonly prescribed in PD without regard to their pathobiological effects. The authors investigated the effects of psychotropics on pathobiological proteins, proteasomal activity, mitochondrial functions, apoptosis, neuroinflammation, trophic factors, stem cells, and neurogenesis. Only findings replicated in at least 2 studies were considered for these actions. Additionally, PD-related gene transcription, animal model, and human neuroprotective clinical trial data were reviewed. Results indicate that, from a PD pathobiology perspective, the safest drugs (i.e., drugs least likely to promote cellular neurodegenerative mechanisms balanced against their likelihood of promoting neuroprotective mechanisms) include pramipexole, valproate, lithium, desipramine, escitalopram, and dextromethorphan. Fluoxetine favorably affects transcription of multiple genes (e.g., MAPT, GBA, CCDC62, HIP1R), although it and desipramine reduced MPTP mouse survival. Haloperidol is best avoided. The most promising neuroprotective investigative priorities will involve disease-modifying trials of the safest agents alone or in combination to capture salutary effects on H3 histone deacetylase, gene transcription, glycogen synthase kinase-3, α-synuclein, reactive oxygen species (ROS), reactive nitrogen species (RNS), apoptosis, inflammation, and trophic factors including GDNF and BDNF. PMID:22254151

Concurrent Validity of a Portable Force Plate Using Vertical Jump Force-Time Characteristics.

PubMed

Lake, Jason; Mundy, Peter; Comfort, Paul; McMahon, John J; Suchomel, Timothy J; Carden, Patrick

2018-05-29

This study examined concurrent validity of countermovement vertical jump (CMJ) reactive strength index modified and force-time characteristics recorded using a one dimensional portable and laboratory force plate system. Twenty-eight men performed bilateral CMJs on two portable force plates placed on top of two in-ground force plates, both recording vertical ground reaction force at 1000 Hz. Time to take-off, jump height, reactive strength index modified, braking and propulsion impulse, mean net force, and duration were calculated from the vertical force from both force plate systems. Results from both systems were highly correlated (r≥.99). There were small (d<.12) but significant differences between their respective braking impulse, braking mean net force, propulsion impulse, and propulsion mean net force (p<.001). However, limits of agreement yielded a mean value of 1.7% relative to the laboratory force plate system (95% CL: .9% to 2.5%), indicating very good agreement across all of the dependent variables. The largest limits of agreement belonged to jump height (2.1%), time to take-off (3.4%), and reactive strength index modified (3.8%). The portable force plate system provides a valid method of obtaining reactive strength measures, and several underpinning force-time variables, from unloaded CMJ and practitioners can use both force plates interchangeably.

A cross-reactive sensor array for the fluorescence qualitative analysis of heavy metal ions.

PubMed

Kang, Huaizhi; Lin, Liping; Rong, Mingcong; Chen, Xi

2014-11-01

A cross-reactive sensor array using mercaptopropionic acid modified cadmium telluride (CdTe), glutathione modified CdTe, poly(methacrylic acid) modified silver nanoclusters, bovine serum albumin modified gold nanoclusters, rhodamine derivative and calcein blue as fluorescent indicators has been designed for the detection of seven heavy metal ions (Ag(+), Hg(2+), Pb(2+), Cu(2+), Cr(3+), Mn(2+) and Cd(2+)). The discriminatory capacity of the sensor array to different heavy metal ions in different pH solutions has been tested and the results have been analyzed with linear discriminant analysis. Results showed that the sensor array could be used to qualitatively analyze the selected heavy metal ions. The array performance was also evaluated in the identification of known and unknown samples and the preliminary results suggested the promising practicability of the designed sensor assay. Copyright © 2014 Elsevier B.V. All rights reserved.

Generation of B-cell chronic lymphocytic leukemia (B-CLL)-reactive T-cell lines and clones from HLA class I-matched donors using modified B-CLL cells as stimulators: implications for adoptive immunotherapy.

PubMed

Hoogendoorn, M; Wolbers, J Olde; Smit, W M; Schaafsma, M R; Barge, R M Y; Willemze, R; Falkenburg, J H F

2004-07-01

Allogeneic stem cell transplantation following reduced-intensity conditioning is being evaluated in patients with advanced B-cell chronic lymphocytic leukemia (B-CLL). The curative potential of this procedure is mediated by donor-derived alloreactive T cells, resulting in a graft-versus-leukemia effect. However, B-CLL may escape T-cell-mediated immune reactivity since these cells lack expression of costimulatory molecules. We examined the most optimal method to transform B-CLL cells into efficient antigen-presenting cells (APC) using activating cytokines, by triggering toll-like receptors (TLRs) using microbial pathogens and by CD40 stimulation with CD40L-transfected fibroblasts. CD40 activation in the presence of IL-4 induced strongest upregulation of costimulatory and adhesion molecules on B-CLL cells and induced the production of high amounts of IL-12 by the leukemic cells. In contrast to primary B-CLL cells as stimulator cells, these malignant APCs were capable of inducing the generation of B-CLL-reactive CD8(+) CTL lines and clones from HLA class I-matched donors. These CTL lines and clones recognized and killed primary B-CLL as well as patient-derived lymphoblasts, but not donor cells. These results show the feasibility of ex vivo generation of B-CLL-reactive CD8(+) CTLs. This opens new perspectives for adoptive immunotherapy, following allogeneic stem cell transplantation in patients with advanced B-CLL.

Coupling of carboxylic groups onto the surface of polystyrene parts during fused filament fabrication

NASA Astrophysics Data System (ADS)

Nagel, Jürgen; Zimmermann, Philipp; Schubert, Oliver; Simon, Frank; Schlenstedt, Kornelia

2017-11-01

A method for the fabrication of polystyrene parts, modified with carboxylic groups during Fused Filament Fabrication (FFF), is being introduced. This method is based on the application of a thin layer of a reactive polymer carrying carboxylic groups on a substrate surface. A polystyrene film is printed on top of this layer. During contact between the hot melt and the reactive layer, a Friedel-Crafts type acylation using a green catalyst takes place, which attaches the reactive polymer to the polystyrene surface. The modified surface is homogeneous, hydrophilic and able to bind copper ions. The method could be used to fabricate unique parts of polystyrene with tailored surface functionalisation. It could be applied for laboratory use, e.g. for the manufacture of lab-on-a-chip devices.

Natural zeolite reactivity towards ozone: the role of compensating cations.

PubMed

Valdés, Héctor; Alejandro, Serguei; Zaror, Claudio A

2012-08-15

Among indoor pollutants, ozone is recognised to pose a threat to human health. Recently, low cost natural zeolites have been applied as alternative materials for ozone abatement. In this work, the effect of compensating cation content of natural zeolite on ozone removal is studied. A Chilean natural zeolite is used here as starting material. The amount of compensating cations in the zeolite framework was modified by ion exchange using an ammonium sulphate solution (0.1 mol L(-1)). Characterisation of natural and modified zeolites were performed by X-ray powder diffraction (XRD), nitrogen adsorption at 77K, elemental analysis, X-ray fluorescence (XRF), thermogravimetric analysis coupled with mass spectroscopy (TGA-MS), and temperature-programmed desorption of ammonia (NH(3)-TPD). Ozone adsorption and/or decomposition on natural and modified zeolites were studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Results show that the zeolite compensating cation content affects ozone interaction with zeolite active sites. Ammonium ion-exchange treatments followed by thermal out-gassing at 823 K, reduces ozone diffusion resistance inside the zeolite framework, increasing ozone abatement on zeolite surface active sites. Weak and strong Lewis acid sites of zeolite surface are identified here as the main active sites responsible of ozone removal. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of Mindfulness-Based Stress Reduction (MBSR) on Emotion Regulation in Social Anxiety Disorder

PubMed Central

Goldin, Philippe R.; Gross, James J.

2014-01-01

Mindfulness-based stress reduction (MBSR) is an established program shown to reduce symptoms of stress, anxiety, and depression. MBSR is believed to alter emotional responding by modifying cognitive–affective processes. Given that social anxiety disorder (SAD) is characterized by emotional and attentional biases as well as distorted negative self-beliefs, we examined MBSR-related changes in the brain-behavior indices of emotional reactivity and regulation of negative self-beliefs in patients with SAD. Sixteen patients underwent functional MRI while reacting to negative self-beliefs and while regulating negative emotions using 2 types of attention deployment emotion regulation—breath-focused attention and distraction-focused attention. Post-MBSR, 14 patients completed neuroimaging assessments. Compared with baseline, MBSR completers showed improvement in anxiety and depression symptoms and self-esteem. During the breath-focused attention task (but not the distraction-focused attention task), they also showed (a) decreased negative emotion experience, (b) reduced amygdala activity, and (c) increased activity in brain regions implicated in attentional deployment. MBSR training in patients with SAD may reduce emotional reactivity while enhancing emotion regulation. These changes might facilitate reduction in SAD-related avoidance behaviors, clinical symptoms, and automatic emotional reactivity to negative self-beliefs in adults with SAD. PMID:20141305

Adsorbed poly(aspartate) coating limits the adverse effects of dissolved groundwater solutes on Fe0 nanoparticle reactivity with trichloroethylene.

PubMed

Phenrat, Tanapon; Schoenfelder, Daniel; Kirschling, Teresa L; Tilton, Robert D; Lowry, Gregory V

2018-03-01

For in situ groundwater remediation, polyelectrolyte-modified nanoscale zerovalent iron particles (NZVIs) have to be delivered into the subsurface, where they degrade pollutants such as trichloroethylene (TCE). The effect of groundwater organic and ionic solutes on TCE dechlorination using polyelectrolyte-modified NZVIs is unexplored, but is required for an effective remediation design. This study evaluates the TCE dechlorination rate and reaction by-products using poly(aspartate) (PAP)-modified and bare NZVIs in groundwater samples from actual TCE-contaminated sites in Florida, South Carolina, and Michigan. The effects of groundwater solutes on short- and intermediate-term dechlorination rates were evaluated. An adsorbed PAP layer on the NZVIs appeared to limit the adverse effect of groundwater solutes on the TCE dechlorination rate in the first TCE dechlorination cycle (short-term effect). Presumably, the pre-adsorption of PAP "trains" and the Donnan potential in the adsorbed PAP layer prevented groundwater solutes from further blocking NZVI reactive sites, which appeared to substantially decrease the TCE dechlorination rate of bare NZVIs. In the second and third TCE dechlorination cycles (intermediate-term effect), TCE dechlorination rates using PAP-modified NZVIs increased substantially (~100 and 200%, respectively, from the rate of the first spike). The desorption of PAP from the surface of NZVIs over time due to salt-induced desorption is hypothesized to restore NZVI reactivity with TCE. This study suggests that NZVI surface modification with small, charged macromolecules, such as PAP, helps to restore NZVI reactivity due to gradual PAP desorption in groundwater.

Reaction Mechanism of Covalent Modification of Phosphatidylethanolamine Lipids by Reactive Aldehydes 4-Hydroxy-2-nonenal and 4-Oxo-2-nonenal.

PubMed

Vazdar, Katarina; Vojta, Danijela; Margetić, Davor; Vazdar, Mario

2017-03-20

4-Hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) are biologically important reactive aldehydes formed during oxidative stress in phospholipid bilayers. They are highly reactive species due to presence of several reaction centers and can react with amino acids in peptides and proteins, as well as phosphoethanolamine (PE) lipids, thus modifying their biological activity. The aim of this work is to study in a molecular detail the reactivity of HNE and ONE toward PE lipids in a simplified system containing only lipids and reactive aldehydes in dichloromethane as an inert solvent. We use a combination of quantum chemical calculations, 1 H NMR measurements, FT-IR spectroscopy, and mass spectrometry experiments and show that for both reactive aldehydes two types of chemical reactions are possible: formation of Michael adducts and Schiff bases. In the case of HNE, an initially formed Michael adduct can also undergo an additional cyclization step to a hemiacetal derivative, whereas no cyclization occurs in the case of ONE and a Michael adduct is identified. A Schiff base product initially formed when HNE is added to PE lipid can also further cyclize to a pyrrole derivative in contrast to ONE, where only a Schiff base product is isolated. The suggested reaction mechanism by quantum-chemical calculations is in a qualitative agreement with experimental yields of isolated products and is also additionally investigated by 1 H NMR measurements, FT-IR spectroscopy, and mass spectrometry experiments.

Investigation of Ag-TiO2 nanostructures photocatalytic properties prepared by modified dip coating method

NASA Astrophysics Data System (ADS)

AlArfaj, Esam

2016-05-01

In this article, titanium dioxide and silver nanostructures were deposited on glass substrates using modified sol-gel methods and dip-coating technique. The films were characterised chemically and physically using different techniques (TLC, UV-Vis and XRD) and tested for environmental applications regarding degradation of aromatic hydrocarbons. The photocatalytic activity of the TiO2 nanostructures is tested with different small concentrations of phenol in water and reaction mechanisms discussed. Considerable enhancement is observed in the photodegradation activity of Ag-modified (3 wt.%) TiO2 compared to unmodified TiO2 nanostructures for phenol concentrations within the pseudo-first-order Langmuir-Hinshelwood (LH) model for reaction kinetics. The pseudo-first-order global degradation rate constant increased from <0.005 min-1 for TiO2 to 0.013 min-1 for 3 mol% Ag-modified TiO2. The enhancement is attributed to the incorporation of Ag which promotes the generation of reactive oxygen species and increases the carrier recombination life-time. In addition, Ag has been observed to extend the absorption to the visible region by its surface plasmon resonances and to suppress the anatase-rutile phase transformation. Moreover, TiO2 grain size prepared was found to be 10 nm which maximises the active surface area. For phenol initial concentrations as low as 0.0002 M, saturation trend in the degradation process occurred at 0.00014 M and the reaction rate can be fitted with half-order LH kinetics.

Detecting T-cell reactivity to whole cell vaccines

PubMed Central

Brusic, Ana; Hainz, Ursula; Wadleigh, Martha; Neuberg, Donna; Su, Mei; Canning, Christine M.; DeAngelo, Daniel J.; Stone, Richard M.; Lee, Jeng-Shin; Mulligan, Richard C.; Ritz, Jerome; Dranoff, Glenn; Sasada, Tetsuro; Wu, Catherine J.

2012-01-01

BCR-ABL+ K562 cells hold clinical promise as a component of cancer vaccines, either as bystander cells genetically modified to express immunostimulatory molecules, or as a source of leukemia antigens. To develop a method for detecting T-cell reactivity against K562 cell-derived antigens in patients, we exploited the dendritic cell (DC)-mediated cross-presentation of proteins generated from apoptotic cells. We used UVB irradiation to consistently induce apoptosis of K562 cells, which were then fed to autologous DCs. These DCs were used to both stimulate and detect antigen-specific CD8+ T-cell reactivity. As proof-of-concept, we used cross-presented apoptotic influenza matrix protein-expressing K562 cells to elicit reactivity from matrix protein-reactive T cells. Likewise, we used this assay to detect increased anti-CML antigen T-cell reactivity in CML patients that attained long-lasting clinical remissions following immunotherapy (donor lymphocyte infusion), as well as in 2 of 3 CML patients vaccinated with lethally irradiated K562 cells that were modified to secrete high levels of granulocyte macrophage colony-stimulating factor (GM-CSF). This methodology can be readily adapted to examine the effects of other whole tumor cell-based vaccines, a scenario in which the precise tumor antigens that stimulate immune responses are unknown. PMID:23170257

Simulations of the modified gap experiment

NASA Astrophysics Data System (ADS)

Sutherland, Gerrit T.; Benjamin, Richard; Kooker, Douglas

2017-01-01

Modified gap experiment (test) hydrocode simulations predict the trends seen in experimental excess free surface velocity versus input pressure curves for explosives with both large and modest failure diameters. Simulations were conducted for explosive "A", an explosive with a large failure diameter, and for cast TNT, which has a modest failure diameter. Using the best available reactive rate models, the simulations predicted sustained ignition thresholds similar to experiment. This is a threshold where detonation is likely given a long enough run distance. For input pressures greater than the sustained ignition threshold pressure, the simulations predicted too little velocity for explosive "A" and too much velocity for TNT. It was found that a better comparison of experiment and simulation requires additional experimental data for both explosives. It was observed that the choice of reactive rate model for cast TNT can lead to large differences in the predicted modified gap experiment result. The cause of the difference is that the same data was not used to parameterize both models; one set of data was more shock reactive than the other.

The Acoculco caldera magmas: genesis, evolution and relation with the Acoculco geothermal system

NASA Astrophysics Data System (ADS)

Sosa-Ceballos, G.; Macías, J. L.; Avellán, D.

2017-12-01

The Acoculco Caldera Complex (ACC) is located at the eastern part of the Trans Mexican Volcanic Belt; México. This caldera complex have been active since 2.7 Ma through reactivations of the system or associated magmatism. Therefore the ACC is an excellent case scenario to investigate the relation between the magmatic heat supply and the evolution processes that modified magmatic reservoirs in a potential geothermal field. We investigated the origin and the magmatic processes (magma mixing, assimilation and crystallization) that modified the ACC rocks by petrography, major oxides-trace element geochemistry, and isotopic analysis. Magma mixing is considered as the heat supply that maintain active the magmatic system, whereas assimilation yielded insights about the depth at which processes occurred. In addition, we performed a series of hydrothermal experiments in order to constrain the storage depth for the magma tapped during the caldera collapse. Rocks from the ACC were catalogued as pre, syn and post caldera. The post caldera rocks are peralkaline rhyolites, in contrast to all other rocks that are subalkaline. Our investigation is focus to investigate if the collapse modified the plumbing system and the depth at which magmas stagnate and recorded the magmatic processes.

Multifunctional Pt(II) Reagents: Covalent Modifications of Pt Complexes Enable Diverse Structural Variation and In-Cell Detection.

PubMed

White, Jonathan D; Haley, Michael M; DeRose, Victoria J

2016-01-19

To enhance the functionality of Pt-based reagents, several strategies have been developed that utilize Pt compounds modified with small, reactive handles. This Account encapsulates work done by us and other groups regarding the use of Pt(II) compounds with reactive handles for subsequent elaboration with fluorophores or other functional moieties. Described strategies include the incorporation of substituents for well-known condensation or nucleophilic displacement-type reactions and their use, for example, to tether spectroscopic handles to Pt reagents for in vivo investigation. Other chief uses of displacement-type reactions have included tethering various small molecules exhibiting pharmacological activity directly to Pt, thus adding synergistic effects. Click chemistry-based ligation techniques have also been applied, primarily with azide- and alkyne-appended Pt complexes. Orthogonally reactive click chemistry reactions have proven invaluable when more traditional nucleophilic displacement reactions induce side-reactivity with the Pt center or when systematic functionalization of a larger number of Pt complexes is desired. Additionally, a diverse assortment of Pt-fluorophore conjugates have been tethered via click chemistry conjugation. In addition to providing a convenient synthetic path for diversifying Pt compounds, the use of click-capable Pt complexes has proved a powerful strategy for postbinding covalent modification and detection with fluorescent probes. This strategy bypasses undesirable influences of the fluorophore camouflaged as reactivity due to Pt that may be present when detecting preattached Pt-fluorophore conjugates. Using postbinding strategies, Pt reagent distributions in HeLa and lung carcinoma (NCI-H460) cell cultures were observed with two different azide-modified Pt compounds, a monofunctional Pt(II)-acridine type and a difunctional Pt(II)-neutral complex. In addition, cellular distribution was observed with an alkyne-appended difunctional Pt(II)-neutral complex analogous in structure to the aforementioned difunctional azide-Pt(II) reagent. In all cases, significant accumulation of Pt in the nucleolus of cells was observed, in addition to broader localization in the nucleus and cytoplasm of the cell. Using the same strategy of postbinding click modification with fluorescent probes, Pt adducts were detected and roughly quantified on rRNA and tRNA from Pt-treated Saccharomyces cerevisiae; rRNA adducts were found to be relatively long-lived and not targeted for immediate degradation. Finally, the utility and feasibility of the alkyne-appended Pt(II) compound has been further demonstrated with a turn-on fluorophore, dansyl azide, in fluorescent detection of DNA in vitro. In all, these modifications utilizing reactive handles have allowed for the diversification of new Pt reagents, as well as providing cellular localization information on the modified Pt compounds.

Study of the Photodynamic Activity of N-Doped TiO2 Nanoparticles Conjugated with Aluminum Phthalocyanine

PubMed Central

Pan, Xiaobo; Liang, Xinyue; Yao, Longfang; Wang, Xinyi; Jing, Yueyue; Fei, Yiyan; Chen, Li

2017-01-01

TiO2 nanoparticles modified with phthalocyanines (Pc) have been proven to be a potential photosensitizer in the application of photodynamic therapy (PDT). However, the generation of reactive oxygen species (ROS) by TiO2 nanoparticles modified with Pc has not been demonstrated clearly. In this study, nitrogen-doped TiO2 conjugated with Pc (N-TiO2-Pc) were studied by means of monitoring the generation of ROS. The absorbance and photokilling effect on HeLa cells upon visible light of different regions were also studied and compared with non-doped TiO2-Pc and Pc. Both N-TiO2-Pc and TiO2-Pc can be activated by visible light and exhibited much higher photokilling effect on HeLa cells than Pc. In addition, nitrogen-doping can greatly enhance the formation of 1O2 and •O2−, while it suppresses the generation of OH•. This resulted in significant photodynamic activity. Therefore, N-TiO2-Pc can be an excellent candidate for a photosensitizer in PDT with wide-spectrum visible irradiation. PMID:29053580

Rate and Selectivity Control in Thioether and Alkene Oxidation with H 2 O 2 over Phosphonate-Modified Niobium(V)-Silica Catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thornburg, Nicholas E.; Notestein, Justin M.

Supported metal oxide catalysts are versatile materials for liquid-phase oxidations, including alkene epoxidation and thioether sulfoxidation with H2O2. Periodic trends in H2O2 activation was recently demonstrated for alkene epoxidation, highlighting Nb-SiO2 as a more active and selective catalyst than Ti-SiO2. Three representative catalysts are studied consisting of NbV, TiIV, and ZrIV on silica, each made through a molecular precursor approach that yields highly dispersed oxide sites, for thioanisole oxidation by H2O2. Initial rates trend Nb>Ti>>Zr, as for epoxidation, and Nb outperforms Ti for a number of other thioethers. In contrast, selectivity to sulfoxide vs. sulfone trends Ti>Nb>>Zr at all conversions.more » Modifying the Nb-SiO2 catalyst with phenylphosphonic acid does not completely remove sulfoxidation reactivity, as it did for photooxidation and epoxidation, and results in an unusual material active for sulfoxidation but neither epoxidation nor overoxidation to the sulfone.« less

Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer.

PubMed

McMillan, Donald C; Crozier, Joseph E M; Canna, Khalid; Angerson, Wilson J; McArdle, Colin S

2007-08-01

The aim of the study was to examine the value of the combination of an elevated C-reactive protein and hypoalbuminaemia (GPS) in predicting cancer-specific survival after resection for colon and rectal cancer. The GPS was constructed as follows: Patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminaemia (<35 g/l) were allocated a score of 2. Patients in whom only one or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. A GPS of 1 (n = 109) was mainly due to an elevated C-reactive protein concentration and the remainder due to hypoalbuminaemia. In those patients with a GPS of 1 due to hypoalbuminaemia (n = 16), the 3-year overall survival rate was 94% compared with 62% in those patients with a GPS of 1 due to an elevated C-reactive protein concentration (n = 93, p = 0.0094). Therefore, the GPS was modified such that patients with hypoalbuminaemia were assigned a score of 0 in the absence of an elevated C-reactive protein. On univariate analysis of those patients with colon and rectal cancer, the modified GPS (p < 0.0001) was significantly associated with overall and cancer specific survival. On univariate survival analysis of those patients with Dukes B colon and rectal cancer, the modified GPS (p < 0.01) was significantly associated with overall and cancer specific survival. The results of the present study indicate that the GPS, before surgery, predicts overall and cancer-specific survival after resection of colon and rectal cancer.

Increasing the hydrolysis constant of the reactive site upon introduction of an engineered Cys¹⁴-Cys³⁹ bond into the ovomucoid third domain from silver pheasant.

PubMed

Hemmi, Hikaru; Kumazaki, Takashi; Kojima, Shuichi; Yoshida, Takuya; Ohkubo, Tadayasu; Yokosawa, Hideyoshi; Miura, Kin-Ichiro; Kobayashi, Yuji

2011-08-01

P14C/N39C is the disulfide variant of the ovomucoid third domain from silver pheasant (OMSVP3) introducing an engineered Cys¹⁴-Cys³⁹ bond near the reactive site on the basis of the sequence homology between OMSVP3 and ascidian trypsin inhibitor. This variant exhibits a narrower inhibitory specificity. We have examined the effects of introducing a Cys¹⁴-Cys³⁹ bond into the flexible N-terminal loop of OMSVP3 on the thermodynamics of the reactive site peptide bond hydrolysis, as well as the thermal stability of reactive site intact inhibitors. P14C/N39C can be selectively cleaved by Streptomyces griseus protease B at the reactive site of OMSVP3 to form a reactive site modified inhibitor. The conversion rate of intact to modified P14C/N39C is much faster than that for wild type under any pH condition. The pH-independent hydrolysis constant (K(hyd) °) is estimated to be approximately 5.5 for P14C/N39C, which is higher than the value of 1.6 for natural OMSVP3. The reactive site modified form of P14C/N39C is thermodynamically more stable than the intact one. Thermal denaturation experiments using intact inhibitors show that the temperature at the midpoint of unfolding at pH 2.0 is 59 °C for P14C/N39C and 58 °C for wild type. There have been no examples, except P14C/N39C, where introducing an engineered disulfide causes a significant increase in K(hyd) °, but has no effect on the thermal stability. The site-specific disulfide introduction into the flexible N-terminal loop of natural Kazal-type inhibitors would be useful to further characterize the thermodynamics of the reactive site peptide bond hydrolysis. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.

Foundations for Streaming Model Transformations by Complex Event Processing.

PubMed

Dávid, István; Ráth, István; Varró, Dániel

2018-01-01

Streaming model transformations represent a novel class of transformations to manipulate models whose elements are continuously produced or modified in high volume and with rapid rate of change. Executing streaming transformations requires efficient techniques to recognize activated transformation rules over a live model and a potentially infinite stream of events. In this paper, we propose foundations of streaming model transformations by innovatively integrating incremental model query, complex event processing (CEP) and reactive (event-driven) transformation techniques. Complex event processing allows to identify relevant patterns and sequences of events over an event stream. Our approach enables event streams to include model change events which are automatically and continuously populated by incremental model queries. Furthermore, a reactive rule engine carries out transformations on identified complex event patterns. We provide an integrated domain-specific language with precise semantics for capturing complex event patterns and streaming transformations together with an execution engine, all of which is now part of the Viatra reactive transformation framework. We demonstrate the feasibility of our approach with two case studies: one in an advanced model engineering workflow; and one in the context of on-the-fly gesture recognition.

Measuring the reactivity of a silicon-terminated probe

NASA Astrophysics Data System (ADS)

Sweetman, Adam; Stirling, Julian; Jarvis, Samuel Paul; Rahe, Philipp; Moriarty, Philip

2016-09-01

It is generally accepted that the exposed surfaces of silicon crystals are highly reactive due to the dangling bonds which protrude into the vacuum. However, surface reconstruction not only modifies the reactivity of bulk silicon crystals, but also plays a key role in determining the properties of silicon nanocrystals. In this study we probe the reactivity of silicon clusters at the end of a scanning probe tip by examining their interaction with closed-shell fullerene molecules. Counter to intuitive expectations, many silicon clusters do not react strongly with the fullerene cage, and we find that only specific highly oriented clusters have sufficient reactivity to break open the existing carbon-carbon bonds.

Studies of the kinetics and mechanisms of perfluoroether reactions on iron and oxidized iron surfaces

NASA Technical Reports Server (NTRS)

Napier, Mary E.; Stair, Peter C.

1992-01-01

Polymeric perfluoroalkylethers are being considered for use as lubricants in high temperature applications, but have been observed to catalytically decompose in the presence of metals. X-ray photoelectron spectroscopy (XPS) and temperature programmed desorption (TPD) were used to explore the decomposition of three model fluorinated ethers on clean polycrystalline iron surfaces and iron surfaces chemically modified with oxygen. Low temperature adsorption of the model fluorinated ethers on the clean, oxygen modified and oxidized iron surfaces was molecular. Thermally activated defluorination of the three model compounds was observed on the clean iron surface at remarkably low temperatures, 155 K and below, with formation of iron fluoride. Preferential C-F bond scission occurred at the terminal fluoromethoxy, CF3O, of perfluoro-1-methoxy-2-ethoxy ethane and perfluoro-1-methoxy-2-ethoxy propane and at CF3/CF2O of perfluoro-1,3-diethoxy propane. The reactivity of the clean iron toward perfluoroalkylether decomposition when compared to other metals is due to the strength of the iron fluoride bond and the strong electron donating ability of the metallic iron. Chemisorption of an oxygen overlayer lowered the reactivity of the iron surface to the adsorption and decomposition of the three model fluorinated ethers by blocking active sites on the metal surface. Incomplete coverage of the iron surface with chemisorbed oxygen results in a reaction which resembles the defluorination reaction observed on the clean iron surface. Perfluoro-1-methoxy-2-ethoxy ethane reacts on the oxidized iron surface at 138 K, through a Lewis acid assisted cleavage of the carbon oxygen bond, with preferential attack at the terminal fluoromethoxy, CF3O. The oxidized iron surface did not passivate, but became more reactive with time. Perfluoro-1-methoxy-2-ethoxy propane and perfluoro-1,3-diethoxy propane desorbed prior to the observation of decomposition on the oxidized iron surface.

Herbal bioactivation: the good, the bad and the ugly.

PubMed

Zhou, Shufeng; Koh, Hwee-Ling; Gao, Yihuai; Gong, Zhi-yuan; Lee, Edmund Jon Deoon

2004-01-09

It has been well established that the formation of reactive metabolites of drugs is associated with drug toxicity. Similarly, there are accumulating data suggesting the role of the formation of reactive metabolites/intermediates through bioactivation in herbal toxicity and carcinogenicity. It has been hypothesized that the resultant reactive metabolites following herbal bioactivation covalently bind to cellular proteins and DNA, leading to toxicity via multiple mechanisms such as direct cytotoxicity, oncogene activation, and hypersensitivity reactions. This is exemplified by aristolochic acids present in Aristolochia spp, undergoing reduction of the nitro group by hepatic cytochrome P450 (CYP1A1/2) or peroxidases in extrahepatic tissues to reactive cyclic nitrenium ion. The latter was capable of reacting with DNA and proteins, resulting in activation of H-ras oncogene, gene mutation and finally carcinogenesis. Other examples are pulegone present in essential oils from many mint species; and teucrin A, a diterpenoid found in germander (Teuchrium chamaedrys) used as an adjuvant to slimming diets. Extensive pulegone metabolism generated p-cresol that was a glutathione depletory, and the furan ring of the diterpenoids in germander was oxidized by CYP3A4 to reactive epoxide which reacts with proteins such as CYP3A and epoxide hydrolase. On the other hand, some herbal/dietary constituents were shown to form reactive intermediates capable of irreversibly inhibiting various CYPs. The resultant metabolites lead to CYP inactivation by chemical modification of the heme, the apoprotein, or both as a result of covalent binding of modified heme to the apoprotein. Some examples include bergamottin, a furanocoumarin of grapefruit juice; capsaicin from chili peppers; glabridin, an isoflavan from licorice root; isothiocyanates found in all cruciferous vegetables; oleuropein rich in olive oil; dially sulfone found in garlic; and resveratrol, a constituent of red wine. CYPs have been known to metabolize more than 95% therapeutic drugs and activate a number of procarcinogens as well. Therefore, mechanism-based inhibition of CYPs may provide an explanation for some reported herb-drug interactions and chemopreventive activity of herbs. Due to the wide use and easy availability of herbal medicines, there is increasing concern about herbal toxicity. The safety and quality of herbal medicine should be ensured through greater research, pharmacovigilance, greater regulatory control and better communication between patients and health professionals.

STRUCTURAL CHANGES IN SURFACTANT-MODIFIED SORBENTS DURING FURNACE INJECTION

EPA Science Inventory

A calcium hydroxide [Ca(OH)2] sorbent modified by the addition of calcium lignosulfonate has recently been developed for use in the Environmental Protection Agency's limestone injection multistage burner process. The increased reactivity with sulfur dioxide (SO2) displayed by thi...

Active oligonucleotides incorporating alkylating an agent as potential sequence- and base selective modifier of gene expression.

PubMed

Sasaki, S

2001-04-01

A number of cross-linking (alkylating) agents have been developed and incorporated into the oligonulceotides for sequence selective control of gene expression. Recently, potential application of such active oligonucleotides has been expanding from use for improvement of inhibition efficiency to new biotechnology that may enable chemical alteration of genetic information. These interests in active oligonucleotides have encouraged the generation of new cross-linking agents that exhibit high efficiency for application of either in vitro or in vivo. This mini review summarizes structures of alkylating agents, in particular, a new basic skeleton for cross-linking, a 2'-deoxyribose derivative of 2-amino-6-vinylpurine that has been recently developed by the author's group. The 2-amino-6-vinylpurine has been shown to form a complex with cytidine under acidic conditions, and brings the vinyl and the amino reactive groups into proximity to achieve efficient alkylation. A new strategy was designed so that the reactivity of 2-amino-6-vinylpurine can be induced from the corresponding phenylsulfoxide derivative within a duplex with the complementary strand. The validity of the new strategy has been proven by achievement of cytidine-selective cross-linking with remarkably efficiency.

A Generalizable Platform for Interrogating Target- and Signal-Specific Consequences of Electrophilic Modifications in Redox-Dependent Cell Signaling

PubMed Central

Lin, Hong-Yu; Haegele, Joseph A.; Disare, Michael T.; Lin, Qishan; Aye, Yimon

2015-01-01

Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized “electrophile toolbox” with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology—T-REX (targetable reactive electrophiles & oxidants)—is established by: (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein—one of several redox-sensitive regulators of the Nrf2–ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2–ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background. PMID:25909755

A generalizable platform for interrogating target- and signal-specific consequences of electrophilic modifications in redox-dependent cell signaling.

PubMed

Lin, Hong-Yu; Haegele, Joseph A; Disare, Michael T; Lin, Qishan; Aye, Yimon

2015-05-20

Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.

Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: a modified kinetic approach.

PubMed

Worek, Franz; Wille, Timo; Aurbek, Nadine; Eyer, Peter; Thiermann, Horst

2010-12-15

Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary high MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning. Copyright © 2010 Elsevier Inc. All rights reserved.

Enhanced activity and stability of copper oxide/γ-alumina catalyst in catalytic wet-air oxidation: Critical roles of cerium incorporation

NASA Astrophysics Data System (ADS)

Zhang, Yongli; Zhou, Yanbo; Peng, Chao; Shi, Junjun; Wang, Qingyu; He, Lingfeng; Shi, Liang

2018-04-01

By successive impregnation method, the Ce-modified Cu-O/γ-Al2O3 catalyst was prepared and characterized using nitrogen adsorption-desorption, scanning electron microscopy energy dispersive X-ray analysis (SEM-EDS), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman, and H2-Temperature programming reduction (H2-TPR). In catalytic wet-air oxidation (CWAO) process for the printing and dyeing wastewater (PDW), the effects of Ce addition on performance, mechanism and kinetics of the catalyst were investigated. The Ce addition increases the Brunauer-Emmett-Teller (BET) surface area and pore volume of the catalyst and makes the active components uniformly distributed on the catalyst surface. Formation of a stable CuAl2O4 solid solution by anchoring Cu onto the γ-Al2O3 crystal lattice leads to a significant decrease in metal leaching of the Ce-modified catalyst. The proportion of lattice oxygen in the catalyst substantially increases and the apparent activation energy of Cu-O/γ-Al2O3 catalyst decreases owing to Ce addition. Therefore, the catalytic activity and stability of the Ce-modified catalyst are considerably improved. The scavengers experiments identify the active species existed in the CWAO reaction system, with the order of reactivity: h+ > O2•- > H2O2 > HO•. This novel Cu-Ce-O/γ-Al2O3 catalyst has great potential in applications for treatment of concentrated organic wastewater due to its superior catalytic activity and improved stability.

Thiol-Based Redox Switches and Gene Regulation

PubMed Central

2011-01-01

Abstract Cysteine is notable among the universal, proteinogenic amino acids for its facile redox chemistry. Cysteine thiolates are readily modified by reactive oxygen species (ROS), reactive electrophilic species (RES), and reactive nitrogen species (RNS). Although thiol switches are commonly triggered by disulfide bond formation, they can also be controlled by S-thiolation, S-alkylation, or modification by RNS. Thiol-based switches are common in both prokaryotic and eukaryotic organisms and activate functions that detoxify reactive species and restore thiol homeostasis while repressing functions that would be deleterious if expressed under oxidizing conditions. Here, we provide an overview of the best-understood examples of thiol-based redox switches that affect gene expression. Intra- or intermolecular disulfide bond formation serves as a direct regulatory switch for several bacterial transcription factors (OxyR, OhrR/2-Cys, Spx, YodB, CrtJ, and CprK) and indirectly regulates others (the RsrA anti-σ factor and RegB sensory histidine kinase). In eukaryotes, thiol-based switches control the yeast Yap1p transcription factor, the Nrf2/Keap1 electrophile and oxidative stress response, and the Chlamydomonas NAB1 translational repressor. Collectively, these regulators reveal a remarkable range of chemical modifications exploited by Cys residues to effect changes in gene expression. Antioxid. Redox Signal. 14, 1049—1063. PMID:20626317

Kinetic characterization of factor Xa binding using a quenched fluorescent substrate based on the reactive site of factor Xa inhibitor from Bauhinia ungulata seeds.

PubMed

Oliva, M L V; Andrade, S A; Juliano, M A; Sallai, R C; Torquato, R J; Sampaio, M U; Pott, V J; Sampaio, C A M

2003-07-01

The specific Kunitz Bauhinia ungulata factor Xa inhibitor (BuXI) and the Bauhinia variegata trypsin inhibitor (BvTI) blocked the activity of trypsin, chymotrypsin, plasmin, plasma kallikrein and factor XIIa, and factor Xa inhibition was achieved only by BuXI (K(i) 14 nM). BuXI and BvTI are highly homologous (70%). The major differences are the methionine residues at BuXI reactive site, which are involved in the inhibition, since the oxidized protein no longer inhibits factor Xa but maintains the trypsin inhibition. Quenched fluorescent substrates based on the reactive site sequence of the inhibitors were synthesized and the kinetic parameters of the hydrolysis were determined using factor Xa and trypsin. The catalytic efficiency k(cat)/K(m) 4.3 x 10(7) M(-1)sec(>-1) for Abz-VMIAALPRTMFIQ-EDDnp (lead peptide) hydrolysis by factor Xa was 10(4)-fold higher than that of Boc-Ile-Glu-Gly-Arg-AMC, widely used as factor Xa substrate. Lengthening of the substrate changed its susceptibility to factor Xa hydrolysis. Both methionine residues in the substrate influence the binding to factor Xa. Serine replacement of threonine (P(1)') decreases the catalytic efficiency by four orders of magnitude. Factor Xa did not hydrolyze the substrate containing the reactive site sequence of BvTI, that inhibits trypsin inhibitor but not factor Xa. Abz-VMIAALPRTMFIQ-EDDnp prolonged both the prothrombin time and the activated partial thromboplastin time, and the other modified substrates used in this experiment altered blood-clotting assays.

Reactive oxygen species are key mediators of the nitric oxide apoptotic pathway in anterior pituitary cells.

PubMed

Machiavelli, Leticia I; Poliandri, Ariel H; Quinteros, Fernanda A; Cabilla, Jimena P; Duvilanski, Beatriz H

2007-03-01

We previously showed that long-term exposure of anterior pituitary cells to nitric oxide (NO) induces apoptosis. The intracellular signals underlying this effect remained unclear. In this study, we searched for possible mechanisms involved in the early stages of the NO apoptotic cascade. Caspase 3 was activated by NO with no apparent disruption of mitochondrial membrane potential. NO caused a rapid increase of reactive oxygen species (ROS), and this increase seems to be dependent of mitochondrial electron transport chain. The antioxidant N-acetyl-cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and reduced the NO apoptotic effect. Catalase was inactivated by NO, while glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not modified at first, but increased at later times of NO exposure. The increase of GSH level is important for the scavenging of the NO-induced ROS overproduction. Our results indicate that ROS have an essential role as a trigger of the NO apoptotic cascade in anterior pituitary cells. The permanent inhibition of catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH level augment in response to the oxidative damage, though this increase seems not to be enough to rescue the cells from the NO effect.

Possible mechanisms of dose-dependent cough suppressive effect of Althaea officinalis rhamnogalacturonan in guinea pigs test system.

PubMed

Sutovská, M; Nosálová, G; Sutovský, J; Franová, S; Prisenznáková, L; Capek, P

2009-07-01

The rhamnogalacturonan, isolated from the roots of medicinal plant Althaea officinalis L., showed various biological effects on the citric acid-induced cough reflex and reactivity of airways smooth muscle in vitro and in vivo conditions. It possessed dose-dependent cough suppression effect comparable with opioid agonist codeine. However, reactivity of the airways smooth muscle, measured in vitro as well as in vivo conditions was not significantly affected by rhamnogalacturonan and thus bronchodilatory activity did not participate in the cough suppression effect of polysaccharide tested. Moreover, the cough suppression effect of the polymer was not significantly modified by pretreatment of K(+)(ATP) ion channels with selective antagonist and therefore activation of this type of ion channels is not involved in the mechanism of rhamnogalacturonan cough suppressive ability. On the contrary, pretreatment of animals with selective 5-HT(2) receptors antagonist significantly decreased rhamnogalacturonan antitussive efficacy. From this point of view it seems that the cough suppression effect of the polymer is associated with the serotonergic 5-HT(2) receptor's function.

Mild and modular surface modification of cellulose via hetero Diels-Alder (HDA) cycloaddition.

PubMed

Goldmann, Anja S; Tischer, Thomas; Barner, Leonie; Bruns, Michael; Barner-Kowollik, Christopher

2011-04-11

A combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and hetero Diels-Alder (HDA) cycloaddition was used to effect, under mild (T ≈ 20 °C), fast, and modular conditions, the grafting of poly(isobornyl acrylate) (M(n) = 9800 g mol(-1), PDI = 1.19) onto a solid cellulose substrate. The active hydroxyl groups expressed on the cellulose fibers were converted to tosylate leaving groups, which were subsequently substituted by a highly reactive cyclopentadienyl functionality (Cp). By employing the reactive Cp-functionality as a diene, thiocarbonyl thio-capped poly(isobornyl acrylate) synthesized via RAFT polymerization (mediated by benzyl pyridine-2-yldithioformiate (BPDF)) was attached to the surface under ambient conditions by an HDA cycloaddition (reaction time: 15 h). The surface-modified cellulose samples were analyzed in-depth by X-ray photoelectron spectroscopy, scanning electron microscopy, elemental analysis, Fourier transform infrared (FT-IR) spectroscopy as well as Fourier transform infrared microscopy employing a focal plane array detector for imaging purposes. The analytical results provide strong evidence that the reaction of suitable dienophiles with Cp-functional cellulose proceeds under mild reaction conditions (T ≈ 20 °C) in an efficient fashion. In particular, the visualization of individual modified cellulose fibers via high-resolution FT-IR microscopy corroborates the homogeneous distribution of the polymer film on the cellulose fibers.

Responses of human birch pollen allergen-reactive T cells to chemically modified allergens (allergoids).

PubMed

Dormann, D; Ebner, C; Jarman, E R; Montermann, E; Kraft, D; Reske-Kunz, A B

1998-11-01

Allergoids are widely used in specific immunotherapy for the treatment of IgE-mediated allergic diseases. The aim of this study was to analyse whether a modification of birch pollen allergens with formaldehyde affects the availability of T-cell epitopes. Efficient modification of the allergens was verified by determining IgE and IgG binding activity using ELISA inhibition tests. T-cell responses to birch pollen allergoids were analysed in polyclonal systems, using peripheral blood mononuclear cells (PBMC) of five birch pollen-allergic individuals, as well as birch pollen extract-reactive T-cell lines (TCL), established from the peripheral blood of 14 birch pollen-allergic donors. To determine whether the modification of natural (n)Bet v 1 with formaldehyde or maleic anhydride results in epitope-specific changes in T-cell reactivities, 22 Bet v 1-specific T-cell clones (TCC), established from nine additional birch pollen-allergic individuals, were tested for their reactivity with these products. The majority of PBMC and TCL showed a reduced response to the birch pollen extract allergoid. Bet v 1-specific TCC could be divided into allergoid-reactive and -non-reactive TCC. No simple correlation between possible modification sites of formaldehyde in the respective T-cell epitopes and the stimulatory potential of the allergoid was observed. Mechanisms of suppression or of anergy induction were excluded as an explanation for the non-reactivity of representative TCC. All TCC could be stimulated by maleylated and unmodified nBet v 1 to a similar extent. These results demonstrate differences in the availability of T-cell epitopes between allergoids and unmodified allergens, which are most likely due to structural changes within the allergen molecule.

Cytosolic Irradiation of Femtosecond Laser Induces Mitochondria-dependent Apoptosis-like Cell Death via Intrinsic Reactive Oxygen Cascades

PubMed Central

Yoon, Jonghee; Ryu, Seung-wook; Lee, Seunghee; Choi, Chulhee

2015-01-01

High-intensity femtosecond lasers have recently been used to irreversibly disrupt nanoscale structures, such as intracellular organelles, and to modify biological functions in a reversible manner: so-called nanosurgery and biophotomodulation. Femtosecond laser pulses above the threshold intensity sufficient for reversible biophotomodulation can cause irreversible changes in the irradiated cell, eventually leading to cell death. Here, we demonstrated that cytosolic irradiation with a femtosecond laser produced intrinsic cascades of reactive oxygen species (ROS), which led to rapid apoptosis-like cell death via a caspase and poly (ADP-ribose) polymerase 1 (PARP-1) signaling pathway. We further showed that cells with enhanced mitochondrial fusion activity are more resilient to laser-induced stress compared to those with enforced mitochondrial fission. Taken together, these findings provide fundamental insight into how optical stimulation intervenes in intrinsic cellular signaling pathways and functions. PMID:25648455

Cytosolic irradiation of femtosecond laser induces mitochondria-dependent apoptosis-like cell death via intrinsic reactive oxygen cascades.

PubMed

Yoon, Jonghee; Ryu, Seung-Wook; Lee, Seunghee; Choi, Chulhee

2015-02-04

High-intensity femtosecond lasers have recently been used to irreversibly disrupt nanoscale structures, such as intracellular organelles, and to modify biological functions in a reversible manner: so-called nanosurgery and biophotomodulation. Femtosecond laser pulses above the threshold intensity sufficient for reversible biophotomodulation can cause irreversible changes in the irradiated cell, eventually leading to cell death. Here, we demonstrated that cytosolic irradiation with a femtosecond laser produced intrinsic cascades of reactive oxygen species (ROS), which led to rapid apoptosis-like cell death via a caspase and poly (ADP-ribose) polymerase 1 (PARP-1) signaling pathway. We further showed that cells with enhanced mitochondrial fusion activity are more resilient to laser-induced stress compared to those with enforced mitochondrial fission. Taken together, these findings provide fundamental insight into how optical stimulation intervenes in intrinsic cellular signaling pathways and functions.

Metal Oxide Nanoparticles: The Importance of Size, Shape, Chemical Composition, and Valence State in Determining Toxicity

NASA Astrophysics Data System (ADS)

Dunnick, Katherine

Nanoparticles, which are defined as a structure with at least one dimension between 1 and 100 nm, have the potential to be used in a variety of consumer products due to their improved functionality compared to similar particles of larger size. Their small size is associated with increased strength, improved catalytic properties, and increased reactivity; however, their size is also associated with increased toxicity in vitro and in vivo. Numerous toxicological studies have been conducted to determine the properties of nanomaterials that increase their toxicity in order to manufacture new nanomaterials with decreased toxicity. Data indicates that size, shape, chemical composition, and valence state of nanomaterials can dramatically alter their toxicity profile. Therefore, the purpose of this dissertation was to determine how altering the shape, size, and chemical composition of various metal oxide nanoparticles would affect their toxicity. Metal oxides are used in variety of consumer products, from spray-sun screens, to food coloring agents; thus, understanding the toxicity of metal oxides and determining which aspects affect their toxicity may provide safe alternatives nanomaterials for continued use in manufacturing. Tungstate nanoparticles toxicity was assessed in an in vitro model using RAW 264.7 cells. The size, shape, and chemical composition of these nanomaterials were altered and the effect on reactive oxygen species and general cytotoxicity was determined using a variety of techniques. Results demonstrate that shape was important in reactive oxygen species production as wires were able to induce significant reactive oxygen species compared to spheres. Shape, size, and chemical composition did not have much effect on the overall toxicity of these nanoparticles in RAW 264.7 cells over a 72 hour time course, implicating that the base material of the nanoparticles was not toxic in these cells. To further assess how chemical composition can affect toxicity, cerium oxide nanoparticles were chemically modified using a process known as doping, to alter their valence state. The size and shape of the cerium oxide nanoparticles remained constant. Overall, results indicated that cerium oxide was not toxic in both RLE-6TN and NR8383 pulmonary rat cells, however, chemically modifying the valence state of the nanomaterial did affect the antioxidant potential. To determine if this trend was measureable in vivo, rats were exposed to various cerium oxide nanoparticles via intratracheal instillation and damage, changes in pulmonary cell differentials, and phagocytic cell activity were assessed. Results implicate that chemically modifying the nanoparticles had an effect on the overall damage induced by the material but did not dramatically affect inflammatory potential or phagocytic cell activity. Overall the data from these studies imply that size, shape, chemical composition, and valence state of nanomaterials can be manipulated to alter their toxicity.

MODELING THE ATMOSPHERE FORMATION OF REACTIVE MERCURY IN FLORIDA AND THE GREAT LAKES

EPA Science Inventory

Reactive mercury in the troposphere is affected by a complex mix of local emissions, global-scale transport, and gas and aqueous-phase chemistry. Here, we describe a modified version of the EPA model for urban/regional air quality (CMAQ) to include the chemistry of mercury, and m...

Modified artificial bee colony algorithm for reactive power optimization

NASA Astrophysics Data System (ADS)

Sulaiman, Noorazliza; Mohamad-Saleh, Junita; Abro, Abdul Ghani

2015-05-01

Bio-inspired algorithms (BIAs) implemented to solve various optimization problems have shown promising results which are very important in this severely complex real-world. Artificial Bee Colony (ABC) algorithm, a kind of BIAs has demonstrated tremendous results as compared to other optimization algorithms. This paper presents a new modified ABC algorithm referred to as JA-ABC3 with the aim to enhance convergence speed and avoid premature convergence. The proposed algorithm has been simulated on ten commonly used benchmarks functions. Its performance has also been compared with other existing ABC variants. To justify its robust applicability, the proposed algorithm has been tested to solve Reactive Power Optimization problem. The results have shown that the proposed algorithm has superior performance to other existing ABC variants e.g. GABC, BABC1, BABC2, BsfABC dan IABC in terms of convergence speed. Furthermore, the proposed algorithm has also demonstrated excellence performance in solving Reactive Power Optimization problem.

Sexual Orientation Modulates Endocrine Stress Reactivity

PubMed Central

Juster, Robert-Paul; Hatzenbuehler, Mark L.; Mendrek, Adrianna; Pfaus, James G.; Smith, Nathan Grant; Johnson, Philip Jai; Lefebvre-Louis, Jean-Philippe; Raymond, Catherine; Marin, Marie-France; Sindi, Shireen; Lupien, Sonia J.; Pruessner, Jens C.

2015-01-01

BACKGROUND Biological sex differences and sociocultural gender diversity influence endocrine stress reactivity. Although numerous studies have shown that men typically activate stronger stress responses than women when exposed to laboratory-based psychosocial stressors, it is unclear whether sexual orientation further modulates stress reactivity. Given that lesbian, gay, and bisexual (LGB) individuals frequently report heightened distress secondary to stigma-related stressors, we investigated whether cortisol stress reactivity differs between LGB individuals and heterosexual individuals in response to a well-validated psychosocial stressor. METHODS The study population comprised 87 healthy adults (mean age, 25 years) who were grouped according to their biological sex and their gendered sexual orientation: lesbian/bisexual women (n = 20), heterosexual women (n = 21), gay/bisexual men (n = 26), and heterosexual men (n = 20). Investigators collected 10 salivary cortisol samples throughout a 2-hour afternoon visit involving exposure to the Trier Social Stress Test modified to maximize between-sex differences. RESULTS Relative to heterosexual women, lesbian/bisexual women showed higher cortisol stress reactivity 40 min after exposure to the stressor. In contrast, gay/bisexual men displayed lower overall cortisol concentrations throughout testing compared with heterosexual men. Main findings were significant while adjusting for sex hormones (estradiol-to-progesterone ratio in women and testosterone in men), age, self-esteem, and disclosure status (whether LGB participants had completed their “coming out”). CONCLUSIONS Our results provide novel evidence for gender-based modulation of cortisol stress reactivity based on sexual orientation that goes beyond well-established between-sex differences. This study raises several important avenues for future research related to the physiologic functioning of LGB populations and gender diversity more broadly. PMID:25444167

Mechanisms underlying hemodynamic and neuroendocrine stress reactivity at different phases of the menstrual cycle

PubMed Central

Gordon, Jennifer L.; Girdler, Susan S.

2014-01-01

This study examined the association of menstrual cycle phase with stress reactivity as well as the hormonal and neuroendocrine mechanisms contributing to cycle effects. Fifty-seven women underwent a modified Trier Social Stress Test (TSST) during the early follicular, late follicular and luteal phases of the menstrual cycle. Greater increases in cardiac index (CI) and greater decreases in vascular resistance index (VRI) during speech were observed in the luteal phase relative to other phases, while greater increases in epinephrine (EPI) was observed during the late follicular and luteal phases compared to the early follicular phase. Luteal phase estradiol predicted luteal EPI reactivity but not CI or VRI reactivity while luteal phase EPI reactivity predicted luteal phase CI and VRI reactivity. Thus, cycle-related changes in EPI reactivity may be a stronger determinant of cycle effects on hemodynamic reactivity than sex hormones per se. PMID:24397365

[Being physically active modifies the detrimental effect of sedentary behavior on obesity and cardiometabolic markers in adults].

PubMed

Salas, Carlos; Cristi-Montero, Carlos; Fan, Yu; Durán, Eliana; Labraña, Ana María; Martínez, María Adela; Leiva, Ana María; Alvarez, Cristian; Aguilar-Farías, Nicolás; Ramírez-Campillo, Rodrigo; Martínez, Ximena Díaz; Sanzana-Inzunza, Ruth; Celis-Morales, Carlos

2016-11-01

Sedentary behavior is a major risk factor for cardiovascular disease and mortality. To investigate whether the associations between sedentary behavior and cardiometabolic markers differs across physical activity levels. Cross sectional study of 314 participants aged 18 to 65 years. Body mass index (BMI) and waist circumference were measured, and body fat was derived from the sum of four skinfolds. Physical activity was measured objectively using accelerometers (Actigraph GT1M, USA®). A fasting blood sample was obtained to measure glucose, insulin, HOMA-IR, lipid profile and high sensitive C reactive protein (hsCRP). Those participants with an activity level > 600 MET.min-1.week-1 were classified as physically active. Thirty four percent of participants were physically inactive and spent an average of 8.7 h.day-1 in sedentary pursuits. Physically inactive individuals had poorer cardiometabolic health than their physically active counterparts. Per one hour decrease in overall sedentary behavior, there was a significant improvement in glucose (-8.46 and -4.68 mg.dl-1), insulin (-2.12 and -1.77 pmol.l-1), HOMA-IR (-0.81 and -0.56) BMI (-0.93 and -0.62 kg.m-2) and waist circumference (-2.32 and -1.65 cm) in physically active and inactive participants, respectively. Being physically active may modify the detrimental effects of sedentary behavior on cardiometabolic and obesity-related traits.

Protein oxidation and peroxidation

PubMed Central

Davies, Michael J.

2016-01-01

Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals and chain reactions with alcohols and carbonyls as major products; the latter are commonly used markers of protein damage. Direct oxidation of cysteine (and less commonly) methionine residues is a major reaction; this is typically faster than with H2O2, and results in altered protein activity and function. Unlike H2O2, which is rapidly removed by protective enzymes, protein peroxides are only slowly removed, and catabolism is a major fate. Although turnover of modified proteins by proteasomal and lysosomal enzymes, and other proteases (e.g. mitochondrial Lon), can be efficient, protein hydroperoxides inhibit these pathways and this may contribute to the accumulation of modified proteins in cells. Available evidence supports an association between protein oxidation and multiple human pathologies, but whether this link is causal remains to be established. PMID:27026395

Chemical modification of polyvinyl chloride and silicone elastomer in inhibiting adhesion of Aeromonas hydrophila.

PubMed

Kregiel, Dorota; Berlowska, Joanna; Mizerska, Urszula; Fortuniak, Witold; Chojnowski, Julian; Ambroziak, Wojciech

2013-07-01

Disease-causing bacteria of the genus Aeromonas are able to adhere to pipe materials, colonizing the surfaces and forming biofilms in water distribution systems. The aim of our research was to study how the modification of materials used commonly in the water industry can reduce bacterial cell attachment. Polyvinyl chloride and silicone elastomer surfaces were activated and modified with reactive organo-silanes by coupling or co-crosslinking silanes with the native material. Both the native and modified surfaces were tested using the bacterial strain Aeromonas hydrophila, which was isolated from the Polish water distribution system. The surface tension of both the native and modified surfaces was measured. To determine cell viability and bacterial adhesion two methods were used, namely plate count and luminometry. Results were expressed in colony-forming units (c.f.u.) and in relative light units (RLU) per cm(2). Almost all the chemically modified surfaces exhibited higher anti-adhesive and anti-microbial properties in comparison to the native surfaces. Among the modifying agents examined, poly[dimethylsiloxane-co-(N,N-dimethyl-N-n-octylammoniopropyl chloride) methylsiloxane)] terminated with hydroxydimethylsilyl groups (20 %) in silicone elastomer gave the most desirable results. The surface tension of this modifier, was comparable to the non-polar native surface. However, almost half of this value was due to the result of polar forces. In this case, in an adhesion analysis, only 1 RLU cm(-2) and less than 1 c.f.u. cm(-2) were noted. For the native gumosil, the results were 9,375 RLU cm(-2) and 2.5 × 10(8) c.f.u. cm(-2), respectively. The antibacterial activity of active organo-silanes was associated only with the carrier surface because no antibacterial compounds were detected in liquid culture media, in concentrations that were able to inhibit cell growth.

Reactivity of the cadmium ion in concentrated phosphoric acid solutions.

PubMed

De Gyves, J; Gonzales, J; Louis, C; Bessiere, J

1989-07-01

The solvation transfer coefficients which characterize the changes of ion reactivity with phosphoric acid concentration have been calculated for cadmium from the constants of the successive chloride complexes, and for silver and diethyldithiophosphate from potentiometric measurements. They evidence the strong desolvation of the cadmium species in concentrated phosphoric acid media, causing a remarkable increase of its reactivity. They allow the results of liquid-liquid extraction, precipitation and flotation reactions to be correctly interpreted and their changes to be foreseen when the reagents are modified.

Influence of Parameters of a Reactive Interatomic Potential on the Properties of Saturated Hydrocarbons

DTIC Science & Technology

2017-01-01

Methodology 3 2.1 Modified Embedded-Atom Method Theory 3 2.1.1 Embedding Energy Function 3 2.1.2 Screening Factor 8 2.1.3 Modified Embedded-Atom...Simulation Methodology 2.1 Modified Embedded-Atom Method Theory In the EAM and MEAM formalisms1,2,5 the total energy of a system of atoms (Etot) is...An interatomic potential for saturated hydrocarbons using the modified embedded-atom method (MEAM), a semiempirical many-body potential based on

Combustion of chlorinated volatile organic compounds (VOCs) using bimetallic chromium-copper supported on modified H-ZSM-5 catalyst.

PubMed

Abdullah, Ahmad Zuhairi; Bakar, Mohamad Zailani Abu; Bhatia, Subhash

2006-02-28

The paper reports on the performance of chromium or/and copper supported on H-ZSM-5(Si/Al = 240) modified with silicon tetrachloride (Cr1.5/SiCl4-Z, Cu1.5/SiCl4-Z and Cr1.0Cu0.5/SiCl4-Z) as catalysts in the combustion of chlorinated VOCs (Cl-VOCs). A reactor operated at a gas hourly space velocity (GHSV) of 32,000 h(-1), a temperature between 100 and 500 degrees C with 2500 ppm of dichloromethane (DCM), trichloromethane (TCM) and trichloroethylene (TCE) is used for activity studies. The deactivation study is conducted at a GHSV of 3800 h(-1), at 400 degrees C for up to 12 h with a feed concentration of 35,000 ppm. Treatment with silicon tetrachloride improves the chemical resistance of H-ZSM-5 against hydrogen chloride. TCM is more reactive compared to DCM but it produces more by-products due to its high chlorine content. The stabilization of TCE is attributed to resonance effects. Water vapor increases the carbon dioxide yield through its role as hydrolysis agent forming reactive carbocations and acting as hydrogen-supplying agent to suppress chlorine-transfer reactions. The deactivation of Cr1.0Cu0.5/SiCl4-Z is mainly due to the chlorination of its metal species, especially with higher Cl/H feed. Coking is limited, particularly with DCM and TCM. In accordance with the Mars-van Krevelen model, the weakening of overall metal reducibility due to chlorination leads to a loss of catalytic activity.

ROLE OF REDUCTANTS IN THE ENHANCED DESORPTION AND TRANSFORMATION OF CHOROALIPHATIC COMPOUNDS BY MODIFIED FENTON'S REACTIONS. (R826163)

EPA Science Inventory

The mechanism for enhanced desorption of chloroaliphatic compounds from a
silty loam soil by modified Fenton's reagent was investigated using a series of
probe compounds of varying hydrophobicities. Hexachloroethane, which has
negligible reactivity with hydroxyl ra...

C-type natriuretic peptide-modified lipid vesicles: fabrication and use for the treatment of brain glioma.

PubMed

Wu, Jia-Shuan; Mu, Li-Min; Bu, Ying-Zi; Liu, Lei; Yan, Yan; Hu, Ying-Jie; Bai, Jing; Zhang, Jing-Ying; Lu, Weiyue; Lu, Wan-Liang

2017-06-20

Chemotherapy of brain glioma faces a major obstacle owing to the inability of drug transport across the blood-brain barrier (BBB). Besides, neovasculatures in brain glioma site result in a rapid infiltration, making complete surgical removal virtually impossible. Herein, we reported a novel kind of C-type natriuretic peptide (CNP) modified vinorelbine lipid vesicles for transferring drug across the BBB, and for treating brain glioma along with disrupting neovasculatures. The studies were performed on brain glioma U87-MG cells in vitro and on glioma-bearing nude mice in vivo. The results showed that the CNP-modified vinorelbine lipid vesicles could transport vinorelbine across the BBB, kill the brain glioma, and destroy neovasculatures effectively. The above mechanisms could be associated with the following aspects, namely, long circulation in the blood; drug transport across the BBB via natriuretic peptide receptor B (NPRB)-mediated transcytosis; elimination of brain glioma cells and disruption of neovasculatures by targeting uptake and cytotoxic injury. Besides, CNP-modified vinorelbine lipid vesicles could induce apoptosis of the glioma cells. The mechanisms could be related to the activations of caspase 8, caspase 3, p53, and reactive oxygen species (ROS), and inhibition of survivin. Hence, CNP-modified lipid vesicles could be used as a carrier material for treating brain glioma and disabling glioma neovasculatures.

Screening for Natural Chemoprevention Agents that Modify Human Keap1

PubMed Central

Hu, Chenqi; Nikolic, Dejan; Eggler, Aimee L.; Mesecar, Andrew D.; van Breemen, Richard B.

2012-01-01

Upregulation of cytoprotective enzymes by therapeutic agents to prevent damage by reactive oxygen species and xenobiotic electrophiles is a strategy for cancer chemoprevention. The Kelch-like ECH-associated protein 1 (Keap1) and its binding partner, transcription factor NF-E2-related factor-2 (Nrf2), are chemoprevention targets because of their role in regulating the antioxidant response element (ARE) in response to oxidative stress and exposure to electrophiles. Modification of the sensor protein Keap1 by electrophiles such as the isothiocyanate sulforaphane can direct Nrf2 accumulation in the nucleus and subsequent ARE activation. Since our previous matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS)-based screening method to discover natural products that modify Keap1 does not detect covalent modification of Keap1 by some highly reversible agents such as sulforaphane, a more sensitive screening assay was developed. In this new assay, electrophiles that have reversibly modified Keap1 can be released, trapped and detected as β-mercaptoethanol adducts by mass spectrometry. Isoliquiritigenin and sulforaphane, known ARE activators that target Keap1, were used to validate the assay. To determine the ability of the assay to identify electrophiles in complex matrixes that modify Keap1, sulforaphane was spiked into a cocoa extract, and LC-MS/MS using high resolution mass spectrometry with accurate mass measurement was used to identify β-mercaptoethanol adducts of sulforaphane that had been released from Keap1. This screening assay permits identification of potential chemoprevention agents in complex natural product mixtures that reversibly modify Keap1 but cannot be detected using MALDI-TOF MS. PMID:22074792

Older and Stronger Object Memories are Selectively Destabilized by Reactivation in the Presence of New Information

ERIC Educational Resources Information Center

Winters, Boyer D.; Tucci, Mark C.; DaCosta-Furtado, Melynda

2009-01-01

Reactivation can destabilize previously consolidated memories, rendering them vulnerable to disruption and necessitating a process of reconsolidation in order for them to be maintained. This process of destabilization and reconsolidation has commonly been cited as a means by which established memories can be updated or modified. However, little…

A Case-Controlled Investigation of Tactile Reactivity in Young Children with and without Global Developmental Delay

ERIC Educational Resources Information Center

Barney, Chantel C.; Tervo, Raymond; Wilcox, George L.; Symons, Frank J.

2017-01-01

Assessing tactile function among children with intellectual, motor, and communication impairments remains a clinical challenge. A case control design was used to test whether children with global developmental delays (GDD; n = 20) would be more/less reactive to a modified quantitative sensory test (mQST) compared to controls (n = 20). Reactivity…

Role of NADPH oxidases and reactive oxygen species in regulation of bone turnover and the skeletal toxicity of alcohol

USDA-ARS?s Scientific Manuscript database

Recent studies with genetically modified mice and dietary antioxidants have suggested an important role for superoxide derived from NADPH oxidase (NOX) enzymes and other reactive oxygen species (ROS) such as hydrogen peroxide in regulation of normal bone turnover during development and also in the r...

In Vitro and In Vivo Biocompatibility Evaluation of Polyallylamine and Macromolecular Heparin Conjugates Modified Alginate Microbeads.

PubMed

Vaithilingam, Vijayaganapathy; Steinkjer, Bjørg; Ryan, Liv; Larsson, Rolf; Tuch, Bernard Edward; Oberholzer, Jose; Rokstad, Anne Mari

2017-09-15

Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC). The PAV-CHC strategy resulted in uniform and stable coatings with increased anti-clot activity and low cytotoxicity. In human whole blood, PAV coating at high dose (100 µg/ml) induced elevated complement, leukocyte CD11b and inflammatory mediators, and in Wistar rats increased fibrotic overgrowth. Coating of high dose PAV with CHC significantly reduced these responses. Low dose PAV (10 µg/ml) ± CHC and unmodified alginate microbeads showed low responses. That the human whole blood inflammatory reactions paralleled the host response shows a link between inflammatory potential and initial fibrotic response. CHC possessed anti-inflammatory activity, but failed to improve overall biocompatibility. We conclude that the human whole blood assay is an efficient first-phase screening model for inflammation, and a guiding tool in development of new generation microspheres for cell encapsulation therapy.

Hydrogen Peroxide Modifies Human Sperm Peroxiredoxins in a Dose-Dependent Manner1

PubMed Central

O'Flaherty, Cristian; Rico de Souza, Angela

2010-01-01

Low levels of reactive oxygen species (ROS) modulate signaling pathways required for human sperm activation, but high levels impair sperm function, leading to infertility. Peroxiredoxins (PRDXs) are enzymes with a dual role as ROS scavengers and modulators of ROS-dependent signaling. The present study aimed to characterize PRDXs in human spermatozoa and possible modifications resulting from hydrogen peroxide (H2O2). We found PRDX1, PRDX4, PRDX5, and PRDX6 in both seminal plasma and spermatozoa. Using immunocytochemistry, we demonstrated that these PRDXs are differentially localized in the head, acrosome, mitochondrial sheath, and flagellum. These observations were confirmed by immunoblotting using cytosolic, Triton-soluble and -insoluble, and head and flagella sperm fractions. PRDXs are dose-dependently modified by H2O2, as seen by the formation of disulfide bridges and high-molecular-mass complexes. This first study, to our knowledge, on PRDXs in human spermatozoa indicates that PRDX1, PRDX4, PRDX5, and PRDX6 are modified when spermatozoa are challenged with H2O2. This suggests that PRDXs may protect these cells at high levels of H2O2 but could also control H2O2 levels within different cell compartments so that normal sperm activation can occur. PMID:20864641

Co-Introduced Functional CCR2 Potentiates In Vivo Anti-Lung Cancer Functionality Mediated by T Cells Double Gene-Modified to Express WT1-Specific T-Cell Receptor

PubMed Central

Asai, Hiroaki; Fujiwara, Hiroshi; An, Jun; Ochi, Toshiki; Miyazaki, Yukihiro; Nagai, Kozo; Okamoto, Sachiko; Mineno, Junichi; Kuzushima, Kiyotaka; Shiku, Hiroshi; Inoue, Hirofumi; Yasukawa, Masaki

2013-01-01

Background and Purpose Although gene-modification of T cells to express tumor-related antigen-specific T-cell receptor (TCR) or chimeric antigen receptor (CAR) has clinically proved promise, there still remains room to improve the clinical efficacy of re-directed T-cell based antitumor adoptive therapy. In order to achieve more objective clinical responses using ex vivo-expanded tumor-responsive T cells, the infused T cells need to show adequate localized infiltration into the tumor. Methodology/Principal Findings Human lung cancer cells variously express a tumor antigen, Wilms' Tumor gene product 1 (WT1), and an inflammatory chemokine, CCL2. However, CCR2, the relevant receptor for CCL2, is rarely expressed on activated T-lymphocytes. A HLA-A2402+ human lung cancer cell line, LK79, which expresses high amounts of both CCL2 and WT1 mRNA, was employed as a target. Normal CD8+ T cells were retrovirally gene-modified to express both CCR2 and HLA-A*2402-restricted and WT1235–243 nonapeptide-specific TCR as an effector. Anti-tumor functionality mediated by these effector cells against LK79 cells was assessed both in vitro and in vivo. Finally the impact of CCL2 on WT1 epitope-responsive TCR signaling mediated by the effector cells was studied. Introduced CCR2 was functionally validated using gene-modified Jurkat cells and human CD3+ T cells both in vitro and in vivo. Double gene-modified CD3+ T cells successfully demonstrated both CCL2-tropic tumor trafficking and cytocidal reactivity against LK79 cells in vitro and in vivo. CCL2 augmented the WT1 epitope-responsive TCR signaling shown by relevant luciferase production in double gene-modified Jurkat/MA cells to express luciferase and WT1-specific TCR, and CCL2 also dose-dependently augmented WT1 epitope-responsive IFN-γ production and CD107a expression mediated by these double gene-modifiedCD3+ T cells. Conclusion/Significance Introduction of the CCL2/CCR2 axis successfully potentiated in vivo anti-lung cancer reactivity mediated by CD8+ T cells double gene-modified to express WT1-specific TCR and CCR2 not only via CCL2-tropic tumor trafficking, but also CCL2-enhanced WT1-responsiveness. PMID:23441216

Peroxide-modified titanium dioxide: a chemical analog of putative Martian soil oxidants

NASA Technical Reports Server (NTRS)

Quinn, R. C.; Zent, A. P.

1999-01-01

Hydrogen peroxide chemisorbed on titanium dioxide (peroxide-modified titanium dioxide) is investigated as a chemical analog to the putative soil oxidants responsible for the chemical reactivity seen in the Viking biology experiments. When peroxide-modified titanium dioxide (anatase) was exposed to a solution similar to the Viking labeled release (LR) experiment organic medium, CO2 gas was released into the sample cell headspace. Storage of these samples at 10 degrees C for 48 hr prior to exposure to organics resulted in a positive response while storage for 7 days did not. In the Viking LR experiment, storage of the Martian surface samples for 2 sols (approximately 49 hr) resulted in a positive response while storage for 141 sols essentially eliminated the initial rapid release of CO2. Heating the peroxide-modified titanium dioxide to 50 degrees C prior to exposure to organics resulted in a negative response. This is similar to, but not identical to, the Viking samples where heating to approximately 46 degrees C diminished the response by 54-80% and heating to 51.5 apparently eliminated the response. When exposed to water vapor, the peroxide-modified titanium dioxide samples release O2 in a manner similar to the release seen in the Viking gas exchange experiment (GEx). Reactivity is retained upon heating at 50 degrees C for three hours, distinguishing this active agent from the one responsible for the release of CO2 from aqueous organics. The release of CO2 by the peroxide-modified titanium dioxide is attributed to the decomposition of organics by outer-sphere peroxide complexes associated with surface hydroxyl groups, while the release of O2 upon humidification is attributed to more stable inner-sphere peroxide complexes associated with Ti4+ cations. Heating the peroxide-modified titanium dioxide to 145 degrees C inhibited the release of O2, while in the Viking experiments heating to this temperature diminished but did not eliminated the response. Although the thermal stability of the titanium-peroxide complexes in this work is lower than the stability seen in the Viking experiments, it is expected that similar types of complexes will form in titanium containing minerals other than anatase and the stability of these complexes will vary with surface hydroxylation and mineralogy.

Reactivation of meristem activity and sprout growth in potato tubers require both cytokinin and gibberellin.

PubMed

Hartmann, Anja; Senning, Melanie; Hedden, Peter; Sonnewald, Uwe; Sonnewald, Sophia

2011-02-01

Reactivation of dormant meristems is of central importance for plant fitness and survival. Due to their large meristem size, potato (Solanum tuberosum) tubers serve as a model system to study the underlying molecular processes. The phytohormones cytokinins (CK) and gibberellins (GA) play important roles in releasing potato tuber dormancy and promoting sprouting, but their mode of action in these processes is still obscure. Here, we established an in vitro assay using excised tuber buds to study the dormancy-releasing capacity of GA and CK and show that application of gibberellic acid (GA(3)) is sufficient to induce sprouting. In contrast, treatment with 6-benzylaminopurine induced bud break but did not support further sprout growth unless GA(3) was administered additionally. Transgenic potato plants expressing Arabidopsis (Arabidopsis thaliana) GA 20-oxidase or GA 2-oxidase to modify endogenous GA levels showed the expected phenotypical changes as well as slight effects on tuber sprouting. The isopentenyltransferase (IPT) from Agrobacterium tumefaciens and the Arabidopsis cytokinin oxidase/dehydrogenase1 (CKX) were exploited to modify the amounts of CK in transgenic potato plants. IPT expression promoted earlier sprouting in vitro. Strikingly, CKX-expressing tubers exhibited a prolonged dormancy period and did not respond to GA(3). This supports an essential role of CK in terminating tuber dormancy and indicates that GA is not sufficient to break dormancy in the absence of CK. GA(3)-treated wild-type and CKX-expressing tuber buds were subjected to a transcriptome analysis that revealed transcriptional changes in several functional groups, including cell wall metabolism, cell cycle, and auxin and ethylene signaling, denoting events associated with the reactivation of dormant meristems.

Roles of vascular and metabolic components in cognitive dysfunction of Alzheimer disease: short- and long-term modification by non-genetic risk factors.

PubMed

Sato, Naoyuki; Morishita, Ryuichi

2013-11-05

It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD). Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of (1) compromised vascular reactivity, (2) vascular lesions, (3) hypo/hyperglycemia, and (4) exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. β-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: (1) functional MRI or SPECT for cerebrovascular reactivity, (2) MRI for ischemic lesions and atrophy, (3) clinical episodes of hypoglycemia and hyperglycemia, (4) amyloid-PET and tau-PET for pathological features of AD, would be required.

The role of endogenous serotonin in methamphetamine-induced neurotoxicity to dopamine nerve endings of the striatum.

PubMed

Thomas, David M; Angoa Pérez, Mariana; Francescutti-Verbeem, Dina M; Shah, Mrudang M; Kuhn, Donald M

2010-11-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the striatum where long-term DA depletion and microglial activation are maximal. Endogenous DA has been implicated as a critical participant in METH-induced neurotoxicity, most likely as a substrate for non-enzymatic oxidation by METH-generated reactive oxygen species. The striatum is also extensively innervated by serotonin (5HT) nerve endings and this neurochemical system is modified by METH in much the same manner as seen in DA nerve endings (i.e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores). 5HT can also be modified by reactive oxygen species to form highly reactive species that damage neurons but its role in METH neurotoxicity has not been assessed. Increases in 5HT levels with 5-hydroxytryptophan do not change METH-induced neurotoxicity to the DA nerve endings as revealed by reductions in DA, tyrosine hydroxylase and dopamine transporter levels. Partial reductions in 5HT with p-chlorophenylalanine are without effect on METH toxicity, despite the fact that p-chlorophenylalanine largely prevents METH-induced hyperthermia. Mice lacking the gene for brain tryptophan hydroxylase 2 are devoid of brain 5HT and respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia. Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA nerve endings of the striatum. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.

Enhanced removal of azo dye using modified PAN nanofibrous membrane Fe complexes with adsorption/visible-driven photocatalysis bifunctional roles

NASA Astrophysics Data System (ADS)

Li, Fu; Dong, Yongchun; Kang, Weimin; Cheng, Bowen; Cui, Guixin

2017-05-01

A series of polyacrylonitrile (PAN) nanofibrous membrane Fe complexes as the Fenton heterogeneous catalysts were fabricated through surface modification with different ratio of hydrazine hydrate (HH) and hydroxylamine (HA) and subsequent coordination with Fe3+ ions for the synergistic removal of a typical azo dye, Reactive Red 195 (RR 195) via adsorption and visible-driven photocatalytic oxidation. Effect of molar ratio of HH and HA on surface structure characteristics of the resulting complexes were examined. Their adsorptive or photocatalytic activity was also compared by changing molar ratio of HH and HA. The results indicated that three PAN nanofibrous membrane Fe complexes prepared with simultaneous modification of HA and HH exhibited much higher adsorption and visible photocatalytic activities than the complex modified solely with HA or HH due to their distinctive surface structures containing more active sites. Their adsorption and visible photocatalytic kinetics of RR 195 followed pseudo-second-order model equation. Their high photocatalytic rate constant and large amount of dye adsorption were regarded as the main reasons for better dye removal efficiency and durability in cyclic reuse by means of the synergistic adsorption-photocatalysis process.

π-Clamp-mediated cysteine conjugation

NASA Astrophysics Data System (ADS)

Zhang, Chi; Welborn, Matthew; Zhu, Tianyu; Yang, Nicole J.; Santos, Michael S.; van Voorhis, Troy; Pentelute, Bradley L.

2016-02-01

Site-selective functionalization of complex molecules is one of the most significant challenges in chemistry. Typically, protecting groups or catalysts must be used to enable the selective modification of one site among many that are similarly reactive, and general strategies that selectively tune the local chemical environment around a target site are rare. Here, we show a four-amino-acid sequence (Phe-Cys-Pro-Phe), which we call the ‘π-clamp’, that tunes the reactivity of its cysteine thiol for site-selective conjugation with perfluoroaromatic reagents. We use the π-clamp to selectively modify one cysteine site in proteins containing multiple endogenous cysteine residues. These examples include antibodies and cysteine-based enzymes that would be difficult to modify selectively using standard cysteine-based methods. Antibodies modified using the π-clamp retained binding affinity to their targets, enabling the synthesis of site-specific antibody-drug conjugates for selective killing of HER2-positive breast cancer cells. The π-clamp is an unexpected approach to mediate site-selective chemistry and provides new avenues to modify biomolecules for research and therapeutics.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osna, Natalia A., E-mail: nosna@UNMC.edu; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105; White, Ronda L.

The proteasome is a multi-catalytic protein degradation enzyme that is regulated by ethanol-induced oxidative stress; such suppression is attributed to CYP2E1-generated metabolites. However, under certain conditions, it appears that in addition to oxidative stress, other mechanisms are also involved in proteasome regulation. This study investigated whether impaired protein methylation that occurs during exposure of liver cells to ethanol, may contribute to suppression of proteasome activity. We measured the chymotrypsin-like proteasome activity in Huh7CYP cells, hepatocytes, liver cytosols and nuclear extracts or purified 20S proteasome under conditions that maintain or prevent protein methylation. Reduction of proteasome activity of hepatoma cell andmore » hepatocytes by ethanol or tubercidin was prevented by simultaneous treatment with S-adenosylmethionine (SAM). Moreover, the tubercidin-induced decline in proteasome activity occurred in both nuclear and cytosolic fractions. In vitro exposure of cell cytosolic fractions or highly purified 20S proteasome to low SAM:S-adenosylhomocysteine (SAH) ratios in the buffer also suppressed proteasome function, indicating that one or more methyltransferase(s) may be associated with proteasomal subunits. Immunoblotting a purified 20S rabbit red cell proteasome preparation using methyl lysine-specific antibodies revealed a 25 kDa proteasome subunit that showed positive reactivity with anti-methyl lysine. This reactivity was modified when 20S proteasome was exposed to differential SAM:SAH ratios. We conclude that impaired methylation of proteasome subunits suppressed proteasome activity in liver cells indicating an additional, yet novel mechanism of proteasome activity regulation by ethanol.« less

Nonenzymatic Reactions above Phospholipid Surfaces of Biological Membranes: Reactivity of Phospholipids and Their Oxidation Derivatives

PubMed Central

Solís-Calero, Christian; Ortega-Castro, Joaquín; Frau, Juan; Muñoz, Francisco

2015-01-01

Phospholipids play multiple and essential roles in cells, as components of biological membranes. Although phospholipid bilayers provide the supporting matrix and surface for many enzymatic reactions, their inherent reactivity and possible catalytic role have not been highlighted. As other biomolecules, phospholipids are frequent targets of nonenzymatic modifications by reactive substances including oxidants and glycating agents which conduct to the formation of advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs). There are some theoretical studies about the mechanisms of reactions related to these processes on phosphatidylethanolamine surfaces, which hypothesize that cell membrane phospholipids surface environment could enhance some reactions through a catalyst effect. On the other hand, the phospholipid bilayers are susceptible to oxidative damage by oxidant agents as reactive oxygen species (ROS). Molecular dynamics simulations performed on phospholipid bilayers models, which include modified phospholipids by these reactions and subsequent reactions that conduct to formation of ALEs and AGEs, have revealed changes in the molecular interactions and biophysical properties of these bilayers as consequence of these reactions. Then, more studies are desirable which could correlate the biophysics of modified phospholipids with metabolism in processes such as aging and diseases such as diabetes, atherosclerosis, and Alzheimer's disease. PMID:25977746

Flexible strategy for immobilizing redox-active compounds using in situ generation of diazonium salts. Investigations of the blocking and catalytic properties of the layers.

PubMed

Noël, Jean-Marc; Sjöberg, Béatrice; Marsac, Rémi; Zigah, Dodzi; Bergamini, Jean-François; Wang, Aifang; Rigaut, Stéphane; Hapiot, Philippe; Lagrost, Corinne

2009-11-03

A versatile two-step method is developed to covalently immobilize redox-active molecules onto carbon surfaces. First, a robust anchoring platform is grafted onto surfaces by electrochemical reduction of aryl diazonium salts in situ generated. Depending on the nature of the layer termini, -COOH or -NH(2), a further chemical coupling involving ferrocenemethylamine or ferrocene carboxylic acid derivatives leads to the covalent binding of ferrocene centers. The chemical strategy using acyl chloride activation is efficient and flexible, since it can be applied either to surface-reactive end groups or to reactive species in solution. Cyclic voltammetry analyses point to the covalent binding of ferrocene units restricted to the upper layers of the underlying aryl films, while AFM measurements show a lost of compactness of the layers after the chemical attachment of ferrocene centers. The preparation conditions of the anchoring layers were found to determine the interfacial properties of the resulted ferrocenyl-modified electrodes. The ferrocene units promoted effective redox mediation providing that the free redox probes are adequately chosen (i.e., vs size/formal potential) and the underlying layers exhibit strong blocking properties. For anchoring films with weaker blocking effect, the coexistence of two distinct phenomena, redox mediation and ET at pinholes could be evidenced.

Sexual orientation modulates endocrine stress reactivity.

PubMed

Juster, Robert-Paul; Hatzenbuehler, Mark L; Mendrek, Adrianna; Pfaus, James G; Smith, Nathan Grant; Johnson, Philip Jai; Lefebvre-Louis, Jean-Philippe; Raymond, Catherine; Marin, Marie-France; Sindi, Shireen; Lupien, Sonia J; Pruessner, Jens C

2015-04-01

Biological sex differences and sociocultural gender diversity influence endocrine stress reactivity. Although numerous studies have shown that men typically activate stronger stress responses than women when exposed to laboratory-based psychosocial stressors, it is unclear whether sexual orientation further modulates stress reactivity. Given that lesbian, gay, and bisexual (LGB) individuals frequently report heightened distress secondary to stigma-related stressors, we investigated whether cortisol stress reactivity differs between LGB individuals and heterosexual individuals in response to a well-validated psychosocial stressor. The study population comprised 87 healthy adults (mean age, 25 years) who were grouped according to their biological sex and their gendered sexual orientation: lesbian/bisexual women (n = 20), heterosexual women (n = 21), gay/bisexual men (n = 26), and heterosexual men (n = 20). Investigators collected 10 salivary cortisol samples throughout a 2-hour afternoon visit involving exposure to the Trier Social Stress Test modified to maximize between-sex differences. Relative to heterosexual women, lesbian/bisexual women showed higher cortisol stress reactivity 40 min after exposure to the stressor. In contrast, gay/bisexual men displayed lower overall cortisol concentrations throughout testing compared with heterosexual men. Main findings were significant while adjusting for sex hormones (estradiol-to-progesterone ratio in women and testosterone in men), age, self-esteem, and disclosure status (whether LGB participants had completed their "coming out"). Our results provide novel evidence for gender-based modulation of cortisol stress reactivity based on sexual orientation that goes beyond well-established between-sex differences. This study raises several important avenues for future research related to the physiologic functioning of LGB populations and gender diversity more broadly. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Altered UV absorbance and cytotoxicity of chlorinated sunscreen agents.

PubMed

Sherwood, Vaughn F; Kennedy, Steven; Zhang, Hualin; Purser, Gordon H; Sheaff, Robert J

2012-12-01

Sunscreens are widely utilized due to the adverse effects of ultraviolet (UV) radiation on human health. The safety of their active ingredients as well as that of any modified versions generated during use is thus of concern. Chlorine is used as a chemical disinfectant in swimming pools. Its reactivity suggests sunscreen components might be chlorinated, altering their absorptive and/or cytotoxic properties. To test this hypothesis, the UV-filters oxybenzone, dioxybenzone, and sulisobenzone were reacted with chlorinating agents and their UV spectra analyzed. In all cases, a decrease in UV absorbance was observed. Given that chlorinated compounds can be cytotoxic, the effect of modified UV-filters on cell viability was examined. Chlorinated oxybenzone and dioxybenzone caused significantly more cell death than unchlorinated controls. In contrast, chlorination of sulisobenzone actually reduced cytotoxicity of the parent compound. Exposing a commercially available sunscreen product to chlorine also resulted in decreased UV absorbance, loss of UV protection, and enhanced cytotoxicity. These observations show chlorination of sunscreen active ingredients can dramatically decrease UV absorption and generate derivatives with altered biological properties.

A magnetically drivable nanovehicle for curcumin with antioxidant capacity and MRI relaxation properties.

PubMed

Magro, Massimiliano; Campos, René; Baratella, Davide; Lima, Giuseppina; Holà, Katerina; Divoky, Clemens; Stollberger, Rudolf; Malina, Ondrej; Aparicio, Claudia; Zoppellaro, Giorgio; Zbořil, Radek; Vianello, Fabio

2014-09-08

Curcumin possesses wide-ranging anti-inflammatory and anti-cancer properties and its biological activity can be linked to its potent antioxidant capacity. Superparamagnetic maghemite (γ-Fe2 O3 ), called surface-active maghemite nanoparticles (SAMNs) were surface-modified with curcumin molecules, due to the presence of under-coordinated Fe(III) atoms on the nanoparticle surface. The so-obtained curcumin-modified SAMNs (SAMN@curcumin) had a mean size of 13±4 nm. SAMN@curcumin was characterized by transmission and scanning electron microscopy, UV/Vis, FTIR, and Mössbauer spectroscopy, X-ray powder diffraction, bulk susceptibility (SQUID), and relaxometry measurements (MRI imaging). The high negative contrast proclivity of SAMN@curcumin to act as potential contrast agent in MRI screenings was also tested. Moreover, the redox properties of bound curcumin were probed by electrochemistry. SAMN@curcumin was studied in the presence of different electroactive molecules, namely hydroquinone, NADH and ferrocyanide, to assess its redox behavior. Finally, SAMN@curcumin was electrochemically probed in the presence of hydrogen peroxide, demonstrating the stability and reactivity of bound curcumin. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vertically aligned nanowires from boron-doped diamond.

PubMed

Yang, Nianjun; Uetsuka, Hiroshi; Osawa, Eiji; Nebel, Christoph E

2008-11-01

Vertically aligned diamond nanowires with controlled geometrical properties like length and distance between wires were fabricated by use of nanodiamond particles as a hard mask and by use of reactive ion etching. The surface structure, electronic properties, and electrochemical functionalization of diamond nanowires were characterized by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) as well as electrochemical techniques. AFM and STM experiments show that diamond nanowire etched for 10 s have wire-typed structures with 3-10 nm in length and with typically 11 nm spacing in between. The electrode active area of diamond nanowires is enhanced by a factor of 2. The functionalization of nanowire tips with nitrophenyl molecules is characterized by STM on clean and on nitrophenyl molecule-modified diamond nanowires. Tip-modified diamond nanowires are promising with respect to biosensor applications where controlled biomolecule bonding is required to improve chemical stability and sensing significantly.

Differentiating Challenge Reactivity from Psychomotor Activity in Studies of Children’s Psychophysiology: Considerations for Theory and Measurement

PubMed Central

Bush, Nicole R.; Alkon, Abbey; Obradović, Jelena; Stamperdahl, Juliet; Boyce, W. Thomas

2014-01-01

Current methods of assessing children’s physiologic “stress reactivity” may be confounded by psychomotor activity, biasing estimates of the relation between reactivity and health. We examine the joint and independent contributions of psychomotor activity and challenge reactivity during a protocol for children ages 5–6 (N=338). Measures of parasympathetic (RSA) and sympathetic (PEP) reactivity were calculated for social, cognitive, sensory, and emotional challenge tasks. Reactivity was calculated relative to both resting and a paired comparison task that accounted for psychomotor activity effects during each challenge. Results indicated that comparison tasks themselves elicited RSA and PEP responses, and reactivity adjusted for psychomotor activity was incongruent with reactivity calculated using rest. Findings demonstrate the importance of accounting for confounding psychomotor activity effects on physiologic reactivity. PMID:21524757

Reactive postural control deficits in patients with posterior parietal cortex lesions after stroke and the influence of auditory cueing.

PubMed

Lin, Ying-Hui; Tang, Pei-Fang; Wang, Yao-Hung; Eng, Janice J; Lin, Keh-Chung; Lu, Lu; Jeng, Jiann-Shing; Chen, Shih-Ching

2014-10-01

The purpose of this study was to investigate the ways in which stroke-induced posterior parietal cortex (PPC) lesions affect reactive postural responses and whether providing auditory cues modulates these responses. Seventeen hemiparetic patients after stroke, nine with PPC lesions (PPCLesion) and eight with intact PPCs (PPCSpared), and nine age-matched healthy adults completed a lateral-pull perturbation experiment under noncued and cued conditions. The activation rates of the gluteus medius muscle ipsilateral (GMi) and contralateral to the pull direction, the rates of occurrence of three types of GM activation patterns, and the GMi contraction latency were investigated. In noncued pulls toward the paretic side, of the three groups, the PPCLesion group exhibited the lowest activation rate (56%) of the GMi (P < 0.05), which is the primary postural muscle involved in this task, and the highest rate of occurrence (33%) of the gluteus medius muscle contralateral-activation-only pattern (P < 0.05), which is a compensatory activation pattern. In contrast, in cued pulls toward the paretic side, the PPCLesion group was able to increase the activation rate of the GMi to a level (81%) such that there became no significant differences in activation rate of the GMi among the three groups (P > 0.05). However, there were no significant differences in the GM activation patterns and GMi contraction latency between the noncued and cued conditions for the PPCLesion group (P > 0.05). The PPCLesion patients had greater deficits in recruiting paretic muscles and were more likely to use the compensatory muscle activation pattern for postural reactions than the PPCSpared patients, suggesting that PPC is part of the neural circuitry involved in reactive postural control in response to lateral perturbations. The auditory cueing used in this study, however, did not significantly modify the muscle activation patterns in the PPCLesion patients. More research is needed to explore the type and structure of cueing that could effectively improve patterns and speed of postural responses in these patients.

Absolute quantitation of NAPQI-modified rat serum albumin by LC-MS/MS: monitoring acetaminophen covalent binding in vivo.

PubMed

LeBlanc, André; Shiao, Tze Chieh; Roy, René; Sleno, Lekha

2014-09-15

Acetaminophen is known to cause hepatoxicity via the formation of a reactive metabolite, N-acetyl p-benzoquinone imine (NAPQI), as a result of covalent binding to liver proteins. Serum albumin (SA) is known to be covalently modified by NAPQI and is present at high concentrations in the bloodstream and is therefore a potential biomarker to assess the levels of protein modification by NAPQI. A newly developed method for the absolute quantitation of serum albumin containing NAPQI covalently bound to its active site cysteine (Cys34) is described. This optimized assay represents the first absolute quantitation of a modified protein, with very low stoichiometric abundance, using a protein-level standard combined with isotope dilution. The LC-MS/MS assay is based on a protein standard modified with a custom-designed reagent, yielding a surrogate peptide (following digestion) that is a positional isomer to the target peptide modified by NAPQI. To illustrate the potential of this approach, the method was applied to quantify NAPQI-modified SA in plasma from rats dosed with acetaminophen. The resulting method is highly sensitive (capable of quantifying down to 0.0006% of total RSA in its NAPQI-modified form) and yields excellent precision and accuracy statistics. A time-course pharmacokinetic study was performed to test the usefulness of this method for following acetaminophen-induced covalent binding at four dosing levels (75-600 mg/kg IP), showing the viability of this approach to directly monitor in vivo samples. This approach can reliably quantify NAPQI-modified albumin, allowing direct monitoring of acetaminophen-related covalent binding.

Towards nanoscale biomedical devices in medicine: biofunctional and spectroscopic characterization of superparamagnetic nanoparticles.

PubMed

Parracino, Antonietta; Gajula, Gnana Prakash; di Gennaro, Ane Kold; Neves-Petersen, Maria Teresa; Rafaelsen, Jens; Petersen, Steffen B

2011-03-01

Medical interest in nanotechnology originates from a belief that nanoscale therapeutic devices can be constructed and directed towards its target inside the human body. Such nanodevices can be engineered by coupling superparamagnetic nanoparticle to biomedically active proteins. We hereby report the immobilization of a PhEst, a S-formylglutathione hydrolase from the psychrophilic P. haloplanktis TAC125 onto the gold coated surface of modified superparamagnetic core-shell nanoparticles (Fe(3)O(4)@Au). The synthesis of the nanoparticles is also reported. S-formylglutathione hydrolases constitute a family of ubiquitous enzymes which play a key role in formaldehyde detoxification both in prokaryotes and eukaryotes. PhEst was originally annotated as a putative feruloyl esterase, an enzyme that releases ferulic acid (an antioxidant reactive towards free radicals such as reactive oxygen species) from polysaccharides esters. Dynamic light scattering, scanning electron microscopy with energy dispersive X-ray spectroscopy, UV-visible absorption spectroscopy, fluorescence spectroscopy, magnetic separation technique and enzyme catalytic assay confirmed the chemical composition of the gold covered superparamagnetic nanoparticles, the binding and activity of the enzyme onto the nanoparticles. Activity data in U/ml confirmed that the immobilized enzyme is approximately 2 times more active than the free enzyme in solution. Such particles can be directed with external magnetic fields for bio-separation and focused towards a medical target for therapeutical as well as bio-sensor applications. © Springer Science+Business Media, LLC 2010

Disulfide S-monoxides convert xanthine dehydrogenase into oxidase in rat liver cytosol more potently than their respective disulfides.

PubMed

Sakuma, Satoru; Fujita, Junko; Nakanishi, Masahiko; Wada, Shun-ich; Fujimoto, Yohko

2008-05-01

Xanthine oxidase (XO)/xanthine dehydrogenase (XD) oxidizes oxypurines to uric acid, with only the XO form producing reactive oxygen species. In the present study, the effects of cystamine S-monoxide and cystine S-monoxide (disulfide S-monoxides) on the conversion of XD to XO in rat liver were examined. A partially purified enzyme fraction from the rat liver was incubated with xanthine in the presence or absence of NAD+, and the uric acid formed was measured by HPLC. Under basal conditions, XO activity represented about 15% of the total XO plus XD activity. Cystamine S-monoxide and cystine S-monoxide converted XD into XO in a dose-dependent manner, and the concentrations required to increase XO activity by 50% were approximately 1 and 2 microM, respectively. Their respective thiols (cysteamine and cysteine) and disulfides (cystamine and cystine) up to 10 microM showed weak or no effects on the activities of XO and XD and their conversion. Experiments utilizing a sulfhydryl reducing reagent (dithiothreitol) and sulfhydryl modifiers (4,4'-dithiodipyridine and 1-fluoro-2,4-dinitrobenzene) indicated that disulfide S-monoxides-induced conversion of XD to XO occurs via disulfide bridge formation in XD, but not the modification of sulfhydryl groups. These results suggest that disulfide S-monoxides have the potential to increase the generation of reactive oxygen species through the conversion of XD to XO in liver.

S-sulfhydration: a cysteine posttranslational modification in plant systems.

PubMed

Aroca, Ángeles; Serna, Antonio; Gotor, Cecilia; Romero, Luis C

2015-05-01

Hydrogen sulfide is a highly reactive molecule that is currently accepted as a signaling compound. This molecule is as important as carbon monoxide in mammals and hydrogen peroxide in plants, as well as nitric oxide in both eukaryotic systems. Although many studies have been conducted on the physiological effects of hydrogen sulfide, the underlying mechanisms are poorly understood. One of the proposed mechanisms involves the posttranslational modification of protein cysteine residues, a process called S-sulfhydration. In this work, a modified biotin switch method was used for the detection of Arabidopsis (Arabidopsis thaliana) proteins modified by S-sulfhydration under physiological conditions. The presence of an S-sulfhydration-modified cysteine residue on cytosolic ascorbate peroxidase was demonstrated using liquid chromatography-tandem mass spectrometry analysis, and a total of 106 S-sulfhydrated proteins were identified. Immunoblot and enzyme activity analyses of some of these proteins showed that the sulfide added through S-sulfhydration reversibly regulates the functions of plant proteins in a manner similar to that described in mammalian systems. © 2015 American Society of Plant Biologists. All Rights Reserved.

Allogeneic chimeric antigen receptor-modified cells for adoptive cell therapy of cancer.

PubMed

Marcus, Assaf; Eshhar, Zelig

2014-07-01

Chimeric antigen (or antibody) receptors (CAR) are fusion proteins typically combining an antibody-derived targeting fragment with signaling domains capable of activating immune cells. Recent clinical trials have shown the tremendous potential of adoptive cell transfer (ACT) of autologous T cells engineered to express a CD19-specific CAR targeting B-cell malignancies. Building on this approach, ACT therapies employing allogeneic CAR-expressing cytotoxic cells are now being explored. The basic principles of CAR-ACT are introduced. The potential benefits as well as problems of using allogeneic CAR-modified cells against tumor antigens are discussed. Various approaches to allogeneic CAR therapy are presented, including donor leukocyte infusion, CAR-redirected γδ T cells and natural killer cells, strategies to avoid graft-versus-host disease, modulation of lymphocyte migration, and exploitation of graft-versus-host reactivity. CAR-modified allogeneic cells have the potential to act as universal effector cells, which can be administered to any patient regardless of MHC type. Such universal effector cells could be used as an 'off-the-shelf' cell-mediated treatment for cancer.

Serum lipids modify periodontal infection - C-reactive protein association.

PubMed

Haro, Anniina; Saxlin, Tuomas; Suominen, Anna-Liisa; Ylöstalo, Pekka; Leiviskä, Jaana; Tervonen, Tellervo; Knuuttila, Matti

2012-09-01

To investigate whether low-grade inflammation-related factors such as serum low-density (LDL-C) and high-density lipoprotein cholesterol (HDL-C) modify the association between periodontal infection and C-reactive protein. This study was based on a subpopulation of the Health 2000 Survey, which consisted of dentate, non-diabetic, non-rheumatic subjects who were 30-49 years old (n = 2710). The extent of periodontal infection was measured by means of the number of teeth with periodontal pocket ≥4 mm and teeth with periodontal pocket ≥6 mm and systemic inflammation using high sensitive C-reactive protein. The extent of periodontal infection was associated with elevated levels of C-reactive protein among those subjects whose HDL-C value was below the median value of 1.3 mmol/l or LDL-C above the median value of 3.4 mmol/l. Among those with HDL-C ≥ 1.3 mmol/l or LDL-C ≤ 3.4 mmol/l, the association between periodontal infection and serum concentrations of C-reactive protein was practically non-existent. This study suggests that the relation of periodontal infection to the systemic inflammatory condition is more complicated than previously presumed. The findings of this study suggest that the possible systemic effect of periodontal infection is dependent on serum lipid composition. © 2012 John Wiley & Sons A/S.

Modeling and sensitivity analysis of mass transfer in active multilayer polymeric film for food applications

NASA Astrophysics Data System (ADS)

Bedane, T.; Di Maio, L.; Scarfato, P.; Incarnato, L.; Marra, F.

2015-12-01

The barrier performance of multilayer polymeric films for food applications has been significantly improved by incorporating oxygen scavenging materials. The scavenging activity depends on parameters such as diffusion coefficient, solubility, concentration of scavenger loaded and the number of available reactive sites. These parameters influence the barrier performance of the film in different ways. Virtualization of the process is useful to characterize, design and optimize the barrier performance based on physical configuration of the films. Also, the knowledge of values of parameters is important to predict the performances. Inverse modeling and sensitivity analysis are sole way to find reasonable values of poorly defined, unmeasured parameters and to analyze the most influencing parameters. Thus, the objective of this work was to develop a model to predict barrier properties of multilayer film incorporated with reactive layers and to analyze and characterize their performances. Polymeric film based on three layers of Polyethylene terephthalate (PET), with a core reactive layer, at different thickness configurations was considered in the model. A one dimensional diffusion equation with reaction was solved numerically to predict the concentration of oxygen diffused into the polymer taking into account the reactive ability of the core layer. The model was solved using commercial software for different film layer configurations and sensitivity analysis based on inverse modeling was carried out to understand the effect of physical parameters. The results have shown that the use of sensitivity analysis can provide physical understanding of the parameters which highly affect the gas permeation into the film. Solubility and the number of available reactive sites were the factors mainly influencing the barrier performance of three layered polymeric film. Multilayer films slightly modified the steady transport properties in comparison to net PET, giving a small reduction in the permeability and oxygen transfer rate values. Scavenging capacity of the multilayer film increased linearly with the increase of the reactive layer thickness and the oxygen absorption reaction at short times decreased proportionally with the thickness of the external PET layer.

Modeling and sensitivity analysis of mass transfer in active multilayer polymeric film for food applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bedane, T.; Di Maio, L.; Scarfato, P.

The barrier performance of multilayer polymeric films for food applications has been significantly improved by incorporating oxygen scavenging materials. The scavenging activity depends on parameters such as diffusion coefficient, solubility, concentration of scavenger loaded and the number of available reactive sites. These parameters influence the barrier performance of the film in different ways. Virtualization of the process is useful to characterize, design and optimize the barrier performance based on physical configuration of the films. Also, the knowledge of values of parameters is important to predict the performances. Inverse modeling and sensitivity analysis are sole way to find reasonable values ofmore » poorly defined, unmeasured parameters and to analyze the most influencing parameters. Thus, the objective of this work was to develop a model to predict barrier properties of multilayer film incorporated with reactive layers and to analyze and characterize their performances. Polymeric film based on three layers of Polyethylene terephthalate (PET), with a core reactive layer, at different thickness configurations was considered in the model. A one dimensional diffusion equation with reaction was solved numerically to predict the concentration of oxygen diffused into the polymer taking into account the reactive ability of the core layer. The model was solved using commercial software for different film layer configurations and sensitivity analysis based on inverse modeling was carried out to understand the effect of physical parameters. The results have shown that the use of sensitivity analysis can provide physical understanding of the parameters which highly affect the gas permeation into the film. Solubility and the number of available reactive sites were the factors mainly influencing the barrier performance of three layered polymeric film. Multilayer films slightly modified the steady transport properties in comparison to net PET, giving a small reduction in the permeability and oxygen transfer rate values. Scavenging capacity of the multilayer film increased linearly with the increase of the reactive layer thickness and the oxygen absorption reaction at short times decreased proportionally with the thickness of the external PET layer.« less

Goat's milk allergy without cow's milk allergy: suppression of non-cross-reactive epitopes on caprine β-casein.

PubMed

Hazebrouck, S; Ah-Leung, S; Bidat, E; Paty, E; Drumare, M-F; Tilleul, S; Adel-Patient, K; Wal, J-M; Bernard, H

2014-04-01

Goat's milk (GM) allergy associated with tolerance to cow's milk (CM) has been reported in patients without history of CM allergy and in CM-allergic children successfully treated with oral immunotherapy. The IgE antibodies from GM-allergic/CM-tolerant patients recognize caprine β-casein (βcap) without cross-reacting with bovine β-casein (βbov) despite a sequence identity of 91%. In this study, we investigated the non-cross-reactive IgE-binding epitopes of βcap. Recombinant βcap was genetically modified by substituting caprine domains with the bovine counterparts and by performing site-directed mutagenesis. We then evaluated the recognition of modified βcap by IgE antibodies from 11 GM-allergic/CM-tolerant patients and 11 CM-allergic patients or by monoclonal antibodies (mAb) raised against caprine caseins. The allergenic potency of modified βcap was finally assessed by degranulation tests of humanized rat basophil leukaemia (RBL)-SX38 cells. Non-cross-reactive epitopes of βcap were found in domains 44-88 and 130-178. The substitutions A55T/T63P/L75P and P148H/S152P induced the greatest decrease in IgE reactivity of GM-allergic/CM-tolerant patients towards βcap. The pivotal role of threonine 63 was particularly revealed as its substitution also impaired the recognition of βcap by specific mAb, which could discriminate between βcap and βbov. The modified βcap containing the five substitutions was then unable to trigger the degranulation of RBL-SX38 cells passively sensitized with IgE antibodies from GM-allergic/CM-tolerant patients. Although IgE-binding epitopes are spread all over βcap, a non-cross-linking version of βcap was generated with only five amino acid substitutions and could thus provide new insight for the design of hypoallergenic variants. © 2013 John Wiley & Sons Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Z; Li, B; Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences

Purpose: The aim of this research was to investigate the feasibility of Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model in analyzing hepatitis B virus (HBV) reactivation in patients receiving conformal radiotherapy for patients with hepatocellular carcinoma (HCC). Methods: Between June 2009 and June 2012, 108 HBV-related HCC patients (90 were specifically selected and 18 patients were excluded) treated with conformal RT at three centers were enrolled in this retrospective study. They were all diagnosed as HCC by pathology or cytology. All 90 patients were followed up to September 2013 with a median follow-up time of 25.2 months. The parametersmore » (TD50 (1), n, and m) of the modified LKB NTCP model were derived using maximum likelihood estimation. Bootstrap and leave-one-out were employed to test the generalizability of the results for use in a general population. Results: The incidences of complications in the study population were as follows: radiation-induced liver diseases (RILD) were 17.6%, HBV reactivation was 24.8%, and HBV reactivation-induced hepatitis was 22.7%, respectively. In multivariate analysis, the NTCP (p<0.001), and V20 were associated with HBV reactivation. TD50 (1), m and n were 42.9Gy (95% CI) (38.2–46.8), 0.14 (0.12–0.15) and 0.30 (0.2–0.33), respectively, for HBV reactivation. Bootstrap and leave-one-out results showed that the HBV parameter fits were extremely robust. Conclusion: A modified LKB NTCP model has been established to predict HBV reactivation for patients with HCC receiving conformal RT. The finding derives parameters set to predict potential endpoints of HBV reactivation.« less

LC-MS-based characterization of the peptide reactivity of chemicals to improve the in vitro prediction of the skin sensitization potential.

PubMed

Natsch, Andreas; Gfeller, Hans

2008-12-01

A key step in the skin sensitization process is the formation of a covalent adduct between skin sensitizers and endogenous proteins and/or peptides in the skin. Based on this mechanistic understanding, there is a renewed interest in in vitro assays to determine the reactivity of chemicals toward peptides in order to predict their sensitization potential. A standardized peptide reactivity assay yielded a promising predictivity. This published assay is based on high-performance liquid chromatography with ultraviolet detection to quantify peptide depletion after incubation with test chemicals. We had observed that peptide depletion may be due to either adduct formation or peptide oxidation. Here we report a modified assay based on both liquid chromatography-mass spectrometry (LC-MS) analysis and detection of free thiol groups. This approach allows simultaneous determination of (1) peptide depletion, (2) peptide oxidation (dimerization), (3) adduct formation, and (4) thiol reactivity and thus generates a more detailed characterization of the reactivity of a molecule. Highly reactive molecules are further discriminated with a kinetic measure. The assay was validated on 80 chemicals. Peptide depletion could accurately be quantified both with LC-MS detection and depletion of thiol groups. The majority of the moderate/strong/extreme sensitizers formed detectable peptide adducts, but many sensitizers were also able to catalyze peptide oxidation. Whereas adduct formation was only observed for sensitizers, this oxidation reaction was also observed for two nonsensitizing fragrance aldehydes, indicating that peptide depletion might not always be regarded as sufficient evidence for rating a chemical as a sensitizer. Thus, this modified assay gives a more informed view of the peptide reactivity of chemicals to better predict their sensitization potential.

Development of an evidence-based protocol for care of pilonidal sinus wounds healing by secondary intent using a modified reactive Delphi procedure. Part one: the literature review*.

PubMed

Harris, Connie L; Holloway, Samantha

2012-04-01

This article is in two parts. The overall aim of this section was to review the literature in relation to pilonidal sinus wounds (PSW) healing by secondary intent for a Master's of Science in Wound Healing and Tissue Repair thesis. The purpose of the literature review was to determine if an evidence-based guideline or consensus document existed for the care of these wounds, and if not, to determine the topics from which to develop items for the first round of a modified reactive Delphi questionnaire. Part two will describe the iterative process, the analysis and the results. The review found no best practice guidelines concerning PSW, and only one clinical pathway. Seventeen areas of interest were identified that may contribute to optimal healing conditions or to delayed healing. These included microbiology of infected PSW, signs and symptoms of localised or deeper (spreading) chronic wound infection, swab for c&s, role of topical antiseptics or antimicrobials, systemic antibiotics, local wound interventions, optimal positioning, wound cleansing, principles of moist wound healing/dressing selection, topical negative pressure (TNP) therapy, peri-wound skin decontamination and depilation, pain control, physical activities, optimal nutrition and patient education. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Allergen-specific sublingual immunotherapy in the treatment of migraines: a prospective study.

PubMed

Theodoropoulos, D S; Katzenberger, D R; Jones, W M; Morris, D L; Her, C; Cullen, N A M; Morrisa, D L

2011-10-01

Inflammation is a cardinal feature of migraines. A number of observations point to the possibility that an allergic component of a type I (IgE-mediated) nature may be involved in at least some migraineurs. Not only are migraines frequent among patients with allergic rhinitis but quite frequently the same medical approaches are beneficial in both diseases: anti-inflammatories, adrenergic tone modifiers, immune suppressants. The effect that immunotherapy for allergic rhinitis has upon migraines is studied. Patients were recruited who suffered from typical migraines but were not treated with regular migraine controllers (beta blockers, antiepileptics, tricyclics, etc.). They underwent allergen-specific, sublingual immunotherapy with physician-formulated, individually-prepared airborne allergen extracts. Response to treatment was assessed with serum C-reactive protein level changes and symptom scores. Serum C-reactive protein (CRP), an acute phase reactant, was chosen as a marker because its usefulness has already been assessed in interictal migraine activity. Interictal serum CRP levels decline was observed in the course of sublingual immunotherapy. Concurrent improvement in symptom scores for both rhinitis and migraines was also observed. In patients with allergic rhinitis, migraine development and course may have a significant allergic component. Assessment of migraineurs for the possibility of coexisting allergic rhinitis is justified. Treatment of allergic rhinitis by immune response modifiers, such as immunotherapy, may have a place in the management of migraines for these patients.

Modified C-reactive protein is expressed by stroke neovessels and is a potent activator of angiogenesis in vitro.

PubMed

Slevin, Mark; Matou-Nasri, Sabine; Turu, Marta; Luque, Ana; Rovira, Norma; Badimon, Lina; Boluda, Susana; Potempa, Lawrence; Sanfeliu, Coral; de Vera, Nuria; Krupinski, Jerzy

2010-01-01

Native C-reactive protein (nCRP) is a pentameric oligo-protein and an acute phase reactant whose serum expression is increased in patients with inflammatory disease. We have identified by immunohistochemistry, significant expression of a tissue-binding insoluble modified version or monomeric form of CRP (mCRP) associated with angiogenic microvessels in peri-infarcted regions of patients studied with acute ischaemic stroke. mCRP, but not nCRP was expressed in the cytoplasm and nucleus of damaged neurons. mCRP co-localized with CD105, a marker of angiogenesis in regions of revascularisation. In vitro investigations demonstrated that mCRP was preferentially expressed in human brain microvessel endothelial cells following oxygen-glucose deprivation and mCRP (but not column purified nCRP) associated with the endothelial cell surface, and was angiogenic to vascular endothelial cells, stimulating migration and tube formation in matrigel more strongly than fibroblast growth factor-2. The mechanism of signal transduction was not through the CD16 receptor. Western blotting showed that mCRP stimulated phosphorylation of the key down-stream mitogenic signalling protein ERK1/2. Pharmacological inhibition of ERK1/2 phosphorylation blocked the angiogenic effects of mCRP. We propose that mCRP may contribute to the neovascularization process and because of its abundant presence, be important in modulating angiogenesis in both acute stroke and later during neuro-recovery.

Ebselen protects against behavioral and biochemical toxicities induced by 3-nitropropionic acid in rats: correlations between motor coordination, reactive species levels, and succinate dehydrogenase activity.

PubMed

Wilhelm, Ethel A; Bortolatto, Cristiani F; Jesse, Cristiano R; Luchese, Cristiane

2014-12-01

The protective effect of ebselen was investigated against 3-nitropropionic acid (3-NP)-induced behavioral and biochemical toxicities in rats. Ebselen (10 or 25 mg/kg, intragastrically) was administered to rats 30 min before 3-NP (20 mg/kg, intraperitoneally) once a day for a period of 4 days. Locomotor activity, motor coordination, and body weight gain were determined. The striatal content of reactive oxygen species (ROS), reduced glutathione (GSH), ascorbic acid (AA), and protein carbonyl as well as catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST) activities was determined 24 h after the last dose of 3-NP. Na(+)/ K(+)-ATPase, succinate dehydrogenase (SDH), and δ-aminolevulinic dehydratase (δ-ALA-D) activities were also determined. The results demonstrated that ebselen at a dose of 25 mg/kg, but not at 10 mg/kg, protected against (1) a decrease in locomotor activity, motor coordination impairment, and body weight loss; (2) striatal oxidative damage, which was characterized by an increase in ROS levels, protein carbonyl content, and GR activity, an inhibition of CAT and GPx activities, and a decrease in GSH levels; and (3) an inhibition of SDH and Na(+)/K(+)-ATPase activities, induced by 3-NP. GST activity and AA levels were not modified by ebselen or 3-NP. Ebselen was not effective against the inhibition of δ-ALA-D activity induced by 3-NP. The results revealed a significant correlation between SDH activity and ROS levels, and SDH activity and latency to fall (rotarod test). The present study highlighted the protective effect of ebselen against 3-NP-induced toxicity in rats.

Surface functionalized nanofibrillar cellulose (NFC) film as a platform for immunoassays and diagnostics.

PubMed

Orelma, Hannes; Filpponen, Ilari; Johansson, Leena-Sisko; Osterberg, Monika; Rojas, Orlando J; Laine, Janne

2012-12-01

We introduce a new method to modify films of nanofibrillated cellulose (NFC) to produce non-porous, water-resistant substrates for diagnostics. First, water resistant NFC films were prepared from mechanically disintegrated NFC hydrogel, and then their surfaces were carboxylated via TEMPO-mediated oxidation. Next, the topologically functionalized film was activated via EDS/NHS chemistry, and its reactivity verified with bovine serum albumin and antihuman IgG. The surface carboxylation, EDC/NHS activation and the protein attachment were confirmed using quartz crystal microbalance with dissipation, contact angle measurements, conductometric titrations, X-ray photoelectron spectroscopy and fluorescence microscopy. The surface morphology of the prepared films was investigated using confocal laser scanning microscopy and atomic force microscopy. Finally, we demonstrate that antihuman IgG can be immobilized on the activated NFC surface using commercial piezoelectric inkjet printing.

The analysis of false prolongation of the activated partial thromboplastin time (activator: silica): Interference of C-reactive protein.

PubMed

Liu, Jie; Li, Fanfan; Shu, Kuangyi; Chen, Tao; Wang, Xiaoou; Xie, Yaoqi; Li, Shanshan; Zhang, Zhaohua; Jin, Susu; Jiang, Minghua

2018-05-13

To investigate the effect of C-reactive protein on the activated partial thromboplastin time (APTT) (different activators) in different detecting systems. The C-reactive protein and coagulation test of 112 patients with the infectious disease were determined by automation protein analyzer IMMAG 800 and automation coagulation analyzer STA-R Evolution, respectively. The pooled plasma APTT with different concentrations of C-reactive protein was measured by different detecting system: STA-R Evolution (activator: silica, kaolin), Sysmex CS-2000i (activator: ellagic acid), and ACL TOP 700 (activator: colloidal silica). In addition, the self-made platelet lysate (phospholipid) was added to correct the APTT prolonged by C-reactive protein (150 mg/L) on STA-R Evolution (activator: silica) system. The good correlation between C-reactive protein and APTT was found on the STA-R Evolution (activator: silica) system. The APTT on the STA-R Evolution (activator: silica) system was prolonged by 24.6 second, along with increasing C-reactive protein concentration. And the APTT of plasma containing 150 mg/L C-reactive protein was shortened by 3.4-6.9 second when the plasma was mixed with self-made platelet lysate. However, the APTT was prolonged unobviously on other detecting systems including STA-R Evolution (activator: kaolin), Sysmex CS-2000i, and ACL TOP 700. C-reactive protein interferes with the detection of APTT, especially in STA-R Evolution (activator: silica) system. The increasing in C-reactive protein results in a false prolongation of the APTT (activator: silica), and it is most likely that C-reactive protein interferes the coagulable factor binding of phospholipid. © 2018 Wiley Periodicals, Inc.

MAOA-uVNTR genotype predicts interindividual differences in experimental aggressiveness as a function of the degree of provocation.

PubMed

Kuepper, Yvonne; Grant, Phillip; Wielpuetz, Catrin; Hennig, Juergen

2013-06-15

The MAOA-uVNTR has been suggested to play a role regarding aggression, however, results are inconsistent. We aimed at further elucidating potential effects of the MAOA-uVNTR on aggressiveness with respect to potential modulators: sex, experimental vs. trait aggressiveness and type of aggressiveness (proactive vs. reactive aggressiveness). We tested 239 healthy young adults (88 men/151 women). Participants were genotyped for the MAOA-uVNTR and performed a modified version of a competitive reaction time task - a commonly used and well established tool to elicit and measure aggressiveness. Furthermore, they completed a self-report scale measuring trait aggressiveness. We found a main effect of MAOA-uVNTR on a measure of reactive aggressiveness for both men and women, whereby the low-activity alleles of the MAOA-uVNTR were associated with substantially increased aggressive reactions (p<.05). This effect was unique for reactive aggressiveness. Measures of proactive aggressiveness or self reports were not associated with the MAOA-uVNTR-genotype. Our data are in line with earlier studies and indicate the MAOA-uVNTR-genotype to be specifically associated with measures of reactive impulsive experimental aggressiveness in healthy men and women. Furthermore the association between the MAOA-uVNTR genotype and aggressive responses increases in a fashion linear to the degree of provocation. This indicates that the low-functional alleles of the MAOA-uVNTR are not associated with increased aggressive behavior per se, but rather with an increased aggressive reactivity to provocation. Copyright © 2013 Elsevier B.V. All rights reserved.

Low to moderate temperature nanolaminate heater

DOEpatents

Eckels, J Del [Livermore, CA; Nunes, Peter J [Danville, CA; Simpson, Randall L [Livermore, CA; Hau-Riege, Stefan [Fremont, CA; Walton, Chris [Oakland, CA; Carter, J Chance [Livermore, CA; Reynolds, John G [San Ramon, CA

2011-01-11

A low to moderate temperature heat source comprising a high temperature energy source modified to output low to moderate temperatures wherein the high temperature energy source modified to output low to moderate temperatures is positioned between two thin pieces to form a close contact sheath. In one embodiment the high temperature energy source modified to output low to moderate temperatures is a nanolaminate multilayer foil of reactive materials that produces a heating level of less than 200.degree. C.

Electrophysiological correlates of competitor activation predict retrieval-induced forgetting.

PubMed

Hellerstedt, Robin; Johansson, Mikael

2014-06-01

The very act of retrieval modifies the accessibility of memory for knowledge and past events and can also cause forgetting. A prominent theory of such retrieval-induced forgetting (RIF) holds that retrieval recruits inhibition to overcome interference from competing memories, rendering these memories inaccessible. The present study tested a fundamental tenet of the inhibitory-control account: The competition-dependence assumption. Event-related potentials (ERPs) were recorded while participants engaged in a competitive retrieval task. Competition levels were manipulated within the retrieval task by varying the cue-item associative strength of competing items. In order to temporally separate ERP correlates of competitor activation and target retrieval, memory was probed with the sequential presentation of 2 cues: A category cue, to reactivate competitors, and a target cue. As predicted by the inhibitory-control account, competitors with strong compared with weak cue-competitor association were more susceptible to forgetting. Furthermore, competition-sensitive ERP modulations, elicited by the category cue, were observed over anterior regions and reflected individual differences in ensuing forgetting. The present study demonstrates ERP correlates of the reactivation of tightly bound associated memories (the competitors) and provides support for the inhibitory-control account of RIF.

Immunomodulation: the future cure for allergic diseases.

PubMed

Tsitoura, Daphne C; Tassios, Yannis

2006-11-01

Allergies are the result of aberrant immune reactivity against common innocuous environmental proteins (allergens). A pivotal component of allergic pathogenesis is the generation of allergen-specific Th cells with an effector phenotype. These Th cells activate a complex immune cascade that triggers the release of potent mediators and enhances the mobilization of several inflammatory cells types, which in turn elicit the acute allergic reactions and promote the development of chronic inflammation. The current therapies for allergic diseases focus primarily on pharmacological control of symptoms and suppression of inflammation. This approach is beneficial, but not curative, since the underlying immune pathology is not inhibited. In an attempt to develop more effective therapeutic strategies, the scientific interest has been directed toward methods down-modulating the immune mechanisms that initiate and maintain the allergic cascade. Today, the only widely used disease-modifying form of allergy treatment is the specific immunotherapy with allergen extracts. More recently the use of anti-IgE has been approved for patients with allergic asthma. Other immunomodulatory methods being currently explored are the administration of microbial adjuvants that inhibit Th2 reactivity and the design of molecules that interrupt the activity of key allergic cytokines, chemokines, or other Th2 effector mediators.

Activation of CO and CO2 on homonuclear boron bonds of fullerene-like BN cages: first principles study

NASA Astrophysics Data System (ADS)

Sinthika, S.; Kumar, E. Mathan; Surya, V. J.; Kawazoe, Y.; Park, Noejung; Iyakutti, K.; Thapa, Ranjit

2015-12-01

Using density functional theory we investigate the electronic and atomic structure of fullerene-like boron nitride cage structures. The pentagonal ring leads to the formation of homonuclear bonds. The homonuclear bonds are also found in other BN structures having pentagon line defect. The calculated thermodynamics and vibrational spectra indicated that, among various stable configurations of BN-60 cages, the higher number of homonuclear N-N bonds and lower B:N ratio can result in the more stable structure. The homonuclear bonds bestow the system with salient catalytic properties that can be tuned by modifying the B atom bonding environment. We show that homonuclear B-B (B2) bonds can anchor both oxygen and CO molecules making the cage to be potential candidates as catalyst for CO oxidation via Langmuir-Hinshelwood (LH) mechanism. Moreover, the B-B-B (B3) bonds are reactive enough to capture, activate and hydrogenate CO2 molecules to formic acid. The observed trend in reactivity, viz B3 > B2 > B1 is explained in terms of the position of the boron defect state relative to the Fermi level.

Activation of CO and CO2 on homonuclear boron bonds of fullerene-like BN cages: first principles study

PubMed Central

Sinthika, S.; Kumar, E. Mathan; Surya, V. J.; Kawazoe, Y.; Park, Noejung; Iyakutti, K.; Thapa, Ranjit

2015-01-01

Using density functional theory we investigate the electronic and atomic structure of fullerene-like boron nitride cage structures. The pentagonal ring leads to the formation of homonuclear bonds. The homonuclear bonds are also found in other BN structures having pentagon line defect. The calculated thermodynamics and vibrational spectra indicated that, among various stable configurations of BN-60 cages, the higher number of homonuclear N-N bonds and lower B:N ratio can result in the more stable structure. The homonuclear bonds bestow the system with salient catalytic properties that can be tuned by modifying the B atom bonding environment. We show that homonuclear B-B (B2) bonds can anchor both oxygen and CO molecules making the cage to be potential candidates as catalyst for CO oxidation via Langmuir–Hinshelwood (LH) mechanism. Moreover, the B-B-B (B3) bonds are reactive enough to capture, activate and hydrogenate CO2 molecules to formic acid. The observed trend in reactivity, viz B3 > B2 > B1 is explained in terms of the position of the boron defect state relative to the Fermi level. PMID:26626147

Activation of CO and CO2 on homonuclear boron bonds of fullerene-like BN cages: first principles study.

PubMed

Sinthika, S; Kumar, E Mathan; Surya, V J; Kawazoe, Y; Park, Noejung; Iyakutti, K; Thapa, Ranjit

2015-12-02

Using density functional theory we investigate the electronic and atomic structure of fullerene-like boron nitride cage structures. The pentagonal ring leads to the formation of homonuclear bonds. The homonuclear bonds are also found in other BN structures having pentagon line defect. The calculated thermodynamics and vibrational spectra indicated that, among various stable configurations of BN-60 cages, the higher number of homonuclear N-N bonds and lower B:N ratio can result in the more stable structure. The homonuclear bonds bestow the system with salient catalytic properties that can be tuned by modifying the B atom bonding environment. We show that homonuclear B-B (B2) bonds can anchor both oxygen and CO molecules making the cage to be potential candidates as catalyst for CO oxidation via Langmuir-Hinshelwood (LH) mechanism. Moreover, the B-B-B (B3) bonds are reactive enough to capture, activate and hydrogenate CO2 molecules to formic acid. The observed trend in reactivity, viz B3 > B2 > B1 is explained in terms of the position of the boron defect state relative to the Fermi level.

Oxidative Stress: A New Target for Pancreatic Cancer Prognosis and Treatment

PubMed Central

Martinez-Useros, Javier; Li, Weiyao; Cabeza-Morales, Marticela; Garcia-Foncillas, Jesus

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumors, and its incidence is rising worldwide. Survival can be improved when tumors are detected at an early stage; however, this cancer is usually asymptomatic, and the disease only becomes apparent after metastasis. Several risk factors are associated to this disease. Chronic pancreatitis, diabetes, and some infectious disease are the most relevant risk factors. Incidence of PDAC has increased in the last decades. It is hypothesized it could be due to other acquired risk habits, like smoking, high alcohol intake, and obesity. Indeed, adipose tissue is a dynamic endocrine organ that secretes different pro-inflammatory cytokines, enzymes, and other factors that activate oxidative stress. Reactive oxygen species caused by oxidative stress, damage DNA, proteins, and lipids, and produce several toxic and high mutagenic metabolites that could modify tumor behavior, turning it into a malignant phenotype. Anti-oxidant compounds, like vitamins, are considered protective factors against cancer. Here, we review the literature on oxidative stress, the molecular pathways that activate or counteract oxidative stress, and potential treatment strategies that target reactive oxygen species suitable for this kind of cancer. PMID:28282928

Effects of pesticide chemicals on the activity of metabolic enzymes: focus on thiocarbamates.

PubMed

Mathieu, Cécile; Duval, Romain; Xu, Ximing; Rodrigues-Lima, Fernando; Dupret, Jean-Marie

2015-01-01

Thiocarbamates are chemicals widely used as pesticides. Occupational exposure is associated with acute intoxication. Populations can be exposed through food and water. Moreover, certain thiocarbamates are used clinically. The widespread use of thiocarbamates raises many issues regarding their toxicological and pharmacological impact. Thiocarbamates and their metabolites can modify biological macromolecules functions, in particular enzymes, through modification of cysteine residues, chelation of metal ions or modulation of the oxidative stress. Loss of enzyme activity can lead to the disruption of metabolic pathways, and explain, at least in part, the effects of these pesticides. Additionally, their reactivity and ability to easily cross biological barrier confer them a great interest for development of clinical applications. Many advances in the study of thiocarbamates metabolism and reactivity have led to a better knowledge of biological effects of these compounds. However, more data are needed on the determination of targets and specificity. Only few data concerning the exposure to a cocktail of pesticides/chemicals are available, raising the need to evaluate the toxic side effects of representative pesticides mixtures. Moreover, the dithiocarbamate Disulfiram has shown great potential in therapeutic applications and leads to the development of pharmacological thiocarbamates derivatives, highly specific to their target and easily distributed.

A heuristic approach to incremental and reactive scheduling

NASA Technical Reports Server (NTRS)

Odubiyi, Jide B.; Zoch, David R.

1989-01-01

An heuristic approach to incremental and reactive scheduling is described. Incremental scheduling is the process of modifying an existing schedule if the initial schedule does not meet its stated initial goals. Reactive scheduling occurs in near real-time in response to changes in available resources or the occurrence of targets of opportunity. Only minor changes are made during both incremental and reactive scheduling because a goal of re-scheduling procedures is to minimally impact the schedule. The described heuristic search techniques, which are employed by the Request Oriented Scheduling Engine (ROSE), a prototype generic scheduler, efficiently approximate the cost of reaching a goal from a given state and effective mechanisms for controlling search.

An Overview of the Chemistry and Biology of Reactive Aldehydes

PubMed Central

Fritz, Kristofer S.; Petersen, Dennis R.

2012-01-01

The non-enzymatic free radical generation of reactive aldehydes is known to contribute to diseases of sustained oxidative stress including rheumatoid arthritis, atherosclerosis, neurodegenerative and a number of liver diseases. At the same time, the accumulation of lipid electrophiles has been demonstrated to play a role in cell signaling events through modification of proteins critical for cellular homeostasis. Given the broad scope of reactivity profiles and the ability to modify numerous proteomic and genomic processes, new emphasis is being placed on a systems-based analysis of the consequences of electrophilic adduction. This review focuses on the generation and chemical reactivity of lipid-derived aldehydes with a special focus on the homeostatic responses to electrophilic stress. PMID:22750507

Emotional Reactivity and Internalizing Symptoms: Moderating Role of Emotion Regulation

PubMed Central

Shapero, Benjamin G.; Abramson, Lyn Y.; Alloy, Lauren B.

2015-01-01

Emotion dysregulation has been associated with increases in many forms of psychopathology in adolescents and adults. The development of effective emotion regulation skills is important during adolescence, especially as stressful life events increase during this time. The current study examined two emotion regulation strategies, cognitive reappraisal and affective suppression, in interaction with self-report and biological measures of emotional reactivity as predictors of internalizing symptoms. A community sample of adolescents (n = 127), at an age of risk for depression and anxiety, completed self-report measures of emotional reactivity and internalizing symptoms. In addition, they completed a modified social stress task and were assessed on biological measures of reactivity and regulation. Findings suggested that the trait tendency to reappraise was associated with a reduced impact of emotional reactivity on depressive, but not anxiety symptoms. Implications for shared and specific aspects of emotional reactivity and regulation are discussed. PMID:27231404

Site-selective modification of cellulose nanocrystals with isophorone diisocyanate and formation of polyurethane-CNC composites

Treesearch

Natalie M. Girouard; Shanhong Xu; Gregory T. Schueneman; Meisha L. Shofner; J. Carson Meredith

2016-01-01

The unequal reactivity of the two isocyanate groups in an isophorone diisocyante (IPDI) monomer was exploited to yield modified cellulose nanocrystals (CNCs) with both urethane and isocyanate functionality. The chemical functionality of the modified CNCs was verified with ATR-FTIR analysis and elemental analysis. The selectivity for the secondary isocyanate group using...

Low HAP Materials

DTIC Science & Technology

2009-09-01

Use maleinized triglycerides to replace UPE • Use novel bio-based reactive diluent to replace styrene Bio-Based Carbon Fibers and Thermosetting Resins...SERDP proposed new start, FY10 • Microbially breakdown lignin into oligomers that can be melt spun and carbonized • Modify renewable...D5045-93 • Designed plant oil-based toughening agents • Uses phase separation to capture MFA reactive diluent • Increases toughness while decreasing

Improving TCO-Conjugated Antibody Reactivity for Bioorthogonal Pretargeting

NASA Astrophysics Data System (ADS)

Chu, Tina Tingyi

Cancer remains a major cause of death because of its unpredictable progression. Utilizing bioorthogonal chemistry between trans-cyclooctene (TCO) and tetrazine to target imaging agents to tumors in two subsequent steps offers a more versatile platform for molecular imaging. This is accomplished by pretargeting TCO-modified primary antibody to cell surface biomarkers, followed by delivery of tetrazine-modified imaging probes. In previous work, it has been established that TCO-tetrazine chemistry can be applied to in vivo imaging, resulting in precise tumor detection. However, most TCO modifications on an antibody are not reactive because they are buried within hydrophobic domains. To expose and improve the reactivity, Rahim et al. incorporated a polyethylene glycol (PEG) linker through a two-step reaction with DBCO-azide, which successfully maintained 100% TCO functionality. In this project, various types of linkers were studied to improve the reactivity in a single step. Three primary types of linkers were studied: hydrophilic PEG chains, hydrophobic short linkers, and amphiphilic linkers. Our results show that PEG chain alone can only maintain 40% TCO reactivity. Unexpectedly, a short alkyl chain (valeric acid) provided superior results, with 60% TCO reactivity. Lengthening the alkyl chain did not improve results further. Finally, an amphiphilic linker containing valeric acid and PEG performed worse than either linker type alone, at ˜30% functionality. We conclude that our previous 100% functional TCO result obtained with the two-step coupling may have stemmed from generation of the DBCO/azide cycloaddition product. Future work will explore factors such as rigidity of linker structure, polarity, or charges.

Ion-mobility study of two functionalized pentacene structural isomers using a modified electrospray/triple quadrupole mass spectrometer

NASA Astrophysics Data System (ADS)

Prada, Svitlana V.; Bohme, Diethard K.; Baranov, Vladimir I.

2007-03-01

We report ion-mobility measurements with a modified triple quadrupole mass spectrometer fitted with an ion molecule reactor (IMR) designed to investigate ion molecule reactivity in organic mass spectrometry. Functionalized pentacene ions, which are generally unreactive were chosen for study to decouple drift/diffusion effects from reactivity (including clustering). The IMR is equipped with a variable axial electrostatic drift field (ADF) and is able to trap ions. These capabilities were successfully employed in the measurement of ion mobilities in different modes of IMR operation. Theoretical modeling of the drift dynamics and the special localization of the large ion packet was successfully implemented. The contribution of the quadrupole RF field to the drift dynamics also was taken into consideration.

A nonallergenic birch pollen allergy vaccine consisting of hepatitis PreS-fused Bet v 1 peptides focuses blocking IgG toward IgE epitopes and shifts immune responses to a tolerogenic and Th1 phenotype.

PubMed

Marth, Katharina; Breyer, Isabella; Focke-Tejkl, Margarete; Blatt, Katharina; Shamji, Mohamed H; Layhadi, Janice; Gieras, Anna; Swoboda, Ines; Zafred, Domen; Keller, Walter; Valent, Peter; Durham, Stephen R; Valenta, Rudolf

2013-04-01

Allergen-specific immunotherapy is the only allergen-specific and disease-modifying treatment for allergy. The construction and characterization of a vaccine for birch pollen allergy is reported. Two nonallergenic peptides, PA and PB, derived from the IgE-reactive areas of the major birch pollen allergen Bet v 1 were fused to the hepatitis B surface protein, PreS, in four recombinant fusion proteins containing different numbers and combinations of the peptides. Fusion proteins expressed in Escherichia coli and purified to homogeneity showed a lack of IgE reactivity and allergenic activity when tested with sera and basophils from patients allergic to birch pollen. Compared to Bet v 1 allergen, peptides PA and PB showed reduced T cell activation in PBMCs from allergic patients, whereas PreS fusion proteins induced less IL-5 and more IL-10 and IFN-γ. Immunization of rabbits with the fusion proteins, in particular with a PreS fusion protein 2PAPB-PreS, containing two copies of each peptide, induced high levels of IgG Abs against the major IgE-reactive site on Bet v 1 and related allergens. These IgG Abs inhibited allergic patients' IgE binding to Bet v 1 better than did IgG induced by immunization with complete Bet v 1. Furthermore, 2PAPB-PreS-induced IgG inhibited Bet v 1-induced basophil activation in allergic patients and CD23-facilitated allergen presentation. Our study exemplifies novel beneficial features for a PreS carrier-based peptide vaccine for birch pollen, which, in addition to the established reduction in allergenic activity, include the enhanced focusing of blocking Ab responses toward IgE epitopes, immunomodulatory activity, and reduction of CD23-facilitated allergen presentation.

A Nonallergenic Birch Pollen Allergy Vaccine Consisting of Hepatitis PreS–Fused Bet v 1 Peptides Focuses Blocking IgG toward IgE Epitopes and Shifts Immune Responses to a Tolerogenic and Th1 Phenotype

PubMed Central

Marth, Katharina; Breyer, Isabella; Focke-Tejkl, Margarete; Blatt, Katharina; Shamji, Mohamed H.; Layhadi, Janice; Gieras, Anna; Swoboda, Ines; Zafred, Domen; Keller, Walter; Valent, Peter; Durham, Stephen R.; Valenta, Rudolf

2014-01-01

Allergen-specific immunotherapy is the only allergen-specific and disease-modifying treatment for allergy. The construction and characterization of a vaccine for birch pollen allergy is reported. Two nonallergenic peptides, PA and PB, derived from the IgE-reactive areas of the major birch pollen allergen Bet v 1 were fused to the hepatitis B surface protein, PreS, in four recombinant fusion proteins containing different numbers and combinations of the peptides. Fusion proteins expressed in Escherichia coli and purified to homogeneity showed a lack of IgE reactivity and allergenic activity when tested with sera and basophils from patients allergic to birch pollen. Compared to Bet v 1 allergen, peptides PA and PB showed reduced T cell activation in PBMCs from allergic patients, whereas PreS fusion proteins induced less IL-5 and more IL-10 and IFN-γ. Immunization of rabbits with the fusion proteins, in particular with a PreS fusion protein 2PAPB-PreS, containing two copies of each peptide, induced high levels of IgG Abs against the major IgE-reactive site on Bet v 1 and related allergens. These IgG Abs inhibited allergic patients’ IgE binding to Bet v 1 better than did IgG induced by immunization with complete Bet v 1. Furthermore, 2PAPB-PreS–induced IgG inhibited Bet v 1–induced basophil activation in allergic patients and CD23-facilitated allergen presentation. Our study exemplifies novel beneficial features for a PreS carrier–based peptide vaccine for birch pollen, which, in addition to the established reduction in allergenic activity, include the enhanced focusing of blocking Ab responses toward IgE epitopes, immunomodulatory activity, and reduction of CD23-facilitated allergen presentation. PMID:23440415

Vitamin E as a functional and biocompatibility modifier of synthetic hemodialyzer membranes: an overview of the literature on vitamin E-modified hemodialyzer membranes.

PubMed

Piroddi, Marta; Pilolli, Francesca; Aritomi, Masaharu; Galli, Francesco

2012-01-01

Along with one century of history, research has provided many solutions for hemodialysis (HD) biomaterials, encompassing several generations of copolymers that have found wide application in the development of hollow-fiber dialyzer membranes. Polysulfone-based biomaterials have gained increasing consideration and are now the gold standard in the production of biocompatible hemodialyzers. However, even the highest biocompatibility now available cannot exclude that dialyzer membranes and the overall extracorporeal circulation may produce at the subclinical level immunoinflammatory reactions and thus an increased cardiovascular risk of patients on regular HD therapy. The lipophilic antioxidant and radical scavenger vitamin E has been used (as α-tocopherol) to modify cellulosic and synthetic hollow-fiber membranes with the ultimate goal to neutralize harmful reactive species and to mimic lipid structures of blood cell plasmalemma and lipoprotein particles. Besides filtration and biocompatibility, this modifier has introduced a third function of dialyzer membranes, namely 'antioxidant bioactivity'. Vitamin E can also serve as a template molecule to produce synthetic redox-active and -silent (non-antioxidant) modifiers for future generations of dialyzer membranes. This mini-review article describes the evolution of vitamin E-derived copolymers as a generation of biomaterials that has offered a clinical challenge and still represents a chance to further improving the quality of HD therapy. Copyright © 2012 S. Karger AG, Basel.

Identification of total reversible cysteine oxidation in an atherosclerosis model using a modified biotin switch assay.

PubMed

Li, Ru; Huang, Jiqing; Kast, Juergen

2015-05-01

Oxidative stress due to the imbalance of reactive oxygen species (ROS) and the resulting reversible cysteine oxidation (CysOX) are involved in the early proatherogenic aspect of atherosclerosis. Given that the corresponding redox signaling pathways are still unclear, a modified biotin switch assay was developed to quantify the reversible CysOX in an atherosclerosis model established by using a monocytic cell line treated with platelet releasate. The accumulation of ROS was observed in the model system and validated in human primary monocytes. Through the application of the modified biotin switch assay, we obtained the first reversible CysOX proteome for this model. A total of 75 peptides, corresponding to 53 proteins, were quantified with oxidative modification. The bioinformatics analysis of these CysOX-containing proteins highlighted biological processes including glycolysis, cytoskeleton arrangement, and redox regulation. Moreover, the reversible oxidation of three glycolysis enzymes was observed using this method, and the regulation influence was verified by an enzyme activity assay. NADPH oxidase (NOX) inhibition treatment, in conjunction with the modified biotin switch method, was used to evaluate the global CysOX status. In conclusion, this versatile modified biotin switch assay provides an approach for the quantification of all reversible CysOX and for the study of redox signaling in atherosclerosis as well as in diseases in other biological systems.

Mechanisms of mindfulness training: Monitor and Acceptance Theory (MAT).

PubMed

Lindsay, Emily K; Creswell, J David

2017-02-01

Despite evidence linking trait mindfulness and mindfulness training with a broad range of effects, still little is known about its underlying active mechanisms. Mindfulness is commonly defined as (1) the ongoing monitoring of present-moment experience (2) with an orientation of acceptance. Building on conceptual, clinical, and empirical work, we describe a testable theoretical account to help explain mindfulness effects on cognition, affect, stress, and health outcomes. Specifically, Monitor and Acceptance Theory (MAT) posits that (1), by enhancing awareness of one's experiences, the skill of attention monitoring explains how mindfulness improves cognitive functioning outcomes, yet this same skill can increase affective reactivity. Second (2), by modifying one's relation to monitored experience, acceptance is necessary for reducing affective reactivity, such that attention monitoring and acceptance skills together explain how mindfulness improves negative affectivity, stress, and stress-related health outcomes. We discuss how MAT contributes to mindfulness science, suggest plausible alternatives to the account, and offer specific predictions for future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanisms of Mindfulness Training: Monitor and Acceptance Theory (MAT)1

PubMed Central

Lindsay, Emily K.; Creswell, J. David

2016-01-01

Despite evidence linking trait mindfulness and mindfulness training with a broad range of effects, still little is known about its underlying active mechanisms. Mindfulness is commonly defined as (1) the ongoing monitoring of present-moment experience (2) with an orientation of acceptance. Building on conceptual, clinical, and empirical work, we describe a testable theoretical account to help explain mindfulness effects on cognition, affect, stress, and health outcomes. Specifically, Monitor and Acceptance Theory (MAT) posits that (1), by enhancing awareness of one’s experiences, the skill of attention monitoring explains how mindfulness improves cognitive functioning outcomes, yet this same skill can increase affective reactivity. Second (2), by modifying one’s relation to monitored experience, acceptance is necessary for reducing affective reactivity, such that attention monitoring and acceptance skills together explain how mindfulness improves negative affectivity, stress, and stress-related health outcomes. We discuss how MAT contributes to mindfulness science, suggest plausible alternatives to the account, and offer specific predictions for future research. PMID:27835764

Getting the Message? Native Reactive Electrophiles Pass Two Out of Three Thresholds to be Bona Fide Signaling Mediators.

PubMed

Poganik, Jesse R; Long, Marcus J C; Aye, Yimon

2018-05-01

Precision cell signaling activities of reactive electrophilic species (RES) are arguably among the most poorly-understood means to transmit biological messages. Latest research implicates native RES to be a chemically-distinct subset of endogenous redox signals that influence cell decision making through non-enzyme-assisted modifications of specific proteins. Yet, fundamental questions remain regarding the role of RES as bona fide second messengers. Here, we lay out three sets of criteria we feel need to be met for RES to be considered as true cellular signals that directly mediate information transfer by modifying "first-responding" sensor proteins. We critically assess the available evidence and define the extent to which each criterion has been fulfilled. Finally, we offer some ideas on the future trajectories of the electrophile signaling field taking inspiration from work that has been done to understand canonical signaling mediators. Also see the video abstract here: https://youtu.be/rG7o0clVP0c. © 2018 WILEY Periodicals, Inc.

Identification of a Novel Class of Covalent Modifiers of Hemoglobin as Potential Antisickling Agents

PubMed Central

Omar, A. M.; Mahran, M. A.; Ghatge, M. S.; Chowdhury, N.; Bamane, F. H. A.; El-Araby, M. E.; Abdulmalik, O.; Safo, M. K.

2015-01-01

Aromatic aldehydes and ethacrynic acid (ECA) exhibit antipolymerization properties that are beneficial for sickle cell disease therapy. Based on ECA pharmacophore and its atomic interaction with hemoglobin, we designed and synthesized several compounds--designated as KAUS (imidazolylacryloyl derivatives)--that we hypothesized would bind covalently to βCys93 of hemoglobin and inhibit sickling. The compounds surprisingly showed weak allosteric and antisickling properties. X-ray studies of hemoglobin in complex with representative KAUS compounds revealed an unanticipated mode of Michael addition reaction between the β-unsaturated carbon and the N-terminal αVal1 nitrogen at the α-cleft of hemoglobin, with no observable interaction with βCys93. Interestingly, the compounds exhibited almost no reactivity with the free amino acids, L-Val, L-His and L-Lys, however showed some reactivity with both glutathione and L-Cys. Our findings provide a molecular level explanation to the compounds biological activities and an important framework for targeted modifications that would yield novel potent antisickling agents. PMID:25974708

Sulfur Denitrosylation by an Engineered Trx-like DsbG Enzyme Identifies Nucleophilic Cysteine Hydrogen Bonds as Key Functional Determinant.

PubMed

Lafaye, Céline; Van Molle, Inge; Tamu Dufe, Veronica; Wahni, Khadija; Boudier, Ariane; Leroy, Pierre; Collet, Jean-François; Messens, Joris

2016-07-15

Exposure of bacteria to NO results in the nitrosylation of cysteine thiols in proteins and low molecular weight thiols such as GSH. The cells possess enzymatic systems that catalyze the denitrosylation of these modified sulfurs. An important player in these systems is thioredoxin (Trx), a ubiquitous, cytoplasmic oxidoreductase that can denitrosylate proteins in vivo and S-nitrosoglutathione (GSNO) in vitro However, a periplasmic or extracellular denitrosylase has not been identified, raising the question of how extracytoplasmic proteins are repaired after nitrosative damage. In this study, we tested whether DsbG and DsbC, two Trx family proteins that function in reducing pathways in the Escherichia coli periplasm, also possess denitrosylating activity. Both DsbG and DsbC are poorly reactive toward GSNO. Moreover, DsbG is unable to denitrosylate its specific substrate protein, YbiS. Remarkably, by borrowing the CGPC active site of E. coli Trx-1 in combination with a T200M point mutation, we transformed DsbG into an enzyme highly reactive toward GSNO and YbiS. The pKa of the nucleophilic cysteine, as well as the redox and thermodynamic properties of the engineered DsbG are dramatically changed and become similar to those of E. coli Trx-1. X-ray structural insights suggest that this results from a loss of two direct hydrogen bonds to the nucleophilic cysteine sulfur in the DsbG mutant. Our results highlight the plasticity of the Trx structural fold and reveal that the subtle change of the number of hydrogen bonds in the active site of Trx-like proteins is the key factor that thermodynamically controls reactivity toward nitrosylated compounds. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Sulforaphane Restores Cellular Glutathione Levels and Reduces Chronic Periodontitis Neutrophil Hyperactivity In Vitro

PubMed Central

Dias, Irundika H. K.; Chapple, Ian L. C.; Milward, Mike; Grant, Melissa M.; Hill, Eric; Brown, James; Griffiths, Helen R.

2013-01-01

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 . - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients’ neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 . - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. PMID:23826097

Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro.

PubMed

Dias, Irundika H K; Chapple, Ian L C; Milward, Mike; Grant, Melissa M; Hill, Eric; Brown, James; Griffiths, Helen R

2013-01-01

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 (. -) by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 (. -) production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis.

Induction of Macrophage Chemotaxis by Aortic Extracts from Patients with Marfan Syndrome Is Related to Elastin Binding Protein

PubMed Central

Guo, Gao; Gehle, Petra; Doelken, Sandra; Martin-Ventura, José Luis; von Kodolitsch, Yskert; Hetzer, Roland; Robinson, Peter N.

2011-01-01

Marfan syndrome is an autosomal dominantly inherited disorder of connective tissue with prominent skeletal, ocular, and cardiovascular manifestations. Aortic aneurysm and dissection are the major determinants of premature death in untreated patients. In previous work, we showed that extracts of aortic tissues from the mgR mouse model of Marfan syndrome showed increased chemotactic stimulatory activity related to the elastin-binding protein. Aortic samples were collected from 6 patients with Marfan syndrome and 8 with isolated aneurysms of the ascending aorta. Control samples were obtained from 11 organ donors without known vascular or connective tissue diseases. Soluble proteins extracted from the aortic samples of the two patient groups were compared against buffer controls and against the aortic samples from controls with respect to the ability to induce macrophage chemotaxis as measured using a modified Boyden chamber, as well as the reactivity to a monoclonal antibody BA4 against bioactive elastin peptides using ELISA. Samples from Marfan patients displayed a statistically significant increase in chemotactic inductive activity compared to control samples. Additionally, reactivity to BA4 was significantly increased. Similar statistically significant increases were identified for the samples from patients with idiopathic thoracic aortic aneurysm. There was a significant correlation between the chemotactic index and BA4 reactivity, and the increases in chemotactic activity of extracts from Marfan patients could be inhibited by pretreatment with lactose, VGVAPG peptides, or BA4, which indicates the involvement of EBP in mediating the effects. Our results demonstrate that aortic extracts of patients with Marfan syndrome can elicit macrophage chemotaxis, similar to our previous study on aortic extracts of the mgR mouse model of Marfan syndrome (Guo et al., Circulation 2006; 114:1855-62). PMID:21647416

From hemobiology to vascular disease: a review of the potential of gliclazide to influence the pathogenesis of diabetic vascular disease.

PubMed

Jennings, P E

1994-01-01

Patients with type II diabetes commonly die from thrombotic vascular disease. Large vessel occlusion due to thrombosis or atherosclerotic stenosis is a process accelerated by diabetes and results in premature death. Diabetic small vessel disease, with its unique microangiopathic process, underlies many of the large vessel changes as well as causing retinopathy and nephropathy. The microangiopathic changes produce a prothrombotic tendency that has been widely reported in type II diabetes. There is reduced endothelial cell production of prostacyclin and the activators of fibrinolysis, together with increased platelet reactivity. In addition, there is increased lipid peroxidation and oxidative stress due to excess free-radical activity and impaired antioxidant defenses particularly in the presence of microvascular disease. The development of many of these abnormalities is associated with poor long-term glycemic control. However, the changes are also seen in atherosclerosis in nondiabetic patients where the progression of the disease can be modified by antiplatelet agents and antioxidants. The process of vascular damage is accelerated by diabetes, often due to co-existing disease and aging, although it is not clear that improvement in long-term glycemic control by lowering blood glucose levels to near to the nondiabetic state reduces the development of small and large vessel disease. Although the biochemical mechanism underlying this observation remains uncertain, protein glycosylation and increased platelet reactivity are implicated and interrelated. Increased oxidative stress due to excess free-radical activity may be central to diabetic vascular disease as endothelial cell damage, lipoprotein oxidation, modification of both platelet reactivity and arachidonic acid cascade are all properties of free radicals and their reaction products lipid peroxides.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioactive ruthenium(II)-arene complexes containing modified 18β-glycyrrhetinic acid ligands.

PubMed

Kong, Yaqiong; Chen, Feng; Su, Zhi; Qian, Yong; Wang, Fang-Xin; Wang, Xiuxiu; Zhao, Jing; Mao, Zong-Wan; Liu, Hong-Ke

2018-05-01

Metal-arene complexes containing bioactive natural-product derived ligands can have new and unusual properties. We report the synthesis, characterization and antiproliferative activity of two new Ru(II) arene complexes with imidazole (dichlorido complex 1) or bipyridyl (chlorido complex 2) ligands conjugated to 18β-glycyrrhetinic acid, an active triterpenoid metabolite of Glycyrrhiza glabra. In general, the conjugated ligands and complexes showed only moderate activity against HeLa (cervical), MCF-7 (breast) and A2780 (ovarian) cancer cells, although the activity of complex 2 in the former two cell lines approached that of the drug cisplatin. Complex 2 (in contrast to complex 1) also exhibited significant activity towards both Gram-positive S. aureus and Gram-negative E. coil bacteria. Complex 2 can induce condensation of DNA and enhances the generation of intracellular reactive oxygen species (ROS). The conjugation of natural products to ligands in organometallic half-sandwich complexes provides a strategy to enhance their biological activities. Copyright © 2018 Elsevier Inc. All rights reserved.

Family-oriented cardiac risk estimator: a Java web-based applet.

PubMed

Crouch, Michael A; Jadhav, Ashwin

2003-01-01

We developed a Java applet that calculates four different estimates of a person's 10-year risk for heart attack: (1) Estimate based on Framingham equation (2) Framingham equation estimate modified by C-reactive protein (CRP) level (3) Framingham estimate modified by family history of heart disease in parents or siblings (4) Framingham estimate modified by both CRP and family heart disease history. This web-based, family-oriented cardiac risk estimator uniquely considers family history and CRP while estimating risk.

Ubiquitin C-terminal electrophiles are activity-based probes for identification and mechanistic study of ubiquitin conjugating machinery.

PubMed

Love, Kerry Routenberg; Pandya, Renuka K; Spooner, Eric; Ploegh, Hidde L

2009-04-17

Protein modification by ubiquitin (Ub) and ubiquitin-like modifiers (Ubl) requires the action of activating (E1), conjugating (E2), and ligating (E3) enzymes and is a key step in the specific destruction of proteins. Deubiquitinating enzymes (DUBs) deconjugate substrates modified with Ub/Ubl's and recycle Ub inside the cell. Genome mining based on sequence homology to proteins with known function has assigned many enzymes to this pathway without confirmation of either conjugating or DUB activity. Function-dependent methodologies are still the most useful for rapid identification or assessment of biological activity of expressed proteins from cells. Activity-based protein profiling uses chemical probes that are active-site-directed for the classification of protein activities in complex mixtures. Here we show that the design and use of an expanded set of Ub-based electrophilic probes allowed us to recover and identify members of each enzyme class in the ubiquitin-proteasome system, including E3 ligases and DUBs with previously unverified activity. We show that epitope-tagged Ub-electrophilic probes can be used as activity-based probes for E3 ligase identification by in vitro labeling and activity studies of purified enzymes identified from complex mixtures in cell lysate. Furthermore, the reactivity of our probe with the HECT domain of the E3 Ub ligase ARF-BP1 suggests that multiple cysteines may be in the vicinity of the E2-binding site and are capable of the transfer of Ub to self or to a substrate protein.

Associations between time spent sitting and cancer-related biomarkers in postmenopausal women: an exploration of effect modifiers

PubMed Central

Paxton, Raheem J.; Vitolins, Mara Z.; Fenton, Jenifer; Paskett, Electra; Pollak, Michael; Hays-Grudo, Jennifer; Hursting, Stephen D.; Chang, Shine

2015-01-01

Purpose Despite evidence that prolonged periods of sitting may influence biological mediators of cancer development, few studies have considered these relationships in a cancer-specific context. Methods This cross-sectional study included 755 post-menopausal women enrolled in an ancillary study of the Women’s Health Initiative. Plasma levels of Insulin-like growth factor-I (IGF-I), IGF-binding protein-3, leptin, insulin, C-peptide, C-reactive protein (CRP), and Interleukin (IL)-6 were measured. The time spent sitting per day was categorized as quartiles (Qs). The relationships between sedentary time and biomarkers were modified by race, physical activity, and exogenous estrogen use. Results IGF-I levels among African American (AA) women were higher than those of white women across the Qs of sedentary time. Likewise, IL-6 levels in AA women were higher than those in white women at Q3 and Q4 of sedentary time. IGFBP-3 levels were higher and insulin levels were lower across the Qs of sedentary time among women meeting guidelines for physical activity than women who were not. Additionally, CRP levels were higher among estrogen users than nonusers at Q1, Q2, and Q4 of sedentary time. Conclusions These results suggest that relationship between time spent sitting and cancer-related biomarkers may not be simply linear, but differ in the context of effect modifiers. PMID:25238978

Iron-catalyzed oxidative biaryl cross-couplings via mixed diaryl titanates: significant influence of the order of combining aryl Grignard reagents with titanate.

PubMed

Liu, Kun Ming; Wei, Juan; Duan, Xin Fang

2015-03-18

The mixed diaryl titanates were used for the first time to modify the reactivity of two aryl Grignard reagents. Two titanate intermediates, Ar[Ar'Ti(OR)3]MgX and Ar'[ArTi(OR)3]MgX, formed via alternating the sequence of combining Grignard reagents with ClTi(OR)3 showed a significant reactivity difference. Taking advantage of such different reactivity, two highly structurally similar aryl groups could be facilely assembled through iron-catalyzed oxidative cross-couplings using oxygen as the oxidant.

A Multi-agent Based Cooperative Voltage and Reactive Power Control

NASA Astrophysics Data System (ADS)

Ishida, Masato; Nagata, Takeshi; Saiki, Hiroshi; Shimada, Ikuhiko; Hatano, Ryousuke

In order to maintain system voltage within the optimal range and prevent voltage instability phenomena before they occur, a variety of phase modifying equipment is installed in optimal locations throughout the power system network and a variety of methods of voltage reactive control are employed. The proposed system divided the traditional method to control voltage and reactive power into two sub problems; “voltage control” to adjust the secondary bus voltage of substations, and “reactive power control” to adjust the primary bus voltage. In this system, two types of agents are installed in substations in order to cooperate “voltage control” and “reactive power control”. In order to verify the performance of the proposed method, it has been applied to the model network system. The results confirm that our proposed method is able to control violent fluctuations in load.

Effect of functionalized and non-functionalized nanodiamond on the morphology and activities of antioxidant enzymes of lung epithelial cells (A549).

PubMed

Solarska-Ściuk, Katarzyna; Gajewska, Agnieszka; Glińska, Sława; Michlewska, Sylwia; Balcerzak, Łucja; Jamrozik, Agnieszka; Skolimowski, Janusz; Burda, Květoslava; Bartosz, Grzegorz

2014-10-05

The development of nanotechnology opens up new ways for biomedical applications of unmodified and modified diamond nanoparticles which are one of the most popular nanomaterials used in biology, biotechnology, medicine, cosmetics and engineering. They have been applied as diagnostic and therapeutic agents because they can be targeted to and localized in cells causing apoptosis and necrosis. The problem of biocompatibility of nanodiamonds at higher concentrations is thus of primary importance. The first step in the modification of DNPs is usually the introduction of hydrogen groups, which can bind other functional groups. The basic method to introduce -OH groups onto nanoparticles is the Fenton reaction. The aim of this study was to compare the effect of unmodified nanodiamond particles and nanoparticles modified by introduction of -OH groups and etoposide onto their surface reaction on human non-small lung cancer cells. A549 cells were incubated with 2-100μg/ml nanopowders and at 0.6-24μg/ml etoposide in the DMEM medium. We observed a decrease of cells viability and generation of reactive oxygen/ nitrogen species in the cells after incubation, estimated by oxidation of H2DCF-DA and DAF-FM-DA. Modified detonation nanoparticles affected also the cellular content of glutathione and activities of main antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase and catalase). The results of TEM microscopy show changes in cell morphology. These data demonstrate that modified nanoparticles induce oxidative stress in the target cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease.

PubMed

Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A; Ravindranath, Vijayalakshmi

2017-12-01

Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APP Swe /PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9-10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269-1280.

Bactericidal effects of plasma-modified surface chemistry of silicon nanograss

NASA Astrophysics Data System (ADS)

Ostrikov, Kola; Macgregor-Ramiasa, Melanie; Cavallaro, Alex; (Ken Ostrikov, Kostya; Vasilev, Krasimir

2016-08-01

The surface chemistry and topography of biomaterials regulate the adhesion and growth of microorganisms in ways that are still poorly understood. Silicon nanograss structures prepared via inductively coupled plasma etching were coated with plasma deposited nanometer-thin polymeric films to produce substrates with controlled topography and defined surface chemistry. The influence of surface properties on Staphylococcus aureus proliferation is demonstrated and explained in terms of nanograss substrate wetting behaviour. With the combination of the nanograss topography; hydrophilic plasma polymer coatings enhanced antimicrobial activity while hydrophobic coatings reduced it. This study advances the understanding of the effects of surface wettability on the bactericidal properties of reactive nano-engineered surfaces.

Metabolic control of the epigenome in systemic Lupus erythematosus

PubMed Central

Oaks, Zachary; Perl, Andras

2014-01-01

Epigenetic mechanisms are proposed to underlie aberrant gene expression in systemic lupus erythematosus (SLE) that results in dysregulation of the immune system and loss of tolerance. Modifications of DNA and histones require substrates derived from diet and intermediary metabolism. DNA and histone methyltransferases depend on S-adenosylmethionine (SAM) as a methyl donor. SAM is generated from adenosine triphosphate (ATP) and methionine by methionine adenosyltransferase (MAT), a redox-sensitive enzyme in the SAM cycle. The availability of B vitamins and methionine regulate SAM generation. The DNA of SLE patients is hypomethylated, indicating dysfunction in the SAM cycle and methyltransferase activity. Acetyl-CoA, which is necessary for histone acetylation, is generated from citrate produced in mitochondria. Mitochondria are also responsible for de novo synthesis of flavin adenine dinucleotide (FAD) for histone demethylation. Mitochondrial oxidative phosphorylation is the dominant source of ATP. The depletion of ATP in lupus T cells may affect MAT activity as well as adenosine monophosphate (AMP) activated protein kinase (AMPK), which phosphorylates histones and inhibits mechanistic target of rapamycin (mTOR). In turn, mTOR can modify epigenetic pathways including methylation, demethylation, and histone phosphorylation and mediates enhanced T-cell activation in SLE. Beyond their role in metabolism, mitochondria are the main source of reactive oxygen intermediates (ROI), which activate mTOR and regulate the activity of histone and DNA modifying enzymes. In this review we will focus on the sources of metabolites required for epigenetic regulation and how the flux of the underlying metabolic pathways affects gene expression. PMID:24128087

Chemical characterization and in vitro toxicity of diesel exhaust particulate matter generated under varying conditions

PubMed Central

Cox, David P.; Drury, Bertram E.; Gould, Timothy R.; Kavanagh, Terrance J.; Paulsen, Michael H.; Sheppard, Lianne; Simpson, Christopher D.; Stewart, James A.; Larson, Timothy V.; Kaufman, Joel D.

2014-01-01

Epidemiologic studies have linked diesel exhaust (DE) to cardiovascular and respiratory morbidity and mortality, as well as lung cancer. DE composition is known to vary with many factors, although it is unclear how this influences toxicity. We generated eight DE atmospheres by applying a 2×2×2 factorial design and altering three parameters in a controlled exposure facility: (1) engine load (27 vs 82 %), (2) particle aging (residence time ~5 s vs ~5 min prior to particle collection), and (3) oxidation (with or without ozonation during dilution). Selected exposure concentrations of both diesel exhaust particles (DEPs) and DE gases, DEP oxidative reactivity via DTT activity, and in vitro DEP toxicity in murine endothelial cells were measured for each DE atmosphere. Cell toxicity was assessed via measurement of cell proliferation (colony formation assay), cell viability (MTT assay), and wound healing (scratch assay). Differences in DE composition were observed as a function of engine load. The mean 1-nitropyrene concentration was 15 times higher and oxidative reactivity was two times higher for low engine load versus high load. There were no substantial differences in measured toxicity among the three DE exposure parameters. These results indicate that alteration of applied engine load shifts the composition and can modify the biological reactivity of DE. While engine conditions did not affect the selected in vitro toxicity measures, the change in oxidative reactivity suggests that toxicological studies with DE need to take into account engine conditions in characterizing biological effects. PMID:26539254

Emotional reactivity: Beware its involvement in traffic accidents.

PubMed

M'bailara, Katia; Atzeni, Thierry; Contrand, Benjamin; Derguy, Cyrielle; Bouvard, Manuel-Pierre; Lagarde, Emmanuel; Galéra, Cédric

2018-04-01

Reducing risk attributable to traffic accidents is a public health challenge. Research into risk factors in the area is now moving towards identification of the psychological factors involved, particularly emotional states. The aim of this study was to evaluate the link between emotional reactivity and responsibility in road traffic accidents. We hypothesized that the more one's emotional reactivity is disturbed, the greater the likelihood of being responsible for a traffic accident. This case-control study was based on a sample of 955 drivers injured in a motor vehicle crash. Responsibility levels were determined with a standardized method adapted from the quantitative Robertson and Drummer crash responsibility instrument. Emotional reactivity was assessed with the MATHYS. Hierarchical cluster analysis discriminated four distinctive driver's emotional reactivity profiles: basic emotional reactivity (54%), mild emotional hyper-reactivity (29%), emotional hyper-reactivity (11%) and emotional hypo-reactivity (6%). Drivers who demonstrated emotional hypo-reactivity had a 2.3-fold greater risk of being responsible for a traffic accident than those with basic emotional reactivity. Drivers' responsibility in traffic accidents depends on their emotional status. The latter can change the ability of drivers, modifying their behavior and thus increasing their propensity to exhibit risk behavior and to cause traffic accidents. Copyright © 2017 Elsevier B.V. All rights reserved.

Proteins oxidation and autoantibodies' reactivity against hydrogen peroxide and malondialdehyde -oxidized thyroid antigens in patients' plasmas with Graves' disease and Hashimoto Thyroiditis.

PubMed

Mseddi, Malek; Ben Mansour, Riadh; Gargouri, Bochra; Mnif, Fatma; El Ghawi, Samir; Hammami, Boutheina; Ghorbel, Abdelmonem; Abid, Mohamed; Lassoued, Saloua

2017-06-25

The aim of this study was to evaluate proteins oxidation in plasmas of two autoimmune thyroid diseases (AITD): Graves' disease (GD) and Hashimoto Thyroiditis (HT), and to determine whether oxidative modification of thyroid antigens (T.Ag) enhanced the reactivity of autoantibodies in plasmas of AITD patients compared with the reactivity towards native T.Ag. Carbonyl and thiol groups and MDA-protein adducts were assessed spectrophotometric methods in plasmas of 74 AITD patients and 65 healthy controls. The reactivities immunoglobulin (Ig)G autoantibodies towards malondialdéhyde (MDA)-modified T.Ag, hydrogen peroxide (H 2 O 2 )-modified T.Ag, native T.Ag and native derm were checked by enzyme-linked immunosorbent assay (ELISA). Evaluation of oxidized proteins exhibited high levels of MDA bound to proteins and carbonyl groups, as well as reduced thiol level in plasmas of AITD patients by comparison to healthy controls (p < 0.05). The ELISA test showed that AITD patients' plasmas' reactivity to native T.Ag was significantly increased to the reactivity towards native derm, whereas, no differences were found in the reactivity to native T.Ag and derm in controls plasmas. In addition, treatment of T.Ag by oxidants revealed enhanced reactivity of IgG circulating autoantibodies against H 2 O 2 -oxidized T.Ag compared to native ones (p < 0.001) in plasmas of both AITD. Also, reactivity's to MDA-oxidized T.Ag in GD plasmas decreased compared to native ones (p < 0.05) and no changes were noted for HT. Pearson correlation study resulted in positive correlation between reactivity's to H 2 O 2 -oxidized T.Ag and free triodotyronine level in GD patients (r = 0.42, p < 0.05) in one hand and thyroid stimulating hormone level in HT patients in the other (r = 0.65, p < 0.001). The data suggest that high production of H 2 O 2 probably occurred during hormone synthesis could contribute to protein oxidation in AITD and to create neoepitopes responsible for autoantibody reactivity's to H 2 O 2 -oxidized T.Ag enhancement. These results provide support to the involvement of oxidative stress in AITD development and/or exacerbation. Copyright © 2017 Elsevier B.V. All rights reserved.

Degradation of aniline by electrochemical activation of peroxydisulfate at MWCNT cathode: The proofed concept of nonradical oxidation process.

PubMed

Nie, Chunyang; Ao, Zhimin; Duan, Xiaoguang; Wang, Chengying; Wang, Shaobin; An, Taicheng

2018-05-07

Enhanced elimination of aniline in aqueous solution was achieved by coupling electrosorption of aniline and electrochemical activation of peroxydisulfate (PDS) at multi-walled carbon nanotube (MWCNT) cathode, in which a synergistic effect occurred. It was found that PDS could be effectively activated under a small voltage at MWCNT cathode owing to the specific pore structures of MWCNTs. A nonradical oxidation pathway instead of radical-based oxidation was proposed from the cathodic activation of PDS, wherein PDS molecules with a modified electronic structure was suggested to be the principal reactive species. Meanwhile, the influences of various operation parameters such as electrode potential, PDS concentration, presence of chloride ions on the elimination efficiency, and the stability of MWCNT electrode were also attempted. Therefore, the electrochemical activation of PDS by MWCNT cathode is a promising energy-saving method for the treatment of organic pollutants in wastewater. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pathway and Cell-Specific Kappa-Opioid Receptor Modulation of Excitatory-Inhibitory Balance Differentially Gates D1 and D2 Accumbens Neuron Activity

PubMed Central

Tejeda, Hugo A.; Wu, Jocelyn; Kornspun, Alana R.; Pignatelli, Marco; Kashtelyan, Vadim; Krashes, Michael J.; Lowell, Brad B.; Carlezon, William A.; Bonci, Antonello

2018-01-01

Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic KOR inhibition decreases excitatory drive of D1 MSN activity by the amygdala, but not hippocampus. Conversely, presynaptic inhibition by KORs of inhibitory synapses on D2 MSNs enhances integration of excitatory drive by the amygdala and hippocampus. In conclusion, we describe a circuit-based mechanism showing differential gating of afferent control of D1 and D2 MSN activity by KORs in a pathway specific manner. PMID:28056342

Tribology of alternative bearings.

PubMed

Fisher, John; Jin, Zhongmin; Tipper, Joanne; Stone, Martin; Ingham, Eileen

2006-12-01

The tribological performance and biological activity of the wear debris produced has been compared for highly cross-linked polyethylene, ceramic-on-ceramic, metal-on-metal, and modified metal bearings in a series of in vitro studies from a single laboratory. The functional lifetime demand of young and active patients is 10-fold greater than the estimated functional lifetime of traditional polyethylene. There is considerable interest in using larger diameter heads in these high demand patients. Highly cross-linked polyethylene show a four-fold reduction in functional biological activity. Ceramic-on-ceramic bearings have the lowest wear rates and least reactive wear debris. The functional biological activity is 20-fold lower than with highly cross-linked polyethylene. Hence, ceramic-on-ceramic bearings address the tribological lifetime demand of highly active patients. Metal-on-metal bearings have substantially lower wear rates than highly cross-linked polyethylene and wear decreases with head diameter. Bedding in wear is also lower with reduced radial clearance. Differential hardness ceramic-on-metal bearings and the application of ceramic-like coatings reduce metal wear and ion levels.

Modeling covalent-modifier drugs.

PubMed

Awoonor-Williams, Ernest; Walsh, Andrew G; Rowley, Christopher N

2017-11-01

In this review, we present a summary of how computer modeling has been used in the development of covalent-modifier drugs. Covalent-modifier drugs bind by forming a chemical bond with their target. This covalent binding can improve the selectivity of the drug for a target with complementary reactivity and result in increased binding affinities due to the strength of the covalent bond formed. In some cases, this results in irreversible inhibition of the target, but some targeted covalent inhibitor (TCI) drugs bind covalently but reversibly. Computer modeling is widely used in drug discovery, but different computational methods must be used to model covalent modifiers because of the chemical bonds formed. Structural and bioinformatic analysis has identified sites of modification that could yield selectivity for a chosen target. Docking methods, which are used to rank binding poses of large sets of inhibitors, have been augmented to support the formation of protein-ligand bonds and are now capable of predicting the binding pose of covalent modifiers accurately. The pK a 's of amino acids can be calculated in order to assess their reactivity towards electrophiles. QM/MM methods have been used to model the reaction mechanisms of covalent modification. The continued development of these tools will allow computation to aid in the development of new covalent-modifier drugs. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.

Glutathionylation regulates cytosolic NADP+-dependent isocitrate dehydrogenase activity.

PubMed

Shin, Seoung Woo; Oh, Chang Joo; Kil, In Sup; Park, Jeen-Woo

2009-04-01

Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) is susceptible to inactivation by numerous thiol-modifying reagents. This study now reports that Cys269 of IDPc is a target for S-glutathionylation and that this modification is reversed by dithiothreitol as well as enzymatically by cytosolic glutaredoxin in the presence of GSH. Glutathionylated IDPc was significantly less susceptible than native protein to peptide fragmentation by reactive oxygen species and proteolytic digestion. Glutathionylation may play a protective role in the degradation of protein through the structural alterations of IDPc. HEK293 cells treated with diamide displayed decreased IDPc activity and accumulated glutathionylated enzyme. Using immunoprecipitation with an anti-IDPc IgG and immunoblotting with an anti-GSH IgG, we purified and positively identified glutathionylated IDPc from the kidneys of mice subjected to ischemia/reperfusion injury and from the livers of ethanol-administered rats. These results suggest that IDPc activity is modulated through enzymatic glutathionylation and deglutathionylation during oxidative stress.

Promoted Iron Nanocrystals Obtained via Ligand Exchange as Active and Selective Catalysts for Synthesis Gas Conversion

PubMed Central

2017-01-01

Colloidal synthesis routes have been recently used to fabricate heterogeneous catalysts with more controllable and homogeneous properties. Herein a method was developed to modify the surface composition of colloidal nanocrystal catalysts and to purposely introduce specific atoms via ligands and change the catalyst reactivity. Organic ligands adsorbed on the surface of iron oxide catalysts were exchanged with inorganic species such as Na2S, not only to provide an active surface but also to introduce controlled amounts of Na and S acting as promoters for the catalytic process. The catalyst composition was optimized for the Fischer–Tropsch direct conversion of synthesis gas into lower olefins. At industrially relevant conditions, these nanocrystal-based catalysts with controlled composition were more active, selective, and stable than catalysts with similar composition but synthesized using conventional methods, possibly due to their homogeneity of properties and synergic interaction of iron and promoters. PMID:28824820

Enhancement of catalytic activity of platinum-based nanoparticles towards electrooxidation of ethanol through interfacial modification with heteropolymolybdates

NASA Astrophysics Data System (ADS)

Barczuk, Piotr J.; Lewera, Adam; Miecznikowski, Krzysztof; Zurowski, Artur; Kulesza, Pawel J.

As evidenced from the increase of electrocatalytic currents measured under voltammetric and chronoamperometric conditions, the activity of bimetallic Pt-Ru and Pt-Sn nanoparticles towards oxidation of ethanol is increased by modification of their surfaces with ultra-thin films of phosphododecamolybdic acid (H 3PMo 12O 40). The enhancement effect has been most pronounced in a case of heteropolymolybdate-modified carbon-supported Pt-Sn catalysts. Independent high-resolution XPS measurements indicate the ability of heteropolymolybdates to stabilize tin (in bimetallic Pt-Sn particles) at higher oxidation states (presumably as tin oxo species). The overall activation effect may also be ascribed to changes in the morphology of catalytic films following modification with heteropolymolybdates. Presence of the polyoxometallate is also likely to increase of the interfacial population of reactive oxo groups in the vicinity of platinum centers.

Tuning the reactivity of semiconductor surfaces by functionalization with amines of different basicity

PubMed Central

Bent, Stacey F.; Kachian, Jessica S.; Rodríguez-Reyes, Juan Carlos F.; Teplyakov, Andrew V.

2011-01-01

Surface functionalization of semiconductors has been the backbone of the newest developments in microelectronics, energy conversion, sensing device design, and many other fields of science and technology. Over a decade ago, the notion of viewing the surface itself as a chemical reagent in surface reactions was introduced, and adding a variety of new functionalities to the semiconductor surface has become a target of research for many groups. The electronic effects on the substrate have been considered as an important consequence of chemical modification. In this work, we shift the focus to the electronic properties of the functional groups attached to the surface and their role on subsequent reactivity. We investigate surface functionalization of clean Si(100)-2 × 1 and Ge(100)-2 × 1 surfaces with amines as a way to modify their reactivity and to fine tune this reactivity by considering the basicity of the attached functionality. The reactivity of silicon and germanium surfaces modified with ethylamine (CH3CH2NH2) and aniline (C6H5NH2) is predicted using density functional theory calculations of proton attachment to the nitrogen of the adsorbed amine to differ with respect to a nucleophilic attack of the surface species. These predictions are then tested using a model metalorganic reagent, tetrakis(dimethylamido)titanium (((CH3)2N)4Ti, TDMAT), which undergoes a transamination reaction with sufficiently nucleophilic amines, and the reactivity tests confirm trends consistent with predicted basicities. The identity of the underlying semiconductor surface has a profound effect on the outcome of this reaction, and results comparing silicon and germanium are discussed. PMID:21068370

Tyrosines of Human and Mouse Transferrin Covalently Labeled by Organophosphorus Agents: A New Motif for Binding to Proteins that Have No Active Site Serine

PubMed Central

Li, Bin; Schopfer, Lawrence M.; Grigoryan, Hasmik; Thompson, Charles M.; Hinrichs, Steven H.; Masson, Patrick; Lockridge, Oksana

2009-01-01

The expectation from the literature is that organophosphorus (OP) agents bind to proteins that have an active site serine. However, transferrin, a protein with no active site serine, was covalently modified in vitro by 0.5mM 10-fluoroethoxyphosphinyl-N-biotinamido pentyldecanamide, chlorpyrifos oxon, diisopropylfluorophosphate, dichlorvos, sarin, and soman. The site of covalent attachment was identified by analyzing tryptic peptides in the mass spectrometer. Tyr 238 and Tyr 574 in human transferrin and Tyr 238, Tyr 319, Tyr 429, Tyr 491, and Tyr 518 in mouse transferrin were labeled by OP. Tyrosine in the small synthetic peptide ArgTyrThrArg made a covalent bond with diisopropylfluorophosphate, chlorpyrifos oxon, and dichlorvos at pH 8.3. These results, together with our previous demonstration that albumin and tubulin bind OP on tyrosine, lead to the conclusion that OP bind covalently to tyrosine, and that OP binding to tyrosine is a new OP-binding residue. The OP-reactive tyrosines are activated by interaction with Arg or Lys. It is suggested that many proteins in addition to those already identified may be modified by OP on tyrosine. The extent to which tyrosine modification by OP can occur in vivo and the toxicological implications of such modifications require further investigation. PMID:18930948

Re-Active Passive devices for control of noise transmission through a panel

NASA Astrophysics Data System (ADS)

Carneal, James P.; Giovanardi, Marco; Fuller, Chris R.; Palumbo, Dan

2008-01-01

Re-Active Passive devices have been developed to control low-frequency (<1000 Hz) noise transmission through a panel. These devices use a combination of active, re-active, and passive technologies packaged into a single unit to control a broad frequency range utilizing the strength of each technology over its best suited frequency range. The Re-Active Passive device uses passive constrained layer damping to cover relatively high-frequency range (>150 Hz), reactive distributed vibration absorber to cover the medium-frequency range (50-200 Hz), and active control for controlling low frequencies (<150 Hz). The actuator was applied to control noise transmission through a panel mounted in the Transmission Loss Test Facility at Virginia Tech. Experimental results are presented for the bare panel, and combinations of passive treatment, reactive treatment, and active control. Results indicate that three Re-Active Passive devices were able to increase the overall broadband (15-1000 Hz) transmission loss by 9.4 dB. These three devices added a total of 285 g to the panel mass of 6.0 kg, or approximately 5%, not including control electronics.

Modifying ceria (111) with a TiO2 nanocluster for enhanced reactivity.

PubMed

Nolan, Michael

2013-11-14

Modification of ceria catalysts is of great interest for oxidation reactions such as oxidative dehydrogenation of alcohols. Improving the reactivity of ceria based catalysts for these reactions means that they can be run at lower temperatures and density functional theory (DFT) simulations of new structures and compositions are proving valuable in the development of these catalysts. In this paper, we have used DFT+U (DFT corrected for on-site Coulomb interactions) to examine the reactivity of a novel modification of ceria, namely, modifying with TiO2, using the example of a Ti2O4 species adsorbed on the ceria (111) surface. The oxygen vacancy formation energy in the Ti2O4-CeO2 system is significantly reduced over the bare ceria surfaces, which together with previous work on ceria-titania indicates that the presence of the interface favours oxygen vacancy formation. The energy gain upon hydrogenation of the catalyst, which is the rate determining step in oxidative dehydrogenation, further points to the improved oxidation power of this catalyst structure.

Chemical modification of M13 bacteriophage and its application in cancer cell imaging.

PubMed

Li, Kai; Chen, Yi; Li, Siqi; Nguyen, Huong Giang; Niu, Zhongwei; You, Shaojin; Mello, Charlene M; Lu, Xiaobing; Wang, Qian

2010-07-21

The M13 bacteriophage has been demonstrated to be a robust scaffold for bionanomaterial development. In this paper, we report on the chemical modifications of three kinds of reactive groups, i.e., the amino groups of lysine residues or N-terminal, the carboxylic acid groups of aspartic acid or glutamic acid residues, and the phenol group of tyrosine residues, on M13 surface. The reactivity of each group was identified through conjugation with small fluorescent molecules. Furthermore, the regioselectivity of each reaction was investigated by HPLC-MS-MS. By optimizing the reaction condition, hundreds of fluorescent moieties could be attached to create a highly fluorescent M13 bacteriophage. In addition, cancer cell targeting motifs such as folic acid could also be conjugated onto the M13 surface. Therefore, dual-modified M13 particles with folic acid and fluorescent molecules were synthesized via the selective modification of two kinds of reactive groups. Such dual-modified M13 particles showed very good binding affinity to human KB cancer cells, which demonstrated the potential applications of M13 bacteriophage in bioimaging and drug delivery.

[Clinical observation of modified Da Chaihu decoction in treating essential hypertension with anxiety].

PubMed

Zhang, Xiang-Dong; Cheng, Wang-Qiang; Wang, Yong-Gang; Zhang, Zheng

2017-06-01

To observe the clinical efficacy of modified Da Chaihu decoction in treating essential hypertension with anxiety, the randomized, controlled, clinical trial was performed in this study. One hundred and twenty-six hypertensive patients with anxiety meeting the inclusive criteria were randomized into the treatment group and the control group. All of the included patients in the above 2 groups were treated by amlodipine besylate tablets. Patients in the treatment group were given Chinese herbal medicine modified Da Chaihu decoction every day. And patients in the control group were given flupentixol and melitracen tablets. The treatment course was 4 weeks. Blood pressure, the score of traditional Chinese medicine syndrome, blood lipids, C reactive protein, the Hamilton anxiety scale score and adverse effects were observed. It has been identified that, both systolic and diastolic blood pressure were significantly reduced (P<0.05). However, no significant difference between the treatment group and the control group was identified. For traditional Chinese medicine syndrome, it was significantly improved in the treatment group (P<0.05). For blood lipids, TC, TG, HDL-C, and LDL-C were significantly improved in the treatment group (P<0.05). After treatment, only TC was significantly reduced in the treatment group when compared to the control group (P<0.05). For C reactive protein, it was significantly reduced in the treatment group after treatment (P<0.05). For anxiety, no significant difference between the treatment group and the control group on the Hamilton anxiety scale score was identified. For adverse effect, no severe adverse effect was identified in this study. The modified Da Chaihu decoction maybe effective in the treatment of essential hypertension with anxiety. In addition to a certain role in lowering blood pressure, the modified Da Chaihu decoction was also effective in improving traditional Chinese medicine syndrome and blood lipids, reducing the level of C reactive protein, relieving anxiety with little adverse effect. Copyright© by the Chinese Pharmaceutical Association.

Reactive Diazonium-Modified Silica Fillers for High-Performance Polymers.

PubMed

Sandomierski, Mariusz; Strzemiecka, Beata; Chehimi, Mohamed M; Voelkel, Adam

2016-11-08

We describe a simple way of modification of three silica-based fillers with in situ generated 4-hydroxymethylbenzenediazonium salt ( + N 2 -C 6 H 4 -CH 2 OH). The rationale for using a hydroxyl-functionalized diazonium salt is that it provides surface-functionalized fillers that can react with phenolic resins. The modification of silica by diazonium salts was assessed using Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). FTIR spectroscopy permitted the tracking of benzene ring breathing and C-C. The absence of the characteristic N≡N stretching vibration in the 2200-2300 cm -1 range indicates the loss of the diazonium group. XPS results indicate a higher C/Si atomic ratio after the diazonium modification of fillers and the presence of π-π* C1s satellite peaks characteristic of the surface-tethered aromatic species. Adhesion of aryl layers to the silicas is excellent because they withstand harsh thermal and organic solvent treatments. Phenolic resins (used, for example, as binders in abrasive products) were filled with diazonium-modified silicas at 10-25 wt %. The reactivity of the fillers toward phenolic resins was evaluated by the determination of the flow distance. After annealing at 180 °C, the diazonium-modified silica/phenolic resin composites were mechanically tested using the three-point flexural method. The flexural strength was found to be up to 35% higher than that of the composites prepared without any diazonium salts. Diazonium-modified silica with surface-bound -CH 2 -OH groups is thus ideal reactive filler for phenolic resins. Such filler ensures interfacial chemical reactions with the matrix and imparts robust mechanical properties to the final composites. This specialty diazonium-modified silica will find potential application as fillers in the composites for the abrasive industry. More generally, aryl diazonium salts are a unique new series of compounds for tailoring the surface properties of fillers and tuning the physicochemical and mechanical properties of polymer composites.

A cobalt oxyhydroxide-modified upconversion nanosystem for sensitive fluorescence sensing of ascorbic acid in human plasma

NASA Astrophysics Data System (ADS)

Cen, Yao; Tang, Jun; Kong, Xiang-Juan; Wu, Shuang; Yuan, Jing; Yu, Ru-Qin; Chu, Xia

2015-08-01

Ascorbic acid (AA), a potent antioxidant readily scavenging reactive species, is a crucial micronutrient involved in many biochemical processes. Here, we have developed a cobalt oxyhydroxide (CoOOH)-modified upconversion nanosystem for fluorescence sensing of AA activity in human plasma. The nanosystem consists of upconversion nanoparticles (UCNPs) NaYF4:30% Yb,0.5% Tm@NaYF4, which serve as energy donors, and CoOOH nanoflakes formed on the surface of UCNPs, which act as efficient energy acceptors. The fluorescence resonance energy transfer (FRET) process from the UCNPs to the absorbance of the CoOOH nanoflakes occurs in the nanosystem. The AA-mediated specific redox reaction reduces CoOOH into Co2+, leading to the inhibition of FRET, and resulting in the recovery of upconversion emission spectra. On the basis of these features, the nanosystem can be used for sensing AA activity with sensitivity and selectivity. Moreover, due to the minimizing background interference provided by UCNPs, the nanosystem has been applied to monitoring AA levels in human plasma sample with satisfactory results. The proposed approach may potentially provide an analytical platform for research and clinical diagnosis of AA related diseases.Ascorbic acid (AA), a potent antioxidant readily scavenging reactive species, is a crucial micronutrient involved in many biochemical processes. Here, we have developed a cobalt oxyhydroxide (CoOOH)-modified upconversion nanosystem for fluorescence sensing of AA activity in human plasma. The nanosystem consists of upconversion nanoparticles (UCNPs) NaYF4:30% Yb,0.5% Tm@NaYF4, which serve as energy donors, and CoOOH nanoflakes formed on the surface of UCNPs, which act as efficient energy acceptors. The fluorescence resonance energy transfer (FRET) process from the UCNPs to the absorbance of the CoOOH nanoflakes occurs in the nanosystem. The AA-mediated specific redox reaction reduces CoOOH into Co2+, leading to the inhibition of FRET, and resulting in the recovery of upconversion emission spectra. On the basis of these features, the nanosystem can be used for sensing AA activity with sensitivity and selectivity. Moreover, due to the minimizing background interference provided by UCNPs, the nanosystem has been applied to monitoring AA levels in human plasma sample with satisfactory results. The proposed approach may potentially provide an analytical platform for research and clinical diagnosis of AA related diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03588k

Impact of a heteroatom in a structure-activity relationship study on analogues of phenyl glycidyl ether (PGE) from epoxy resin systems.

PubMed

Niklasson, Ida B; Delaine, Tamara; Luthman, Kristina; Karlberg, Ann-Therese

2011-04-18

Epoxy resins are among the most common causes of occupational contact dermatitis. They are normally used in so-called epoxy resin systems (ERS). These commercial products are combinations of epoxy resins, curing agents, modifiers, and reactive diluents. The most frequently used resins are diglycidyl ethers based on bisphenol A (DGEBA) and bisphenol F (DGEBF). In this study, we have investigated the contact allergenic properties of a series of analogues to the reactive diluent phenyl glycidyl ether (PGE), all with similar basic structures but with varying heteroatoms or with no heteroatom present. The chemical reactivity of the compounds in the test series toward the hexapeptide H-Pro-His-Cys-Lys-Arg-Met-OH was investigated. All epoxides were shown to bind covalently to both cysteine and proline residues. The percent depletion of nonreacted peptide was also studied resulting in ca. 60% depletion when using either PGE, phenyl 2,3-epoxypropyl sulfide (2), or N-(2,3-epoxypropyl)aniline (3), and only 15% when using 1,2-epoxy-4-phenylbutane (4) at the same time point. The skin sensitization potencies of the epoxides using the murine local lymph node assay (LLNA) were evaluated in relation to the observed physicochemical and reactivity properties. To enable determination of statistical significance between structurally closely related compounds, a nonpooled LLNA was performed. It was found that all investigated compounds containing a heteroatom in the α-position to the epoxide were strong sensitizers, congruent with the reactivity data, indicating that the impact of a heteroatom is crucial for the sensitizing capacity for this type of epoxides.

The effects of trait impulsivity on proactive and reactive interference control.

PubMed

Xiang, Ling; Chen, Yan; Chen, Antao; Zhang, Fenghua; Xu, Fuming; Wang, Baoxi

2018-02-01

The current study used event-related brain potentials (ERPs) to explore whether self-reported trait impulsivity in healthy individuals might be differentially related to proactive and reactive interference control. Participants with high and low impulsivity (HI and LI, respectively) performed a modified version of the prime-target interference task. Proactive interference control was induced in the mostly incongruent (MI) context and reactive interference control was induced in the mostly congruent (MC) context. Although the behavioral data revealed no difference between HI and LI individuals in terms of the interference effects (incongruent - congruent) under both contexts, the ERP results showed that impulsivity has a different influence on the interference effects under different task contexts. In the MC context, the interference effects on the medial frontal negativity (MFN) and the negative sustained potential (N-SP) were greater, while that on the positive sustained potential (P-SP) were smaller in the HI compared to those in the LI group. This suggests that high levels of impulsivity might be associated with a reduced efficiency of the processes supporting reactive control to resolve interference when interference is not expected. In contrast, the three ERP indices (MFN, P-SP, and N-SP) of interference processing in the MI context were insensitive to variations in impulsivity. This suggests that HI individuals might be as effective as LI individuals in recruiting proactive control for sustained active maintenance of task goals to anticipate and prevent interference throughout the experimental blocks where interference occurs frequently. In conclusion, these results indicate that impulsivity has a more negative influence on reactive interference control than on proactive interference control. Copyright © 2017. Published by Elsevier B.V.

Identification of the residue in human CYP3A4 that is covalently modified by bergamottin and the reactive intermediate that contributes to the grapefruit juice effect.

PubMed

Lin, Hsia-Lien; Kenaan, Cesar; Hollenberg, Paul F

2012-05-01

Previous studies have demonstrated that bergamottin (BG), a component of grapefruit juice, is a mechanism-based inactivator of CYP3A4 and contributes, in part, to the grapefruit juice-drug interaction. Although the covalent binding of [(14)C]BG to the CYP3A4 apoprotein has been demonstrated by SDS-polyacrylamide gel electrophoresis, the identity of the modified amino acid residue and the reactive intermediate species of BG responsible for the inactivation have not been reported. In the present study, we show that inactivation of CYP3A4 by BG results in formation of a modified apoprotein-3A4 and a GSH conjugate, both exhibiting mass increases of 388 Da, which corresponds to the mass of 6',7'-dihydroxybergamottin (DHBG), a metabolite of BG, plus one oxygen atom. To identify the adducted residue, BG-inactivated 3A4 was digested with trypsin, and the digests were then analyzed by liquid chromatography-tandem mass spectrometry (MS/MS). A mass shift of 388 Da was used for the SEQUEST database search, which revealed a mass increase of 388 Da for the peptide with the sequence (272)LQLMIDSQNSK(282), and MS/MS analysis of the adducted peptide demonstrated that Gln273 is the residue modified. Mutagenesis studies showed that the Gln273 to Val mutant was resistant to inactivation by BG and DHBG and did not generate two of the major metabolites of BG formed by 3A4 wild type. In conclusion, we have determined that the reactive intermediate, oxygenated DHBG, covalently binds to Gln273 and thereby contributes to the mechanism-based inactivation of CYP3A4 by BG.

Psychophysiology of Delayed Extinction and Reconsolidation in Humans

DTIC Science & Technology

2013-02-01

to modify or block it. The aim of this project is to create an experimental assay in the form of an optimal Pavlovian differential fear- conditioning ...group. Data from the pharmacological group demonstrate that participants show differential conditioning learning on Day 1, supporting the validity of...our modified fear- conditioning paradigm. Results suggest that propranolol administration at the time of memory reactivation does not decrease the fear

The role of sleep in changing our minds: A psychologist's discussion of papers on memory reactivation and consolidation in sleep

PubMed Central

Cartwright, Rosalind D.

2004-01-01

The group of papers on memory reactivation and consolidation during sleep included in this volume represents cutting edge work in both animals and humans. They support that the two types of sleep serve different necessary functions. The role of slow wave sleep (SWS) is reactivation of the hippocampal-neocortical circuits activated during a waking learning period, while REM sleep is responsible for the consolidation of this new learning into long-term memory. These studies provide further insights into mechanisms involved in brain plasticity. Robeiro has demonstrated the upregulation of an immediate-early gene (IEG zif 268) to waking levels, which occurs only in REM and only in connection with new learning. McNaughton and his group have identified electrical indicators that the hippocampus and neocortex are talking to each other by testing the coactivation of hippocampal sharp wave bursts in SWS and shifts from down to up states of activation in the neocortex. In human studies Smith's group reports work on individual differences such as intelligence and presleep alcohol that affect postsleep performance, and Stickgold and collaborators report that a short nap will improve performance if it contains REM sleep. Payne and Nadel suggest that the recall benefit associated with REM sleep may be due to its association with increased cortisol levels. These papers are important not only in their individual contributions but also in revitalizing the work coordinating waking and sleep. This promises to further the understanding of how our unique capacity to learn from experience and modify our behavior takes place. PMID:15576882

Oxaliplatin antagonizes HIV-1 latency by activating NF-κB without causing global T cell activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Xiaoli; Liu, Sijie; Wang, Pengfei

Highlights: • The chemotherapeutic drug oxaliplatin reactivates latent HIV-1 in this cell line model of HIV-1 latency. • Reactivation is synergized when oxaliplatin is used in combination with valproic acid. • Oxaliplatin reactivates latent HIV-1 through activation of NF-kB and does not induce T cell activation. - Abstract: Reactivation of latent HIV-1 is a promising strategy for the clearance of the viral reservoirs. Because of the limitations of current agents, identification of new latency activators is urgently required. Using an established model of HIV-1 latency, we examined the effect of Oxaliplatin on latent HIV-1 reactivation. We showed that Oxaliplatin, alonemore » or in combination with valproic acid (VPA), was able to reactivate HIV-1 without inducing global T cell activation. We also provided evidence that Oxaliplatin reactivated HIV-1 expression by inducing nuclear factor kappa B (NF-κB) nuclear translocation. Our results indicated that Oxaliplatin could be a potential drug candidate for anti-latency therapies.« less

Enhanced Reactive Oxygen Species Production, Acidic Cytosolic pH and Upregulated Na+/H+ Exchanger (NHE) in Dicer Deficient CD4+ T Cells.

PubMed

Singh, Yogesh; Zhou, Yuetao; Zhang, Shaqiu; Abdelazeem, Khalid N M; Elvira, Bernat; Salker, Madhuri S; Lang, Florian

2017-01-01

MicroRNAs (miRNAs) negatively regulate gene expression at a post-transcriptional level. Dicer, a cytoplasmic RNase III enzyme, is required for the maturation of miRNAs from precursor miRNAs. Dicer, therefore, is a critical enzyme involved in the biogenesis and processing of miRNAs. Several biological processes are controlled by miRNAs, including the regulation of T cell development and function. T cells generate reactive oxygen species (ROS) with parallel H+ extrusion accomplished by the Na+/H+-exchanger 1 (NHE1). The present study explored whether ROS production, as well as NHE1 expression and function are sensitive to the lack of Dicer (miRNAs deficient) and could be modified by individual miRNAs. CD4+ T cells were isolated from CD4 specific Dicer deficient (DicerΔ/Δ) mice and the respective control mice (Dicerfl/fl). Transcript and protein levels were quantified with RT-PCR and Western blotting, respectively. For determination of intracellular pH (pHi) cells were incubated with the pH sensitive dye bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) and Na+/H+ exchanger (NHE) activity was calculated from re-alkalinization after an ammonium pulse. Changes in cell volume were measured using the forward scatter in flow cytometry, and ROS production utilizing 2',7' -dichlorofluorescin diacetate (DCFDA) fluorescence. Transfection of miRNA-control and mimics in T cells was performed using DharmaFECT3 reagent. ROS production, cytosolic H+ concentration, NHE1 transcript and protein levels, NHE activity, and cell volume were all significantly higher in CD4+ T cells from DicerΔ/Δ mice than in CD4+ T cells from Dicerfl/fl mice. Furthermore, individual miR-200b and miR-15b modify pHi and NHE activity in Dicerfl/fl and DicerΔ/Δ CD4+ T cells, respectively. Lack of Dicer leads to oxidative stress, cytosolic acidification, upregulated NHE1 expression and activity as well as swelling of CD4+ T cells, functions all reversed by miR-15b or miR-200b. © 2017 The Author(s). Published by S. Karger AG, Basel.

Modifying interpretation biases: Effects on symptomatology, behavior, and physiological reactivity in social anxiety.

PubMed

Nowakowski, Matilda E; Antony, Martin M; Koerner, Naomi

2015-12-01

The present study investigated the effects of computerized interpretation training and cognitive restructuring on symptomatology, behavior, and physiological reactivity in an analogue social anxiety sample. Seventy-two participants with elevated social anxiety scores were randomized to one session of computerized interpretation training (n = 24), cognitive restructuring (n = 24), or an active placebo control condition (n = 24). Participants completed self-report questionnaires focused on interpretation biases and social anxiety symptomatology at pre and posttraining and a speech task at posttraining during which subjective, behavioral, and physiological measures of anxiety were assessed. Only participants in the interpretation training condition endorsed significantly more positive than negative interpretations of ambiguous social situations at posttraining. There was no evidence of generalizability of interpretation training effects to self-report measures of interpretation biases and symptomatology or the anxiety response during the posttraining speech task. Participants in the cognitive restructuring condition were rated as having higher quality speeches and showing fewer signs of anxiety during the posttraining speech task compared to participants in the interpretation training condition. The present study did not include baseline measures of speech performance or computer assessed interpretation biases. The results of the present study bring into question the generalizability of computerized interpretation training as well as the effectiveness of a single session of cognitive restructuring in modifying the full anxiety response. Clinical and theoretical implications are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acclimation capacity of the three-spined stickleback (Gasterosteus aculeatus, L.) to a sudden biological stress following a polymetallic exposure.

PubMed

Le Guernic, Antoine; Sanchez, Wilfried; Palluel, Olivier; Bado-Nilles, Anne; Floriani, Magali; Turies, Cyril; Chadili, Edith; Vedova, Claire Della; Cavalié, Isabelle; Adam-Guillermin, Christelle; Porcher, Jean-Marc; Geffard, Alain; Betoulle, Stéphane; Gagnaire, Béatrice

2016-10-01

To get closer to the environmental reality, ecotoxicological studies should no longer consider the evaluation of a single pollutant, but rather combination of stress and their interaction. The aim of this study was to determine if responses of a fish to a sudden biological stress could be modified by a prior exposure to a chemical stress (a polymetallic contamination). For this purpose, in situ experiment was conducted in three ponds in the Haute-Vienne department (France). One pond was chosen for its high uranium concentration due to uranium mine tailings, and the two other ponds, which were not submitted to these tailings. Three-spined sticklebacks (Gasterosteus aculeatus) were caged in these ponds for 14 days. After this period, fish were submitted to a biological stress, exerted by lipopolysaccharides injection after anesthesia, and were sacrificed 4 days after these injections for multi-biomarkers analyses (leucocyte viability, phagocytic capacity and reactive oxygen species production, antioxidant peptide and enzymes, lipid peroxidation and DNA damage). The pond which received uranium mine tailings had higher metallic concentrations. Without biological stress, sticklebacks caged in this pond presented an oxidative stress, with increasing of reactive oxygen species levels, modification of some parts of the antioxidant system, and lipid peroxidation. Caging in the two most metal-contaminated ponds resulted in an increase of susceptibility of sticklebacks to the biological stress, preventing their phagocytic responses to lipopolysaccharides and modifying their glutathione contents and glutathione-S-transferase activity.

The impact of carbon dioxide and exhaust gas recirculation on the oxidative reactivity of soot from ethylene flames and diesel engines

NASA Astrophysics Data System (ADS)

Al-Qurashi, Khalid O.

Restrictive emissions standards to reduce nitrogen oxides (NOx) and particulate matter (PM) emissions from diesel engines necessitate the development of advanced emission control technology. The engine manufacturers in the United States have implemented the exhaust gas recirculation (EGR) and diesel particulate filters (DPF) to meet the stringent emissions limits on NOx and PM, respectively. Although the EGR-DPF system is an effective means to control diesel engine emissions, there are some concerns associated with its implementation. The chief concern with this system is the DPF regenerability, which depends upon several factors, among which are the physicochemical properties of the soot. Despite the plethora of research that has been conducted on DPF regenerability, the impact of EGR on soot reactivity and DPF regenerability is yet to be examined. This work concerns the impact of EGR on the oxidative reactivity of diesel soot. It is part of ongoing research to bridge the gap in establishing a relationship between soot formation conditions, properties, and reactivity. This work is divided into three phases. In the first phase, carbon dioxide (CO2) was added to the intake charge of a single cylinder engine via cylinders of compressed CO2. This approach simulates the cold-particle-free EGR. The results showed that inclusion of CO2 changes the soot properties and yields synergistic effects on the oxidative reactivity of the resulting soot. The second phase of this research was motivated by the findings from the first phase. In this phase, post-flame ethylene soot was produced from a laboratory co-flow laminar diffusion flame to better understand the mechanism by which the CO2 affects soot reactivity. This phase was accomplished by successfully isolating the dilution, thermal, and chemical effects of the CO2. The results showed that all of these effects account for a measurable increase in soot reactivity. Nevertheless, the thermal effect was found to be the most important factor governing the soot reactivity. In the third phase of this research, diesel soot was generated under 0 and 20% EGR using a four-cylinder, four-stroke, turbocharged common rail direct injection (DI) DDC diesel engine. The objective of this work was to examine the relevance of the single cylinder engine and flame studies to practical engine operation. The key engine parameters such as load, speed, and injection timing were kept constant to isolate the EGR effect on soot properties from any other engine effects. The thermokinetic analyses of the flame soot and engine soot showed a significant increase in soot oxidation rate as a result of the CO2 or EGR inclusion into the combustion process. The activation energy of soot oxidation was found to be independent of soot origin or formation history. The increase in soot oxidation rate is attributed solely to the increase in soot active sites, which are presented implicitly in the pre-exponential factor (A) of the oxidation rate equation. This latter statement was confirmed by measuring the initial active site area (ASA i) of all soot samples considered in this study. As expected, higher oxidation rates are associated with higher ASAi. The chemical properties of the soot were investigated to determine their effects upon soot reactivity. The results showed that the H/C and O/C ratios were not modified by CO2 or EGR addition. Therefore, these ratios are not reactivity parameters and their effects upon soot reactivity were ruled out. In distinct contrast, the physical properties of the soot were modified by the addition of CO2 or EGR. The interlayer spacing (d002) between the aromatic sheets increased, the crystallite width (La) decreased and the crystallite height (Lc) decreased as a consequence of CO 2 or EGR addition. The modified physical properties of the soot are responsible for the increased rate of soot oxidation. In order to examine the soot oxidation behavior in the DPF, the soot samples produced from the DDC engine under 0 and 20% EGR were partially oxidized in a thermogravimetric analyzer (TGA) to specific conversion levels. Unreacted and partially oxidized soot samples were then subjected to comprehensive characterization. The Raman spectroscopy showed that the disordered fraction of the soot (ID/IG) decreases with the oxidation progression. Electron energy loss spectroscopy (EELS) results showed an increase in the (I pi/Isigma) for soot generated under 0% EGR but no significant increase in this ratio was observed for the soot generated under 20% EGR. These results indicate that soot generated without EGR is likely to be more highly ordered in its nanostructure. Visual inspection of the unreacted and partially oxidized soot (produced under 0 and 20% EGR) was obtained by the use of high resolution transmission electron microscopy (HRTEM). The results suggested that the initial nanostructure of the soot primary particles is the same for soot produced under 0 and 20% EGR. However, soot produced under 0% EGR condition exhibits strictly external burning (i.e., from the outside in). On the other hand, soot generated under 20% EGR possesses dual burning modes, that is, slow external burning and fast internal burning. This internal burning of the 20% EGR soot clarifies the importance of the burning modes upon soot reactivity. This study confirmed that EGR exerted a strong influence on the diesel soot physical properties. Consistent with the flame study, a separate engine study confirmed that the most important factors to enhance the soot reactivity are the thermal effect of the EGR followed by the dilution effect.

Advanced glycation end-products: modifiable environmental factors profoundly mediate insulin resistance

PubMed Central

Ottum, Mona S.; Mistry, Anahita M.

2015-01-01

Advanced glycation end-products are toxic by-products of metabolism and are also acquired from high-temperature processed foods. They promote oxidative damage to proteins, lipids and nucleotides. Aging and chronic diseases are strongly associated with markers for oxidative stress, especially advanced glycation end-products, and resistance to peripheral insulin-mediated glucose uptake. Modifiable environmental factors including high levels of refined and simple carbohydrate diets, hypercaloric diets and sedentary lifestyles drive endogenous formation of advanced glycation end-products via accumulation of highly reactive glycolysis intermediates and activation of the polyol/aldose reductase pathway producing high intracellular fructose. High advanced glycation end-products overwhelm innate defenses of enzymes and receptor-mediated endocytosis and promote cell damage via the pro-inflammatory and pro-oxidant receptor for advanced glycation end-products. Oxidative stress disturbs cell signal transduction, especially insulin-mediated metabolic responses. Here we review emerging evidence that restriction of dietary advanced glycation end-products significantly reduces total systemic load and insulin resistance in animals and humans in diabetes, polycystic ovary syndrome, healthy populations and dementia. Of clinical importance, this insulin sensitizing effect is independent of physical activity, caloric intake and adiposity level. PMID:26236094

Differentiating Challenge Reactivity from Psychomotor Activity in Studies of Children's Psychophysiology: Considerations for Theory and Measurement

ERIC Educational Resources Information Center

Bush, Nicole R.; Alkon, Abbey; Obradovic, Jelena; Stamperdahl, Juliet; Boyce, W. Thomas

2011-01-01

Current methods of assessing children's physiological "stress reactivity" may be confounded by psychomotor activity, biasing estimates of the relation between reactivity and health. We examined the joint and independent contributions of psychomotor activity and challenge reactivity during a protocol for 5- and 6-year-old children (N = 338).…

Inhibiting polysulfides diffusion of lithium-sulfur batteries using an acetylene black-CoS2 modified separator: Mechanism research and performance improvement

NASA Astrophysics Data System (ADS)

Zeng, Pan; Huang, Liwu; Zhang, Xinling; Han, Yamiao; Chen, Yungui

2018-01-01

Lithium-sulfur (Li-S) batteries are considered as one of the most promising chemistries in secondary energy storage field owing to their high energy density. However, the poor electrochemical performance mainly associated with the polysulfides shuttle has greatly hampered their practical application. Herein, a simple acetylene black (AB)-CoS2 coated separator is first designed to suppress the migration of polysulfides. The AB-CoS2 modified separator can not only efficiently capture the polysulfides by forming strong chemical bonding but also guarantee the rapid lithium ions diffusion. Moreover, the AB-CoS2 coating could serve as an upper current collector to accelerate electron transport for reinforcing the utilization of sulfur and ensuring the reactivation of the trapped active material. Consequently, the Li-S cell using AB-CoS2 modified separator shows a long-term cycling stability with an extremely low decay rate (0.09% per cycle) up to 450 cycles at a high rate of 2 C (3350 mA g-1). It also exhibits excellent rate capabilities, which maintains a capacity of 475 mAh g-1 even at 4.0 C rate.

Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving Disease-Modifying Antirheumatic Drugs: A Systematic Review and Meta-Analysis.

PubMed

Lin, Tzu-Chieh; Yoshida, Kazuki; Tedeschi, Sara K; de Abreu, Mirhelen Mendes; Hashemi, Nikroo; Solomon, Daniel H

2018-05-01

To assess hepatitis B virus (HBV) reactivation rates in patients with resolved or chronic HBV infection, receiving disease-modifying antirheumatic drugs (DMARDs) and with or without antiviral prophylaxis. We conducted a systematic review and meta-analysis. Electronic searches were conducted in PubMed, Medline, and Embase using Ovid through December 31, 2015. A search strategy was developed for each database using the following inclusion criteria: for participants, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and resolved or chronic HBV infection; for intervention, tumor necrosis factor (TNF) inhibitors or non-TNF biologic or nonbiologic DMARDs; and for outcome, HBV reactivation. Four reviewers independently extracted study data and assessed study quality using the Newcastle-Ottawa Scale. To determine the pooled HBV reactivation rate, the variances of the raw proportions were stabilized using a Freeman-Tukey-type arcsine square root transformation, using a random-effects model. Twenty-five studies met the inclusion criteria. The overall pooled rate of HBV reactivation was 1.6% (95% confidence interval [95% CI] 0.8-2.6) in patients with resolved HBV. Similar rates were observed in resolved patients taking TNF inhibitors (1.4% [95% CI 0.5-2.6]), non-TNF biologics (6.1% [95% CI 0.0-16.6]), and nonbiologic DMARDs (1.7% [95% CI 0.2-4.2]). We also found that the reactivation rate was lower in patients with chronic HBV infection who received antiviral prophylaxis (9.0% [95% CI 4.1-15.5]) than in those who did not (14.6% [95% CI 4.3-29.0]). We found that the HBV reactivation rate in inflammatory arthritis patients receiving DMARDs was low in resolved patients and moderate in patients with chronic HBV infection. Further, lower rates were observed in patients with chronic HBV infection who were using antiviral prophylaxis. © 2017, American College of Rheumatology.

Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition.

PubMed

Jancinová, Viera; Perecko, Tomás; Nosál, Radomír; Kostálová, Daniela; Bauerová, Katarína; Drábiková, Katarína

2009-06-10

Diferuloylmethane (curcumin) has been shown to act beneficially in arthritis, particularly through downregulated expression of proinflammatory cytokines and collagenase as well as through the modulated activities of T lymphocytes and macrophages. In this study its impact on activated neutrophils was investigated both in vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded on the basis of luminol- or isoluminol-enhanced chemiluminescence. Phosphorylation of neutrophil protein kinases C alpha and beta II was assessed by Western blotting, using phosphospecific antibodies. Adjuvant arthritis was induced in Lewis rats by heat-killed Mycobacterium butyricum. Diferuloylmethane or methotrexate was administered over a period of 28 days after arthritis induction. Under in vitro conditions, diferuloylmethane (1-100 microM) reduced dose-dependently oxidant formation both at extra- and intracellular level and it effectively reduced protein kinase C activation. Adjuvant arthritis was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as PMA (phorbol myristate acetate) stimulated chemiluminescence. Whereas the arthritis-related alterations in neutrophil count and in spontaneous chemiluminescence were not modified by diferuloylmethane, the increased reactivity of neutrophils to PMA was less evident in diferuloylmethane-treated animals. The effects of diferuloylmethane were comparable with those of methotrexate. Diferuloylmethane was found to be a potent inhibitor of neutrophil functions both in vitro and in experimental arthritis. As neutrophils are considered to be cells with the greatest capacity to inflict damage within diseased joints, the observed effects could represent a further mechanism involved in the antirheumatic activity of diferuloylmethane.

Melatonin administration modifies circadian motor activity under constant light depending on the lighting conditions during suckling.

PubMed

Carpentieri, Agata R; Oliva, Clara; Díez-Noguera, Antoni; Cambras, Trinitat

2015-01-01

Early lighting conditions have been described to produce long-term effects on circadian behavior, which may also influence the response to agents acting on the circadian system. It has been suggested that melatonin (MEL) may act on the circadian pacemaker and as a scavenger of reactive oxygen and nitrogen species. Here, we studied the oxidative and behavioral changes caused by prolonged exposure to constant light (LL) in groups of rats that differed in MEL administration and in lighting conditions during suckling. The rats were exposed to either a light-dark cycle (LD) or LL. At 40 days old, rats were treated for 2 weeks with a daily subcutaneous injection of MEL (10 mg/kg body weight) or a vehicle at activity onset. Blood samples were taken before and after treatment, to determine catalase (CAT) activity and nitrite level in plasma. As expected, LL-reared rats showed a more stable motor activity circadian rhythm than LD rats. MEL treatment produced more reactivity in LD- than in LL rats, and was also able to alter the phase of the rhythm in LD rats. There were no significant differences in nitrite levels or CAT activity between the groups, although both variables increased with time. Finally, we also tested depressive signs by means of sucrose consumption, and anhedonia was found in LD males treated with MEL. The results suggest that the lighting conditions in early infancy are important for the long-term functionality of the circadian system, including rhythm manifestation, responses to MEL and mood alterations.

1,4-Naphthoquinone activates the HSP90/HSF1 pathway through the S-arylation of HSP90 in A431 cells: Negative regulation of the redox signal transduction pathway by persulfides/polysulfides.

PubMed

Abiko, Yumi; Sha, Liang; Shinkai, Yasuhiro; Unoki, Takamitsu; Luong, Nho Cong; Tsuchiya, Yukihiro; Watanabe, Yasuo; Hirose, Reiko; Akaike, Takaaki; Kumagai, Yoshito

2017-03-01

The current consensus is that environmental electrophiles activate redox signal transduction pathways through covalent modification of sensor proteins with reactive thiol groups at low concentrations, while they cause cell damage at higher concentrations. We previously exposed human carcinoma A431 cells to the atmospheric electrophile 1,4-naphthoquinone (1,4-NQ) and found that heat shock protein 90 (HSP90), a negative regulator of heat shock factor 1 (HSF1), was a target of 1,4-NQ. In the study presented here, we determined whether 1,4-NQ activates HSF1. We also examined whether such redox signaling could be regulated by nucleophilic sulfur species. Exposure of A431 cells to 1,4-NQ covalently modified cellular HSP90, resulting in repression of the association between HSF1 with HSP90, thereby enhancing HSF1 translocation into the nuclei. Liquid chromatography-tandem mass spectrometry analysis with recombinant HSP90 revealed that the modifications site were Cys412 and Cys564. We found that HSF1 activation mediated by 1,4-NQ upregulated downstream genes, such as HSPA6. HSF1 knockdown accelerated 1,4-NQ-mediated cytotoxicity in the cells. While simultaneous treatment with reactive persulfide and polysulfide, Na 2 S 2 and Na 2 S 4 , blocked 1,4-NQ-dependent protein modification and HSF1 activation in A431 cells, the knockdown of Cys persulfide producing enzymes cystathionine β-synthase (CBS) and/or cystathionine γ-lyase (CSE) enhanced these phenomena. 1,4-NQ-thiol adduct and 1,4-NQ-S-1,4-NQ adduct were produced during the enzymatic reaction of recombinant CSE in the presence of 1,4-NQ. The results suggest that activation of the HSP90-HSF1 signal transduction pathway mediated by 1,4-NQ protects cells against 1,4-NQ and that per/polysulfides can diminish the reactivity of 1,4-NQ by forming sulfur adducts. Copyright © 2017 Elsevier Inc. All rights reserved.

Cerebrovascular Pressure Reactivity in Children With Traumatic Brain Injury.

PubMed

Lewis, Philip M; Czosnyka, Marek; Carter, Bradley G; Rosenfeld, Jeffrey V; Paul, Eldho; Singhal, Nitesh; Butt, Warwick

2015-10-01

Traumatic brain injury is a significant cause of morbidity and mortality in children. Cerebral autoregulation disturbance after traumatic brain injury is associated with worse outcome. Pressure reactivity is a fundamental component of cerebral autoregulation that can be estimated using the pressure-reactivity index, a correlation between slow arterial blood pressure, and intracranial pressure fluctuations. Pressure-reactivity index has shown prognostic value in adult traumatic brain injury, with one study confirming this in children. Pressure-reactivity index can identify a cerebral perfusion pressure range within which pressure reactivity is optimal. An increasing difference between optimal cerebral perfusion pressure and cerebral perfusion pressure is associated with worse outcome in adult traumatic brain injury; however, this has not been investigated in children. Our objective was to study pressure-reactivity index and optimal cerebral perfusion pressure in pediatric traumatic brain injury, including associations with outcome, age, and cerebral perfusion pressure. Prospective observational study. ICU, Royal Children's Hospital, Melbourne, Australia. Patients with traumatic brain injury who are 6 months to 16 years old, are admitted to the ICU, and require arterial blood pressure and intracranial pressure monitoring. None. Arterial blood pressure, intracranial pressure, and end-tidal CO2 were recorded electronically until ICU discharge or monitoring cessation. Pressure-reactivity index and optimal cerebral perfusion pressure were computed according to previously published methods. Clinical data were collected from electronic medical records. Outcome was assessed 6 months post discharge using the modified Glasgow Outcome Score. Thirty-six patients were monitored, with 30 available for follow-up. Pressure-reactivity index correlated with modified Glasgow Outcome Score (Spearman ρ = 0.42; p = 0.023) and was higher in patients with unfavorable outcome (0.23 vs -0.09; p = 0.0009). A plot of pressure-reactivity index averaged within 5 mm Hg cerebral perfusion pressure bins showed a U-shape, reaffirming the concept of cerebral perfusion pressure optimization in children. Optimal cerebral perfusion pressure increased with age (ρ = 0.40; p = 0.02). Both the duration and magnitude of negative deviations in the difference between cerebral perfusion pressure and optimal cerebral perfusion pressure were associated with unfavorable outcome. In pediatric patients with traumatic brain injury, pressure-reactivity index has prognostic value and can identify cerebral perfusion pressure targets that may differ from treatment protocols. Our results suggest but do not confirm that cerebral perfusion pressure targeting using pressure-reactivity index as a guide may positively impact on outcome. This question should be addressed by a prospective clinical study.

Late-stage chemoselective functional-group manipulation of bioactive natural products with super-electrophilic silylium ions

NASA Astrophysics Data System (ADS)

Bender, Trandon A.; Payne, Philippa R.; Gagné, Michel R.

2018-01-01

The selective (and controllable) modification of complex molecules with disparate functional groups (for example, natural products) is a long-standing challenge that has been addressed using catalysts tuned to perform singular transformations (for example, C-H hydroxylation). A method whereby reactions with diverse functional groups within a single natural product are feasible depending on which catalyst or reagent is chosen would widen the possible structures one could obtain. Fluoroarylborane catalysts can heterolytically split Si-H bonds to yield an oxophilic silylium (R3Si+) equivalent along with a reducing (H-) equivalent. Together, these reactive intermediates enable the reduction of multiple functional groups. Exogenous phosphine Lewis bases further modify the catalyst speciation and attenuate aggressive silylium ions for the selective modification of complex natural products. Manipulation of the catalyst, silane reagent and the reaction conditions provides experimental control over which site is modified (and how). Applying this catalytic method to complex bioactive compounds (natural products or drugs) provides a powerful tool for studying structure-activity relationships.

Cellular redox homeostasis in endothelial cells treated with nonmodified and Fenton-modified nanodiamond powders.

PubMed

Solarska-Ściuk, K; Gajewska, A; Skolimowski, J; Gajek, A; Bartosz, G

2014-01-01

Diamond nanoparticles find numerous applications in pharmacy, medicine, cosmetics, and biotechnology. However, possible adverse cellular effects of diamond nanoparticle cells have been reported, which may limit their use. The aim of this study was to compare the effect of nonmodified diamond nanoparticles (D) and diamond nanoparticles modified by the Fenton reaction (D+OH) on human umbilical cord endothelial cells (HUVEC-ST). We found that both D and D+OH show time- and concentration-dependent cytotoxicity, inducing apoptosis and necrosis of HUVEC-ST. Interaction with D and D+OH also induced changes in the production of reactive oxygen and nitrogen species and changes in the level of glutathione and activities of antioxidant enzymes in the cells. These data demonstrate that diamond nanoparticles may induce oxidative stress in human endothelial cells, which contributes to their cytotoxic effects seen at higher concentrations of D and D+OH. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

Polypyrrole Coated Cellulosic Substrate Modified by Copper Oxide as Electrode for Nitrate Electroreduction

NASA Astrophysics Data System (ADS)

Hamam, A.; Oukil, D.; Dib, A.; Hammache, H.; Makhloufi, L.; Saidani, B.

2015-08-01

The aim of this work is to synthesize polypyrrole (PPy) films on nonconducting cellulosic substrate and modified by copper oxide particles for use in the nitrate electroreduction process. Firstly, the chemical polymerization of polypyrrole onto cellulosic substrate is conducted by using FeCl3 as an oxidant and pyrrole as monomer. The thickness and topography of the different PPy films obtained were estimated using a profilometer apparatus. The electrochemical reactivity of the obtained electrodes was tested by voltamperometry technique and electrochemical impedance spectroscopy. Secondly, the modification of the PPy film surface by incorporation of copper oxide particles is conducted by applying a galvanostatic procedure from a CuCl2 solution. The SEM, EDX and XRD analysis showed the presence of CuO particles in the polymer films with dimensions less than 50 nm. From cyclic voltamperometry experiments, the composite activity for the nitrate electroreduction reaction was evaluated and the peak of nitrate reduction is found to vary linearly with initial nitrate concentration.

Solid-phase synthesis of protein-polymers on reversible immobilization supports.

PubMed

Murata, Hironobu; Carmali, Sheiliza; Baker, Stefanie L; Matyjaszewski, Krzysztof; Russell, Alan J

2018-02-27

Facile automated biomacromolecule synthesis is at the heart of blending synthetic and biologic worlds. Full access to abiotic/biotic synthetic diversity first occurred when chemistry was developed to grow nucleic acids and peptides from reversibly immobilized precursors. Protein-polymer conjugates, however, have always been synthesized in solution in multi-step, multi-day processes that couple innovative chemistry with challenging purification. Here we report the generation of protein-polymer hybrids synthesized by protein-ATRP on reversible immobilization supports (PARIS). We utilized modified agarose beads to covalently and reversibly couple to proteins in amino-specific reactions. We then modified reversibly immobilized proteins with protein-reactive ATRP initiators and, after ATRP, we released and analyzed the protein polymers. The activity and stability of PARIS-synthesized and solution-synthesized conjugates demonstrated that PARIS was an effective, rapid, and simple method to generate protein-polymer conjugates. Automation of PARIS significantly reduced synthesis/purification timelines, thereby opening a path to changing how to generate protein-polymer conjugates.

Coping Style Modifies General and Affective Autonomic Reactions of Domestic Pigs in Different Behavioral Contexts

PubMed Central

Krause, Annika; Puppe, Birger; Langbein, Jan

2017-01-01

Based on individual adaptive strategies (coping), animals may react differently to environmental challenges in terms of behavior and physiology according to their emotional perception. Emotional valence as well as arousal may be derived by measuring vagal and sympathetic tone of the autonomic nervous system (ANS). We investigated the situation-dependent autonomic response of 16 domestic pigs with either a reactive or a proactive coping style, previously selected according to the backtest which is accepted in piglets to assess escape behavior. At 11 weeks of age, the pigs were equipped with an implantable telemetric device, and heart rate (HR), blood pressure (BP) and their respective variabilities (HRV, BPV) were recorded for 1 h daily over a time period of 10 days and analyzed in four behavioral contexts (resting, feeding, idling, handling). Additionally, the first minute of feeding and handling was used for a short-term analysis of these parameters in 10-s intervals. Data from day 1–3 (period 1) and day 8–10 (period 2) were grouped into two separate periods. Our results revealed general differences between the coping styles during feeding, resting and handling, with proactive pigs showing higher HR compared to reactive pigs. This elevated HR was based on either lower vagal (resting) or elevated sympathetic activation (feeding, handling). The short-term analysis of the autonomic activation during feeding revealed a physiological anticipation reaction in proactive pigs in period 1, whereas reactive pigs showed this reaction only in period 2. Food intake was characterized by sympathetic arousal with concurrent vagal withdrawal, which was more pronounced in proactive pigs. In contrast, neither coping style resulted in an anticipation reaction to handling. Vagal activation increased in reactive pigs during handling, while proactive pigs showed an increase in sympathetically driven arousal in period 2. Our findings confirm significant context-related differences in the general autonomic reaction of pigs with different coping styles. Additionally, the two coping styles differ in their affective appraisal over the time course of the experiment, underlining the importance of taking individual differences into account when studying affect and emotion in humans and animals. PMID:28611608

Coping Style Modifies General and Affective Autonomic Reactions of Domestic Pigs in Different Behavioral Contexts.

PubMed

Krause, Annika; Puppe, Birger; Langbein, Jan

2017-01-01

Based on individual adaptive strategies (coping), animals may react differently to environmental challenges in terms of behavior and physiology according to their emotional perception. Emotional valence as well as arousal may be derived by measuring vagal and sympathetic tone of the autonomic nervous system (ANS). We investigated the situation-dependent autonomic response of 16 domestic pigs with either a reactive or a proactive coping style, previously selected according to the backtest which is accepted in piglets to assess escape behavior. At 11 weeks of age, the pigs were equipped with an implantable telemetric device, and heart rate (HR), blood pressure (BP) and their respective variabilities (HRV, BPV) were recorded for 1 h daily over a time period of 10 days and analyzed in four behavioral contexts (resting, feeding, idling, handling). Additionally, the first minute of feeding and handling was used for a short-term analysis of these parameters in 10-s intervals. Data from day 1-3 (period 1) and day 8-10 (period 2) were grouped into two separate periods. Our results revealed general differences between the coping styles during feeding, resting and handling, with proactive pigs showing higher HR compared to reactive pigs. This elevated HR was based on either lower vagal (resting) or elevated sympathetic activation (feeding, handling). The short-term analysis of the autonomic activation during feeding revealed a physiological anticipation reaction in proactive pigs in period 1, whereas reactive pigs showed this reaction only in period 2. Food intake was characterized by sympathetic arousal with concurrent vagal withdrawal, which was more pronounced in proactive pigs. In contrast, neither coping style resulted in an anticipation reaction to handling. Vagal activation increased in reactive pigs during handling, while proactive pigs showed an increase in sympathetically driven arousal in period 2. Our findings confirm significant context-related differences in the general autonomic reaction of pigs with different coping styles. Additionally, the two coping styles differ in their affective appraisal over the time course of the experiment, underlining the importance of taking individual differences into account when studying affect and emotion in humans and animals.

Hydrolase stabilization via entanglement in poly(propylene sulfide) nanoparticles: stability towards reactive oxygen species.

PubMed

Allen, Brett L; Johnson, Jermaine D; Walker, Jeremy P

2012-07-27

In the advancement of green syntheses and sustainable reactions, enzymatic biocatalysis offers extremely high reaction rates and selectivity that goes far beyond the reach of chemical catalysts; however, these enzymes suffer from typical environmental constraints, e.g. operational temperature, pH and tolerance to oxidative environments. A common hydrolase enzyme, diisopropylfluorophosphatase (DFPase, EC 3.1.8.2), has demonstrated a pronounced efficacy for the hydrolysis of a variety of substrates for potential toxin remediation, but suffers from the aforementioned limitations. As a means to enhance DFPase's stability in oxidative environments, enzymatic covalent immobilization within the polymeric matrix of poly(propylene sulfide) (PPS) nanoparticles was performed. By modifying the enzyme's exposed lysine residues via thiolation, DFPase is utilized as a comonomer/crosslinker in a mild emulsion polymerization. The resultant polymeric polysulfide shell acts as a 'sacrificial barrier' by first oxidizing to polysulfoxides and polysulfones, rendering DFPase in an active state. DFPase-PPS nanoparticles thus retain activity upon exposure to as high as 50 parts per million (ppm) of hypochlorous acid (HOCl), while native DFPase is observed as inactive at 500 parts per billion (ppb). This trend is also confirmed by enzyme-generated (chloroperoxidase (CPO), EC 1.11.1.10) reactive oxygen species (ROS) including both HOCl (3 ppm) and ClO(2) (100 ppm).

Synthesis of 2-Butanol by Selective Hydrogenolysis of 1,4-Anhydroerythritol over Molybdenum Oxide-Modified Rhodium-Supported Silica.

PubMed

Arai, Takahiro; Tamura, Masazumi; Nakagawa, Yoshinao; Tomishige, Keiichi

2016-07-07

Rh-MoOx /SiO2 (Mo/Rh=0.13) is an effective catalyst for the hydrogenolysis of 1,4-anhydroerythritol (1,4-AHERY) and provides 2-BuOH in high yield of 51 %. This is the first report of the production of 2-BuOH from 1,4-AHERY by hydrogenolysis. 1,4-AHERY was more suitable as a starting material than erythritol because the 2-BuOH yield from erythritol was low (34 %). Based on the kinetics and comparison of reactivities of the related compounds using Rh-MoOx /SiO2 and Rh/SiO2 catalysts, the modification of Rh/SiO2 with MoOx leads to the high activity and high selectivity to 2-BuOH because of the generation of reactive hydride species and the strong adsorption of 1,4-AHERY on MoOx species. The reaction proceeds by main two routes, (I) the combination of single C-O hydrogenolysis with the desorption of intermediates, a usual route in hydrogenolysis, and (II) multiple C-O hydrogenolysis without the desorption of intermediates from the active site, and the reaction mechanism for Route (II) is proposed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Emotional reactivity to daily life stress in spousal caregivers of people with dementia: An experience sampling study.

PubMed

van Knippenberg, Rosalia J M; de Vugt, Marjolein E; Ponds, Rudolf W; Verhey, Frans R J; Myin-Germeys, Inez

2018-01-01

Caregivers differ in their emotional response when facing difficult situations during the caregiving process. Individual differences in vulnerabilities and resources could play an exacerbating or buffering role in caregivers' reactivity to daily life stress. This study examines which caregiver characteristics modify emotional stress reactivity in dementia caregivers. Thirty caregivers collected momentary data, as based on the experience sampling methodology, to assess (1) appraised subjective stress related to events and minor disturbances in daily life, and (2) emotional reactivity to these daily life stressors, conceptualized as changes in negative affect. Caregiver characteristics (i.e. vulnerabilities and resources) were administered retrospectively. Caregivers who more frequently used the coping strategies 'seeking distraction', 'seeking social support', and 'fostering reassuring thoughts' experienced less emotional reactivity towards stressful daily events. A higher educational level and a higher sense of competence and mastery lowered emotional reactivity towards minor disturbances in daily life. No effects were found for age, gender, and hours of care and contact with the person with dementia. Caregiver resources can impact emotional reactivity to daily life stress. Interventions aimed at empowerment of caregiver resources, such as sense of competence, mastery, and coping, could help to reduce stress reactivity in dementia caregivers.

A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques

PubMed Central

Mutschler, James P.; Kingstad-Bakke, Brock; Schultz-Darken, Nancy; Broman, Karl W.; Osorio, Jorge E.

2017-01-01

The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a “mosaic” hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Modified vaccinia Ankara (MVA) expressing this H5 mosaic (MVA-H5M) protected mice against multiple homosubtypic H5N1 strains and a heterosubtypic H1N1 virus. To assess its potential as a human vaccine we evaluated the ability of MVA-H5M to provide heterosubtypic immunity to influenza viruses in a non-human primate model. Rhesus macaques received an initial dose of either MVA-H5M or plasmid DNA encoding H5M, followed by a boost of MVA-H5M, and then were challenged, together with naïve controls, with the heterosubtypic virus A/California/04/2009 (H1N1pdm). Macaques receiving either vaccine regimen cleared H1N1pdm challenge faster than naïve controls. Vaccination with H5M elicited antibodies that bound H1N1pdm HA, but did not neutralize the H1N1pdm challenge virus. Plasma from vaccinated macaques activated NK cells in the presence of H1N1pdm HA, suggesting that vaccination elicited cross-reactive antibodies capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Although HA-specific T cell responses to the MVA-H5M vaccine were weak, responses after challenge were stronger in vaccinated macaques than in control animals. Together these data suggest that mosaic HA antigens may provide a means for inducing broadly cross-reactive immunity to influenza viruses. PMID:28771513

A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques.

PubMed

Florek, Nicholas W; Kamlangdee, Attapon; Mutschler, James P; Kingstad-Bakke, Brock; Schultz-Darken, Nancy; Broman, Karl W; Osorio, Jorge E; Friedrich, Thomas C

2017-01-01

The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a "mosaic" hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Modified vaccinia Ankara (MVA) expressing this H5 mosaic (MVA-H5M) protected mice against multiple homosubtypic H5N1 strains and a heterosubtypic H1N1 virus. To assess its potential as a human vaccine we evaluated the ability of MVA-H5M to provide heterosubtypic immunity to influenza viruses in a non-human primate model. Rhesus macaques received an initial dose of either MVA-H5M or plasmid DNA encoding H5M, followed by a boost of MVA-H5M, and then were challenged, together with naïve controls, with the heterosubtypic virus A/California/04/2009 (H1N1pdm). Macaques receiving either vaccine regimen cleared H1N1pdm challenge faster than naïve controls. Vaccination with H5M elicited antibodies that bound H1N1pdm HA, but did not neutralize the H1N1pdm challenge virus. Plasma from vaccinated macaques activated NK cells in the presence of H1N1pdm HA, suggesting that vaccination elicited cross-reactive antibodies capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Although HA-specific T cell responses to the MVA-H5M vaccine were weak, responses after challenge were stronger in vaccinated macaques than in control animals. Together these data suggest that mosaic HA antigens may provide a means for inducing broadly cross-reactive immunity to influenza viruses.

Social evaluative threat with verbal performance feedback alters neuroendocrine response to stress.

PubMed

Phan, Jenny M; Schneider, Ekaterina; Peres, Jeremy; Miocevic, Olga; Meyer, Vanessa; Shirtcliff, Elizabeth A

2017-11-01

Laboratory stress tasks such as the Trier Social Stress Test (TSST) have provided a key piece to the puzzle for how psychosocial stress impacts the hypothalamic-pituitary-adrenal axis, other stress-responsive biomarkers, and ultimately wellbeing. These tasks are thought to work through biopsychosocial processes, specifically social evaluative threat and the uncontrollability heighten situational demands. The present study integrated an experimental modification to the design of the TSST to probe whether additional social evaluative threat, via negative verbal feedback about speech performance, can further alter stress reactivity in 63 men and women. This TSST study confirmed previous findings related to stress reactivity and stress recovery but extended this literature in several ways. First, we showed that additional social evaluative threat components, mid-task following the speech portion of the TSST, were still capable of enhancing the psychosocial stressor. Second, we considered stress-reactive hormones beyond cortisol to include dehydroepiandrosterone (DHEA) and testosterone, and found these hormones were also stress-responsive, and their release was coupled with one another. Third, we explored whether gain- and loss-framing incentive instructions, meant to influence performance motivation by enhancing the personal relevance of task performance, impacted hormonal reactivity. Results showed that each hormone was stress reactive and further had different responses to the modified TSST compared to the original TSST. Beyond the utility of showing how the TSST can be modified with heightened social evaluative threat and incentive-framing instructions, this study informs about how these three stress-responsive hormones have differential responses to the demands of a challenge and a stressor. Copyright © 2017 Elsevier Inc. All rights reserved.

Controlling enzymatic activity by immobilization on graphene oxide

NASA Astrophysics Data System (ADS)

Bolibok, Paulina; Wiśniewski, Marek; Roszek, Katarzyna; Terzyk, Artur P.

2017-04-01

In this study, graphene oxide (GO) has been applied as a matrix for enzyme immobilization. The protein adsorption capacity of GO is much higher than of other large surface area carbonaceous materials. Its structure and physicochemical properties are reported beneficial also for enzymatic activity modifications. The experimental proof was done here that GO-based biocatalytic systems with immobilized catalase are modifiable in terms of catalyzed reaction kinetic constants. It was found that activity and stability of catalase, considered here as model enzyme, closely depend on enzyme/GO ratio. The changes in kinetic parameters can be related to secondary structure alterations. The correlation between enzyme/GO ratio and kinetic and structure parameters is reported for the first time and enables the conscious control of biocatalytic processes and their extended applications. The biological activity of obtained biocatalytic systems was confirmed in vitro by the use of functional test. The addition of immobilized catalase improved the cells' viability after they were exposed to hydrogen peroxide and tert-butyl-hydroperoxide used as source of reactive oxygen species.

Constructing TiO2 decorated Bi2WO6 architectures with enhanced visible-light-driven photocatalytic activity

NASA Astrophysics Data System (ADS)

Yang, Zhiyuan; Chen, Lu; Yang, Yun; Wang, Junjie; Huang, Yongkui; Liu, Xiaoxia; Yang, Shuijin

2017-06-01

TiO2 nanoparticles modified Bi2WO6 photocatalysts were prepared via a facile hydrothermal process. The photocatalytic activity of as-prepared TiO2/Bi2WO6 composites was investigated sufficiently by the photodegradation of rhodamine B (RhB), tetracycline hydrochloride (TC) and ciprofloxacin (CIP). The TiO2/Bi2WO6 composites, in which the molar ratio of TiO2 to Bi2WO6 is 1:1, exhibited optimum photocatalytic activity, which is found to increase by about 2.4 times more than that of pristine Bi2WO6 for the photodegradation of TC. The enhanced photocatalytic activity may be attributed to the higher surface area and the highly efficient charge separation between Bi2WO6 nanosheets and TiO2 nanoparticles. The mechanism of the photocatalysts is investigated by the determination of reactive species in the photocatalytic reactions, the photoluminescence measurement and photoelectrochemical analyses.

Improved properties of recycled polypropylene by introducing the long chain branched structure through reactive extrusion.

PubMed

Li, Yingchun; Jia, Shuai; Du, Shuanli; Wang, Yafei; Lv, Lida; Zhang, Jianbin

2018-06-01

An approach originated from preparing long chain branched polypropylene (PP) was applied to modify the properties of recycled PP that involved reactive extrusion to introduce a branched chain structure onto recycled PP under the assistance of chemical reaction between maleic anhydride (MAH) monomer and glycidyl methacrylate (GMA) grafts. The results from Fourier transformed infrared spectroscopy (FTIR) indicated the reaction took place during melt mixing, and the intensity of ester increased with increasing amount of MAH. Several rheological plots including complex viscosity, storage modulus, loss modulus, loss tangent and Cole-Cole plot were used to investigate the rheological properties of recycled PP and modified PP with MAH, which indicated an additional longer relaxation time that was not shown in recycled PP. The effects of branched structure on melting and crystallization behaviors were also investigated, demonstrating the branched chains acted as nucleating agent. Moreover, the branched structure of modified samples gave rise to enhance mechanical properties, especially, the higher impact strength compared with recycled PP. Copyright © 2018 Elsevier Ltd. All rights reserved.

Physical and chemical basics of modification of poly(vinyl chloride) by means of polyisocyanate

NASA Astrophysics Data System (ADS)

Islamov, Anvar; Fakhrutdinova, Venera; Abdrakhmanova, Lyailya

2016-01-01

This research presents data relating to polyvinyl chloride (PVC) modification by means of reactive oligomer and measures technological, physical and mechanical properties of the modified composites. Polyisocyanate (PIC) has been chosen as the modifying reactive oligomer. It has been shown that insertion of the oligomer has a double effect on PVC. Primarily, PIC produces a plasticizing effect on PVC and in particular leads to an increase in thermal stability and melt flow index at the stage of processing. In addition, the molded PVC composites possess higher strength properties and lower deformability when exposed to temperature because of chemical transformations of PIC in polymer matrix and, as the result, the formation of cross-linked systems takes place. In this case, semi-interpenetrating structures are formed based on cross-linked products of PIC chemical transformations homogeneously distributed in the PVC matrix. It has been determined by means of IR-spectroscopy that the basic products of PIC curing are compounds with urea and biuret groups which leads to modifying effect on PVC especially: increase in strength, thermal and mechanical properties, and chemical resistance.

Using the theory of small perturbations in performance calculations of the RBMK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isaev, N.V.; Druzhinin, V.E.; Pogosbekyan, L.R.

The theory of small perturbations in reactor physics is discussed and applied to two-dimensional calculations of the RBMK. The classical theory of small perturbations implies considerable errors in calculations because the perturbations cannot be considered small. The modified theory of small perturbations presented here can be used in atomic power stations for determining reactivity effects and reloading rates of channels in reactors and also for assessing the reactivity storage in control rods.

GUINEVERE experiment: Kinetic analysis of some reactivity measurement methods by deterministic and Monte Carlo codes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bianchini, G.; Burgio, N.; Carta, M.

The GUINEVERE experiment (Generation of Uninterrupted Intense Neutrons at the lead Venus Reactor) is an experimental program in support of the ADS technology presently carried out at SCK-CEN in Mol (Belgium). In the experiment a modified lay-out of the original thermal VENUS critical facility is coupled to an accelerator, built by the French body CNRS in Grenoble, working in both continuous and pulsed mode and delivering 14 MeV neutrons by bombardment of deuterons on a tritium-target. The modified lay-out of the facility consists of a fast subcritical core made of 30% U-235 enriched metallic Uranium in a lead matrix. Severalmore » off-line and on-line reactivity measurement techniques will be investigated during the experimental campaign. This report is focused on the simulation by deterministic (ERANOS French code) and Monte Carlo (MCNPX US code) calculations of three reactivity measurement techniques, Slope ({alpha}-fitting), Area-ratio and Source-jerk, applied to a GUINEVERE subcritical configuration (namely SC1). The inferred reactivity, in dollar units, by the Area-ratio method shows an overall agreement between the two deterministic and Monte Carlo computational approaches, whereas the MCNPX Source-jerk results are affected by large uncertainties and allow only partial conclusions about the comparison. Finally, no particular spatial dependence of the results is observed in the case of the GUINEVERE SC1 subcritical configuration. (authors)« less

Cross-reactivity between methylisothiazolinone, octylisothiazolinone and benzisothiazolinone using a modified local lymph node assay.

PubMed

Schwensen, J F; Menné Bonefeld, C; Zachariae, C; Agerbeck, C; Petersen, T H; Geisler, C; Bollmann, U E; Bester, K; Johansen, J D

2017-01-01

In the light of the exceptionally high rates of contact allergy to the preservative methylisothiazolinone (MI), information about cross-reactivity between MI, octylisothiazolinone (OIT) and benzisothiazolinone (BIT) is needed. To study cross-reactivity between MI and OIT, and between MI and BIT. Immune responses to MI, OIT and BIT were studied in vehicle and MI-sensitized female CBA mice by a modified local lymph node assay. The inflammatory response was measured by ear thickness, cell proliferation of CD4 + and CD8 + T cells, and CD19 + B cells in the auricular draining lymph nodes. MI induced significant, strong, concentration-dependent immune responses in the draining lymph nodes following a sensitization phase of three consecutive days. Groups of MI-sensitized mice were challenged on day 23 with 0·4% MI, 0·7% OIT and 1·9% BIT - concentrations corresponding to their individual EC3 values. No statistically significant difference in proliferation of CD4 + and CD8 + T cells was observed between mice challenged with MI compared with mice challenged with BIT and OIT. The data indicate cross-reactivity between MI, OIT and BIT, when the potency of the chemical was taken into account in choice of challenge concentration. This means that MI-sensitized individuals may react to OIT and BIT if exposed to sufficient concentrations. © 2016 British Association of Dermatologists.

Growth of ZnO nanowires on polypropylene membrane surface-Characterization and reactivity

NASA Astrophysics Data System (ADS)

Bojarska, Marta; Nowak, Bartosz; Skowroński, Jarosław; Piątkiewicz, Wojciech; Gradoń, Leon

2017-01-01

Need for a new membrane is clearly visible in recent studies, mostly due to the fouling phenomenon. Authors, focused on problem of biofouling caused by microorganisms that are present in water environment. An attempt to form a new membrane with zinc oxide (ZnO) nanowires was made; where plasma treatment was used as a first step of modification followed by chemical bath deposition. Such membrane will exhibit additional reactive properties. ZnO, because of its antibacterial and photocatalytic properties, is more and more often used in commercial applications. The authors used SEM imaging, measurement of the contact angle, XRD and the FT-IR analysis for membrane characterization. Amount of ZnO deposited on membrane surface was also investigated by dithizone method. Photocatalytic properties of such membranes were examined through methylene blue and humic acid degradation in laboratory scale modules with LEDs as either: wide range white or UV light source. Antibacterial and antifouling properties of polypropylene membranes modified with ZnO nanowires were examined through a series of tests involving microorganisms: model gram-positive and -negative bacteria. The obtained results showed that it is possible to modify the membrane surface in such a way, that additional reactive properties will be given. Thus, not only did the membrane become a physical barrier, but also turned out to be a reactive one.

Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.

PubMed

Shahab, Uzma; Moinuddin; Ahmad, Saheem; Dixit, Kiran; Habib, Safia; Alam, Khursheed; Ali, Asif

2013-01-01

The interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP) and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. The genotoxic and the carcinogenic effects of 4-ABP are exhibited only when it is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA and induce lesions. Although several studies have reported the formation of 4-ABP-DNA adducts, no extensive work has been done to investigate the immunogenicity of 4-ABP-modified DNA and its possible involvement in the generation of antibodies in bladder cancer patients. Human DNA was modified by N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP), a reactive metabolite of 4-ABP. Structural perturbations in the N-OH-AABP modified DNA were assessed by ultraviolet, fluorescence, and circular dichroic spectroscopy as well as by agarose gel electrophoresis. Genotoxicity of N-OH-AABP modified DNA was ascertained by comet assay. High performance liquid chromatography (HPLC) analysis of native and modified DNA samples confirmed the formation of N-(deoxyguanosine-8-yl)-4-aminobiphenyl (dG-C8-4ABP) in the N-OH-AABP damaged DNA. The experimentally induced antibodies against N-OH-AABP-modified DNA exhibited much better recognition of the DNA isolated from bladder cancer patients as compared to the DNA obtained from healthy individuals in competitive binding ELISA. This work shows epitope sharing between the DNA isolated from bladder cancer patients and the N-OH-AABP-modified DNA implicating the role of 4-ABP metabolites in the DNA damage and neo-antigenic epitope generation that could lead to the induction of antibodies in bladder cancer patients.

Rolling contact fatigue of surface modified 440C using a 'Ge-Polymet' type disc rod test rig

NASA Technical Reports Server (NTRS)

Thom, Robert L.

1989-01-01

Through hardened 440 C martensitic stainless steel test specimens were surface modified and tested for changes in rolling contact fatigue using a disc on rod test rig. The surface modifications consisted of nitrogen, boron, titanium, chromium, tantalum, carbon, or molybdenum ion implantation at various ion fluences and energies. Tests were also performed on specimens reactively sputtered with titanium nitride.

Design of water-soluble, thiol-reactive polymers of controlled molecular weight: a novel multivalent scaffold

NASA Astrophysics Data System (ADS)

Carrillo, Alvaro; Gujraty, Kunal V.; Rai, Prakash R.; Kane, Ravi S.

2005-07-01

Multivalent molecules, i.e. scaffolds presenting multiple copies of a suitable ligand, constitute an emerging class of nanoscale therapeutics. We present a novel approach for the design of multivalent ligands, which allows the biofunctionalization of polymers with proteins or peptides in a controlled orientation. It consists of the synthesis of water-soluble, activated polymer scaffolds of controlled molecular weight, which can be biofunctionalized with various thiolated ligands in aqueous media under mild conditions. These polymers were synthesized by ring-opening metathesis polymerization (ROMP) and further modified to make them water-soluble. The incorporation of chloride groups activated the polymers to react with thiol-containing peptides or proteins, and the formation of multivalent ligands in aqueous media was demonstrated. This strategy represents a convenient route for synthesizing multivalent ligands of controlled dimensions and valency.

Clinical scale rapid expansion of lymphocytes for adoptive cell transfer therapy in the WAVE® bioreactor

PubMed Central

2012-01-01

Background To simplify clinical scale lymphocyte expansions, we investigated the use of the WAVE®, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes. Methods We have developed an optimized rapid expansion protocol for the WAVE bioreactor that produces clinically relevant numbers of cells for our adoptive cell transfer clinical protocols. Results TIL and genetically modified PBL were rapidly expanded to clinically relevant scales in both static bags and the WAVE bioreactor. Both bioreactors produced comparable numbers of cells; however the cultures generated in the WAVE bioreactor had a higher percentage of CD4+ cells and had a less activated phenotype. Conclusions The WAVE bioreactor simplifies the process of rapidly expanding tumor reactive lymphocytes under GMP conditions, and provides an alternate approach to cell generation for ACT protocols. PMID:22475724

Elimination of reactive blue 4 from aqueous solutions using 3-aminopropyl triethoxysilane modified chitosan beads.

PubMed

Vakili, Mohammadtaghi; Rafatullah, Mohd; Salamatinia, Babak; Ibrahim, Mahamad Hakimi; Abdullah, Ahmad Zuhairi

2015-11-05

The adsorption behavior of chitosan (CS) beads modified with 3-aminopropyl triethoxysilane (APTES) for the removal of reactive blue 4 (RB4) in batch studies has been investigated. The effects of modification conditions, such as the APTES concentration, temperature and reaction time on RB4 removal, were studied. The adsorbent prepared at a concentration of 2 wt% APTES for 8h at 50 °C was the most effective one for RB4 adsorption. The adsorption capacity of modified CS beads (433.77 mg/g) was 1.37 times higher than that of unmodified CS beads (317.23 mg/g). The isotherm data are adequately described by a Freundlich model, and the kinetic study revealed that the pseudo-second-order rate model was in better agreement with the experimental data. The negative values of the thermodynamic parameters, including ΔG° (-2.28 and -4.70 kJ/mol at 30 ± 2 °C), ΔH° (-172.18 and -43.82 kJ/mol) and ΔS° (-560.71 and -129.08 J/mol K) for CS beads and APTES modified beads, respectively, suggest that RB4 adsorption is a spontaneous and exothermic process. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitation of exposure to benzo[a]pyrene with monoclonal antibodies.

PubMed Central

Santella, R M; Hsieh, L L; Lin, C D; Viet, S; Weinstein, I B

1985-01-01

It is now possible to quantitate carcinogen adducts on DNA by highly sensitive immunoassays. These techniques are particularly useful for screening human populations for exposure to potential environmental carcinogens. We have developed a panel of monoclonal antibodies that react with benzo(a)pyrene (BP) modified DNA to be used in an enzyme linked immunoassay (ELISA) to quantitate adduct levels of both human and animal samples. BALBc/Cr mice were immunized with either DNA modified by 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo(a)pyrene (BPDE-I-DNA) complexed electrostatically to methylated bovine serum albumin or with BPDE-I-modified guanosine conjugated with bovine serum albumin (BPDE-I-G-BSA). Four stable clones were produced from the spleen cells of animals immunized with BPDE-I-DNA and one from BPDE-I-G-BSA immunized animals. All antibodies were shown to be highly specific for BPDE-I-DNA and did not crossreact with nonmodified DNA or with N-2-acetylaminofluorene or 1-aminopyrene modified DNA. The antibodies differed in their sensitivity to BPDE-II-DNA, BPDE-I-poly G, BPDE-I-tetraols and BPDE-I-dG. In general, all the antibodies showed the greatest affinity for their original antigen. Those generated against modified DNA showed highest reactivity against modified DNA while the one antibody generated against the monoadduct showed highest reactivity with the monoadduct. These antibodies are currently being used in a highly sensitive competitive ELISA to quantitate levels of BP-DNA adducts in various animal and human tissue samples. PMID:4085452

Phosphorylation-Induced Conformational Changes of Photoactivated Rhodopsin Probed by Fluorescent Labeling at Cys140 and Cys316.

PubMed

Rodríguez, Sheerly; Silva, May-Li; Benaím, Gustavo; Bubis, José

2018-05-03

In order to monitor conformational changes following photoactivation and phosphorylation of bovine rhodopsin, the two reactive sulfhydryl groups at Cys 140 and Cys 316 were specifically labeled with the monobromobimane (mBBr) fluorophore. Although alterations in conformation after light exposure of rhodopsin were not detected by fluorescence excitation scans (300-450 nm) of the mBBr-labeled protein, the fluorescence signal was reduced ∼ 90% in samples containing photoactivated phosphorhodopsin. Predominant labeling at either Cys 140 or Cys 316 in light-activated and phosphorylated rhodopsin merely generated a decrease of ∼ 38% and 28%, respectively, in the fluorescence excitation intensity. Thus, neither mBBr-modified Cys 140 nor mBBr-modified Cys 316 were involved single-handedly in the remarkable fall seen on the signal following phosphorylation of the protein; rather, the incorporation of phosphate groups on the mBBr-labeled light-activated rhodopsin appeared to affect its fluorescence signal in a cooperative or synergistic manner. These findings demonstrated that the phosphorylation of specific hydroxyl groups at the carboxyl terminal tail of rhodopsin causes definite conformational changes in the three-dimensional fold of the protein. Apparently, amino acid residues that are buried in the interior of the inactive protein become accessible following bleaching and phosphorylation of rhodopsin, quenching in turn the fluorescence excitation signal of mBBr-modified rhodopsin. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Biophysical analysis of the effect of chemical modification by 4-oxononenal on the structure, stability, and function of binding immunoglobulin protein (BiP)

PubMed Central

Shah, Dinen D.; Singh, Surinder M.; Dzieciatkowska, Monika

2017-01-01

Binding immunoglobulin protein (BiP) is a molecular chaperone important for the folding of numerous proteins, which include millions of immunoglobulins in human body. It also plays a key role in the unfolded protein response (UPR) in the endoplasmic reticulum. Free radical generation is a common phenomenon that occurs in cells under healthy as well as under stress conditions such as ageing, inflammation, alcohol consumption, and smoking. These free radicals attack the cell membranes and generate highly reactive lipid peroxidation products such as 4-oxononenal (4-ONE). BiP is a key protein that is modified by 4-ONE. In this study, we probed how such chemical modification affects the biophysical properties of BiP. Upon modification, BiP shows significant tertiary structural changes with no changes in its secondary structure. The protein loses its thermodynamic stability, particularly, that of the nucleotide binding domain (NBD) where ATP binds. In terms of function, the modified BiP completely loses its ATPase activity with decreased ATP binding affinity. However, modified BiP retains its immunoglobulin binding function and its chaperone activity of suppressing non-specific protein aggregation. These results indicate that 4-ONE modification can significantly affect the structure-function of key proteins such as BiP involved in cellular pathways, and provide a molecular basis for how chemical modifications can result in the failure of quality control mechanisms inside the cell. PMID:28886061

Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease

PubMed Central

Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A.

2017-01-01

Abstract Aims: Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Results: Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APPSwe/PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9–10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Innovation: Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. Conclusions: We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269–1280. PMID:28264587

Rheological Properties and Foaming Behavior of Poly(Ethylene Terephthalates) Modified with Pyromellitic Dianhydride

NASA Astrophysics Data System (ADS)

Yang, Zhao-Ping; Xin, Chun-Ling; Guo, Ya-Feng; Luo, Yi-Wei; He, Ya-Dong

2016-05-01

Improving the melt viscoelasticity of poly(ethylene terephthalate) (PET) is a well-known method to obtain foamable PET. The aim of this study is to prepare high melt strength PET and evaluate the influence of rheological properties of PET on the foaming behavior. For this purpose, pyromelliticdianhydride was used as the chain extender to modify a linear PET through melt reactive processing. The rheological properties of the unmodified and modified PETs were measured by a dynamic rheometer. Results showed that the modified PET had higher complex viscosity than the unmodified one. Furthermore, the batch foaming by using supercritical CO2 as a blowing agent was carried to evaluate the foamability of modified PETs. It was found that an enlarged foaming temperature window was obtained for modified PETs compared to unmodified PET. Moreover, the modified PETs foams exhibited higher expansion ratio, smaller cell size and higher cell density at high temperatures than the neat PET.

The effects of bacteria-nanoparticles interface on the antibacterial activity of green synthesized silver nanoparticles.

PubMed

Ahmad, Aftab; Wei, Yun; Syed, Fatima; Tahir, Kamran; Rehman, Aziz Ur; Khan, Arifullah; Ullah, Sadeeq; Yuan, Qipeng

2017-01-01

Neutralization of bacterial cell surface potential using nanoscale materials is an effective strategy to alter membrane permeability, cytoplasmic leakage, and ultimate cell death. In the present study, an attempt was made to prepare biogenic silver nanoparticles using biomolecules from the aqueous rhizome extract of Coptis Chinensis. The biosynthesized silver nanoparticles were surface modified with chitosan biopolymer. The prepared silver nanoparticles and chitosan modified silver nanoparticles were cubic crystalline structures (XRD) with an average particle size of 15 and 20 nm respectively (TEM, DLS). The biosynthesized silver nanoparticles were surface stabilized by polyphenolic compounds (FTIR). Coptis Chinensis mediated silver nanoparticles displayed significant activity against E. coli and Bacillus subtilus with a zone of inhibition 12 ± 1.2 (MIC = 25 μg/mL) and 18 ± 1.6 mm (MIC = 12.50 μg/mL) respectively. The bactericidal efficacy of these nanoparticles was considerably increased upon surface modification with chitosan biopolymer. The chitosan modified biogenic silver nanoparticles exhibited promising activity against E. coli (MIC = 6.25 μg/mL) and Bacillus subtilus (MIC = 12.50 μg/mL). Our results indicated that the chitosan modified silver nanoparticles were promising agents in damaging bacterial membrane potential and induction of high level of intracellular reactive oxygen species (ROS). In addition, these nanoparticles were observed to induce the release of the high level of cytoplasmic materials especially protein and nucleic acids into the media. All these findings suggest that the chitosan functionalized silver nanoparticles are efficient agents in disrupting bacterial membrane and induction of ROS leading to cytoplasmic leakage and cell death. These findings further conclude that the bacterial-nanoparticles surface potential modulation is an effective strategy in enhancing the antibacterial potency of silver nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ni-Nanocluster Modified Black TiO2 with Dual Active Sites for Selective Photocatalytic CO2 Reduction.

PubMed

Billo, Tadesse; Fu, Fang-Yu; Raghunath, Putikam; Shown, Indrajit; Chen, Wei-Fu; Lien, Hsiang-Ting; Shen, Tzu-Hsien; Lee, Jyh-Fu; Chan, Ting-Shan; Huang, Kuo-You; Wu, Chih-I; Lin, M C; Hwang, Jih-Shang; Lee, Chih-Hao; Chen, Li-Chyong; Chen, Kuei-Hsien

2018-01-01

One of the key challenges in artificial photosynthesis is to design a photocatalyst that can bind and activate the CO 2 molecule with the smallest possible activation energy and produce selective hydrocarbon products. In this contribution, a combined experimental and computational study on Ni-nanocluster loaded black TiO 2 (Ni/TiO 2[Vo] ) with built-in dual active sites for selective photocatalytic CO 2 conversion is reported. The findings reveal that the synergistic effects of deliberately induced Ni nanoclusters and oxygen vacancies provide (1) energetically stable CO 2 binding sites with the lowest activation energy (0.08 eV), (2) highly reactive sites, (3) a fast electron transfer pathway, and (4) enhanced light harvesting by lowering the bandgap. The Ni/TiO 2[Vo] photocatalyst has demonstrated highly selective and enhanced photocatalytic activity of more than 18 times higher solar fuel production than the commercial TiO 2 (P-25). An insight into the mechanisms of interfacial charge transfer and product formation is explored. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Context-dependent switching between proactive and reactive working memory control mechanisms in the right inferior frontal gyrus.

PubMed

Marklund, Petter; Persson, Jonas

2012-11-15

A critical feature of higher cognitive functioning is the capacity to flexibly tailor information processing and behaviors to current situational demands. Recent neurocognitive models have been postulated to account for the dynamic nature of human executive processing by invoking two dissociable cognitive control modes, proactive and reactive control. These may involve partially overlapping, but temporally distinct neural implementation in the prefrontal cortex. Prior brain imaging studies exploring proactive control have mainly used tasks requiring only information about single-items to be retained over unfilled delays. Whether proactive control can also be utilized to facilitate performance in more complex working memory tasks, in which concurrent processing of intervening items and updating is mandatory during contextual cue maintenance remains an open question. To examine this issue and to elucidate the extent to which overlapping neural substrates underlie proactive and reactive control we used fMRI and a modified verbal 3-back paradigm with embedded cues predictive of high-interference trials. This task requires context information to be retained over multiple intervening trials. We found that performance improved with item-specific cues predicting forthcoming lures despite increased working memory load. Temporal dynamics of activation in the right inferior frontal gyrus suggest flexible switching between proactive and reactive control in a context-dependent fashion, with greater sustained responses elicited in the 3-back task involving context maintenance of cue information and greater transient responses elicited in the 3-back task absent of cues. Copyright © 2012 Elsevier Inc. All rights reserved.

In vitro characterization of pralidoxime transport and acetylcholinesterase reactivation across MDCK cells and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs).

PubMed

Gallagher, Erin; Minn, Il; Chambers, Janice E; Searson, Peter C

2016-07-11

Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration in the brain following systemic injection. To assess 2-PAM transport, we studied transwell permeability in three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs). To determine whether 2-PAM is a substrate for common brain efflux pumps, experiments were performed in the MDCKII-MDR1 cell line, transfected to overexpress the P-gp efflux pump, and the MDCKII-FLuc-ABCG2 cell line, transfected to overexpress the BCRP efflux pump. To determine how transcellular transport influences enzyme reactivation, we developed a modified transwell assay where the inhibited acetylcholinesterase enzyme, substrate, and reporter are introduced into the basolateral chamber. Enzymatic activity was inhibited using paraoxon and parathion. The permeability of 2-PAM is about 2 × 10(-6) cm s(-1) in MDCK cells and about 1 × 10(-6) cm s(-1) in BC1-hBMECs. Permeability is not influenced by pre-treatment with atropine. In addition, 2-PAM is not a substrate for the P-gp or BCRP efflux pumps. The low permeability explains poor brain penetration of 2-PAM and therefore the slow enzyme reactivation. This elucidates one of the reasons for the necessity of sustained intravascular (IV) infusion in response to organophosphate poisoning.

Potential side effects of unhealthy lifestyle choices and health risks on basal and reactive heart rate variability in college drinkers.

PubMed

Udo, Tomoko; Mun, Eun-Young; Buckman, Jennifer F; Vaschillo, Evgeny G; Vaschillo, Bronya; Bates, Marsha E

2013-09-01

Emerging adults often begin making independent lifestyle choices during college, yet the association of these choices with fundamental indicators of health and adaptability is unclear. The present study examined the relationship between health risks and neurocardiac function in college drinkers. Heart rate variability (HRV) was assessed at baseline and in reaction to a paced breathing challenge in 212 college drinkers (53.8% women). Basal HRV served as a general indicator of health. Reactive HRV (during paced breathing) was used as a marker of an individual's adaptability to challenge. The relationship of HRV to alcohol use, cigarette use, exercise, sleep, and body mass index (BMI) was assessed. Greater alcohol use and less exercise were associated with lower basal HRV. BMI was unrelated to basal HRV but was negatively associated with reactive HRV during the breathing challenge. High levels of alcohol use and lack of exercise are negative correlates of cardiovascular and general health, even in apparently healthy college drinkers. The negative relationship between BMI and reactive HRV suggests that overweight individuals have reduced ability to psychophysiologically adapt to challenges; understanding the temporal course of this relationship is needed. This study highlights the importance of examining HRV at baseline and in response to a challenge to capture the active neurocardiac processes that contribute to health and adaptive responding. The suppressive effects of health risks on HRV are modifiable; thus, HRV may be useful in evaluating the health benefits of lifestyle change and in promoting change behaviors in college drinkers.

Recent mouse models and vaccine candidates for preventing chronic/latent tuberculosis infection and its reactivation.

PubMed

Pedroza-Roldán, César; Flores-Valdez, Mario Alberto

2017-08-31

Tuberculosis (TB) remains a major challenge in public health worldwide. Until today, the only widely used and approved vaccine is the Mycobacterium bovis bacille Calmette-Guerin (BCG). This vaccine provides a highly variable level of protection against the active, pulmonary form of tuberculosis, and practically none against the latent form of TB infection. This disparity in protection has been extensively studied, and for this reason, several groups have focused their research on the quest for attenuated vaccines based on M. tuberculosis or on the identification of latency-associated antigens that can be incorporated into modified BCG, or that can be used as adjuvanted subunit vaccines. In order to seek new potential antigens relevant for infection, some researchers have performed experiments with highly sensitive techniques such as transcriptomic and proteomic analyses using sputum samples from humans or by using mouse models resembling several aspects of TB. In this review, we focus on reports of new mouse models or mycobacterial antigens recently tested for developing vaccine candidates against chronic/latent tuberculosis and its reactivation.

In situ fluorescence spectroscopy correlates ionomer degradation to reactive oxygen species generation in an operating fuel cell.

PubMed

Prabhakaran, Venkateshkumar; Arges, Christopher G; Ramani, Vijay

2013-11-21

The rate of generation of reactive oxygen species (ROS) within the polymer electrolyte membrane (PEM) of an operating proton exchange member fuel cell (PEMFC) was monitored using in situ fluorescence spectroscopy. A modified barrier layer was introduced between the PEM and the electrocatalyst layer to eliminate metal-dye interactions and fluorescence resonance energy transfer (FRET) effects during measurements. Standard fuel cell operating parameters (temperature, relative humidity, and electrode potential) were systematically varied to evaluate their influence on the rate of ROS generation during PEMFC operation. Independently, the macroscopic rate of PEM degradation was measured by monitoring the fluoride ion emission rate (FER) in the effluent stream at each operating condition. The ROS generation reaction rate constant (estimated from the in situ fluorescence experiments) correlated perfectly with the measured FER across all conditions, demonstrating unequivocally for the first time that a direct correlation exists between in situ ROS generation and PEM macroscopic degradation. The activation energy for ROS generation within the PEM was estimated to be 12.5 kJ mol(-1).

Efficient active-template synthesis of calix[6]arene-based oriented pseudorotaxanes and rotaxanes.

PubMed

Zanichelli, Valeria; Ragazzon, Giulio; Orlandini, Guido; Venturi, Margherita; Credi, Alberto; Silvi, Serena; Arduini, Arturo; Secchi, Andrea

2017-08-16

A substrate can modify its chemical features, including a change of its reactivity, as a consequence of non-covalent interactions upon inclusion within a molecular host. Since the rise of supramolecular chemistry, this phenomenon has stimulated the ingenuity of scientists to emulate the function of enzymes by designing supramolecular systems in which the energetics and selectivity of reactions can be manipulated through programmed host-guest interactions and/or steric confinement. In this paper we investigate how the engulfment of a positively charged pyridinium-based guest inside the π-rich cavity of a tris-(N-phenylureido)calix[6]arene host affects its reactivity towards a S N 2 reaction. We found that the alkylation of complexed substrates leads to the formation of pseudorotaxanes and rotaxanes with faster kinetics and higher yields with respect to the standard procedures exploited so far. More importantly, the strategy described here expands the range of efficient synthetic routes for the formation of mechanically interlocked species with a strict control of the mutual orientation of their non-symmetric molecular components.

Sleep-Dependent Synaptic Down-Selection (I): Modeling the Benefits of Sleep on Memory Consolidation and Integration

PubMed Central

Nere, Andrew; Hashmi, Atif; Cirelli, Chiara; Tononi, Giulio

2013-01-01

Sleep can favor the consolidation of both procedural and declarative memories, promote gist extraction, help the integration of new with old memories, and desaturate the ability to learn. It is often assumed that such beneficial effects are due to the reactivation of neural circuits in sleep to further strengthen the synapses modified during wake or transfer memories to different parts of the brain. A different possibility is that sleep may benefit memory not by further strengthening synapses, but rather by renormalizing synaptic strength to restore cellular homeostasis after net synaptic potentiation in wake. In this way, the sleep-dependent reactivation of neural circuits could result in the competitive down-selection of synapses that are activated infrequently and fit less well with the overall organization of memories. By using computer simulations, we show here that synaptic down-selection is in principle sufficient to explain the beneficial effects of sleep on the consolidation of procedural and declarative memories, on gist extraction, and on the integration of new with old memories, thereby addressing the plasticity-stability dilemma. PMID:24137153

Development of Highly Durable and Reactive Regenerable Magnesium-Based Sorbents for CO2 Separation in Coal Gasification Process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Javad Abbasian; Armin Hassanzadeh Khayyat; Rachid B. Slimane

The specific objective of this project was to develop physically durable and chemically regenerable MgO-based sorbents that can remove carbon dioxide from raw coal gas at operating condition prevailing in IGCC processes. A total of sixty two (62) different sorbents were prepared in this project. The sorbents were prepared either by various sol-gel techniques (22 formulations) or modification of dolomite (40 formulations). The sorbents were prepared in the form of pellets and in granular forms. The solgel based sorbents had very high physical strength, relatively high surface area, and very low average pore diameter. The magnesium content of the sorbentsmore » was estimated to be 4-6 % w/w. To improve the reactivity of the sorbents toward CO{sub 2}, The sorbents were impregnated with potassium salts. The potassium content of the sorbents was about 5%. The dolomite-based sorbents were prepared by calcination of dolomite at various temperature and calcination environment (CO{sub 2} partial pressure and moisture). Potassium carbonate was added to the half-calcined dolomite through wet impregnation method. The estimated potassium content of the impregnated sorbents was in the range of 1-6% w/w. In general, the modified dolomite sorbents have significantly higher magnesium content, larger pore diameter and lower surface area, resulting in significantly higher reactivity compared to the sol-gel sorbents. The reactivities of a number of sorbents toward CO{sub 2} were determined in a Thermogravimetric Analyzer (TGA) unit. The results indicated that at the low CO{sub 2} partial pressures (i.e., 1 atm), the reactivities of the sorbents toward CO{sub 2} are very low. At elevated pressures (i.e., CO{sub 2} partial pressure of 10 bar) the maximum conversion of MgO obtained with the sol-gel based sorbents was about 5%, which corresponds to a maximum CO{sub 2} absorption capacity of less than 1%. The overall capacity of modified dolomite sorbents were at least one order of magnitude higher than those of the sol-gel based sorbents. The results of the tests conducted with various dolomite-based sorbent indicate that the reactivity of the modified dolomite sorbent increases with increasing potassium concentration, while higher calcination temperature adversely affects the sorbent reactivity. Furthermore, the results indicate that as long as the absorption temperature is well below the equilibrium temperature, the reactivity of the sorbent improves with increasing temperature (350-425 C). As the temperature approaches the equilibrium temperature, because of the significant increase in the rate of reverse (i.e., regeneration) reaction, the rate of CO{sub 2} absorption decreases. The results of cyclic tests show that the reactivity of the sorbent gradually decreases in the cyclic process. To improve long-term durability (i.e., reactivity and capacity) of the sorbent, the sorbent was periodically re-impregnated with potassium additive and calcined. The results indicate that, in general, re-treatment improves the performance of the sorbent, and that, the extent of improvement gradually decreases in the cyclic process. The presence of steam significantly enhances the sorbent reactivity and significantly decreases the rate of decline in sorbent deactivation in the cyclic process.« less

Morphogenesis of polycrystalline dendritic patterns from evaporation of a reactive nanofluid sessile drop

NASA Astrophysics Data System (ADS)

Wu, Hua; Briscoe, Wuge H.

2018-04-01

We report polycrystalline residual patterns with dendritic micromorphologies upon fast evaporation of a mixed-solvent sessile drop containing reactive ZnO nanoparticles. The molecular and particulate species generated in situ upon evaporative drying collude with and modify the Marangoni solvent flows and Bénard-Marangoni instabilities, as they undergo self-assembly and self-organization under conditions far from equilibrium, leading to the ultimate hierarchical central cellular patterns surrounded by a peripheral coffee ring upon drying.

Pack Cementation Aluminide Coatings on Superalloys: Codeposition of Cr and Reactive Elements (RE). Technical Report 1. Chromium and Reactive Element(RE)- Modified Aluminide Diffusion Coatings on Superalloys: Environmental Testing. Technical Report 2

DTIC Science & Technology

1992-11-01

Godlewska and K. Godlewski, Oxid. Met., 22 (1984) 117. 4. J.E. Restall, U.S. Patent #4,687,684 (1987). 5. P.N. Walsh, in Proceeding of the Fourth...McCarron, N.R. Lindblad, and D. Chatterji, Corrosion, 32 (1976) 476. 34 33. E. Godlewska and K. Godlewski, Oxid. Met., 22 (1984) 117. 34. B. Pieraggi

Some properties of explosive mixtures containing peroxides Part II. Relationships between detonation parameters and thermal reactivity of the mixtures with triacetone triperoxide.

PubMed

Zeman, Svatopluk; Bartei, Cécile

2008-06-15

This study concerns mixtures of triacetone triperoxide (3,3,6,6,9,9-hexamethyl-1,2,4,5,7,8-hexoxonane, TATP) and ammonium nitrate (AN) with added water (W), as the case may be, and two dry mixtures of TATP with urea nitrate (UN). Relative performances (RP) of the mixtures and their individual components, relative to TNT, were determined by means of ballistic mortar. Thermal reactivity of these mixtures was examined by means of differential thermal analysis and the data were analyzed according to the modified Kissinger method (the peak temperature was replaced by the temperature of decomposition onset in this case). The reactivity, expressed as the EaR(-1) slopes of the Kissinger relationship, correlates with the squares of the calculated detonation velocities for the charge density of 1000 kg m(-3) of the studied energetic materials. Similarly, the relationships between the EaR(-1) values and RP have been found. While the first mentioned correlation (modified Evans-Polanyi-Semenov equation) is connected with the primary chemical micro-mechanism of the mixtures detonation, the relationships in the second case should be connected with the thermochemical aspects of this detonation.

[Immunogenicity of L5178Y cells modified by different reagents].

PubMed

Gómez-Estrada, H; López-de la Rosa, L M; Becerril-Meza, G; Arellano-Blanco, J; Fernández-Quintero, P

1977-01-01

Lymphoma L5178Y cells were treated with neuraminidase of Vibrio cholerae, potassium iodine, dithiotreitol (DTT), mercaptoethanol, glutaraldehyde, iodoacetamide, merthiolate, sodium periodate, urea, papaine, trypsine and EDTA, to increase immunoreaction in tumor cells. Mice were immunized with modified tumor cells every week for one month. Thereafter non modified tumor cells were transplanted to previously immunized mice. Only the immunization with neuraminidase-treated cells rejected the tumor. Although the immunization with cells treated with potassium iodine, DTT and mercaptoethanol did not reject tumor, prolonged significantly span of life. The other reactives had neither effect on tumor rejection nor on span of life.

Dynamically Cross-linked Elastomer Hybrids with Light-Induced Rapid and Efficient Self-Healing Ability and Reprogrammable Shape Memory Behavior.

PubMed

Bai, Jing; Shi, Zixing

2017-08-16

Pristine carbon nanotubes (CNTs) were activated to exhibit Diels-Alder (DA) reactivity in a polymer matrix, which was modified with monomers containing furan groups. The DA-active polymer matrix was transferred into a dynamic reversible cross-linked inorganic-organic network via a Diels-Alder reaction with CNTs, where pristine CNTs were used as dienophile chemicals and furan-modified SBS acted as the macromolecular diene. In this system, the mechanical properties as well as resilience and solvent resistance were greatly improved even with the presence of only 1 wt % CNTs. Meanwhile, the hybrids retained recyclability and exhibited some smart behaviors, including self-healing and reprogrammable shape memory properties. Furthermore, due to the photothermal effect of CNTs, a retro-Diels-Alder (rDA) reaction was activated under laser irradiation, and healing of a crack on the hybrid surface was demonstrated in approximately 10 s with almost complete recovery of the mechanical properties. Such fast and efficient self-healing performance provides a new concept in designing self-healing nanocomposites with tunable structures and mechanical properties. Furthermore, the DA and rDA reactions could be combined to reprogram the shape memory behavior under laser irradiation or thermal treatment, wherein the temporary shape of the sample could be transferred to a permanent shape via the rDA reaction at high temperature.

Lactobacillus delbrueckii subsp. lactis (strain CIDCA 133) stimulates murine macrophages infected with Citrobacter rodentium.

PubMed

Hugo, Ayelén A; Rolny, Ivanna S; Romanin, David; Pérez, Pablo F

2017-03-01

Citrobacter rodentium is a specific murine enteropathogen which causes diarrheal disease characterized by colonic hyperplasia and intestinal inflammation. Recruitment of neutrophils and macrophages constitute a key step to control the infection. Since modulation of the activity of professional phagocytic cells could contribute to improve host´s defences against C. rodentium, we investigated the effect of Lactobacillus delbrueckii subsp. lactis (strain CIDCA 133) on the interaction between murine macrophages (RAW 264.7) and C. rodentium. Phagocytosis, surface molecules and inducible nitric oxide synthase (iNOs) expression were determined by flow cytometry. Reactive oxygen species (ROS) were assessed by fluorescence microscopy. The presence of lactobacilli increased phagocytosis of C. rodentium whereas C. rodentium had no effect on lactobacilli internalization. Survival of internalized C. rodentium diminished when strain CIDCA 133 was present. CD-86, MHCII, iNOs expression and nitrite production were increased when C. rodentium and lactobacilli were present even though strain CIDCA 133 alone had no effect. Strain CIDCA 133 led to a strong induction of ROS activity which was not modified by C. rodentium. Lactobacillus delbrueckii subsp. lactis (strain CIDCA 133) is able to increase the activation of murine macrophages infected with C. rodentium. The sole presence of lactobacilli is enough to modify some stimulation markers (e.g. ROS induction) whereas other markers require the presence of both bacteria; thus, indicating a synergistic effect.

Landscape linkages between geothermal activity and solute composition and ecological response in surface waters draining the Atlantic slope of Costa Rica

USGS Publications Warehouse

Pringle, Catherine M.; Rowe, Gary L.; Triska, Frank J.; Fernandez, Jose F.; West, John

1993-01-01

Surface waters draining three different volcanoes in Costa Rica, ranging from dormant to moderately active to explosive, have a wide range of solute compositions that partly reflects the contribution of different types of solute-rich, geothermal waters. Three major physical transport vectors affect flows of geothermally derived solutes: thermally driven convection of volcanic gases and geothermal fluids; lateral and gravity-driven downward transport of geothermal fluids; and wind dispersion of ash, gases, and acid rain. Specific vector combinations interact to determine landscape patterns in solute chemistry and biota: indicator taxa of algae and bacteria reflect factors such as high temperature, wind-driven or hydrologically transported acidity, high concentrations of various solutes, and chemical precipitation reactions. Many streams receiving geothermally derived solutes have high levels of soluble reactive phosphorus (SRP) (up to 400 µg liter−1), a nutrient that is typically not measured in geochemical studies of geothermal waters. Regional differences in levels of SRP and other solutes among volcanoes were typically not significant due to high local variation in solute levels among geothermally modified streams and between geothermally modified and unmodified streams on each volcano. Geothermal activity along the volcanic spine of Costa Rica provides a natural source of phosphorus, silica, and other solutes and plays an important role in determining emergent landscape patterns in the solute chemistry of surface waters and aquatic biota.

Review of Reactive Power Dispatch Strategies for Loss Minimization in a DFIG-based Wind Farm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Baohua; Hu, Weihao; Hou, Peng

This study reviews and compares the performance of reactive power dispatch strategies for the loss minimization of Doubly Fed Induction Generator (DFIG)-based Wind Farms (WFs). Twelve possible combinations of three WF level reactive power dispatch strategies and four Wind Turbine (WT) level reactive power control strategies are investigated. All of the combined strategies are formulated based on the comprehensive loss models of WFs, including the loss models of DFIGs, converters, filters, transformers, and cables of the collection system. Optimization problems are solved by a Modified Particle Swarm Optimization (MPSO) algorithm. The effectiveness of these strategies is evaluated by simulations onmore » a carefully designed WF under a series of cases with different wind speeds and reactive power requirements of the WF. The wind speed at each WT inside the WF is calculated using the Jensen wake model. The results show that the best reactive power dispatch strategy for loss minimization comes when the WF level strategy and WT level control are coordinated and the losses from each device in the WF are considered in the objective.« less

Principles for integrating reactive species into in vivo biological processes: Examples from exercise physiology.

PubMed

Margaritelis, Nikos V; Cobley, James N; Paschalis, Vassilis; Veskoukis, Aristidis S; Theodorou, Anastasios A; Kyparos, Antonios; Nikolaidis, Michalis G

2016-04-01

The equivocal role of reactive species and redox signaling in exercise responses and adaptations is an example clearly showing the inadequacy of current redox biology research to shed light on fundamental biological processes in vivo. Part of the answer probably relies on the extreme complexity of the in vivo redox biology and the limitations of the currently applied methodological and experimental tools. We propose six fundamental principles that should be considered in future studies to mechanistically link reactive species production to exercise responses or adaptations: 1) identify and quantify the reactive species, 2) determine the potential signaling properties of the reactive species, 3) detect the sources of reactive species, 4) locate the domain modified and verify the (ir)reversibility of post-translational modifications, 5) establish causality between redox and physiological measurements, 6) use selective and targeted antioxidants. Fulfilling these principles requires an idealized human experimental setting, which is certainly a utopia. Thus, researchers should choose to satisfy those principles, which, based on scientific evidence, are most critical for their specific research question. Copyright © 2015 Elsevier Inc. All rights reserved.

Review of Reactive Power Dispatch Strategies for Loss Minimization in a DFIG-based Wind Farm

DOE PAGES

Zhang, Baohua; Hu, Weihao; Hou, Peng; ...

2017-06-27

This study reviews and compares the performance of reactive power dispatch strategies for the loss minimization of Doubly Fed Induction Generator (DFIG)-based Wind Farms (WFs). Twelve possible combinations of three WF level reactive power dispatch strategies and four Wind Turbine (WT) level reactive power control strategies are investigated. All of the combined strategies are formulated based on the comprehensive loss models of WFs, including the loss models of DFIGs, converters, filters, transformers, and cables of the collection system. Optimization problems are solved by a Modified Particle Swarm Optimization (MPSO) algorithm. The effectiveness of these strategies is evaluated by simulations onmore » a carefully designed WF under a series of cases with different wind speeds and reactive power requirements of the WF. The wind speed at each WT inside the WF is calculated using the Jensen wake model. The results show that the best reactive power dispatch strategy for loss minimization comes when the WF level strategy and WT level control are coordinated and the losses from each device in the WF are considered in the objective.« less

Alkylation of histidine residues of Bothrops jararacussu venom proteins and isolated phospholipases A2: a biotechnological tool to improve the production of antibodies.

PubMed

Guimarães, C L S; Andrião-Escarso, S H; Moreira-Dill, L S; Carvalho, B M A; Marchi-Salvador, D P; Santos-Filho, N A; Fernandes, C A H; Fontes, M R M; Giglio, J R; Barraviera, B; Zuliani, J P; Fernandes, C F C; Calderón, L A; Stábeli, R G; Albericio, F; da Silva, S L; Soares, A M

2014-01-01

Crude venom of Bothrops jararacussu and isolated phospholipases A2 (PLA2) of this toxin (BthTX-I and BthTX-II) were chemically modified (alkylation) by p-bromophenacyl bromide (BPB) in order to study antibody production capacity in function of the structure-function relationship of these substances (crude venom and PLA2 native and alkylated). BthTX-II showed enzymatic activity, while BthTX-I did not. Alkylation reduced BthTX-II activity by 50% while this process abolished the catalytic and myotoxic activities of BthTX-I, while reducing its edema-inducing activity by about 50%. Antibody production against the native and alkylated forms of BthTX-I and -II and the cross-reactivity of antibodies to native and alkylated toxins did not show any apparent differences and these observations were reinforced by surface plasmon resonance (SPR) data. Histopathological analysis of mouse gastrocnemius muscle sections after injection of PBS, BthTX-I, BthTX-II, or both myotoxins previously incubated with neutralizing antibody showed inhibition of the toxin-induced myotoxicity. These results reveal that the chemical modification of the phospholipases A2 (PLA2) diminished their toxicity but did not alter their antigenicity. This observation indicates that the modified PLA2 may provide a biotechnological tool to attenuate the toxicity of the crude venom, by improving the production of antibodies and decreasing the local toxic effects of this poisonous substance in animals used to produce antivenom.

How thinking about what could have been affects how we feel about what was.

PubMed

De Brigard, Felipe; Hanna, Eleanor; St Jacques, Peggy L; Schacter, Daniel L

2018-06-01

Episodic counterfactual thoughts (CFT) and autobiographical memories (AM) involve the reactivation and recombination of episodic memory components into mental simulations. Upon reactivation, memories become labile and prone to modification. Thus, reactivating AM in the context of mentally generating CFT may provide an opportunity for editing processes to modify the content of the original memory. To examine this idea, this paper reports the results of two studies that investigated the effect of reactivating negative and positive AM in the context of either imagining a better (i.e. upward CFT) or a worse (i.e. downward CFT) alternative to an experienced event, as opposed to attentively retrieving the memory without mental modification (i.e. remembering) or no reactivation. Our results suggest that attentive remembering was the best strategy to both reduce the negative affect associated with negative AM, and to prevent the decay of positive affect associated with positive AM. In addition, reactivating positive, but not negative, AM with or without CFT modification reduces the perceived arousal of the original memory over time. Finally, reactivating negative AM in a downward CFT or an attentive remembering condition increases the perceived detail of the original memory over time.

Evidence for sex differences in fetal programming of physiological stress reactivity in infancy.

PubMed

Tibu, Florin; Hill, Jonathan; Sharp, Helen; Marshall, Kate; Glover, Vivette; Pickles, Andrew

2014-11-01

Associations between low birth weight and prenatal anxiety and later psychopathology may arise from programming effects likely to be adaptive under some, but not other, environmental exposures and modified by sex differences. If physiological reactivity, which also confers vulnerability or resilience in an environment-dependent manner, is associated with birth weight and prenatal anxiety, it will be a candidate to mediate the links with psychopathology. From a general population sample of 1,233 first-time mothers recruited at 20 weeks gestation, a sample of 316 stratified by adversity was assessed at 32 weeks and when their infants were aged 29 weeks (N = 271). Prenatal anxiety was assessed by self-report, birth weight from medical records, and vagal reactivity from respiratory sinus arrhythmia during four nonstressful and one stressful (still-face) procedure. Lower birth weight for gestational age predicted higher vagal reactivity only in girls (interaction term, p = .016), and prenatal maternal anxiety predicted lower vagal reactivity only in boys (interaction term, p = .014). These findings are consistent with sex differences in fetal programming, whereby prenatal risks are associated with increased stress reactivity in females but decreased reactivity in males, with distinctive advantages and penalties for each sex.

Neighborhood disadvantage and adolescent stress reactivity

PubMed Central

Hackman, Daniel A.; Betancourt, Laura M.; Brodsky, Nancy L.; Hurt, Hallam; Farah, Martha J.

2012-01-01

Lower socioeconomic status (SES) is associated with higher levels of life stress, which in turn affect stress physiology. SES is related to basal cortisol and diurnal change, but it is not clear if SES is associated with cortisol reactivity to stress. To address this question, we examined the relationship between two indices of SES, parental education and concentrated neighborhood disadvantage, and the cortisol reactivity of African–American adolescents to a modified version of the Trier Social Stress Test (TSST). We found that concentrated disadvantage was associated with cortisol reactivity and this relationship was moderated by gender, such that higher concentrated disadvantage predicted higher cortisol reactivity and steeper recovery in boys but not in girls. Parental education, alone or as moderated by gender, did not predict reactivity or recovery, while neither education nor concentrated disadvantage predicted estimates of baseline cortisol. This finding is consistent with animal literature showing differential vulnerability, by gender, to the effects of adverse early experience on stress regulation and the differential effects of neighborhood disadvantage in adolescent males and females. This suggests that the mechanisms underlying SES differences in brain development and particularly reactivity to environmental stressors may vary across genders. PMID:23091454

Molecular architectures and functions of radical enzymes and their (re)activating proteins.

PubMed

Shibata, Naoki; Toraya, Tetsuo

2015-10-01

Certain proteins utilize the high reactivity of radicals for catalysing chemically challenging reactions. These proteins contain or form a radical and therefore named 'radical enzymes'. Radicals are introduced by enzymes themselves or by (re)activating proteins called (re)activases. The X-ray structures of radical enzymes and their (re)activases revealed some structural features of these molecular apparatuses which solved common enigmas of radical enzymes—i.e. how the enzymes form or introduce radicals at the active sites, how they use the high reactivity of radicals for catalysis, how they suppress undesired side reactions of highly reactive radicals and how they are (re)activated when inactivated by extinction of radicals. This review highlights molecular architectures of radical B12 enzymes, radical SAM enzymes, tyrosyl radical enzymes, glycyl radical enzymes and their (re)activating proteins that support their functions. For generalization, comparisons of the recently reported structures of radical enzymes with those of canonical radical enzymes are summarized here. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Electrocatalytic oxidation of small organic molecules in acid medium: enhancement of activity of noble metal nanoparticles and their alloys by supporting or modifying them with metal oxides.

PubMed

Kulesza, Pawel J; Pieta, Izabela S; Rutkowska, Iwona A; Wadas, Anna; Marks, Diana; Klak, Karolina; Stobinski, Leszek; Cox, James A

2013-11-01

Different approaches to enhancement of electrocatalytic activity of noble metal nanoparticles during oxidation of small organic molecules (namely potential fuels for low-temperature fuel cells such as methanol, ethanol and formic acid) are described. A physical approach to the increase of activity of catalytic nanoparticles (e.g. platinum or palladium) involves nanostructuring to obtain highly dispersed systems of high surface area. Recently, the feasibility of enhancing activity of noble metal systems through the formation of bimetallic (e.g. PtRu, PtSn, and PdAu) or even more complex (e.g. PtRuW, PtRuSn) alloys has been demonstrated. In addition to possible changes in the electronic properties of alloys, specific interactions between metals as well as chemical reactivity of the added components have been postulated. We address and emphasize here the possibility of utilization of noble metal and alloyed nanoparticles supported on robust but reactive high surface area metal oxides (e.g. WO 3 , MoO 3 , TiO 2 , ZrO 2 , V 2 O 5 , and CeO 2 ) in oxidative electrocatalysis. This paper concerns the way in which certain inorganic oxides and oxo species can act effectively as supports for noble metal nanoparticles or their alloys during electrocatalytic oxidation of hydrogen and representative organic fuels. Among important issues are possible changes in the morphology and dispersion, as well as specific interactions leading to the improved chemisorptive and catalytic properties in addition to the feasibility of long time operation of the discussed systems.

Electrocatalytic oxidation of small organic molecules in acid medium: enhancement of activity of noble metal nanoparticles and their alloys by supporting or modifying them with metal oxides

PubMed Central

Kulesza, Pawel J.; Pieta, Izabela S.; Rutkowska, Iwona A.; Wadas, Anna; Marks, Diana; Klak, Karolina; Stobinski, Leszek; Cox, James A.

2013-01-01

Different approaches to enhancement of electrocatalytic activity of noble metal nanoparticles during oxidation of small organic molecules (namely potential fuels for low-temperature fuel cells such as methanol, ethanol and formic acid) are described. A physical approach to the increase of activity of catalytic nanoparticles (e.g. platinum or palladium) involves nanostructuring to obtain highly dispersed systems of high surface area. Recently, the feasibility of enhancing activity of noble metal systems through the formation of bimetallic (e.g. PtRu, PtSn, and PdAu) or even more complex (e.g. PtRuW, PtRuSn) alloys has been demonstrated. In addition to possible changes in the electronic properties of alloys, specific interactions between metals as well as chemical reactivity of the added components have been postulated. We address and emphasize here the possibility of utilization of noble metal and alloyed nanoparticles supported on robust but reactive high surface area metal oxides (e.g. WO3, MoO3, TiO2, ZrO2, V2O5, and CeO2) in oxidative electrocatalysis. This paper concerns the way in which certain inorganic oxides and oxo species can act effectively as supports for noble metal nanoparticles or their alloys during electrocatalytic oxidation of hydrogen and representative organic fuels. Among important issues are possible changes in the morphology and dispersion, as well as specific interactions leading to the improved chemisorptive and catalytic properties in addition to the feasibility of long time operation of the discussed systems. PMID:24443590

Surface modification processes during methane decomposition on Cu-promoted Ni–ZrO2 catalysts

PubMed Central

Wolfbeisser, Astrid; Klötzer, Bernhard; Mayr, Lukas; Rameshan, Raffael; Zemlyanov, Dmitry; Bernardi, Johannes; Rupprechter, Günther

2015-01-01

The surface chemistry of methane on Ni–ZrO2 and bimetallic CuNi–ZrO2 catalysts and the stability of the CuNi alloy under reaction conditions of methane decomposition were investigated by combining reactivity measurements and in situ synchrotron-based near-ambient pressure XPS. Cu was selected as an exemplary promoter for modifying the reactivity of Ni and enhancing the resistance against coke formation. We observed an activation process occurring in methane between 650 and 735 K with the exact temperature depending on the composition which resulted in an irreversible modification of the catalytic performance of the bimetallic catalysts towards a Ni-like behaviour. The sudden increase in catalytic activity could be explained by an increase in the concentration of reduced Ni atoms at the catalyst surface in the active state, likely as a consequence of the interaction with methane. Cu addition to Ni improved the desired resistance against carbon deposition by lowering the amount of coke formed. As a key conclusion, the CuNi alloy shows limited stability under relevant reaction conditions. This system is stable only in a limited range of temperature up to ~700 K in methane. Beyond this temperature, segregation of Ni species causes a fast increase in methane decomposition rate. In view of the applicability of this system, a detailed understanding of the stability and surface composition of the bimetallic phases present and the influence of the Cu promoter on the surface chemistry under relevant reaction conditions are essential. PMID:25815163

Disinfection of Escherichia coli Gram negative bacteria using surface modified TiO2: optimization of Ag metallization and depiction of charge transfer mechanism.

PubMed

Gomathi Devi, LakshmipathiNaik; Nagaraj, Basavalingaiah

2014-01-01

The antibacterial activity of silver deposited TiO2 (Ag-TiO2 ) against Gram negative Escherichia coli bacteria was investigated by varying the Ag metal content from 0.10 to 0.50% on the surface of TiO2 . Ag depositions by the photoreduction method were found to be stable. Surface silver metallization was confirmed by EDAX and XPS studies. Photoluminescence studies show that the charge carrier recombination is less for 0.1% Ag-TiO2 and this catalyst shows superior bactericidal activity under solar light irradiation compared to Sol gel TiO2 (SG-TiO2 ) due to the surface plasmon effect. The energy levels of deposited Ag are dependent on the Ag content and it varies from -4.64 eV to -1.30 eV with respect to the vacuum energy level based on atomic silver to bulk silver deposits. The ability of electron transfer from Ag deposit to O2 depends on the position of the energy levels. The 0.25% and 0.50% Ag depositions showed detrimental effect on bactericidal activity due to the mismatch of energy levels. The effect of the EROS (External generation of the Reactive Oxygen Species by 0.1% Ag-TiO2 ) and IROS (Interior generation of Reactive Oxygen Species within the bacteria) on the bactericidal inactivation is discussed in detail. © 2014 The American Society of Photobiology.

In vitro investigation of efficacy of new reactivators on OPC inhibited rat brain acetylcholinesterase.

PubMed

Atanasov, Vasil N; Petrova, Iskra; Dishovsky, Christophor

2013-03-25

Organophosphorus compounds (OPC) were developed as warfare nerve agents. They are also widely used as pesticides. The drug therapy of intoxication with OPC includes mainly combination of cholinesterase (ChE) reactivators and cholinolytics. There is no single ChE reactivator having an ability to reactivate sufficiently the inhibited enzyme due to the high variability of chemical structure of the inhibitors. The difficulties in reactivation of ChE activity and slight antidote effect regarding intoxication with some OPC are some of the reasons for continuous efforts to obtain new reactivators of ChE. The aim of the present study was to evaluate the efficacy of some ChE reactivators against OPC intoxication (tabun, paraoxon and dichlorvos) in in vitro experiments and to compare their activity to that known for some currently used oximes (obidoxime, HI-6, 2-PAM). Experiments were carried out using rat brain acetylcholinesterase (AChE). Reactivators showed different activity in the reactivation of rat brain AChE after dichlorvos, paraoxon and tabun inhibition. AChE was easier reactivated after paraoxon treatment. The best effect showed BT-07-4M, obidoxime, TMB-4 and BT-08 from the group of symmetric oximes, and Toxidin, BT-05 and BT-03 from asymmetric compounds. The reactivation of brain AChE inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure. All compounds showed low activity toward inhibition of AChE caused by dichlorvos. Comparison of two main structure types (symmetric/asymmetric) showed that the symmetric compounds reactivated better AChE, inhibited with this OPC, than asymmetric ones. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques

PubMed Central

Lin, Philana Ling; Dartois, Veronique; Johnston, Paul J.; Janssen, Christopher; Via, Laura; Goodwin, Michael B.; Klein, Edwin; Barry, Clifton E.; Flynn, JoAnne L.

2012-01-01

Targeting Mycobacterium tuberculosis bacilli in low-oxygen microenvironments, such as caseous granulomas, has been hypothesized to have the potential to shorten therapy for active tuberculosis (TB) and prevent reactivation of latent infection. We previously reported that upon low-dose M. tuberculosis infection, equal proportions of cynomolgus macaques develop active disease or latent infection and that latently infected animals reactivated upon neutralization of TNF. Using this model we now show that chemoprophylaxis of latently infected cynomolgus macaques with 6 mo of isoniazid (INH) effectively prevented anti-TNF antibody-induced reactivation. Similarly, 2-mo treatment of latent animals with a combination of INH and rifampicin (RIF) was highly effective at preventing reactivation disease in this model. Metronidazole (MTZ), which has activity only against anaerobic, nonreplicating bacteria, was as effective as either of these treatments in preventing reactivation of latent infection. Because hypoxic lesions also occur during active TB, we further showed that addition of MTZ to INH/RIF effectively treated animals with active TB within 2 mo. Healing lesions were associated with distinct changes in cellular pathology, with a shift toward increasingly fibrotic and calcified lesions. Our data in the nonhuman primate model of active and latent TB supports targeting bacteria in hypoxic environments for preventing reactivation of latent infection and possibly shortening the duration of therapy in active TB. PMID:22826237

Reactivity of sulfide-containing silane toward boehmite and in situ modified rubber/boehmite composites by the silane

NASA Astrophysics Data System (ADS)

Lin, Tengfei; Zhu, Lixin; Chen, Weiwei; Wu, Siwu; Guo, Baochun; Jia, Demin

2013-09-01

The silanization reaction between boehmite (BM) nanoplatelets and bis-[3-(triethoxysilyl)-propyl]-tetrasulfide (TESPT) was characterized in detail. Via such modification process, the grafted sulfide moieties on the BM endow reactivity toward rubber and substantially improved hydrophobicity for BM. Accordingly, TESPT was employed as in situ modifier for the nitrile rubber (NBR)/BM compounds to improve the mechanical properties of the reinforced vulcanizates. The effects of BM content and in situ modification on the mechanical properties, curing characteristics and morphology were investigated. BM was found to be effective in improving the mechanical performance of NBR vulcanizates. The NBR/BM composites could be further strengthened by the incorporation of TESPT. The interfacial adhesion of NBR/BM composites was obviously improved by the addition of TESPT. The substantially improved mechanical performance was correlated to the interfacial reaction and the improved dispersion of BM in rubber matrix.

Tuning the dispersion of multiwall carbon nanotubes in co-continuous polymer blends: a generic approach

NASA Astrophysics Data System (ADS)

Bose, Suryasarathi; Bhattacharyya, Arup R.; Khare, Rupesh A.; Kulkarni, Ajit R.; Umasankar Patro, T.; Sivaraman, P.

2008-08-01

Melt-mixed blends of polyamide 6 and acrylonitrile-butadiene-styrene (PA6/ABS) with multiwall carbon nanotubes (MWNTs) were prepared with the intention to develop conducting composites. A generic strategy, namely specific interactions combined with reactive coupling, was adopted to facilitate and to retain the 'network-like' structure of MWNTs during melt-mixing. This was facilitated by the sodium salt of 6-amino hexanoic acid (Na-AHA) and certain phosphonium based modifiers, where it was envisaged that these modifiers would establish specific interactions (either 'cation-π' or 'π-π' ) with the 'π-electron' clouds of MWNTs, as well as restricting them in the PA6 phase of the blends via reactive coupling. This route eventually led to a remarkable increase in the electrical conductivity and dielectric constant in the blends with MWNTs. Raman, FTIR and TEM investigations further supported these observations.

New Enhanced Artificial Bee Colony (JA-ABC5) Algorithm with Application for Reactive Power Optimization

PubMed Central

2015-01-01

The standard artificial bee colony (ABC) algorithm involves exploration and exploitation processes which need to be balanced for enhanced performance. This paper proposes a new modified ABC algorithm named JA-ABC5 to enhance convergence speed and improve the ability to reach the global optimum by balancing exploration and exploitation processes. New stages have been proposed at the earlier stages of the algorithm to increase the exploitation process. Besides that, modified mutation equations have also been introduced in the employed and onlooker-bees phases to balance the two processes. The performance of JA-ABC5 has been analyzed on 27 commonly used benchmark functions and tested to optimize the reactive power optimization problem. The performance results have clearly shown that the newly proposed algorithm has outperformed other compared algorithms in terms of convergence speed and global optimum achievement. PMID:25879054

New enhanced artificial bee colony (JA-ABC5) algorithm with application for reactive power optimization.

PubMed

Sulaiman, Noorazliza; Mohamad-Saleh, Junita; Abro, Abdul Ghani

2015-01-01

The standard artificial bee colony (ABC) algorithm involves exploration and exploitation processes which need to be balanced for enhanced performance. This paper proposes a new modified ABC algorithm named JA-ABC5 to enhance convergence speed and improve the ability to reach the global optimum by balancing exploration and exploitation processes. New stages have been proposed at the earlier stages of the algorithm to increase the exploitation process. Besides that, modified mutation equations have also been introduced in the employed and onlooker-bees phases to balance the two processes. The performance of JA-ABC5 has been analyzed on 27 commonly used benchmark functions and tested to optimize the reactive power optimization problem. The performance results have clearly shown that the newly proposed algorithm has outperformed other compared algorithms in terms of convergence speed and global optimum achievement.

Modifying sulfomethylated alkali lignin by horseradish peroxidase to improve the dispersibility and conductivity of polyaniline

NASA Astrophysics Data System (ADS)

Yang, Dongjie; Huang, Wenjing; Qiu, Xueqing; Lou, Hongming; Qian, Yong

2017-12-01

Pine and wheat straw alkali lignin (PAL and WAL) were sulfomethylated to improve water solubility, polymerized with horseradish peroxidase (HRP) to improve the molecular weight (Mw) and applied to dope and disperse polyaniline (PANI). The structural effect of lignin from different origins on the reactivities of sulfomethylation and HRP polymerization was investigated. The results show that WAL with less methoxyl groups and lower Mw have higher reactivity in sulfomethylation (SWAL). More phenolic hydroxyl groups and lower Mw benefit the HRP polymerization of sulfomethylated PAL (SPAL). Due to the natural three-dimensional aromatic structure and introduced sulfonic groups, SPAL and SWAL could effectively dope and disperse PANI in water by π-π stacking and electrostatic interaction. HRP modified SPAL (HRP-SPAL) with much higher sulfonation degree and larger Mw significantly increased the conductivity and dispersibility of lignin/PANI composites.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Mingyi; Xu, Xiaoyang, E-mail: xiaoyangxu2012@163.com; Wu, Tao

Highlights: • Graphene oxide (GO) was modified by chemical reactions to functionalized GO (FGO). • The FGOs and the GO were then subjected to in situ free radical polymerization. • Hydroxyl groups of GO were the most reactive grafting sites. - Abstract: Graphene oxide (GO) was modified using chemical reactions to obtain three types of functionalized GO sheets (FGO). The FGO sheets and the GO were then subjected to in situ free radical polymerization in order to study the grafting polymerization. The FGO and grafted-.FGO were analyzed with Fourier transform infrared spectroscopy, scanning electronic microscopy, thermo-gravimetric analysis (TGA) and X-raymore » photoelectron spectroscopy (XPS). The grafting percentages in the materials were calculated using the TGA and XPS results. The FGO sheets with different functional groups exhibited different grafting abilities, and hydroxyl groups were proven to be the most reactive grafting sites for the in situ free radical grafting polymerization of polyacrylamide.« less

Probability and Cumulative Density Function Methods for the Stochastic Advection-Reaction Equation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barajas-Solano, David A.; Tartakovsky, Alexandre M.

We present a cumulative density function (CDF) method for the probabilistic analysis of $d$-dimensional advection-dominated reactive transport in heterogeneous media. We employ a probabilistic approach in which epistemic uncertainty on the spatial heterogeneity of Darcy-scale transport coefficients is modeled in terms of random fields with given correlation structures. Our proposed CDF method employs a modified Large-Eddy-Diffusivity (LED) approach to close and localize the nonlocal equations governing the one-point PDF and CDF of the concentration field, resulting in a $(d + 1)$ dimensional PDE. Compared to the classsical LED localization, the proposed modified LED localization explicitly accounts for the mean-field advectivemore » dynamics over the phase space of the PDF and CDF. To illustrate the accuracy of the proposed closure, we apply our CDF method to one-dimensional single-species reactive transport with uncertain, heterogeneous advection velocities and reaction rates modeled as random fields.« less

Modified reactive tabu search for the symmetric traveling salesman problems

NASA Astrophysics Data System (ADS)

Lim, Yai-Fung; Hong, Pei-Yee; Ramli, Razamin; Khalid, Ruzelan

2013-09-01

Reactive tabu search (RTS) is an improved method of tabu search (TS) and it dynamically adjusts tabu list size based on how the search is performed. RTS can avoid disadvantage of TS which is in the parameter tuning in tabu list size. In this paper, we proposed a modified RTS approach for solving symmetric traveling salesman problems (TSP). The tabu list size of the proposed algorithm depends on the number of iterations when the solutions do not override the aspiration level to achieve a good balance between diversification and intensification. The proposed algorithm was tested on seven chosen benchmarked problems of symmetric TSP. The performance of the proposed algorithm is compared with that of the TS by using empirical testing, benchmark solution and simple probabilistic analysis in order to validate the quality of solution. The computational results and comparisons show that the proposed algorithm provides a better quality solution than that of the TS.

Emotional reactivity to daily life stress in spousal caregivers of people with dementia: An experience sampling study

PubMed Central

2018-01-01

Introduction Caregivers differ in their emotional response when facing difficult situations during the caregiving process. Individual differences in vulnerabilities and resources could play an exacerbating or buffering role in caregivers’ reactivity to daily life stress. This study examines which caregiver characteristics modify emotional stress reactivity in dementia caregivers. Methods Thirty caregivers collected momentary data, as based on the experience sampling methodology, to assess (1) appraised subjective stress related to events and minor disturbances in daily life, and (2) emotional reactivity to these daily life stressors, conceptualized as changes in negative affect. Caregiver characteristics (i.e. vulnerabilities and resources) were administered retrospectively. Results Caregivers who more frequently used the coping strategies ‘seeking distraction’, ‘seeking social support’, and ‘fostering reassuring thoughts’ experienced less emotional reactivity towards stressful daily events. A higher educational level and a higher sense of competence and mastery lowered emotional reactivity towards minor disturbances in daily life. No effects were found for age, gender, and hours of care and contact with the person with dementia. Discussion Caregiver resources can impact emotional reactivity to daily life stress. Interventions aimed at empowerment of caregiver resources, such as sense of competence, mastery, and coping, could help to reduce stress reactivity in dementia caregivers. PMID:29617373

Poly (hydroxyethyl methacrylate-glycidyl methacrylate) films modified with different functional groups: In vitro interactions with platelets and rat stem cells.

PubMed

Bayramoglu, Gulay; Bitirim, Verda; Tunali, Yagmur; Arica, Mehmet Yakup; Akcali, Kamil Can

2013-03-01

Copolymerization of 2-hydroxyethylmethacrylate (HEMA) with glycidylmethacrylate (GMA) in the presence of α-α'-azoisobisbutyronitrile (AIBN) resulted in the formation of hydrogel films carrying reactive epoxy groups. Thirteen kinds of different molecules with pendant NH2 group were used for modifications of the p(HEMA-GMA) films. The NH2 group served as anchor binding site for immobilization of functional groups on the hydrogel film via direct epoxy ring opening reaction. The modified hydrogel films were characterized by FTIR, and contact angle studies. In addition, mechanical properties of the hydrogel films were studied, and modified hydrogel films showed improved mechanical properties compared with the non-modified film, but they are less elastic than the non-modified film. The biological activities of these films such as platelet adhesion, red blood cells hemolysis, and swelling behavior were studied. The effect of modified hydrogel films, including NH2, (using different aliphatic CH2 chain lengths) CH3, SO3H, aromatic groups with substituted OH and COOH groups, and amino acids were also investigated on the adhesion, morphology and survival of rat mesenchymal stem cells (MSCs). The MTT colorimetric assay reveals that the p(HEMA-GMA)-GA-AB, p(HEMA-GMA)-GA-Phe, p(HEMA-GMA)-GA-Trp, p(HEMA-GMA)-GA-Glu formulations have an excellent biocompatibility to promote the cell adhesion and growth. We anticipate that the fabricated p(HEMA-GMA) based hydrogel films with controllable surface chemistry and good stable swelling ratio may find extensive applications in future development of tissue engineering scaffold materials, and in various biotechnological areas. Copyright © 2012 Elsevier B.V. All rights reserved.

Ikkepsilon regulates viral-induced interferon regulatory factor-3 activation via a redox-sensitive pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Indukuri, Hemalatha; Castro, Shawn M.; Liao, S.-M.

2006-09-15

Respiratory syncytial virus (RSV)-induced chemokine gene expression occurs through the activation of a subset of transcription factors, including Interferon Regulatory Factor (IRF)-3. In this study, we have investigated the signaling pathway leading to RSV-induced IRF-3 activation and whether it is mediated by intracellular reactive oxygen species (ROS) generation. Our results show that RSV infection induces expression and catalytic activity of IKK{epsilon}, a noncanonical IKK-like kinase. Expression of a kinase-inactive IKK{epsilon} blocks RSV-induced IRF-3 serine phosphorylation, nuclear translocation and DNA-binding, leading to inhibition of RANTES gene transcription, mRNA expression and protein synthesis. Treatment of alveolar epithelial cells with antioxidants or withmore » NAD(P)H oxidase inhibitors abrogates RSV-induced chemokine secretion, IRF-3 phosphorylation and IKK{epsilon} induction, indicating that ROS generation plays a fundamental role in the signaling pathway leading to IRF-3 activation, therefore, identifying a novel molecular target for the development of strategies aimed to modify the inflammatory response associated with RSV infection of the lung.« less

Early, structured disease modifying anti-rheumatic drug (DMARD) therapy reduces cardiovascular risk in rheumatoid arthritis--a single centre study using non-biologic drugs.

PubMed

Chatterjee, Sumit; Sarkate, Pankaj; Ghosh, Sudip; Biswas, Monodeep; Ghosh, Alakendu

2013-08-01

Rheumatoid arthritis, being a chronic disease requires long-term management of patients with drugs. The increasing cost of biologics in this era of disease management led us to devise a treatment regime, optimal for use in a developing country like India, which was economical as well as effective in controlling disease activity. To investigate if combination therapy with DMARDs can reduce cardiovascular risk in early Rheumatoid Arthritis, besides controlling disease activity. A small cohort of early Rheumatoid subjects with disease duration less than 1 year were treated with a structured DMARD regime and were followed up over a year. Disease activity score, C-reactive protein (CRP) and cardiac risk markers like lipid panel and carotid intima-medial thickness were monitored at 6 months and 1 year. A significant reduction (p < 0.001) of disease activity as well as cardiac risk parameters were observed. Our study showed that treatment of early rheumatoid arthritis with a combination regime of traditional DMARDs is highly effective in controlling disease activity as well as cardiovascular risk.

Baricitinib in Patients with Rheumatoid Arthritis and an Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs in United States and Rest of World: A Subset Analysis.

PubMed

Wells, Alvin F; Greenwald, Maria; Bradley, John D; Alam, Jahangir; Arora, Vipin; Kartman, Cynthia E

2018-06-01

This article evaluates the efficacy and safety of baricitinib 4 mg versus placebo in United States including Puerto Rico (US) and rest of the world (ROW) subpopulations using data pooled from RA-BEAM and RA-BUILD, which enrolled patients with moderate-to-severe adult-onset rheumatoid arthritis (RA). In RA-BEAM, patients with an inadequate response (IR) to methotrexate, at least one X-ray erosion, and high sensitivity C-reactive protein (hsCRP) ≥ 6 mg/L were randomized to placebo or orally administered baricitinib 4 mg daily or subcutaneously administered adalimumab 40 mg every other week. In RA-BUILD, patients with an IR to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) and with hsCRP ≥ 3.6 mg/L were randomized to placebo or baricitinib 2 or 4 mg daily. Patients in both trials were biologic naive. In this post hoc analysis, data from both studies were pooled (714 baricitinib 4 mg-treated, 716 placebo-treated patients). Overall, 188 US and 1242 ROW patients were included. Subgroups differed in baseline characteristics including race, weight, age, time since RA diagnosis, current corticosteroid use, and previous csDMARD use. At weeks 12 and 24, baricitinib-treated patients had larger responses compared to placebo-treated patients for multiple efficacy outcomes: American College of Rheumatology 20/50/70 response, low disease activity, remission, Disease Activity Score 28-C-reactive protein, and Health Assessment Questionnaire-Disability Index. Overall, similar efficacy was observed in US and ROW subgroups with no notable safety differences between subgroups at weeks 12 or 24. Baricitinib 4 mg was efficacious compared to placebo in US and ROW subpopulations. Safety was similar between subgroups. Eli Lilly & Company and Incyte Corporation. ClinicalTrials.gov identifiers, NCT01721057; NCT01710358.

Dietary lipids differentially modulate the initiation of experimental breast carcinogenesis through their influence on hepatic xenobiotic metabolism and DNA damage in the mammary gland.

PubMed

Manzanares, Miguel Ángel; de Miguel, Cristina; Ruiz de Villa, M Carme; Santella, Regina M; Escrich, Eduard; Solanas, Montserrat

2017-05-01

Breast cancer is the most common malignancy among women worldwide. In addition to reproductive factors, environmental factors such as nutrition and xenobiotic exposure have a role in the etiology of this malignancy. A stimulating and a potentially protective effect on experimental breast cancer has been previously described for high corn oil and high extra-virgin olive oil diets, respectively. This work investigates the effect of these lipids on the metabolism of 7,12-dimethylbenz(a)anthracene (DMBA), a polycyclic aromatic hydrocarbon that can initiate carcinogenesis and its consequences in an experimental rat breast cancer model. The PUFA n-6-enriched diet increased expression of Phase I enzymes prior to DMBA administration and raised the activity of CYP1s in the hours immediately after induction, while reducing the activity of Phase II enzymes, mainly NQO1. The levels of reactive metabolites measured in plasma by GC-MS and DMBA-DNA adducts in the mammary gland of the animals fed the high corn oil diet were also higher than in the other groups. On the other hand, the high extra-virgin olive oil diet and the control low-fat diet exhibited better coordinated Phase I and Phase II activity, with a lower production of reactive metabolites and less DNA damage in the mammary gland. The concordance between these effects and the different efficacy of the carcinogenesis process due to the dietary treatment suggest that lipids may differently modify mammary gland susceptibility or resistance to cancer initiation over the exposure to environmental carcinogens. Dietary lipids influence the initiation of DMBA-induced mammary cancer through the modulation of liver xenobiotic metabolism, formation of reactive metabolites and subsequent DNA damage in the target tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Protective Effect of Water Extracted Spirulina maxima on Glutamate-induced Neuronal Cell Death in Mouse Hippocampal HT22 Cell.

PubMed

Lee, Hyeon Yong; Ryu, Ga Hee; Choi, Woon Yong; Yang, Woo Seung; Lee, Hyeon Woo; Ma, Choong Je

2018-01-01

Spirulina maxima was used as important nutritional source in the Aztec civilization because it is rich in proteins and vitamins. It contains various antioxidants such as phycocyanin and flavonoids. Based on abundant antioxidants, S. maxima is known to possess anti-inflammatory effect, especially on neuronal cells. S. maxima was extracted in water and contain of phycocyanin was identified by high-performance liquid chromatography. Cell viability test was performed with treatment of S. maxima extract. After, oxidative stress-related mechanisms were evaluated by detecting the accumulation of reactive oxygen species (ROS) and Ca 2+ influx, and decrease of mitochondrial membrane potential (MMP) level. Then, the glutathione (GSH) related assays were conducted. The water extracted S. maxima exerted the neuroprotective activity by attenuating the ROS and Ca 2+ formation, maintaining the MMP level, and protecting the activity of the antioxidant enzymes by increasing reduced GSH against oxidative stress compared to control. The results suggested that water extracted S. maxima showed powerful neuroprotective effect through the mechanism related to antioxidant activity, able to preventing the radical-mediated cell death. Water extracted Spirulina maxima contains C-phycocyaninWater extracted Spirulina maxima exerts neuroprotective effect on HT22 cellTo investigate the protective mechanisms, reactive oxygen species, Ca 2+ , mitochondrial membrane potential, Glutathione-related assays were performed. Abbreviations used: ROS: Reactive oxygen species; MMP: Mitochondrial membrane potential; GSH: Glutathione; GSSG: Glutathione disulfide, oxidized glutathione; GPx: Glutathione peroxidase; GR: Glutathione reductase; DMEM: Dulbecco's modified Eagle's medium; FBS: Fetal bovine serum; DCF-DA: 2',7'-dichlorofluorescein diacetate; PBS: Phosphate buffered serum; Rho 123: Rhodamine 123; NADPH: Nicotinamide adenine dinucleotide phosphate; DTNB: 5,5'-dithiobis-2-nitrobenzoic acid, Ellman's reagent; GSSG-R: Glutathione disulfide reductase; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; DMSO: Dimethyl sulfoxide; HPLC: High-performance liquid chromatography.

Protective Effect of Water Extracted Spirulina maxima on Glutamate-induced Neuronal Cell Death in Mouse Hippocampal HT22 Cell

PubMed Central

Lee, Hyeon Yong; Ryu, Ga Hee; Choi, Woon Yong; Yang, Woo Seung; Lee, Hyeon Woo; Ma, Choong Je

2018-01-01

Introduction: Spirulina maxima was used as important nutritional source in the Aztec civilization because it is rich in proteins and vitamins. It contains various antioxidants such as phycocyanin and flavonoids. Based on abundant antioxidants, S. maxima is known to possess anti-inflammatory effect, especially on neuronal cells. Materials and Methods: S. maxima was extracted in water and contain of phycocyanin was identified by high-performance liquid chromatography. Cell viability test was performed with treatment of S. maxima extract. After, oxidative stress-related mechanisms were evaluated by detecting the accumulation of reactive oxygen species (ROS) and Ca2+ influx, and decrease of mitochondrial membrane potential (MMP) level. Then, the glutathione (GSH) related assays were conducted. Results: The water extracted S. maxima exerted the neuroprotective activity by attenuating the ROS and Ca2+ formation, maintaining the MMP level, and protecting the activity of the antioxidant enzymes by increasing reduced GSH against oxidative stress compared to control. Conclusion: The results suggested that water extracted S. maxima showed powerful neuroprotective effect through the mechanism related to antioxidant activity, able to preventing the radical-mediated cell death. SUMMARY Water extracted Spirulina maxima contains C-phycocyaninWater extracted Spirulina maxima exerts neuroprotective effect on HT22 cellTo investigate the protective mechanisms, reactive oxygen species, Ca2+, mitochondrial membrane potential, Glutathione-related assays were performed. Abbreviations used: ROS: Reactive oxygen species; MMP: Mitochondrial membrane potential; GSH: Glutathione; GSSG: Glutathione disulfide, oxidized glutathione; GPx: Glutathione peroxidase; GR: Glutathione reductase; DMEM: Dulbecco's modified Eagle's medium; FBS: Fetal bovine serum; DCF-DA: 2',7'-dichlorofluorescein diacetate; PBS: Phosphate buffered serum; Rho 123: Rhodamine 123; NADPH: Nicotinamide adenine dinucleotide phosphate; DTNB: 5,5'-dithiobis-2-nitrobenzoic acid, Ellman's reagent; GSSG-R: Glutathione disulfide reductase; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; DMSO: Dimethyl sulfoxide; HPLC: High-performance liquid chromatography. PMID:29720839

Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection.

PubMed

Moeller, Maria; Haynes, Nicole M; Kershaw, Michael H; Jackson, Jacob T; Teng, Michele W L; Street, Shayna E; Cerutti, Loretta; Jane, Stephen M; Trapani, Joseph A; Smyth, Mark J; Darcy, Phillip K

2005-11-01

Because CD4+ T cells play a key role in aiding cellular immune responses, we wanted to assess whether increasing numbers of gene-engineered antigen-restricted CD4+ T cells could enhance an antitumor response mediated by similarly gene-engineered CD8+ T cells. In this study, we have used retroviral transduction to generate erbB2-reactive mouse T-cell populations composed of various proportions of CD4+ and CD8+ cells and then determined the antitumor reactivity of these mixtures. Gene-modified CD4+ and CD8+ T cells were shown to specifically secrete Tc1 (T cytotoxic-1) or Tc2 cytokines, proliferate, and lyse erbB2+ tumor targets following antigen ligation in vitro. In adoptive transfer experiments using severe combined immunodeficient (scid) mice, we demonstrated that injection of equivalent numbers of antigen-specific engineered CD8+ and CD4+ T cells led to significant improvement in survival of mice bearing established lung metastases compared with transfer of unfractionated (largely CD8+) engineered T cells. Transferred CD4+ T cells had to be antigen-specific (not just activated) and secrete interferon gamma (IFN-gamma) to potentiate the antitumor effect. Importantly, antitumor responses in these mice correlated with localization and persistence of gene-engineered T cells at the tumor site. Strikingly, mice that survived primary tumor challenge could reject a subsequent rechallenge. Overall, this study has highlighted the therapeutic potential of using combined transfer of antigen-specific gene-modified CD8+ and CD4+ T cells to significantly enhance T-cell adoptive transfer strategies for cancer therapy.

Catalytic ozonation of paracetamol using commercial and Pt-supported nanocomposites of Al2O3: The impact of ultrasound.

PubMed

Ziylan-Yavaş, Asu; Ince, Nilsun H

2018-01-01

The study is the assessment of commercial γ-Al 2 O 3 and its sonolytically modified nanocomposite in catalytic ozonation of paracetamol (PCT), which is an emerging water contaminant and a highly reactive compound with ozone. The results showed that commercial alumina was ineffective regardless of the solution pH, due to the low affinity of the catalyst surface for PCT and the high reactivity of the solute with molecular ozone. The modified catalyst, which was synthesized by decoration of the original surface with nanoparticles of platinum provided considerable improvement in the performance of the catalyst, particularly in mineralization of the target compound. The presence of OH scavenging agents in solution markedly retarded the rate of PCT oxidation and organic carbon decay, to signal the importance of radical-mediated reaction mechanisms on the degradation of the compound. Finally, the attempt to accelerate the reactions by running them in the presence of ultrasound was found inadequate for the early oxidation, but highly adequate for the longer mineralization process. The failure was attributed to the diffusion of a large fraction of ozone into the gaseous cavity bubbles (reduced probability of direct reactions) and the extreme conditions of cavitation collapse that partially damaged the catalyst surface. The success (in mineralization) was explained by the shift of the reaction site from the bulk solution (poor adsorption on catalyst surfaces) to the solid surface and the gaseous cavity bubbles (via enhanced hydrophobicity), both being considerably more active reaction media. Copyright © 2017 Elsevier B.V. All rights reserved.

Reactive Oxygen Species and Their Implications on CD4+ T Cells in Type 1 Diabetes.

PubMed

Previte, Dana M; Piganelli, Jon D

2017-11-28

Previous work has indicated that type 1 diabetes (T1D) pathology is highly driven by reactive oxygen species (ROS). One way in which ROS shape the autoimmune response demonstrated in T1D is by promoting CD4 + T cell activation and differentiation. As CD4 + T cells are a significant contributor to pancreatic β cell destruction in T1D, understanding how ROS impact their development, activation, and differentiation is critical. Recent Advances: CD4 + T cells themselves generate ROS via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and electron transport chain activity. Moreover, T cells can also be exposed to exogenous ROS generated by other immune cells (e.g., macrophages and dendritic cells) and β cells. Genetically modified animals and ROS inhibitors have demonstrated that ROS blockade during activation results in CD4 + T cell hyporesponsiveness and reduced diabetes incidence. Critical Issues and Future Directions: Although the majority of studies with regard to T1D and CD4 + T cells have been done to examine the influence of redox on CD4 + T cell activation, this is not the only circumstance in which a T cell can be impacted by redox. ROS and redox have also been shown to play roles in CD4 + T cell-related tolerogenic mechanisms, including thymic selection and regulatory T cell-mediated suppression. However, the effect of these mechanisms with respect to T1D pathogenesis remains elusive. Therefore, pursuing these avenues may provide valuable insight into the global role of ROS and redox in autoreactive CD4 + T cell formation and function. Antioxid. Redox Signal. 00, 000-000.

Measurement of xanthine oxidase inhibition activity of phenolics and flavonoids with a modified cupric reducing antioxidant capacity (CUPRAC) method.

PubMed

Ozyürek, Mustafa; Bektaşoğlu, Burcu; Güçlü, Kubilay; Apak, Reşat

2009-03-16

Various dietary polyphenolics have been found to show an inhibitory effect on xanthine oxidase (XO) which mediates oxidative stress-originated diseases because of its ability to generate reactive oxygen species (ROS), including superoxide anion radical (O(2)(-)) and hydrogen peroxide. XO activity has usually been determined by following the rate of uric acid formation from xanthine-xanthine oxidase (X-XO) system using the classical XO activity assay (UV-method) at 295nm. Since some polyphenolics have strong absorption from the UV to visible region, XO-inhibitory activity of polyphenolics was alternatively determined without interference by directly measuring the formation of uric acid and hydrogen peroxide using the modified CUPRAC (cupric reducing antioxidant capacity) spectrophotometric method at 450nm. The CUPRAC absorbance of the incubation solution due to the reduction of Cu(II)-neocuproine reagent by the products of the X-XO system decreased in the presence of polyphenolics, the difference being proportional to the XO inhibition ability of the tested compound. The structure-activity relationship revealed that the flavones and flavonols with a 7-hydroxyl group such as apigenin, luteolin, kaempferol, quercetin, and myricetin inhibited XO-inhibitory activity at low concentrations (IC(50) values from 1.46 to 1.90microM), while the flavan-3-ols and naringin were less inhibitory. The findings of the developed method for quercetin and catechin in the presence of catalase were statistically alike with those of HPLC. In addition to polyphenolics, five kinds of herbs were evaluated for their XO-inhibitory activity using the developed method. The proposed spectrophotometric method was practical, low-cost, rapid, and could reliably assay uric acid and hydrogen peroxide in the presence of polyphenols (flavonoids, simple phenolic acids and hydroxycinnamic acids), and less open to interferences by UV-absorbing substances.

Green electrochemical modification of RVC foam electrode and improved H2O2 electrogeneration by applying pulsed current for pollutant removal.

PubMed

Zhou, Wei; Ding, Yani; Gao, Jihui; Kou, Kaikai; Wang, Yan; Meng, Xiaoxiao; Wu, Shaohua; Qin, Yukun

2018-02-01

The performance of cathode on H 2 O 2 electrogeneration is a critical factor that limits the practical application of electro-Fenton (EF) process. Herein, we report a simple but effective electrochemical modification of reticulated vitreous carbon foam (RVC foam) electrode for enhanced H 2 O 2 electrogeneration. Cyclic voltammetry, chronoamperometry, and X-ray photoelectron spectrum were used to characterize the modified electrode. Oxygen-containing groups (72.5-184.0 μmol/g) were introduced to RVC foam surface, thus resulting in a 59.8-258.2% higher H 2 O 2 yield. The modified electrodes showed much higher electrocatalytic activity toward O 2 reduction and good stability. Moreover, aimed at weakening the extent of electroreduction of H 2 O 2 in porous RVC foam, the strategy of pulsed current was proposed. H 2 O 2 concentration was 582.3 and 114.0% higher than the unmodified and modified electrodes, respectively. To test the feasibility of modification, as well as pulsed current, EF process was operated for removal of Reactive Blue 19 (RB19). The fluorescence intensity of hydroxybenzoic acid in EF with modified electrode is 3.2 times higher than EF with unmodified electrode, illustrating more hydroxyl radicals were generated. The removal efficiency of RB 19 in EF with unmodified electrode, modified electrode, and unmodified electrode assisted by pulsed current was 53.9, 68.9, and 81.1%, respectively, demonstrating that the green modification approach, as well as pulsed current, is applicable in EF system for pollutant removal. Graphical abstract ᅟ.

Effects of different frequencies of transcutaneous electrical nerve stimulation on venous vascular reactivity

PubMed Central

Franco, O.S.; Paulitsch, F.S.; Pereira, A.P.C.; Teixeira, A.O.; Martins, C.N.; Silva, A.M.V.; Plentz, R.D.M.; Irigoyen, M.C.; Signori, L.U.

2014-01-01

Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia. PMID:24820225

Modifying Matrix Materials to Increase Wetting and Adhesion

NASA Technical Reports Server (NTRS)

Zhong, Katie

2011-01-01

In an alternative approach to increasing the degrees of wetting and adhesion between the fiber and matrix components of organic-fiber/polymer matrix composite materials, the matrix resins are modified. Heretofore, it has been common practice to modify the fibers rather than the matrices: The fibers are modified by chemical and/or physical surface treatments prior to combining the fibers with matrix resins - an approach that entails considerable expense and usually results in degradation (typically, weakening) of fibers. The alternative approach of modifying the matrix resins does not entail degradation of fibers, and affords opportunities for improving the mechanical properties of the fiber composites. The alternative approach is more cost-effective, not only because it eliminates expensive fiber-surface treatments but also because it does not entail changes in procedures for manufacturing conventional composite-material structures. The alternative approach is best described by citing an example of its application to a composite of ultra-high-molecular- weight polyethylene (UHMWPE) fibers in an epoxy matrix. The epoxy matrix was modified to a chemically reactive, polarized epoxy nano-matrix to increase the degrees of wetting and adhesion between the fibers and the matrix. The modification was effected by incorporating a small proportion (0.3 weight percent) of reactive graphitic nanofibers produced from functionalized nanofibers into the epoxy matrix resin prior to combining the resin with the UHMWPE fibers. The resulting increase in fiber/matrix adhesion manifested itself in several test results, notably including an increase of 25 percent in the maximum fiber pullout force and an increase of 60-65 percent in fiber pullout energy. In addition, it was conjectured that the functionalized nanofibers became involved in the cross linking reaction of the epoxy resin, with resultant enhancement of the mechanical properties and lower viscosity of the matrix.

Neural mechanisms of reactivation-induced updating that enhance and distort memory

PubMed Central

St. Jacques, Peggy L.; Olm, Christopher; Schacter, Daniel L.

2013-01-01

We remember a considerable number of personal experiences because we are frequently reminded of them, a process known as memory reactivation. Although memory reactivation helps to stabilize and update memories, reactivation may also introduce distortions if novel information becomes incorporated with memory. Here we used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms mediating reactivation-induced updating in memory for events experienced during a museum tour. During scanning, participants were shown target photographs to reactivate memories from the museum tour followed by a novel lure photograph from an alternate tour. Later, participants were presented with target and lure photographs and asked to determine whether the photographs showed a stop they visited during the tour. We used a subsequent memory analysis to examine neural recruitment during reactivation that was associated with later true and false memories. We predicted that the quality of reactivation, as determined by online ratings of subjective recollection, would increase subsequent true memories but also facilitate incorporation of the lure photograph, thereby increasing subsequent false memories. The fMRI results revealed that the quality of reactivation modulated subsequent true and false memories via recruitment of left posterior parahippocampal, bilateral retrosplenial, and bilateral posterior inferior parietal cortices. However, the timing of neural recruitment and the way in which memories were reactivated contributed to differences in whether memory reactivation led to distortions or not. These data reveal the neural mechanisms recruited during memory reactivation that modify how memories will be subsequently retrieved, supporting the flexible and dynamic aspects of memory. PMID:24191059

Neural mechanisms of reactivation-induced updating that enhance and distort memory.

PubMed

St Jacques, Peggy L; Olm, Christopher; Schacter, Daniel L

2013-12-03

We remember a considerable number of personal experiences because we are frequently reminded of them, a process known as memory reactivation. Although memory reactivation helps to stabilize and update memories, reactivation may also introduce distortions if novel information becomes incorporated with memory. Here we used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms mediating reactivation-induced updating in memory for events experienced during a museum tour. During scanning, participants were shown target photographs to reactivate memories from the museum tour followed by a novel lure photograph from an alternate tour. Later, participants were presented with target and lure photographs and asked to determine whether the photographs showed a stop they visited during the tour. We used a subsequent memory analysis to examine neural recruitment during reactivation that was associated with later true and false memories. We predicted that the quality of reactivation, as determined by online ratings of subjective recollection, would increase subsequent true memories but also facilitate incorporation of the lure photograph, thereby increasing subsequent false memories. The fMRI results revealed that the quality of reactivation modulated subsequent true and false memories via recruitment of left posterior parahippocampal, bilateral retrosplenial, and bilateral posterior inferior parietal cortices. However, the timing of neural recruitment and the way in which memories were reactivated contributed to differences in whether memory reactivation led to distortions or not. These data reveal the neural mechanisms recruited during memory reactivation that modify how memories will be subsequently retrieved, supporting the flexible and dynamic aspects of memory.

n-hydrocarbons conversions over metal-modified solid acid catalysts

NASA Astrophysics Data System (ADS)

Zarubica, A.; Ranđelović, M.; Momčilović, M.; Radulović, N.; Putanov, P.

2013-12-01

The quality of a straight-run fuel oil can be improved if saturated n-hydrocarbons of low octane number are converted to their branched counterparts. Poor reactivity of traditional catalysts in isomerization reactions imposed the need for the development of new catalysts among which noble metal promoted acid catalysts, liquid and/or solid acid catalysts take a prominent place. Sulfated zirconia and metal promoted sulfated zirconia exhibit high activity for the isomerization of light alkanes at low temperatures. The present paper highlights the original results which indicate that the modification of sulfated zirconia by incorporation of metals (platinum and rhenium) significantly affects catalytic performances in n-hydrocarbon conversion reactions. Favourable activity/selectivity of the promoted sulfated zirconia depends on the crystal phase composition, critical crystallites sizes, platinum dispersion, total acidity and type of acidity. Attention is also paid to the recently developed solid acid catalysts used in other conversion reactions of hydrocarbons.

Life and death in the trash heap: The ubiquitin proteasome pathway and UCHL1 in brain aging, neurodegenerative disease and cerebral Ischemia.

PubMed

Graham, Steven H; Liu, Hao

2017-03-01

The ubiquitin proteasome pathway (UPP) is essential for removing abnormal proteins and preventing accumulation of potentially toxic proteins within the neuron. UPP dysfunction occurs with normal aging and is associated with abnormal accumulation of protein aggregates within neurons in neurodegenerative diseases. Ischemia disrupts UPP function and thus may contribute to UPP dysfunction seen in the aging brain and in neurodegenerative diseases. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1), an important component of the UPP in the neuron, is covalently modified and its activity inhibited by reactive lipids produced after ischemia. As a result, degradation of toxic proteins is impaired which may exacerbate neuronal function and cell death in stroke and neurodegenerative diseases. Preserving or restoring UCHL1 activity may be an effective therapeutic strategy in stroke and neurodegenerative diseases. Published by Elsevier B.V.

Daily life stress reactivity in remitted versus non-remitted depressed individuals.

PubMed

van Winkel, M; Nicolson, N A; Wichers, M; Viechtbauer, W; Myin-Germeys, I; Peeters, F

2015-06-01

Little is known about how daily life mood reactivity to minor stressors (stress reactivity) might change following major depressive disorder (MDD) treatment. We investigate whether (i) mood states and appraisals of daily stressors change after treatment; (ii) stress reactivity to event, activity, or social stress differs; (iii) stress reactivity depends on severity of residual depressive symptoms; and (iv) stress reactivity in individuals with remitted or non-remitted depression differ from that of never-depressed individuals. Thirty depressed individuals participated in an experience sampling study before and after a treatment period of 18 months; 39 healthy individuals formed a comparison group. Reactivity of positive affect (PA) and negative affect (NA) to daily stressors were measured. More residual symptoms were associated with larger NA responses to stress. Compared to healthy controls, participants with non-remitted MDD showed higher NA-reactivity to all stressors. In contrast, stress reactivity to event and activity stressors was normalized in remitted patients. However, they still showed heightened NA-reactivity to social stress. Greater stress reactivity to event and activity stress appears to be state-dependent. The heightened social stress reactivity in remitted patients suggests that sensitivity to social stress may reflect an underlying vulnerability in MDD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Simple route for nano-hydroxyapatite properties expansion.

PubMed

Rojas, L; Olmedo, H; García-Piñeres, A J; Silveira, C; Tasic, L; Fraga, F; Montero, M L

2015-10-20

Simple surface modification of nano-hydroxyapatite, through acid-basic reactions, allows expanding the properties of this material. Introduction of organic groups such as hydrophobic alkyl chains, carboxylic acid, and amide or amine basic groups on the hydroxyapatite surface systematically change the polarity, surface area, and reactivity of hydroxyapatite without modifying its phase. Physical and chemical properties of the new derivative particles were analyzed. The biocompatibility of modified Nano-Hap on Raw 264.7 cells was also assessed.

Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions.

PubMed

Jackson, Paul A; Widen, John C; Harki, Daniel A; Brummond, Kay M

2017-02-09

Although Michael acceptors display a potent and broad spectrum of bioactivity, they have largely been ignored in drug discovery because of their presumed indiscriminate reactivity. As such, a dearth of information exists relevant to the thiol reactivity of natural products and their analogues possessing this moiety. In the midst of recently approved acrylamide-containing drugs, it is clear that a good understanding of the hetero-Michael addition reaction and the relative reactivities of biological thiols with Michael acceptors under physiological conditions is needed for the design and use of these compounds as biological tools and potential therapeutics. This Perspective provides information that will contribute to this understanding, such as kinetics of thiol addition reactions, bioactivities, as well as steric and electronic factors that influence the electrophilicity and reversibility of Michael acceptors. This Perspective is focused on α,β-unsaturated carbonyls given their preponderance in bioactive natural products.

A model for the catalytic reduction of NO with CO and N desorption

NASA Astrophysics Data System (ADS)

Díaz, J. J.; Buendía, G. M.

2018-02-01

In this work we have investigated by Monte Carlo simulations the dynamical behavior of a modified Yaldram-Khan (YK) model for the catalytic reduction of NO on a surface. Our model is simulated on a square lattice and includes the individual desorption of CO molecules and N atoms, processes associated with temperature effects. When CO desorption is added, strong fluctuations appear, which are associated with the spreading of N checkerboard structures on the surface. These structures take a long time to coalesce, allowing the existence of a unsteady but long lasting reactive state. N desorption also favors the reactivity of the system, this time by diminishing the size of the N structures and impeding their coalescence. The combined desorption of CO and N produces a reactive state as well, where reactive zones among N structures can take place on the surface.

The effect of interlayer anion on the reactivity of Mg-Al layered double hydroxides: improving and extending the customization capacity of anionic clays.

PubMed

Rojas, Ricardo; Bruna, Felipe; de Pauli, Carlos P; Ulibarri, M Ángeles; Giacomelli, Carla E

2011-07-01

Layered double hydroxides (LDHs) reactivity and interfacial behavior are closely interconnected and control particle properties relevant to the wide range of these solids' applications. Despite their importance, their relationship has been hardly described. In this work, chloride and dodecylsulfate (DDS(-)) intercalated LDHs are studied combining experimental data (electrophoretic mobility and contact angle measurements, hydroxyl and organic compounds uptake) and a simple mathematical model that includes anion-binding and acid-base reactions. This approach evidences the anion effect on LDHs interfacial behavior, reflected in the opposite particle charge and the different surface hydrophobic/hydrophilic character. LDHs reactivity are also determined by the interlayer composition, as demonstrated by the cation uptake capability of the DDS(-) intercalated sample. Consequently, the interlayer anion modifies the LDHs interfacial properties and reactivity, which in turn extends the customization capacity of these solids. Copyright © 2011 Elsevier Inc. All rights reserved.

Synthesis of low-cost adsorbent from rice bran for the removal of reactive dye based on the response surface methodology

NASA Astrophysics Data System (ADS)

Hong, Gui-Bing; Wang, Yi-Kai

2017-11-01

Rice bran is a major by-product of the rice milling industry and is abundant in Taiwan. This study proposed a simple method for modifying rice bran to make it a low-cost adsorbent to remove reactive blue 4 (RB4) from aqueous solutions. The effects of independent variables such as dye concentration (100-500 ppm), adsorbent dosage (20-120 mg) and temperature (30-60 °C) on the dye adsorption capacity of the modified rice bran adsorbent were investigated by using the response surface methodology (RSM). The results showed that the dye maximum adsorption capacity of the modified rice bran adsorbent was 151.3 mg g-1 with respect to a dye concentration of 500 ppm, adsorbent dosage of 65.36 mg, and temperature of 60 °C. The adsorption kinetics data followed the pseudo-second-order kinetic model, and the isotherm data fit the Langmuir isotherm model well. The maximum monolayer adsorption capacity was 178.57-185.19 mg g-1, which was comparable to that of other agricultural waste adsorbents used to remove RB4 from aqueous solutions in the literature. The thermodynamics analysis results indicated that the adsorption of RB4 onto the modified rice bran adsorbent is an endothermic, spontaneous monolayer adsorption that occurs through a physical process.

Oxidation characteristics of gasoline direct-injection (GDI) engine soot: Catalytic effects of ash and modified kinetic correlation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Seungmok; Seong, Heeje

In this paper, experimental analyses are conducted into the GDI soot oxidation characteristics as dependent on engine operating conditions. Soot is sampled at various engine operating conditions of a commercial 2.4 L GDI engine with a naturally aspirated, homogeneous, and stoichiometric operation strategy. The oxidation reactivity, ash composition, and carbon nanostructure of the GDI soot samples are analyzed using thermogravimetric analysis (TGA), scanning electron microscope–energy-dispersive spectroscopy (SEM-EDS), high-resolution transmission electron microscopy (HR-TEM), and Raman spectroscopy. Based on the analyses, a global GDI soot oxidation mechanism is proposed which includes the effects of soluble organic fractions (SOF)/weakly bonded carbon (WBC), andmore » three types of ash on GDI soot oxidation. The results show that GDI soot contains an order of magnitude higher ash fraction than does conventional diesel soot, and oxidation reactivity is significantly enhanced by the catalytic effects of ash, as a function of ash content in soot. A modified empirical kinetic correlation for GDI soot oxidation is suggested on the basis of the results, and the modified kinetic correlation predicts the GDI soot oxidation rate accurately for various engine operation points at wide ranges of soot conversion and temperature without modifying kinetic parameters. The kinetic parameters are determined from isothermal and non-isothermal thremogravimetric analysis (TGA) soot oxidation tests; the methods are elucidated in detail.« less

Oxidation characteristics of gasoline direct-injection (GDI) engine soot: Catalytic effects of ash and modified kinetic correlation

DOE PAGES

Choi, Seungmok; Seong, Heeje

2015-03-02

In this paper, experimental analyses are conducted into the GDI soot oxidation characteristics as dependent on engine operating conditions. Soot is sampled at various engine operating conditions of a commercial 2.4 L GDI engine with a naturally aspirated, homogeneous, and stoichiometric operation strategy. The oxidation reactivity, ash composition, and carbon nanostructure of the GDI soot samples are analyzed using thermogravimetric analysis (TGA), scanning electron microscope–energy-dispersive spectroscopy (SEM-EDS), high-resolution transmission electron microscopy (HR-TEM), and Raman spectroscopy. Based on the analyses, a global GDI soot oxidation mechanism is proposed which includes the effects of soluble organic fractions (SOF)/weakly bonded carbon (WBC), andmore » three types of ash on GDI soot oxidation. The results show that GDI soot contains an order of magnitude higher ash fraction than does conventional diesel soot, and oxidation reactivity is significantly enhanced by the catalytic effects of ash, as a function of ash content in soot. A modified empirical kinetic correlation for GDI soot oxidation is suggested on the basis of the results, and the modified kinetic correlation predicts the GDI soot oxidation rate accurately for various engine operation points at wide ranges of soot conversion and temperature without modifying kinetic parameters. The kinetic parameters are determined from isothermal and non-isothermal thremogravimetric analysis (TGA) soot oxidation tests; the methods are elucidated in detail.« less

Chronobiology and the treatment of rheumatoid arthritis.

PubMed

Cutolo, Maurizio

2012-05-01

As circadian rhythms and biological signaling occur in a complex network with cyclical 24-h period interactions (chronobiology) between the central and the autonomic nervous systems, the endocrine glands and the immune system, this review will explore the involvement of this emerging network in the disease pathophysiology and management. Recent advances regarding nocturnal hormones such as melatonin and prolactin that activate the nighttime immune response, and the successive rise of cortisol that dowregulates the ongoing immune reactivity very early in the morning, will be discussed within the circadian neuroendocrine immune network. In addition, the role of sleep and the daily distribution of body energy, which are important factors for the homoeostatic regulation of circadian physiological/pathological processes of the immune network will be reviewed.In chronic immune/inflammatory conditions such as rheumatoid arthritis (RA), stiffness and functional disability are evident in the early morning hours as under the chronic stress of the disease the nighttime adrenal cortisol production becomes insufficient to inhibit ongoing nocturnal immune/inflammatory activity. Currently, the most advanced approach to optimizing the risk-benefit ratio for long-term glucocorticoid treatment in RA seems to be low-dose chronotherapy with modified nighttime release prednisone (release at 3 a.m.). A similar chronotherapeutical approach could also be effective with disease-modifying antirheumatic drugs such as methotrexate.

Energy determinants GAPDH and NDPK act as genetic modifiers for hepatocyte inclusion formation

PubMed Central

Weerasinghe, Sujith V.W.; Singla, Amika; Leonard, Jessica M.; Hanada, Shinichiro; Andrews, Philip C.; Lok, Anna S.; Omary, M. Bishr

2011-01-01

Genetic factors impact liver injury susceptibility and disease progression. Prominent histological features of some chronic human liver diseases are hepatocyte ballooning and Mallory-Denk bodies. In mice, these features are induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in a strain-dependent manner, with the C57BL and C3H strains showing high and low susceptibility, respectively. To identify modifiers of DDC-induced liver injury, we compared C57BL and C3H mice using proteomic, biochemical, and cell biological tools. DDC elevated reactive oxygen species (ROS) and oxidative stress enzymes preferentially in C57BL livers and isolated hepatocytes. C57BL livers and hepatocytes also manifested significant down-regulation, aggregation, and nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDH knockdown depleted bioenergetic and antioxidant enzymes and elevated hepatocyte ROS, whereas GAPDH overexpression decreased hepatocyte ROS. On the other hand, C3H livers had higher expression and activity of the energy-generating nucleoside-diphosphate kinase (NDPK), and knockdown of hepatocyte NDPK augmented DDC-induced ROS formation. Consistent with these findings, cirrhotic, but not normal, human livers contained GAPDH aggregates and NDPK complexes. We propose that GAPDH and NDPK are genetic modifiers of murine DDC-induced liver injury and potentially human liver disease. PMID:22006949

Adsorption of arsenic(III) into modified lamellar Na-magadiite in aqueous medium-Thermodynamic of adsorption process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lima Guerra, Denis; Azevedo Pinto, Alane; Airoldi, Claudio

2008-12-15

Synthetic Na-magadiite sample was used for organofunctionalization process with N-propyldiethylenetrimethoxysilane and bis[3-(triethoxysilyl)propyl]tetrasulfide, after expanding the interlayer distance with polar organic solvents such as dimethylsulfoxide (DMSO). The resulted materials were submitted to process of adsorption with arsenic solution at pH 2.0 and 298{+-}1 K. The adsorption isotherms were adjusted using a modified Langmuir equation with regression nonlinear; the net thermal effects obtained from calorimetric titration measurements were adjusted to a modified Langmuir equation. The adsorption process was exothermic ({delta}{sub int}H=-4.15-5.98 kJ mol{sup -1}) accompanied by increase in entropy ({delta}{sub int}S=41.32-62.20 J k{sup -1} mol{sup -1}) and Gibbs energy ({delta}{sub int}G=-22.44-24.56 kJmore » mol{sup -1}). The favorable values corroborate with the arsenic (III)/basic reactive centers interaction at the solid-liquid interface in the spontaneous process. - Grapical Abstract: The results suggest that the adsorption capacities increased with an increase of reactive basic centers in the pendant organic chains of the intercalated agent.« less

Versatile antifouling polyethersulfone filtration membranes modified via surface grafting of zwitterionic polymers from a reactive amphiphilic copolymer additive.

PubMed

Zhao, Yi-Fan; Zhang, Pei-Bin; Sun, Jian; Liu, Cui-Jing; Yi, Zhuan; Zhu, Li-Ping; Xu, You-Yi

2015-06-15

Here we describe the development of versatile antifouling polyethersulfone (PES) filtration membranes modified via surface grafting of zwitterionic polymers from a reactive amphiphilic copolymer additive. Amphiphilic polyethersulfone-block-poly(2-hydroxyethyl methacrylate) (PES-b-PHEMA) was beforehand designed and used as the blending additive of PES membranes prepared by phase inversion technique. The surface enriched PHEMA blocks on membrane surface acted as an anchor to immobilize the initiating site. Poly(sulfobetaine methacrylate) (PSBMA) were subsequently grafted onto the PES blend membranes by surface-initiated atom transfer radical polymerization (SI-ATRP). The analysis of surface chemistry confirmed the successful grafting of zwitterionic PSBMA brushes on PES membrane surface. The resulted PES-g-PSBMA membranes were capable of separating proteins from protein solution and oil from oil/water emulsion efficiently. Furthermore, the modified membranes showed high hydrophilicity and strongly antifouling properties due to the incorporation of well-defined PSBMA layer. In addition, the PES-g-PSBMA membranes exhibited excellent blood compatibility and durability during the washing process. The developed antifouling PES membranes are versatile and can find their applications in protein filtration, blood purification and oil/water separation, etc. Copyright © 2015 Elsevier Inc. All rights reserved.

From Anomalies to Essential Scientific Revolution? Intrinsic Brain Activity in the Light of Kuhn's Philosophy of Science.

PubMed

Havlík, Marek

2017-01-01

The first step toward a modern understanding of fMRI resting brain activity was made by Bharat Biswal in 1995. This surprising, and at first rejected, discovery is now associated with many resting state networks, notably the famous default mode network (DMN). Resting state activity and DMN significantly reassessed our traditional beliefs and conventions about the functioning of the brain. For the majority of the twentieth century, neuroscientists assumed that the brain is mainly the "reactive engine" to the environment operating mostly through stimulation. This "reactive convention" was very influential and convenient for the goals of twentieth century neuroscience-non-invasive functional localization based on stimulation. Largely unchallenged, "reactive convention" determined the direction of scientific research for a long time and became the "reactive paradigm" of the twentieth century. Resting state activity brought knowledge that was quite different of the "reactive paradigm." Current research of the DMN, probably the best known resting state network, leads to entirely new observations and conclusions, which were not achievable from the perspective of the "reactive paradigm." This shift from reactive activity to resting state activity of the brain is accompanied by an important question: "Can resting state activity be considered a scientific revolution and the new paradigm of neuroscience, or is it only significant for one branch of neuroscience, such as fMRI?"

Reactivity control assembly for nuclear reactor. [LMFBR

DOEpatents

Bollinger, L.R.

1982-03-17

This invention, which resulted from a contact with the United States Department of Energy, relates to a control mechanism for a nuclear reactor and, more particularly, to an assembly for selectively shifting different numbers of reactivity modifying rods into and out of the core of a nuclear reactor. It has been proposed heretofore to control the reactivity of a breeder reactor by varying the depth of insertion of control rods (e.g., rods containing a fertile material such as ThO/sub 2/) in the core of the reactor, thereby varying the amount of neutron-thermalizing coolant and the amount of neutron-capturing material in the core. This invention relates to a mechanism which can advantageously be used in this type of reactor control system.

CO2 methanation on the catalyst of Ni/MCM-41 promoted with CeO2.

PubMed

Wang, Xiaoliu; Zhu, Lingjun; Liu, Yincong; Wang, Shurong

2018-06-01

CO 2 as a raw feed combined with renewable hydrogen for the production of useful chemicals and alternative energy products is one of the solutions to environmental and energy problems. In this study, a series of Ni-xCeO 2 /MCM-41 catalysts with a nickel content of 20wt% were prepared through deposition precipitation method for CO 2 methanation. Different characterization methods, including BET, XRD, TEM, SEM, H 2 -TPR and H 2 -TPD were applied to help explore the influence mechanism of CeO 2 on Ni/MCM-41 in CO 2 methanation. It was found that all CeO 2 -promoted catalysts exhibited enhanced catalytic activity when compared to Ni/MCM-41. The catalyst modified with 20wt% CeO 2 showed the best catalytic performance, with CO 2 conversion and CH 4 selectivity of 85.6% and 99.8%, respectively, at the temperature of 380°C under atmospheric pressure. The synergetic effects among Ni 0 active sites, the promoter and the support, including nickel dispersion improvement and increased CO 2 adsorption sites due to the addition of CeO 2 , were considered as important factors for high reactivity of the promoted catalysts. The stability test showed that the promoted catalyst maintained its high reactivity after 30h. Copyright © 2017 Elsevier B.V. All rights reserved.

METABOLISM AND DISPOSITION OF ACETAMINOPHEN: RECENT ADVANCES IN RELATION TO HEPATOTOXICITY AND DIAGNOSIS

PubMed Central

McGill, Mitchell R.; Jaeschke, Hartmut

2013-01-01

Acetaminophen (APAP) is one of the most widely used drugs. Though safe at therapeutic doses, overdose causes mitochondrial dysfunction and centrilobular necrosis in the liver. The first studies of APAP metabolism and activation were published more than forty years ago. Most of the drug is eliminated by glucuronidation and sulfation. These reactions are catalyzed by UDP-glucuronosyltransferases (UGT1A1 and 1A6) and sulfotransferases (SULT1A1, 1A3/4, and 1E1), respectively. However, some is converted by CYP2E1 and other cytochrome P450 enzymes to a reactive intermediate that can bind to sulfhydryl groups. The metabolite can deplete liver glutathione (GSH) and modify cellular proteins. GSH binding occurs spontaneously, but may also involve GSH-S-transferases. Protein binding leads to oxidative stress and mitochondrial damage. The glucuronide, sulfate, and GSH conjugates are excreted by transporters in the canalicular (Mrp2 and Bcrp) and basolateral (Mrp3 and Mrp4) hepatocyte membranes. Conditions that interfere with metabolism and metabolic activation can alter the hepatotoxicity of the drug. Recent data providing novel insights into these processes, particularly in humans, are reviewed in the context of earlier work, and the effects of altered metabolism and reactive metabolite formation are discussed. Recent advances in the diagnostic use of serum adducts are covered. PMID:23462933

Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radogna, Flavia; Paternoster, Laura; Istitututo di Chimica Biologica, Universita di Urbino Carlo Bo

Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (< 1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not leadmore » to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.« less

Dendrimeric coating of glass slides for sensitive DNA microarrays analysis

PubMed Central

Le Berre, Véronique; Trévisiol, Emmanuelle; Dagkessamanskaia, Adilia; Sokol, Serguei; Caminade, Anne-Marie; Majoral, Jean Pierre; Meunier, Bernard; François, Jean

2003-01-01

Successful use and reliability of microarray technology is highly dependent on several factors, including surface chemistry parameters and accessibility of cDNA targets to the DNA probes fixed onto the surface. Here, we show that functionalisation of glass slides with homemade dendrimers allow production of more sensitive and reliable DNA microarrays. The dendrimers are nanometric structures of size-controlled diameter with aldehyde function at their periphery. Covalent attachment of these spherical reactive chemical structures on amino-silanised glass slides generates a reactive ∼100 Å layer onto which amino-modified DNA probes are covalently bound. This new grafting chemistry leads to the formation of uniform and homogenous spots. More over, probe concentration before spotting could be reduced from 0.2 to 0.02 mg/ml with PCR products and from 20 to 5 µM with 70mer oligonucleotides without affecting signal intensities after hybridisation with Cy3- and Cy5-labelled targets. More interestingly, while the binding capacity of captured probes on dendrimer-activated glass surface (named dendrislides) is roughly similar to other functionalised glass slides from commercial sources, detection sensitivity was 2-fold higher than with other available DNA microarrays. This detection limit was estimated to 0.1 pM of cDNA targets. Altogether, these features make dendrimer-activated slides ideal for manufacturing cost-effective DNA arrays applicable for gene expression and detection of mutations. PMID:12907740

Protection of host cells by complement regulators.

PubMed

Schmidt, Christoph Q; Lambris, John D; Ricklin, Daniel

2016-11-01

The complement cascade is an ancient immune-surveillance system that not only provides protection from pathogen invasion but has also evolved to participate in physiological processes to maintain tissue homeostasis. The alternative pathway (AP) of complement activation is the evolutionarily oldest part of this innate immune cascade. It is unique in that it is continuously activated at a low level and arbitrarily probes foreign, modified-self, and also unaltered self-structures. This indiscriminate activation necessitates the presence of preformed regulators on autologous surfaces to spare self-cells from the undirected nature of AP activation. Although the other two canonical complement activation routes, the classical and lectin pathways, initiate the cascade more specifically through pattern recognition, their activity still needs to be tightly controlled to avoid excessive reactivity. It is the perpetual duty of complement regulators to protect the self from damage inflicted by inadequate complement activation. Here, we review the role of complement regulators as preformed mediators of defense, explain their common and specialized functions, and discuss selected cases in which alterations in complement regulators lead to disease. Finally, rational engineering approaches using natural complement inhibitors as potential therapeutics are highlighted. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reactive composite compositions and mat barriers

DOEpatents

Langton, Christine A.; Narasimhan, Rajendran; Karraker, David G.

2001-01-01

A hazardous material storage area has a reactive multi-layer composite mat which lines an opening into which a reactive backfill and hazardous material are placed. A water-inhibiting cap may cover the hazardous material storage area. The reactive multi-layer composite mat has a backing onto which is placed an active layer which will neutralize or stabilize hazardous waste and a fronting layer so that the active layer is between the fronting and backing layers. The reactive backfill has a reactive agent which can stabilize or neutralize hazardous material and inhibit the movement of the hazardous material through the hazardous material storage area.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chinthavali, Madhu Sudhan; Wang, Zhiqiang

This paper presents a detailed parametric sensitivity analysis for a wireless power transfer (WPT) system in electric vehicle application. Specifically, several key parameters for sensitivity analysis of a series-parallel (SP) WPT system are derived first based on analytical modeling approach, which includes the equivalent input impedance, active / reactive power, and DC voltage gain. Based on the derivation, the impact of primary side compensation capacitance, coupling coefficient, transformer leakage inductance, and different load conditions on the DC voltage gain curve and power curve are studied and analyzed. It is shown that the desired power can be achieved by just changingmore » frequency or voltage depending on the design value of coupling coefficient. However, in some cases both have to be modified in order to achieve the required power transfer.« less

AMPK signaling in skeletal muscle during exercise: Role of reactive oxygen and nitrogen species.

PubMed

Morales-Alamo, David; Calbet, Jose A L

2016-09-01

Reactive oxygen and nitrogen species (RONS) are generated during exercise depending on intensity, duration and training status. A greater amount of RONS is released during repeated high-intensity sprint exercise and when the exercise is performed in hypoxia. By activating adenosine monophosphate-activated kinase (AMPK), RONS play a critical role in the regulation of muscle metabolism but also in the adaptive responses to exercise training. RONS may activate AMPK by direct an indirect mechanisms. Directly, RONS may activate or deactivate AMPK by modifying RONS-sensitive residues of the AMPK-α subunit. Indirectly, RONS may activate AMPK by reducing mitochondrial ATP synthesis, leading to an increased AMP:ATP ratio and subsequent Thr(172)-AMPK phosphorylation by the two main AMPK kinases: LKB1 and CaMKKβ. In presence of RONS the rate of Thr(172)-AMPK dephosphorylation is reduced. RONS may activate LKB1 through Sestrin2 and SIRT1 (NAD(+)/NADH.H(+)-dependent deacetylase). RONS may also activate CaMKKβ by direct modification of RONS sensitive motifs and, indirectly, by activating the ryanodine receptor (Ryr) to release Ca(2+). Both too high (hypoxia) and too low (ingestion of antioxidants) RONS levels may lead to Ser(485)-AMPKα1/Ser(491)-AMPKα2 phosphorylation causing inhibition of Thr(172)-AMPKα phosphorylation. Exercise training increases muscle antioxidant capacity. When the same high-intensity training is applied to arm and leg muscles, arm muscles show signs of increased oxidative stress and reduced mitochondrial biogenesis, which may be explained by differences in RONS-sensing mechanisms and basal antioxidant capacities between arm and leg muscles. Efficient adaptation to exercise training requires optimal exposure to pulses of RONS. Inappropriate training stimulus may lead to excessive RONS formation, oxidative inactivation of AMPK and reduced adaptation or even maladaptation. Theoretically, exercise programs should be designed taking into account the intrinsic properties of different skeletal muscles, the specific RONS induction and the subsequent signaling responses. Copyright © 2016 Elsevier Inc. All rights reserved.

Improving the reactivity of phenylacetylene macrocycles toward topochemical polymerization by side chains modification

PubMed Central

Daigle, Maxime; Cantin, Katy

2014-01-01

Summary The synthesis and self-assembly of two new phenylacetylene macrocycle (PAM) organogelators were performed. Polar 2-hydroxyethoxy side chains were incorporated in the inner part of the macrocycles to modify the assembly mode in the gel state. With this modification, it was possible to increase the reactivity of the macrocycles in the xerogel state to form polydiacetylenes (PDAs), leading to a significant enhancement of the polymerization yields. The organogels and the PDAs were characterized using Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). PMID:25161718

Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

PubMed Central

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

PubMed

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

ACID FUNCTIONALIZED SINGLE-WALLED CARBON NANOTUBES ENHANCE CARDIAC ISCHEMIC/REPERFUSIOIN INJURY

EPA Science Inventory

Engineered carbon nanotubes are being intensively developed for wide applications. Because of their unique light properties, nanotubes can impose some potentially toxic effects, particularly if they have been modified to express functionally reactive chemical groups on their sur...

ACID-FUNCTIONALIZED SINGLE-WALLED CARBON NANOTUBES ENHANCE CARDIAC ISCHEMIC/REPERFUSION INJURY

EPA Science Inventory

Engineered nanotubes are being intensively developed for biomedical applications such as gene and drug delivery. Because of their unique properties, nanotubes can impose some potentially toxic effects, particularly if they have been modified to express functionally reactive chem...

GRANULAR ACTIVATED CARBON ADSORPTION AND INFRARED REACTIVATION: A CASE STUDY

EPA Science Inventory

A study evaluated the effectiveness and cost of removing trace organic contaminants and surrogates from drinking water by granular activated carbon (GAC) adsorption. The effect of multiple reactivations of spent GAC was also evaluated. Results indicated that reactivated GAC eff...

Increased airway reactivity in a neonatal mouse model of Continuous Positive Airway Pressure (CPAP)

PubMed Central

Mayer, Catherine A.; Martin, Richard J.; MacFarlane, Peter M.

2015-01-01

Background Continuous positive airway pressure (CPAP) is a primary form of respiratory support used in the intensive care of preterm infants, but its long-term effects on airway (AW) function are unknown. Methods We developed a neonatal mouse model of CPAP treatment to determine whether it modifies later AW reactivity. Un-anesthetized spontaneously breathing mice were fitted with a mask to deliver CPAP (6cmH2O, 3hrs/day) for 7 consecutive days starting at postnatal day 1. Airway reactivity to methacholine was assessed using the in vitro living lung slice preparation. Results One week of CPAP increased AW responsiveness to methacholine in male, but not female mice, compared to untreated control animals. The AW hyper-reactivity of male mice persisted for 2 weeks (at P21) after CPAP treatment ended. 4 days of CPAP, however, did not significantly increase AW reactivity. Females also exhibited AW hyper-reactivity at P21, suggesting a delayed response to early (7 days) CPAP treatment. The effects of 7 days of CPAP on hyper-reactivity to methacholine were unique to smaller AWs whereas larger ones were relatively unaffected. Conclusion These data may be important to our understanding of the potential long-term consequences of neonatal CPAP therapy used in the intensive care of preterm infants. PMID:25950451

Secondary metabolite from Nostoc XPORK14A inhibits photosynthesis and growth of Synechocystis PCC 6803.

PubMed

Shunmugam, Sumathy; Jokela, Jouni; Wahlsten, Matti; Battchikova, Natalia; Ateeq ur Rehman; Vass, Imre; Karonen, Maarit; Sinkkonen, Jari; Permi, Perttu; Sivonen, Kaarina; Aro, Eva-Mari; Allahverdiyeva, Yagut

2014-06-01

Screening of 55 different cyanobacterial strains revealed that an extract from Nostoc XPORK14A drastically modifies the amplitude and kinetics of chlorophyll a fluorescence induction of Synechocystis PCC6803 cells.After 2 d exposure to the Nostoc XPORK14A extract, Synechocystis PCC 6803 cells displayed reduced net photosynthetic activity and significantly modified electron transport properties of photosystem II under both light and dark conditions. However, the maximum oxidizable amount of P700 was not strongly affected. The extract also induced strong oxidative stress in Synechocystis PCC 6803 cells in both light and darkness. We identified the secondary metabolite of Nostoc XPORK14A causing these pronounced effects on Synechocystis cells. Mass spectrometry and nuclear magnetic resonance analyses revealed that this compound, designated as M22, has a non-peptide structure. We propose that M22 possesses a dualaction mechanism: firstly, by photogeneration of reactive oxygen species in the presence of light, which in turn affects the photosynthetic machinery of Synechocystis PCC 6803; and secondly, by altering the in vivo redox status of cells, possibly through inhibition of protein kinases.

Properties of photocatalytically generated oxygen species produced by Ag2Se-graphene oxide heterojunction and its application for the visible-light degradation of ammonia

NASA Astrophysics Data System (ADS)

Meng, Ze-Da; Zhao, Wei; Kim, Sukyoung

2017-11-01

Reactive oxygen species (ROS) can be produced by the interactions between sunlight and light-absorbing substances in aqueous environments, and these ROS are capable of destroying various organic pollutants in wastewater. In this study, the photocatalytic degradation of ammonia in petrochemical wastewater was investigated by solar light photocatalysis. We used graphene oxide modified Ag2Se nanoparticles to enhance the activity of photochemically generated oxygen (PGO) species. There was a catastrophic decrease in the surface area and pore volume of the Ag2Se-graphene oxide (Ag2Se-G) samples because of the deposition of Ag2Se. The generation of ROS was detected by the oxidation of 1,5- diphenyl carbazide (DPCI) to 1,5-diphenyl carbazone (DPCO). It was revealed that the photocurrent density and PGO effect increased with the graphene oxide modified. The experimental results indicate that this heterogeneous catalyst achieved a degradation of 88.43% under visiblelight irradiation. The NH3 degradation product was N2 and neither NO2- nor NO3- were detected.[Figure not available: see fulltext.

Cu-modified alkalinized g-C3N4 as photocatalytically assisted heterogeneous Fenton-like catalyst

NASA Astrophysics Data System (ADS)

Dong, Qimei; Chen, Yingying; Wang, Lingli; Ai, Shasha; Ding, Hanming

2017-12-01

Alkalinized graphitic carbon nitride (CNK-OH) has been synthesized by one-step thermal poly-condensation method, and Cu-modified alkalinized g-C3N4 (Cu-CNK-OH) has been prepared by impregnation approach over CNK-OH. These copper species in Cu-CNK-OH are embedded in the frame of CNK-OH mostly via the Cu-N bonds. Cu-CNK-OH has been employed as a heterogeneous Fenton-like catalyst to degrade rhodamine B (RhB). Both the production efficiency of hydroxyl radicals and the transformation rate of Cu(II)/Cu(I) redox pair increase under visible-light irradiation. As a result, Cu-CNK-OH exhibits improved Fenton-like catalytic activity on the degradation of RhB. The synergetic interaction between Fenton-like process and photocatalytic process also contributes such improvement. The hydroxyl radicals and holes are the major reactive species in the photocatalytically assisted Fenton-like process. This study provides a valuable strategy for metal modification of alkalinized g-C3N4 with enhanced Fenton-like catalytic performance for the degradation of organic contaminants.

EndoU is a novel regulator of AICD during peripheral B cell selection

PubMed Central

Poe, Jonathan C.; Kountikov, Evgueni I.; Lykken, Jacquelyn M.; Natarajan, Abirami; Marchuk, Douglas A.

2014-01-01

Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22−/−[B6]) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag–specific B cells in IgTg hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance. PMID:24344237

EndoU is a novel regulator of AICD during peripheral B cell selection.

PubMed

Poe, Jonathan C; Kountikov, Evgueni I; Lykken, Jacquelyn M; Natarajan, Abirami; Marchuk, Douglas A; Tedder, Thomas F

2014-01-13

Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22(-/-[B6])) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag-specific B cells in Ig(Tg) hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance.

Epstein-Barr Virus Lytic Reactivation Activates B Cells Polyclonally and Induces Activation-Induced Cytidine Deaminase Expression: A Mechanism Underlying Autoimmunity and Its Contribution to Graves' Disease.

PubMed

Nagata, Keiko; Kumata, Keisuke; Nakayama, Yuji; Satoh, Yukio; Sugihara, Hirotsugu; Hara, Sayuri; Matsushita, Michiko; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Hayashi, Kazuhiko

2017-04-01

Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity. We showed that the EBV reactivation induces the production of every isotype of Ig and suggested that the Ig production was catalyzed by AID through LMP1 and NF-κB. The results that the amount of IgM was significantly larger compared with IgG suggested the polyclonal B cell activation due to LMP1. We proposed the pathway of EBV reactivation induced Ig production; B cells newly infected with EBV are activated by polyclonal B cell activation and produce Igs through plasma cell differentiation induced by EBV reactivation. LMP1-induced AID enabled B cells to undergo class-switch recombination to produce every isotype of Ig. According to this mechanism, EBV rescues autoreactive B cells to produce autoantibodies, which contribute to the development and exacerbation of autoimmune diseases.

Epstein–Barr Virus Lytic Reactivation Activates B Cells Polyclonally and Induces Activation-Induced Cytidine Deaminase Expression: A Mechanism Underlying Autoimmunity and Its Contribution to Graves' Disease

PubMed Central

Kumata, Keisuke; Nakayama, Yuji; Satoh, Yukio; Sugihara, Hirotsugu; Hara, Sayuri; Matsushita, Michiko; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Hayashi, Kazuhiko

2017-01-01

Abstract Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein–Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity. We showed that the EBV reactivation induces the production of every isotype of Ig and suggested that the Ig production was catalyzed by AID through LMP1 and NF-κB. The results that the amount of IgM was significantly larger compared with IgG suggested the polyclonal B cell activation due to LMP1. We proposed the pathway of EBV reactivation induced Ig production; B cells newly infected with EBV are activated by polyclonal B cell activation and produce Igs through plasma cell differentiation induced by EBV reactivation. LMP1-induced AID enabled B cells to undergo class-switch recombination to produce every isotype of Ig. According to this mechanism, EBV rescues autoreactive B cells to produce autoantibodies, which contribute to the development and exacerbation of autoimmune diseases. PMID:28333576

Non-focusing active warhead

DOEpatents

Hornig, H.C.

1998-12-22

A non-nuclear, non-focusing, active warhead that comprises a high explosive charge contained within a casing of reactive metal is disclosed. When the high explosive is detonated, the reactive metal is dispersed and reacts with the air, which significantly increases the explosive yield of the warhead. The active warhead produces therefore much higher blast effects with significantly reduced weight compared to conventional munitions. The warhead is highly effective against such targets as aircraft which typically have thin fuselages, for example. The explosiveness of this warhead can be enhanced further by elevating the temperature and therefore the reactivity of the reactive metal before or during the explosion. New methods of enhancing the reactivity of the metal are also taught. 4 figs.

Non-focusing active warhead

DOEpatents

Hornig, Howard C.

1998-01-01

A non-nuclear, non-focusing, active warhead that comprises a high explosive charge contained within a casing of reactive metal. When the high explosive is detonated, the reactive metal is dispersed and reacts with the air, which significantly increases the explosive yield of the warhead. The active warhead produces therefore much higher blast effects with significantly reduced weight compared to conventional munitions. The warhead is highly effective against such targets as aircraft which typically have thin fuselages, for example. The explosiveness of this warhead can be enhanced further by elevating the temperature and therefore the reactivity of the reactive metal before or during the explosion. New methods of enhancing the reactivity of the metal are also taught.

Generation and Biological Activities of Oxidized Phospholipids

PubMed Central

Oskolkova, Olga V.; Birukov, Konstantin G.; Levonen, Anna-Liisa; Binder, Christoph J.; Stöckl, Johannes

2010-01-01

Abstract Glycerophospholipids represent a common class of lipids critically important for integrity of cellular membranes. Oxidation of esterified unsaturated fatty acids dramatically changes biological activities of phospholipids. Apart from impairment of their structural function, oxidation makes oxidized phospholipids (OxPLs) markers of “modified-self” type that are recognized by soluble and cell-associated receptors of innate immunity, including scavenger receptors, natural (germ line-encoded) antibodies, and C-reactive protein, thus directing removal of senescent and apoptotic cells or oxidized lipoproteins. In addition, OxPLs acquire novel biological activities not characteristic of their unoxidized precursors, including the ability to regulate innate and adaptive immune responses. Effects of OxPLs described in vitro and in vivo suggest their potential relevance in different pathologies, including atherosclerosis, acute inflammation, lung injury, and many other conditions. This review summarizes current knowledge on the mechanisms of formation, structures, and biological activities of OxPLs. Furthermore, potential applications of OxPLs as disease biomarkers, as well as experimental therapies targeting OxPLs, are described, providing a broad overview of an emerging class of lipid mediators. Antioxid. Redox Signal. 12, 1009–1059. PMID:19686040

Metaplasticity contributes to memory formation in the hippocampus.

PubMed

Crestani, Ana P; Krueger, Jamie N; Barragan, Eden V; Nakazawa, Yuki; Nemes, Sonya E; Quillfeldt, Jorge A; Gray, John A; Wiltgen, Brian J

2018-05-16

Prior learning can modify the plasticity mechanisms that are used to encode new information. For example, NMDA receptor (NMDAR) activation is typically required for new spatial and contextual learning in the hippocampus. However, once animals have acquired this information, they can learn new tasks even if NMDARs are blocked. This finding suggests that behavioral training alters cellular plasticity mechanisms such that NMDARs are not required for subsequent learning. The mechanisms that mediate this change are currently unknown. To address this issue, we tested the idea that changes in intrinsic excitability (induced by learning) facilitate the encoding of new memories via metabotropic glutamate receptor (mGluR) activation. Consistent with this hypothesis, hippocampal neurons exhibited increases in intrinsic excitability after learning that lasted for several days. This increase was selective and only observed in neurons that were activated by the learning event. When animals were trained on a new task during this period, excitable neurons were reactivated and memory formation required the activation of mGluRs instead of NMDARs. These data suggest that increases in intrinsic excitability may serve as a metaplastic mechanism for memory formation.

A Preliminary Investigation of Temperature Dependency of a Shape Memory Actuator with Time-Based Control in Aircraft Interiors

NASA Astrophysics Data System (ADS)

Otibar, Dennis; Weirich, Antonia; Kortenjann, Marcus; Kuhlenkötter, Bernd

2017-06-01

Shape memory alloys (SMA) possess an array of unique functional properties which are influenced by a complex interaction of different factors. Due to thermal sensitivity, slight changes in the environmental temperature may cause the properties to change significantly. This poses a huge challenge especially for the use of SMAs as actuators. The most common and elementary activation strategy of SMA actuators is based on the duration of activation and cooling with constant activation parameters. However, changing environmental influences cause the necessity to modify these parameters. This circumstance needs to be especially considered in the design process of actuator controls. This paper focuses on investigating the influence of environmental temperature changes on time-based activated SMA actuators. The results of the described experiments form the base for designing reactive control strategies for SMA actuators used in alternating environments. An example for application fields with changing environments and particularly changing temperatures are aircraft related implementations. This area also stands to benefit from the actuators’ advantages in ecological efficiency.

Mechanisms and chemistry of dye adsorption on manganese oxides-modified diatomite.

PubMed

Al-Ghouti, Mohammad A; Al-Degs, Yehya S; Khraisheh, Majeda A M; Ahmad, Mohammad N; Allen, Stephen J

2009-08-01

The investigations into structural changes which occur during adsorbent modification and the adsorption mechanisms are essential for an effective design of adsorption systems. Manganese oxides were impregnated onto diatomite to form the type known as delta-birnessite. Initial investigations established the effectiveness of manganese oxides-modified diatomite (MOMD) to remove basic and reactive dyes from aqueous solution. The adsorption capacity of MOMD for methylene blue (MB), hydrolysed reactive black (RB) and hydrolysed reactive yellow (RY) was 320, 419, and 204mg/g, respectively. Various analytical techniques were used to characterise the structure and the mechanisms of the dye adsorption process onto MOMD such as Fourier transform infrared (FTIR), X-ray diffraction (XRD) and atomic absorption spectrometry (A.A.). A small shift to higher values of the d-spacing of dye/MOMD was observed indicating that a small amount of the dye molecules were intercalated in the MOMD structure and other molecules were adsorbed on the external surface of MOMD. Two mechanisms of dye adsorption onto MOMD were proposed; intercalation of the dye in the octahedral layers and adsorption of the dye on the MOMD external surface. Moreover, the results demonstrated that the MOMD structure was changed upon insertion of MB and RY with an obvious decrease in the intensity of the second main peak of the MOMD X-ray pattern.

Blood Pressure Reactivity to Psychological Stress in Young Adults and Cognition in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

PubMed

Yano, Yuichiro; Ning, Hongyan; Reis, Jared P; Lewis, Cora E; Launer, Lenore J; Bryan, R Nick; Yaffe, Kristine; Sidney, Stephen; Albanese, Emiliano; Greenland, Philip; Lloyd-Jones, Donald; Liu, Kiang

2016-01-13

The classic view of blood pressure (BP) reactivity to psychological stress in relation to cardiovascular risks assumes that excess reactivity is worse and lower reactivity is better. Evidence addressing how stress-induced BP reactivity in young adults is associated with midlife cognitive function is sparse. We assessed BP reactivity during a star tracing task and a video game in adults aged 20 to 32 years. Twenty-three years later, cognitive function was assessed with use of the Digit Symbol Substitution Test (a psychomotor speed test), the Rey Auditory Verbal Learning Test (a verbal memory test), and the modified Stroop test (an executive function test). At the time of follow-up, participants (n=3021) had a mean age of 50.2 years; 56% were women, and 44% were black. In linear regression models adjusted for demographic and clinical characteristics including baseline and follow-up resting BP, lower systolic BP (SBP) reactivity during the star tracing and video game was associated with worse Digit Symbol Substitution Test scores (β [SE]: 0.11 [0.02] and 0.05 [0.02], respectively) and worse performance on the Stroop test (β [SE]: -0.06 [0.02] and -0.05 [0.02]; all P<0.01). SBP reactivity was more consistently associated than diastolic BP reactivity with cognitive function scores. The associations between SBP reactivity and cognitive function were mostly similar between blacks and whites. Lower psychological stress-induced SBP reactivity in younger adults was associated with lower cognitive function in midlife. BP reactivity to psychological stressors may have different associations with target organs in hypertension. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

KSHV encoded ORF59 modulates histone arginine methylation of the viral genome to promote viral reactivation

PubMed Central

McDowell-Sargent, Maria; Uppal, Timsy; Purushothaman, Pravinkumar

2017-01-01

Kaposi’s sarcoma associated herpesvirus (KSHV) persists in a highly-ordered chromatin structure inside latently infected cells with the majority of the viral genome having repressive marks. However, upon reactivation the viral chromatin landscape changes into ‘open’ chromatin through the involvement of lysine demethylases and methyltransferases. Besides methylation of lysine residues of histone H3, arginine methylation of histone H4 plays an important role in controlling the compactness of the chromatin. Symmetric methylation of histone H4 at arginine 3 (H4R3me2s) negatively affects the methylation of histone H3 at lysine 4 (H3K4me3), an active epigenetic mark deposited on the viral chromatin during reactivation. We identified a novel binding partner to KSHV viral DNA processivity factor, ORF59-a protein arginine methyl transferase 5 (PRMT5). PRMT5 is an arginine methyltransferase that dimethylates arginine 3 (R3) of histone H4 in a symmetric manner, one hallmark of condensed chromatin. Our ChIP-seq data of symmetrically methylated H4 arginine 3 showed a significant decrease in H4R3me2s on the viral genome of reactivated cells as compared to the latent cells. Reduction in arginine methylation correlated with the binding of ORF59 on the viral chromatin and disruption of PRMT5 from its adapter protein, COPR5 (cooperator of PRMT5). Binding of PRMT5 through COPR5 is important for symmetric methylation of H4R3 and the expression of ORF59 competitively reduces the association of PRMT5 with COPR5, leading to a reduction in PRMT5 mediated arginine methylation. This ultimately resulted in a reduced level of symmetrically methylated H4R3 and increased levels of H3K4me3 marks, contributing to the formation of an open chromatin for transcription and DNA replication. Depletion of PRMT5 levels led to a decrease in symmetric methylation and increase in viral gene transcription confirming the role of PRMT5 in viral reactivation. In conclusion, ORF59 modulates histone-modifying enzymes to alter the chromatin structure during lytic reactivation. PMID:28678843

Reactive polymer coatings: A robust platform towards sophisticated surface engineering for biotechnology

NASA Astrophysics Data System (ADS)

Chen, Hsien-Yeh

Functionalized poly(p-xylylenes) or so-called reactive polymers can be synthesized via chemical vapor deposition (CVD) polymerization. The resulting ultra-thin coatings are pinhole-free and can be conformally deposited to a wide range of substrates and materials. More importantly, the equipped functional groups can served as anchoring sites for tailoring the surface properties, making these reactive coatings a robust platform that can deal with sophisticated challenges faced in biointerfaces. In this work presented herein, surface coatings presenting various functional groups were prepared by CVD process. Such surfaces include aldehyde-functionalized coating to precisely immobilize saccharide molecules onto well-defined areas and alkyne-functionalized coating to click azide-modified molecules via Huisgen 1,3-dipolar cycloaddition reaction. Moreover, CVD copolymerization has been conducted to prepare multifunctional coatings and their specific functions were demonstrated by the immobilization of biotin and NHS-ester molecules. By using a photodefinable coating, polyethylene oxides were immobilized onto a wide range of substrates through photo-immobilization. Spatially controlled protein resistant properties were characterized by selective adsorption of fibrinogen and bovine serum albumin as model systems. Alternatively, surface initiator coatings were used for polymer graftings of polyethylene glycol) methyl ether methacrylate, and the resultant protein- and cell- resistant properties were characterized by adsorption of kinesin motor proteins, fibrinogen, and murine fibroblasts (NIH3T3). Accessibility of reactive coatings within confined microgeometries was systematically studied, and the preparation of homogeneous polymer thin films within the inner surface of microchannels was demonstrated. Moreover, these advanced coatings were applied to develop a dry adhesion process for microfluidic devices. This process provides (i) excellent bonding strength, (ii) extended storage time prior to bonding, and (iii) well-defined surface functionalities for subsequent surface modifications. Finally, we have also prepared surface microstructures and surface patterns using reactive coatings via photopatterning, projection lithography, supramolecular nanostamping (SuNS), and vapor-assisted micropatterning in replica structures (VAMPIR). These patterning techniques can be complimentarily used and provide access to precisely confined microenvironments on flat and curved geometries. Reactive coatings provide a technology platform that creates active, long-term control and may lead to improved mimicry of biological systems for effective bio-functional modifications.

KSHV encoded ORF59 modulates histone arginine methylation of the viral genome to promote viral reactivation.

PubMed

Strahan, Roxanne C; McDowell-Sargent, Maria; Uppal, Timsy; Purushothaman, Pravinkumar; Verma, Subhash C

2017-07-01

Kaposi's sarcoma associated herpesvirus (KSHV) persists in a highly-ordered chromatin structure inside latently infected cells with the majority of the viral genome having repressive marks. However, upon reactivation the viral chromatin landscape changes into 'open' chromatin through the involvement of lysine demethylases and methyltransferases. Besides methylation of lysine residues of histone H3, arginine methylation of histone H4 plays an important role in controlling the compactness of the chromatin. Symmetric methylation of histone H4 at arginine 3 (H4R3me2s) negatively affects the methylation of histone H3 at lysine 4 (H3K4me3), an active epigenetic mark deposited on the viral chromatin during reactivation. We identified a novel binding partner to KSHV viral DNA processivity factor, ORF59-a protein arginine methyl transferase 5 (PRMT5). PRMT5 is an arginine methyltransferase that dimethylates arginine 3 (R3) of histone H4 in a symmetric manner, one hallmark of condensed chromatin. Our ChIP-seq data of symmetrically methylated H4 arginine 3 showed a significant decrease in H4R3me2s on the viral genome of reactivated cells as compared to the latent cells. Reduction in arginine methylation correlated with the binding of ORF59 on the viral chromatin and disruption of PRMT5 from its adapter protein, COPR5 (cooperator of PRMT5). Binding of PRMT5 through COPR5 is important for symmetric methylation of H4R3 and the expression of ORF59 competitively reduces the association of PRMT5 with COPR5, leading to a reduction in PRMT5 mediated arginine methylation. This ultimately resulted in a reduced level of symmetrically methylated H4R3 and increased levels of H3K4me3 marks, contributing to the formation of an open chromatin for transcription and DNA replication. Depletion of PRMT5 levels led to a decrease in symmetric methylation and increase in viral gene transcription confirming the role of PRMT5 in viral reactivation. In conclusion, ORF59 modulates histone-modifying enzymes to alter the chromatin structure during lytic reactivation.

Induction of tolerance towards TNP entails down-regulation of an autoimmune attack.

PubMed Central

Zöller, M; Andrighetto, G

1988-01-01

In order to follow the process of induction and maintainance of tolerance, BALB/c mice were tolerized by free hapten, and effector and regulatory cell interactions were analysed by limiting-dilution (LD) cultures. Injection of trinitrobenzenesulphonic acid (TNBS) resulted, predominantly, in the activation and expansion of self-reactive cytotoxic T cells (CTL), which were observed transiently at frequencies comparable to allo-specific CTL. In addition, self-reactive helper T cells (Th) were activated and expanded in tolerized mice. TNP-specific reactivity was difficult to evaluate, since cytotoxic activity against haptenized self followed the pattern of self-reactivity throughout the test period. But in LD cultures determining proliferation, two populations of Th responding to TNP-self were observed, while only one Th population could be detected in response to self. Expansion/activation of Th and CTL precursors (CTLp) was followed by activation of suppressor T cells (Ts). The suppressor population could be divided into two subpopulations, one interfering with Th, the second interacting directly with CTL (veto cells). The results indicate that during the induction of tolerance, animals pass through an autoimmune attack, with expansion and activation of self-reactive clones (CTL, Th). The final status of non-responsiveness towards TNP is not due to the deletion of effector or regulatory cells, but results from the establishment of a steady state of dominance of self-reactive and TNP-self-reactive suppression. PMID:2965095

Memory traces of long-range coordinated oscillations in the sleeping human brain.

PubMed

Piantoni, Giovanni; Van Der Werf, Ysbrand D; Jensen, Ole; Van Someren, Eus J W

2015-01-01

Cognition involves coordinated activity across distributed neuronal networks. Neuronal activity during learning triggers cortical plasticity that allows for reorganization of the neuronal network and integration of new information. Animal studies have shown post-learning reactivation of learning-elicited neuronal network activity during subsequent sleep, supporting consolidation of the reorganization. However, no previous studies, to our knowledge, have demonstrated reactivation of specific learning-elicited long-range functional connectivity during sleep in humans. We here show reactivation of learning-induced long-range synchronization of magnetoencephalography power fluctuations in human sleep. Visuomotor learning elicited a specific profile of long-range cortico-cortical synchronization of slow (0.1 Hz) fluctuations in beta band (12-30 Hz) power. The parieto-occipital part of this synchronization profile reappeared in delta band (1-3.5 Hz) power fluctuations during subsequent sleep, but not during the intervening wakefulness period. Individual differences in the reactivated synchronization predicted postsleep performance improvement. The presleep resting-state synchronization profile was not reactivated during sleep. The findings demonstrate reactivation of long-range coordination of neuronal activity in humans, more specifically of reactivation of coupling of infra-slow fluctuations in oscillatory power. The spatiotemporal profile of delta power fluctuations during sleep may subserve memory consolidation by echoing coordinated activation elicited by prior learning. © 2014 Wiley Periodicals, Inc.

Androidal fat dominates in predicting cardiometabolic risk in postmenopausal women

USDA-ARS?s Scientific Manuscript database

We hypothesized that soy isoflavones would attenuate the anticipated increase in androidal fat mass in postmenopausal women during the 36-month treatment, and thereby favorably modify the circulating cardiometabolic risk factors: triacylglycerol, LDLC, HDL-C, glucose, insulin, uric acid, C-reactive ...

Diffusional correlations among multiple active sites in a single enzyme.

PubMed

Echeverria, Carlos; Kapral, Raymond

2014-04-07

Simulations of the enzymatic dynamics of a model enzyme containing multiple substrate binding sites indicate the existence of diffusional correlations in the chemical reactivity of the active sites. A coarse-grain, particle-based, mesoscopic description of the system, comprising the enzyme, the substrate, the product and solvent, is constructed to study these effects. The reactive and non-reactive dynamics is followed using a hybrid scheme that combines molecular dynamics for the enzyme, substrate and product molecules with multiparticle collision dynamics for the solvent. It is found that the reactivity of an individual active site in the multiple-active-site enzyme is reduced substantially, and this effect is analyzed and attributed to diffusive competition for the substrate among the different active sites in the enzyme.

The hemoglobin derived peptide LVV-hemorphin-7 evokes behavioral effects mediated by oxytocin receptors.

PubMed

da Cruz, Kellen Rosa; Turones, Larissa Córdova; Camargo-Silva, Gabriel; Gomes, Karina Pereira; Mendonça, Michelle Mendanha; Galdino, Pablinny; Rodrigues-Silva, Christielly; Santos, Robson Augusto Souza; Costa, Elson Alves; Ghedini, Paulo Cesar; Ianzer, Danielle; Xavier, Carlos Henrique

2017-12-01

LVV-hemorphin-7 (LVV-h7) is bioactive peptide resulting from degradation of hemoglobin β-globin chain. LVV-h7 is a specific agonist of angiotensin IV receptor. This receptor belongs to the class of insulin-regulated aminopeptidases (IRAP), which displays oxytocinase activity. Herein, our aims were to assess whether: i) LVV-h7 modifies centrally organized behavior and cardiovascular responses to stress and ii) mechanisms underlying LVV-h7 effects involve activation of oxytocin (OT) receptors, probably as result of reduction of IRAP proteolytic activity upon OT. Adult male Wistar rats (270-370g) received (i.p.) injections of LVV-h7 (153nmol/kg), or vehicle (0.1ml). Different protocols were used: i) open field (OP) test for locomotor/exploratory activities; ii) Elevated Plus Maze (EPM) for anxiety-like behavior; iii) forced swimming test (FST) test for depression-like behavior and iv) air jet for cardiovascular reactivity to acute stress exposure. Diazepam (2mg/kg) and imipramine (15mg/kg) were used as positive control for EPM and FST, respectively. The antagonist of OT receptors (OTr), atosiban (1 and 0,1mg/kg), was used to determine the involvement of oxytocinergic paths. We found that LVV-h7: i) increased the number of entries and the time spent in open arms of the maze, an indicative of anxiolysis; ii) provoked antidepressant effect in the FS test; and iii) increased the exploration and locomotion; iv) did not change the cardiovascular reactivity and neuroendocrine responses to acute stress. Also, increases in locomotion and the antidepressant effects evoked by LVV-h7 were reverted by OTr antagonist. We conclude that LVV-h7 modulates behavior, displays antidepressant and anxiolytic effects that are mediated in part by oxytocin receptors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of Epstein-Barr virus reactivation by the flavonoid apigenin.

PubMed

Wu, Chung-Chun; Fang, Chih-Yeu; Cheng, Yu-Jhen; Hsu, Hui-Yu; Chou, Sheng-Ping; Huang, Sheng-Yen; Tsai, Ching-Hwa; Chen, Jen-Yang

2017-01-05

Lytic reactivation of EBV has been reported to play an important role in human diseases, including NPC carcinogenesis. Inhibition of EBV reactivation is considered to be of great benefit in the treatment of virus-associated diseases. For this purpose, we screened for inhibitory compounds and found that apigenin, a flavonoid, seemed to have the ability to inhibit EBV reactivation. We performed western blotting, immunofluorescence and luciferase analyses to determine whether apigenin has anti-EBV activity. Apigenin inhibited expression of the EBV lytic proteins, Zta, Rta, EAD and DNase in epithelial and B cells. It also reduced the number of EBV-reactivating cells detectable by immunofluorescence analysis. In addition, apigenin has been found to reduce dramatically the production of EBV virions. Luciferase reporter analysis was performed to determine the mechanism by which apigenin inhibits EBV reactivation: apigenin suppressed the activity of the immediate-early (IE) gene Zta and Rta promoters, suggesting it can block initiation of the EBV lytic cycle. Taken together, apigenin inhibits EBV reactivation by suppressing the promoter activities of two viral IE genes, suggesting apigenin is a potential dietary compound for prevention of EBV reactivation.

Football Pools and the Reactivity Series of Metals.

ERIC Educational Resources Information Center

Heselden, Russ

2001-01-01

Describes an activity which presents the reactivity of metals series as a football pool with more reactive metals at the top of the table and unreactive metals at the bottom. Describes how the activity can be applied in different ways for different ability groups. (Author/MM)

Study of crystallinity and thermal behavior of gamma irradiated luffa fiber

NASA Astrophysics Data System (ADS)

Patra, Subhashree; Mohanta, Kamal Lochan; Parida, Chhatrapati

2018-04-01

The purpose of this study is to examine the effect of high energy 6 MV X-ray photon beams on fiber of luffa cylindrica (LC), an agricultural waste of India. Techniques such as XRD, FTIR, SEM and TGA are used to study the structural changes and thermal behavior of fiber after physical modification by X-ray photon. Results illustrated that the crystallinity of cellulose in modified fibers was destroyed. High reactivity of modified LC fiber was ascertained from the presence of carboxylic group in the FT-IR spectrum. TGA study revealed increase in hydrophobicity of the modified fiber. The variation of these properties was analyzed with variation in dose of irradiation. Before treatment, the LC fibers are modified with Ca salts in order to explore their applications in biomedical terrain.

Physical activity, inflammatory biomarkers in gingival crevicular fluid and periodontitis.

PubMed

Sanders, Anne E; Slade, Gary D; Fitzsimmons, Tracy R; Bartold, Peter Mark

2009-05-01

To examine the associations of physical activity with interleukin 1-beta (IL-1beta), C-reactive protein (CRP) and periodontitis and to investigate whether any relationship between physical activity and inflammatory mediators differs between periodontitis cases and non-cases. In this population-based case control study of Australians aged 18+ years, dentists conducted oral epidemiologic examinations identifying cases with moderate or severe periodontitis and periodontally healthy controls. Gingival crevicular fluid samples collected during examinations were analysed for inflammatory biomarkers. Subject-completed questionnaires assessed leisure-time physical activity. Exposure odds ratios (ORs) were estimated in multivariable logistic regression models adjusting for periodontitis risk indicators. Of 751 subjects (359 cases, 392 controls), those meeting a prescribed threshold for leisure-time physical activity had lower adjusted odds of elevated IL-1beta: OR=0.69, (95% CI=0.50-0.94) and detectable CRP: OR=0.70 (0.50-0.98) than less active adults. Physical activity was not associated with periodontitis: OR=1.14 (0.80-1.62). Periodontitis modified the association between levels of physical activity and detectable CRP. Increasing quartiles of physically activity were associated with decreasing probability of detectable CRP, but the effect was limited to periodontitis cases and was not apparent among non-cases. Leisure-time physical activity may protect against an excessive inflammatory response in periodontitis.

Evidence for Consolidation of Neuronal Assemblies after Seizures in Humans

PubMed Central

Stead, Matt; Bower, Regina S.; Kucewicz, Michal T.; Sulc, Vlastimil; Cimbalnik, Jan; Brinkmann, Benjamin H.; Vasoli, Vincent M.; St. Louis, Erik K.; Meyer, Fredric B.; Marsh, W. Richard; Worrell, Gregory A.

2015-01-01

The establishment of memories involves reactivation of waking neuronal activity patterns and strengthening of associated neural circuits during slow-wave sleep (SWS), a process known as “cellular consolidation” (Dudai and Morris, 2013). Reactivation of neural activity patterns during waking behaviors that occurs on a timescale of seconds to minutes is thought to constitute memory recall (O'Keefe and Nadel, 1978), whereas consolidation of memory traces may be revealed and served by correlated firing (reactivation) that appears during sleep under conditions suitable for synaptic modification (Buhry et al., 2011). Although reactivation has been observed in human neuronal recordings (Gelbard-Sagiv et al., 2008; Miller et al., 2013), reactivation during sleep has not, likely because data are difficult to obtain and the effect is subtle. Seizures, however, provide intense and synchronous, yet sparse activation (Bower et al., 2012) that could produce a stronger consolidation effect if seizures activate learning-related mechanisms similar to those activated by learned tasks. Continuous wide-bandwidth recordings from patients undergoing intracranial monitoring for drug-resistant epilepsy revealed reactivation of seizure-related neuronal activity during subsequent SWS, but not wakefulness. Those neuronal assemblies that were most strongly activated during seizures showed the largest correlation changes, suggesting that consolidation selectively strengthened neuronal circuits activated by seizures. These results suggest that seizures “hijack” physiological learning mechanisms and also suggest a novel epilepsy therapy targeting neuronal dynamics during post-seizure sleep. PMID:25609617

Oxygen plasma surface modification augments poly(L-lactide-co-glycolide) cytocompatibility toward osteoblasts and minimizes immune activation of macrophages.

PubMed

Scislowska-Czarnecka, Anna; Szmigiel, Dariusz; Genet, Michel; Dupont-Gillain, Christine; Pamula, Elzbieta; Kolaczkowska, Elzbieta

2015-12-01

Here, we report on modification of one of the model biomedical polymers, poly L-lactide-co-glycolide (PLGA; 85:15), by reactive ion etching (RIE) oxygen plasma treatment. PLGA's major disadvantage is high hydrophobicity which restrains binding of cell-adhesive proteins and host cells. In the current approach, we aimed to answer two questions: (1) will only short (10 s) and moderate (20-200 mTorr, 45-90 W) RIE oxygen plasma treatment, leading to decrease of water contact angle by only up to 10°, sufficiently improve PLGA adherence to cells, and (2) how will this affect osteoblasts and activation of the immune system? All obtained modified PLGAs had improved hydrophilicity but unaltered roughness (as revealed by water contact angle measurements, X-ray photoelectron spectroscopy, and atomic force microscopy) resulting in significantly improved adhesion of osteoblasts (MG-63) and their low activation. Importantly, macrophages (RAW 264.7), one of the key cells initiating inflammation and bone resorption, responded significantly less vigorously to the modified polymers, expressing/releasing lower amounts of nitric oxide, matrix metalloproteinases (MMP-9), and pro-inflammatory cytokines (TNF-α, IL-6, IL-12p70, IFN-γ, IL-10). We conclude that already slight RIE oxygen plasma modification of PLGA is sufficient to improve its surface properties, and enhance cytocompatibility. Most importantly, this type of modification prevents excessive immune response. © 2015 Wiley Periodicals, Inc.

Optical and structural properties of plasma-treated Cordyceps bassiana spores as studied by circular dichroism, absorption, and fluorescence spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Geon Joon, E-mail: gjlee@kw.ac.kr; Sim, Geon Bo; Choi, Eun Ha

To understand the killing mechanism of fungal spores by plasma treatment, the optical, structural, and biological properties of the insect pathogenic fungus Cordyceps bassiana spores were studied. A nonthermal atmospheric-pressure plasma jet (APPJ) was used to treat the spores in aqueous solution. Optical emission spectra of the APPJ acquired in air indicated emission peaks corresponding to hydroxyl radicals and atomic oxygen. When the APPJ entered the aqueous solution, additional reactive species were derived from the interaction of plasma radicals with the aqueous solution. Fluorescence and absorption spectroscopy confirmed the generation of hydroxyl radicals and hydrogen peroxide in the plasma-activated watermore » (PAW). Spore counting showed that plasma treatment significantly reduced spore viability. Absorption spectroscopy, circular dichroism (CD) spectroscopy, and agarose gel electrophoresis of the DNA extracted from plasma-treated spores showed a reduction in spore DNA content. The magnitude of the dip in the CD spectrum was lower in the plasma-treated spores than in the control, indicating that plasma treatment causes structural modifications and/or damage to cellular components. Tryptophan fluorescence intensity was lower in the plasma-treated spores than in the control, suggesting that plasma treatment modified cell wall proteins. Changes in spore viability and DNA content were attributed to structural modification of the cell wall by reactive species coming from the APPJ and the PAW. Our results provided evidence that the plasma radicals and the derived reactive species play critical roles in fungal spore inactivation.« less

Optical and structural properties of plasma-treated Cordyceps bassiana spores as studied by circular dichroism, absorption, and fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Lee, Geon Joon; Sim, Geon Bo; Choi, Eun Ha; Kwon, Young-Wan; Kim, Jun Young; Jang, Siun; Kim, Seong Hwan

2015-01-01

To understand the killing mechanism of fungal spores by plasma treatment, the optical, structural, and biological properties of the insect pathogenic fungus Cordyceps bassiana spores were studied. A nonthermal atmospheric-pressure plasma jet (APPJ) was used to treat the spores in aqueous solution. Optical emission spectra of the APPJ acquired in air indicated emission peaks corresponding to hydroxyl radicals and atomic oxygen. When the APPJ entered the aqueous solution, additional reactive species were derived from the interaction of plasma radicals with the aqueous solution. Fluorescence and absorption spectroscopy confirmed the generation of hydroxyl radicals and hydrogen peroxide in the plasma-activated water (PAW). Spore counting showed that plasma treatment significantly reduced spore viability. Absorption spectroscopy, circular dichroism (CD) spectroscopy, and agarose gel electrophoresis of the DNA extracted from plasma-treated spores showed a reduction in spore DNA content. The magnitude of the dip in the CD spectrum was lower in the plasma-treated spores than in the control, indicating that plasma treatment causes structural modifications and/or damage to cellular components. Tryptophan fluorescence intensity was lower in the plasma-treated spores than in the control, suggesting that plasma treatment modified cell wall proteins. Changes in spore viability and DNA content were attributed to structural modification of the cell wall by reactive species coming from the APPJ and the PAW. Our results provided evidence that the plasma radicals and the derived reactive species play critical roles in fungal spore inactivation.

Pt/Cr and Pt/Ni catalysts for oxygen reduction reaction: to alloy or not to alloy?

PubMed

Escaño, Mary Clare; Gyenge, Elod; Nakanishi, Hiroshi; Kasai, Hideaki

2011-04-01

Bimetallic systems such as Pt-based alloys or non-alloys have exhibited interesting catalytic properties but pose a major challenge of not knowing a priori how the electronic and chemical properties will be modified relative to the parent metals. In this work, we present the origin of the changes in the reactivity of Pt/Cr and Pt/Ni catalysts, which have been of wide interest in fuel cell research. Using spin-polarized density functional theory calculations, we have shown that the modification of Pt surface reactivity in Pt/Ni is purely of geometric origin (strain). We have also found that the Pt-Ni bonding is very weak, which explains the observed instability of Pt-Ni catalysts under electrochemical measurements. On the other hand, Pt/Cr systems are governed by strong ligand effect (metal-metal interaction), which explains the experimentally observed reactivity dependence on the relative composition of the alloying components. The general characteristics of the potential energy curves for O2 dissociative adsorption on the bimetallic systems and the pure Pt clarify why the d-band center still works for Pt/Cr despite the strong Pt-Cr bonding and high spin polarization of Pt d-states. On the basis of the above clarifications, viable Pt-Cr and Pt-Ni structures, which involve nano-sized alloys and non-alloy bulk catalyst, which may strike higher than the currently observed oxidation reduction reaction activity are proposed.

Bioactive surface modifications on inner walls of poly-tetra-fluoro-ethylene tubes using dielectric barrier discharge

NASA Astrophysics Data System (ADS)

Cho, Yong Ki; Park, Daewon; Kim, Hoonbae; Lee, Hyerim; Park, Heonyong; Kim, Hong Ja; Jung, Donggeun

2014-03-01

Bioactive surface modification can be used in a variety of medical polymeric materials in the fields of biochips and biosensors, artificial membranes, and vascular grafts. In this study, the surface modification of the inner walls of poly-tetra-fluoro-ethylene (PTFE) tubing was carried out to improve vascular grafts, which are made of biocompatible material for the human body in the medical field. Focus was centered on the cell attachment of the inner wall of the PTFE by sequential processes of hydrogen plasma treatment, hydrocarbon deposition, and reactive plasma treatment on the PFTE surface using micro plasma discharge. Micro plasma was generated by a medium-frequency alternating current high-voltage generator. The preliminary modification of PTFE was conducted by a plasma of hydrogen and argon gases. The hydrocarbon thin film was deposited on modified PTFE with a mixture of acetylene and argon gases. The reactive plasma treatment using oxygen plasma was done to give biocompatible functionality to the inner wall surface. The hydrophobic surface of bare PTFE is made hydrophilic by the reactive plasma treatment due to the formation of carbonyl groups on the surface. The reactive treatment could lead to improved attachment of smooth muscle cells (SMCs) on the modified PTFE tubing. Fourier transform infrared absorption spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and water contact angle measurement were used for the analysis of the surface modification. The SMC-attached PTFE tube developed will be applicable to in vitro human vasculature-mimetic model systems, and to medical vascular grafts.

Reactive transport modelling to infer changes in soil hydraulic properties induced by non-conventional water irrigation

NASA Astrophysics Data System (ADS)

Valdes-Abellan, Javier; Jiménez-Martínez, Joaquín; Candela, Lucila; Jacques, Diederik; Kohfahl, Claus; Tamoh, Karim

2017-06-01

The use of non-conventional water (e.g., treated wastewater, desalinated water) for different purposes is increasing in many water scarce regions of the world. Its use for irrigation may have potential drawbacks, because of mineral dissolution/precipitation processes, such as changes in soil physical and hydraulic properties (e.g., porosity, permeability), modifying infiltration and aquifer recharge processes or blocking root growth. Prediction of soil and groundwater impacts is essential for achieving sustainable agricultural practices. A numerical model to solve unsaturated water flow and non-isothermal multicomponent reactive transport has been modified implementing the spatio-temporal evolution of soil physical and hydraulic properties. A long-term process simulation (30 years) of agricultural irrigation with desalinated water, based on a calibrated/validated 1D numerical model in a semi-arid region, is presented. Different scenarios conditioning reactive transport (i.e., rainwater irrigation, lack of gypsum in the soil profile, and lower partial pressure of CO2 (pCO2)) have also been considered. Results show that although boundary conditions and mineral soil composition highly influence the reactive processes, dissolution/precipitation of carbonate species is triggered mainly by pCO2, closely related to plant roots. Calcite dissolution occurs in the root zone, precipitation takes place under it and at the soil surface, which will lead a root growth blockage and a direct soil evaporation decrease, respectively. For the studied soil, a gypsum dissolution up to 40 cm depth is expected at long-term, with a general increase of porosity and hydraulic conductivity.

Tissue response to intraperitoneal implants of polyethylene oxide-modified polyethylene terephthalate.

PubMed

Desai, N P; Hubbell, J A

1992-01-01

Polyethylene terephthalate films surface modified with polyethylene oxide of mol wt 18,500 g/mol (18.5 k) by a previously described technique, were implanted in the peritoneal cavity of mice, along with their respective untreated controls, for periods of 1-28 d. The implants were retrieved and examined for tissue reactivity and cellular adherence. The control polyethylene terephthalate surfaces showed an initial inflammatory reaction followed by an extensive fibrotic response with a mean thickness of 60 microns at 28 d. By contrast, polyethylene oxide-modified polyethylene terephthalate showed only a mild inflammatory response and no fibrotic encapsulation throughout the implantation period: at 28 d a cellular monolayer was observed. Apparently either the polyethylene oxide-modified surface was stimulating less inflammation, which was in turn stimulating less fibroblastic overgrowth, or the cellular adhesion to the polyethylene oxide-modified surface was too weak to support cellular multilayers.

Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway.

PubMed

Lucas, Kurt; Maes, Michael

2013-08-01

Activation of the Toll-like receptor 4 (TLR4) complex, a receptor of the innate immune system, may underpin the pathophysiology of many human diseases, including asthma, cardiovascular disorder, diabetes, obesity, metabolic syndrome, autoimmune disorders, neuroinflammatory disorders, schizophrenia, bipolar disorder, autism, clinical depression, chronic fatigue syndrome, alcohol abuse, and toluene inhalation. TLRs are pattern recognition receptors that recognize damage-associated molecular patterns and pathogen-associated molecular patterns, including lipopolysaccharide (LPS) from gram-negative bacteria. Here we focus on the environmental factors, which are known to trigger TLR4, e.g., ozone, atmosphere particulate matter, long-lived reactive oxygen intermediate, pentachlorophenol, ionizing radiation, and toluene. Activation of the TLR4 pathways may cause chronic inflammation and increased production of reactive oxygen and nitrogen species (ROS/RNS) and oxidative and nitrosative stress and therefore TLR-related diseases. This implies that drugs or substances that modify these pathways may prevent or improve the abovementioned diseases. Here we review some of the most promising drugs and agents that have the potential to attenuate TLR-mediated inflammation, e.g., anti-LPS strategies that aim to neutralize LPS (synthetic anti-LPS peptides and recombinant factor C) and TLR4/MyD88 antagonists, including eritoran, CyP, EM-163, epigallocatechin-3-gallate, 6-shogaol, cinnamon extract, N-acetylcysteine, melatonin, and molecular hydrogen. The authors posit that activation of the TLR radical (ROS/RNS) cycle is a common pathway underpinning many "civilization" disorders and that targeting the TLR radical cycle may be an effective method to treat many inflammatory disorders.

Factors Associated With Ischemic Stroke Survival and Recovery in Older Adults.

PubMed

Winovich, Divya Thekkethala; Longstreth, William T; Arnold, Alice M; Varadhan, Ravi; Zeki Al Hazzouri, Adina; Cushman, Mary; Newman, Anne B; Odden, Michelle C

2017-07-01

Little is known about factors that predispose older adults to poor recovery after a stroke. In this study, we sought to evaluate prestroke measures of frailty and related factors as markers of vulnerability to poor outcomes after ischemic stroke. In participants aged 65 to 99 years with incident ischemic strokes from the Cardiovascular Health Study, we evaluated the association of several risk factors (frailty, frailty components, C-reactive protein, interleukin-6, and cystatin C) assessed before stroke with stroke outcomes of survival, cognitive decline (≥5 points on Modified Mini-Mental State Examination), and activities of daily living decline (increase in limitations). Among 717 participants with incident ischemic stroke with survival data, slow walking speed, low grip strength, and cystatin C were independently associated with shorter survival. Among participants <80 years of age, frailty and interleukin-6 were also associated with shorter survival. Among 509 participants with recovery data, slow walking speed, and low grip strength were associated with both cognitive and activities of daily living decline poststroke. C-reactive protein and interleukin-6 were associated with poststroke cognitive decline among men only. Frailty status was associated with activities of daily living decline among women only. Markers of physical function-walking speed and grip strength-were consistently associated with survival and recovery after ischemic stroke. Inflammation, kidney function, and frailty also seemed to be determinants of survival and recovery after an ischemic stroke. These markers of vulnerability may identify targets for differing pre and poststroke medical management and rehabilitation among older adults at risk of poor stroke outcomes. © 2017 American Heart Association, Inc.

An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.

PubMed

Khattri, Ram B; Morris, Daniel L; Davis, Caroline M; Bilinovich, Stephanie M; Caras, Andrew J; Panzner, Matthew J; Debord, Michael A; Leeper, Thomas C

2016-07-16

Selective hits for the glutaredoxin ortholog of Brucella melitensis are determined using STD NMR and verified by trNOE and (15)N-HSQC titration. The most promising hit, RK207, was docked into the target molecule using a scoring function to compare simulated poses to experimental data. After elucidating possible poses, the hit was further optimized into the lead compound by extension with an electrophilic acrylamide warhead. We believe that focusing on selectivity in this early stage of drug discovery will limit cross-reactivity that might occur with the human ortholog as the lead compound is optimized. Kinetics studies revealed that lead compound 5 modified with an ester group results in higher reactivity than an acrylamide control; however, after modification this compound shows little selectivity for bacterial protein versus the human ortholog. In contrast, hydrolysis of compound 5 to the acid form results in a decrease in the activity of the compound. Together these results suggest that more optimization is warranted for this simple chemical scaffold, and opens the door for discovery of drugs targeted against glutaredoxin proteins-a heretofore untapped reservoir for antibiotic agents.

The Improvement of Ion Plated Ag and Au Film Adherence to Si3N4 and SiC Surfaces for Increased Tribological Performance

NASA Technical Reports Server (NTRS)

Spalvins, Talivaldis

1998-01-01

A modified dc-diode plating system, utilizing a metallic screen cage as a cathode and referred as SCREEN CAGE ION PLATING (SCIP), is used to deposit Ag and Au lubricating films on Si3N4 and SiC surfaces. When deposition is performed in Ar or N2, glow discharge, the surface displays poor adhesive strength (less than 5 MPa). A dramatic increase in adhesive strength (less than 80 MPa) is achieved when plating is performed in a reactive 50% 02 + 50% Ar glow discharge. The excited/ionized oxygen species (O2(+)/O(+) in the glow discharge contribute to the oxidation of the Si3N4 or SiC surfaces as determined by X-ray Photoelectron Spectroscopy (XTS) depth profiling. The reactively sputter-oxidized S3N4 or SiC surfaces and the activated-oxidized-metastable Ag or Au species formed in the plasma cooperatively contribute to the increased adherence. As a result, the linear thermal expansion coefficient mismatch at the interface is reduced. These lubricating Ag and Au films under sliding conditions reduce the friction coefficient by a factor of 2-1/2 to 4.

Role of Protein Carbonylation in Skeletal Muscle Mass Loss Associated with Chronic Conditions

PubMed Central

Barreiro, Esther

2016-01-01

Muscle dysfunction, characterized by a reductive remodeling of muscle fibers, is a common systemic manifestation in highly prevalent conditions such as chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), cancer cachexia, and critically ill patients. Skeletal muscle dysfunction and impaired muscle mass may predict morbidity and mortality in patients with chronic diseases, regardless of the underlying condition. High levels of oxidants may alter function and structure of key cellular molecules such as proteins, DNA, and lipids, leading to cellular injury and death. Protein oxidation including protein carbonylation was demonstrated to modify enzyme activity and DNA binding of transcription factors, while also rendering proteins more prone to proteolytic degradation. Given the relevance of protein oxidation in the pathophysiology of many chronic conditions and their comorbidities, the current review focuses on the analysis of different studies in which the biological and clinical significance of the modifications induced by reactive carbonyls on proteins have been explored so far in skeletal muscles of patients and animal models of chronic conditions such as COPD, disuse muscle atrophy, cancer cachexia, sepsis, and physiological aging. Future research will elucidate the specific impact and sites of reactive carbonyls on muscle protein content and function in human conditions. PMID:28248228

Highly Reactive Thiol-Norbornene Photo-Click Hydrogels: Toward Improved Processability.

PubMed

Van Hoorick, Jasper; Gruber, Peter; Markovic, Marica; Rollot, Mélanie; Graulus, Geert-Jan; Vagenende, Maxime; Tromayer, Maximilian; Van Erps, Jürgen; Thienpont, Hugo; Martins, José C; Baudis, Stefan; Ovsianikov, Aleksandr; Dubruel, Peter; Van Vlierberghe, Sandra

2018-06-10

In the present work, gelatin type B is modified with highly reactive norbornene functionalities (Gel-NB) following a one-pot synthesis approach to enable subsequent thiol-ene photo-click crosslinking. The modification strategy displays close control over the amount of introduced functionalities. Additionally, Gel-NB exhibits considerably improved processing capabilities in terms of two-photon polymerization when benchmarked to earlier-reported crosslinkable gelatin derivatives (e.g., gelatin-methacrylamide (Gel-MOD) and gelatin-methacrylamide-aminoethylmethacrylate (Gel-MOD-AEMA)). The improvement is especially apparent in terms of minimally required laser power (20 mW vs ≥60 mW (Gel-MOD) vs ≥40 mW (Gel-MOD-AEMA) at 100 mm s -1 scan speed) and processable concentration range (≥5 w/v% vs ≥10 w/v% (Gel-MOD/Gel-MOD-AEMA)). Furthermore, the proposed functionalization scheme maintains the excellent biocompatibility and cell interactivity of gelatin. Additionally, the norbornene functionalities have potential for straightforward postprocessing "thiol-ene" surface grafting of active molecules. As a consequence, a very promising material toward tissue engineering applications and more specifically, biofabrication, is presented. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anticancer Vitamin K3 Analogs: A Review.

PubMed

Badave, Kirti D; Khan, Ayesha A; Rane, Sandhya Y

2016-01-01

Menadione (Vitamin K3) comprises of 1,4-naphthoquinone (NQ) moiety that can form redox isomers such as napthosemiquinone (NSQ) and catechol by accepting one or two electrons, respectively. The quinone redox cycling ability leads to the generation of "reactive oxygen species" (ROS) as well as arylation reactions, which are of biological relevance. This ability can be modulated with the help of suitable derivatization. A pharmacophore can be appended at suitable position of Vitamin K3 to have a synergistic or additive effect. In the present review, an attempt has been made to accrue such derivatives modified at 1 or 2 position and evaluated for their cytotoxicity activity on different series of human cancer cell lines such as HeLa, HL-60 and MCF- 7 etc. Production of reactive oxygen species (ROS) and mitochondrial dysfunction caused by Vitamin K3 derivatives leads to apoptosis and tumor inhibition. Recently, the CR-108 compound has shown to exhibit oxidative path together with non-oxidative phosphorylation of p38 MAP kinase in human breast cancer cells. Thus the chemical-biological interactions have been discussed which can be further extrapolated for the development of a potent anticancer drug. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The role of H-bond in the high-pressure chemistry of model molecules

NASA Astrophysics Data System (ADS)

Fanetti, Samuele; Citroni, Margherita; Dziubek, Kamil; Medre Nobrega, Marcelo; Bini, Roberto

2018-03-01

Pressure is an extraordinary tool to modify direction and strength of intermolecular interactions with important consequences on the chemical stability of molecular materials. The decrease of the distance among nearest neighbour molecules can give rise to reactive configurations reflecting the crystal arrangement and leading to association processes. In this context, the role of the H-bonds is very peculiar because their usual strengthening with rising pressure does not necessarily configure a decrease of the reaction activation energy but, on the contrary, can give rise to an anomalous stability of the system. In spite of this central role, the mechanisms by which a chemical reaction is favoured or prevented by H-bonding under high pressure conditions is a poorly explored field. Here we review a few studies where the chemical behaviour of simple molecular systems under static compression was related to the H-bonding evolution with pressure. These results are able to clarify a wealth of changes of the chemical and physical properties caused by the strengthening with pressure of the H-bonding network and provide additional tools to understand the mechanisms of high-pressure reactivity, a mandatory step to make these synthetic methods of potential interest for applicative purposes.

Core-shell AgSiO2-protoporphyrin IX nanoparticle: Effect of the Ag core on reactive oxygen species generation

NASA Astrophysics Data System (ADS)

Lismont, M.; Pá; ez-Martinez, C.; Dreesen, L.

2015-03-01

Photodynamic therapy (PDT) for cancer is based on the use of a light sensitive molecule to produce, under specific irradiation, toxic reactive oxygen species (ROS). A way to improve the therapy efficiency is to increase the amount of produced ROS near cancer cells. This aim can be achieved by using a metal enhanced process arising when an optically active molecule is located near a metallic nanoparticle (NP). Here, the coupling effect between silver (Ag) NPs and protoporphyrin IX (PpIX) molecules, a clinically approved photosensitizer, is studied compared first, to PpIX fluorescence yield and second, to ROS production efficiency. By applying a modified Stöber process, PpIX was encapsulated into a silica (SiO2) shell, surrounding a 60 nm sized Ag core. We showed that, compared to SiO2-PpIX NPs, Ag coated SiO2-PpIX NPs dramatically decreased PpIX fluorescence together with singlet oxygen production efficiency. However, after incubation time in the dark, the amount of superoxide anions generated by the Ag doped sample was higher than the control sample one.

Carbon reactivation kinetics in the base of heterojunction GaInP-GaAs bipolar transistors

NASA Astrophysics Data System (ADS)

Mimila-Arroyo, J.; Bland, S. W.; Chevallier, J.

2002-05-01

The reactivation kinetics of carbon acceptors in the base region of GaInP/GaAs heterojunction bipolar transistors was studied. The reactivation was achieved by ex situ thermal annealing, through a multistage annealing experiment where the carrier concentration was monitored at each stage. Results indicate that carbon reactivation follows a first-order kinetics process in which the activation energy appears to be the sum of the energy needed to debond the hydrogen from the carbon-hydrogen complex, and the energy necessary to overcome the electrostatic junction barrier. The reactivation constant is thermally activated with an activation energy of 2.83 eV and an attempt frequency of 1.2×1013 s-1.

Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

PubMed Central

Gorres, Kelly L.; Daigle, Derek; Mohanram, Sudharshan

2014-01-01

ABSTRACT The lytic cycles of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are induced in cell culture by sodium butyrate (NaB), a short-chain fatty acid (SCFA) histone deacetylase (HDAC) inhibitor. Valproic acid (VPA), another SCFA and an HDAC inhibitor, induces the lytic cycle of KSHV but blocks EBV lytic reactivation. To explore the hypothesis that structural differences between NaB and VPA account for their functional effects on the two related viruses, we investigated the capacity of 16 structurally related short- and medium-chain fatty acids to promote or prevent lytic cycle reactivation. SCFAs differentially affected EBV and KSHV reactivation. KSHV was reactivated by all SCFAs that are HDAC inhibitors, including phenylbutyrate. However, several fatty acid HDAC inhibitors, such as isobutyrate and phenylbutyrate, did not reactivate EBV. Reactivation of KSHV lytic transcripts could not be blocked completely by any fatty acid tested. In contrast, several medium-chain fatty acids inhibited lytic activation of EBV. Fatty acids that blocked EBV reactivation were more lipophilic than those that activated EBV. VPA blocked activation of the BZLF1 promoter by NaB but did not block the transcriptional function of ZEBRA. VPA also blocked activation of the DNA damage response that accompanies EBV lytic cycle activation. Properties of SCFAs in addition to their effects on chromatin are likely to explain activation or repression of EBV. We concluded that fatty acids stimulate the two related human gammaherpesviruses to enter the lytic cycle through different pathways. IMPORTANCE Lytic reactivation of EBV and KSHV is needed for persistence of these viruses and plays a role in carcinogenesis. Our direct comparison highlights the mechanistic differences in lytic reactivation between related human oncogenic gammaherpesviruses. Our findings have therapeutic implications, as fatty acids are found in the diet and produced by the human microbiota. Small-molecule inducers of the lytic cycle are desired for oncolytic therapy. Inhibition of viral reactivation, alternatively, may prove useful in cancer treatment. Overall, our findings contribute to the understanding of pathways that control the latent-to-lytic switch and identify naturally occurring molecules that may regulate this process. PMID:24807711

98 Specific IGE and IGG Binding to Allergoids of Phleum pratense

PubMed Central

Cases, Barbara; Fernandez-Caldas, Enrique; Tudela, Jose Ignacio; Fernandez, Eva Abel; Sanchez-Garcia, Silvia; Ibañez, M. Dolores; Escudero, Carmelo; Casanovas, Miguel

2012-01-01

Background Allergoids were first used in the decades of the 60s and 70s of the last century as an effective treatment of allergic respiratory diseases. Allergoids can be modified with formaldehyde or glutaraldehyde. Modified allergens, or allergoids, decrease the risk of adverse reactions while administering higher allergen doses. The objective of this study was to analyse specific IgE and IgG binding to glutaraldehyde modified and non-modified allergen extracts of Phleum pratense. Methods The sera of 69 patients sensitized to P. pratense were tested. All these patients had signs and symptoms of rhinoconjunctivitis with, or without, asthma in May and June of 2011. All these patients had positive skin prick tests to a standardized extract of P. pratense, and other grass species. Most patients were also sensitized to olive pollen. Specific IgE and IgG binding were analysed by direct ELISA against P. pratense native (non-modified) and allergoid extracts. Relative potencies were evaluated through ELISA inhibition assays, and the protein composition of non-modified and allergoid samples was determined by Mass Spectrometry (MS/MS). Results Mean Specific IgE levels against the native extract was 16.68 ± 11.65 Units (U) and against the allergoid: 7.26 ± 8.24 U (P < 0.0001; Mann-Whitney). On the other hand, mean specific IgG binding against the non-modified extract was 90.34 ± 75.57 U versus 76.19 ± 70.31 U against the allergoid (P = 0.16; Mann-Whitney). Linear regression coefficients obtained between immunoglobulin reactivity against both extracts were: r2 = 0.51 for specific IgE and r2 = 0.83 for specific IgG. An important decrease in the allergenic activity, measured by inhibition ELISA, was clearly observed. The MS/MS assay revealed the presence of the mayor allergen, and some isoforms, in non-modified and allergoid extracts. Conclusions Results obtained demonstrate that the glutaraldehyde polymerization process induces an important decrease in specific IgE binding to allergoids of P. pratense while there are no significant differences in specific IgG binding. The allergenic composition of the P. pratense allergoid was equivalent to the non-modified pollen extract.

Preferential recognition of auto-antibodies against 4-hydroxynonenal modified DNA in the cancer patients.

PubMed

Faisal, Mohammad; Shahab, Uzma; Alatar, Abdulrahman A; Ahmad, Saheem

2017-11-01

The structural perturbations in DNA molecule may be caused by a break in a strand, a missing base from the backbone, or a chemically changed base. These alterations in DNA that occurs naturally can result from metabolic or hydrolytic processes. DNA damage plays a major role in the mutagenesis, carcinogenesis, aging and various other patho-physiological conditions. DNA damage can be induced through hydrolysis, exposure to reactive oxygen species (ROS) and other reactive carbonyl metabolites including 4-hydroxynonenal (HNE). 4-HNE is an important lipid peroxidation product which has been implicated in the mutagenesis and carcinogenesis processes. The present study examines to probe the presence of auto-antibodies against 4-hydroxynonenal damaged DNA (HNE-DNA) in various cancer subjects. In this study, the purified calf thymus DNA was damaged by the action of 4-HNE. The DNA was incubated with 4-HNE for 24 h at 37°C temperature. The binding characteristics of cancer auto-antibodies were assessed by direct binding and competitive inhibition ELISA. DNA modifications produced hyperchromicity in UV spectrum and decreased fluorescence intensity. Cancer sera exhibited enhanced binding with the 4-HNE modified calf thymus DNA as compared to its native conformer. The 4-HNE modified DNA presents unique epitopes which may be one of the factors for the auto-antibody induction in cancer patients. The HNE modified DNA presents unique epitopes which may be one of the factors for the autoantibody induction in cancer patients. © 2017 Wiley Periodicals, Inc.

Understanding the Reactivity of Lunar Dust for Future Lunar Missions

NASA Technical Reports Server (NTRS)

Wallace, W. T.; Jeevarajan, A. S.; Taylor, L. A.

2010-01-01

Fluorescence and EPR can be used to measure the reactivity of lunar soil. Lunar soil is highly activated by grinding. Reactivity is dependent upon soil maturity and locale. Maturity is based on the amount of nanophase iron (np-Fe) in a soil relative to the total iron (FeO). Lunar soil activity ia a direct function of the amount of np-Fe present. Reactive soil can be "deactivated" by humid atmosphere.

Children's patterns of emotional reactivity to conflict as explanatory mechanisms in links between interpartner aggression and child physiological functioning.

PubMed

Davies, Patrick T; Sturge-Apple, Melissa L; Cicchetti, Dante; Manning, Liviah G; Zale, Emily

2009-11-01

This paper examined children's fearful, sad, and angry reactivity to interparental conflict as mediators of associations between their exposure to interparental aggression and physiological functioning. Participants included 200 toddlers and their mothers. Assessments of interparental aggression and children's emotional reactivity were derived from maternal surveys and a semi-structured interview. Cortisol levels and cardiac indices of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity were used to assess toddler physiological functioning. Results indicated that toddler exposure to interparental aggression was associated with greater cortisol levels and PNS activity and diminished SNS activity. Toddler angry emotional reactivity mediated associations between interparental aggression and cortisol and PNS functioning. Fearful emotional reactivity was a mediator of the link between interparental aggression and SNS functioning. The results are interpreted within conceptualizations of how exposure and reactivity to family risk organize individual differences in physiological functioning.

Bioactivation of the Cancer Chemopreventive Agent Tamoxifen to Quinone Methides by Cytochrome P4502B6 and Identification of the Modified Residue on the Apoprotein

PubMed Central

Sridar, Chitra; D'Agostino, Jaime

2012-01-01

The nonsteroidal antiestrogen tamoxifen was introduced as a treatment for breast cancer 3 decades ago. It has also been approved as a chemopreventive agent and is prescribed to women at high risk for this disease. However, several studies have shown that use of tamoxifen leads to increased risk of endometrial cancer in humans. One potential pathway of tamoxifen toxicity could involve metabolism via hydroxylation to give 4-hydroxytamoxifen (4OHtam), which may be further oxidized to form a quinone methide. CYP2B6 is a highly polymorphic drug-metabolizing enzyme, and it metabolizes a number of clinically important drugs. Earlier studies from our laboratory have shown that tamoxifen is a mechanism-based inactivator of CYP2B6. The aim of the current study was to investigate the possible formation of reactive intermediates through detection of protein covalent binding and glutathione ethyl ester adduct (GSHEE) formation. The incubation of tamoxifen with 2B6 gave rise to an adduct of 4OHtam with glutathione, which was characterized as the 4OHtam quinone methide + GSHEE with an m/z value of 719, and the structure was characterized by liquid chromatography-tandem mass spectrometry. The metabolic activation of tamoxifen in the CYP2B6 reconstituted system also resulted in the formation of an adduct to the P4502B6 apoprotein, which was identified using liquid chromatography mass spectrometry. The site responsible for the inactivation of CYP2B6 was determined by proteolytic digestion and identification of the labeled peptide. This revealed a tryptic peptide 188FHYQDQE194 with the site of adduct formation localized to Gln193 as the site modified by the reactive metabolite formed during tamoxifen metabolism. PMID:22942317

CRISPR-mediated TCR replacement generates superior anticancer transgenic T cells.

PubMed

Legut, Mateusz; Dolton, Garry; Mian, Afsar Ali; Ottmann, Oliver G; Sewell, Andrew K

2018-01-18

Adoptive transfer of T cells genetically modified to express a cancer-specific T-cell receptor (TCR) has shown significant therapeutic potential for both hematological and solid tumors. However, a major issue of transducing T cells with a transgenic TCR is the preexisting expression of TCRs in the recipient cells. These endogenous TCRs compete with the transgenic TCR for surface expression and allow mixed dimer formation. Mixed dimers, formed by mispairing between the endogenous and transgenic TCRs, may harbor autoreactive specificities. To circumvent these problems, we designed a system where the endogenous TCR-β is knocked out from the recipient cells using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) technology, simultaneously with transduction with a cancer-reactive receptor of choice. This TCR replacement strategy resulted in markedly increased surface expression of transgenic αβ and γδ TCRs, which in turn translated to a stronger, and more polyfunctional, response of engineered T cells to their target cancer cell lines. Additionally, the TCR-plus-CRISPR-modified T cells were up to a thousandfold more sensitive to antigen than standard TCR-transduced T cells or conventional model proxy systems used for studying TCR activity. Finally, transduction with a pan-cancer-reactive γδ TCR used in conjunction with CRISPR/Cas9 knockout of the endogenous αβ TCR resulted in more efficient redirection of CD4 + and CD8 + T cells against a panel of established blood cancers and primary, patient-derived B-cell acute lymphoblastic leukemia blasts compared with standard TCR transfer. Our results suggest that TCR transfer combined with genome editing could lead to new, improved generations of cancer immunotherapies. © 2018 by The American Society of Hematology.

The Role of Endogenous Serotonin in Methamphetamine-Induced Neurotoxicity to Dopamine Nerve Endings of the Striatum

PubMed Central

Thomas, David M.; Angoa-Pérez, Mariana; Francescutti-Verbeem, Dina M.; Shah, Mrudang M.; Kuhn, Donald M.

2010-01-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the striatum where long-term DA depletion and microglial activation are maximal. Endogenous DA has been implicated as a critical participant in METH-induced neurotoxicity, most likely as a substrate for non-enzymatic oxidation by METH-generated reactive oxygen species (ROS). The striatum is also extensively innervated by serotonin (5HT) nerve endings and this neurochemical system is modified by METH in much the same manner as seen in DA nerve endings (i.e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores). 5HT can also be modified by ROS to form highly reactive species that damage neurons but its role in METH neurotoxicity has not been assessed. Increases in 5HT levels with 5HTP do not change METH-induced neurotoxicity to the DA nerve endings as revealed by reductions in DA, tyrosine hydroxylase and dopamine transporter levels. Partial reductions in 5HT with p-chlorophenylalanine (PCPA) are without effect on METH toxicity, despite the fact that PCPA largely prevents METH-induced hyperthermia. Mice lacking the gene for brain tryptophan hydroxylase 2 are devoid of brain 5HT and respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia. Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA nerve endings of the striatum. PMID:20722968

An efficient laser vaporization source for chemically modified metal clusters characterized by thermodynamics and kinetics

NASA Astrophysics Data System (ADS)

Masubuchi, Tsugunosuke; Eckhard, Jan F.; Lange, Kathrin; Visser, Bradley; Tschurl, Martin; Heiz, Ulrich

2018-02-01

A laser vaporization cluster source that has a room for cluster aggregation and a reactor volume, each equipped with a pulsed valve, is presented for the efficient gas-phase production of chemically modified metal clusters. The performance of the cluster source is evaluated through the production of Ta and Ta oxide cluster cations, TaxOy+ (y ≥ 0). It is demonstrated that the cluster source produces TaxOy+ over a wide mass range, the metal-to-oxygen ratio of which can easily be controlled by changing the pulse duration that influences the amount of reactant O2 introduced into the cluster source. Reaction kinetic modeling shows that the generation of the oxides takes place under thermalized conditions at less than 300 K, whereas metal cluster cores are presumably created with excess heat. These characteristics are also advantageous to yield "reaction intermediates" of interest via reactions between clusters and reactive molecules in the cluster source, which may subsequently be mass selected for their reactivity measurements.

A novel strategy for global analysis of the dynamic thiol redox proteome.

PubMed

Martínez-Acedo, Pablo; Núñez, Estefanía; Gómez, Francisco J Sánchez; Moreno, Margoth; Ramos, Elena; Izquierdo-Álvarez, Alicia; Miró-Casas, Elisabet; Mesa, Raquel; Rodriguez, Patricia; Martínez-Ruiz, Antonio; Dorado, David Garcia; Lamas, Santiago; Vázquez, Jesús

2012-09-01

Nitroxidative stress in cells occurs mainly through the action of reactive nitrogen and oxygen species (RNOS) on protein thiol groups. Reactive nitrogen and oxygen species-mediated protein modifications are associated with pathophysiological states, but can also convey physiological signals. Identification of Cys residues that are modified by oxidative stimuli still poses technical challenges and these changes have never been statistically analyzed from a proteome-wide perspective. Here we show that GELSILOX, a method that combines a robust proteomics protocol with a new computational approach that analyzes variance at the peptide level, allows a simultaneous analysis of dynamic alterations in the redox state of Cys sites and of protein abundance. GELSILOX permits the characterization of the major endothelial redox targets of hydrogen peroxide in endothelial cells and reveals that hypoxia induces a significant increase in the status of oxidized thiols. GELSILOX also detected thiols that are redox-modified by ischemia-reperfusion in heart mitochondria and demonstrated that these alterations are abolished in ischemia-preconditioned animals.

Iodine-catalyzed diazo activation to access radical reactivity.

PubMed

Li, Pan; Zhao, Jingjing; Shi, Lijun; Wang, Jin; Shi, Xiaodong; Li, Fuwei

2018-05-17

Transition-metal-catalyzed diazo activation is a classical way to generate metal carbene, which are valuable intermediates in synthetic organic chemistry. An alternative iodine-catalyzed diazo activation is disclosed herein under either photo-initiated or thermal-initiated conditions, which represents an approach to enable carbene radical reactivity. This metal-free diazo activation strategy were successfully applied into olefin cyclopropanation and epoxidation, and applying this method to pyrrole synthesis under thermal-initiated conditions further demonstrates the unique reactivity using this method over typical metal-catalyzed conditions.

Higher modulus compositions incorporating particulate rubber

DOEpatents

Bauman, Bernard D.; Williams, Mark A.

1999-01-01

A plastic article having a number of surfaces with at least one surface being modified by contacting that surface with a reactive gas atmosphere containing F.sub.2, Cl.sub.2, O.sub.2, Ozone, SO.sub.3, oxidative acids, or mixtures thereof, at a temperature and gas partial pressure sufficient to increase the surface energy of the at least one surface being modified to at least 40 dynes/cm at a temperature of 20.degree. C., to enhance bonding of non-slip polymer coatings to the modified surface, to which coatings elastomeric or rigid particles may be admixed for imparting a surface profile and increasing the coefficient of friction between the coated surface and the counter-surface.

Re-active Passive (RAP) Devices for Control of Noise Transmission through a Panel

NASA Technical Reports Server (NTRS)

Carneal, James P.; Giovanardi, Marco; Fuller, Chris R.; Palumbo, Daniel L.

2008-01-01

Re-Active Passive (RAP) devices have been developed to control low frequency (<1000 Hz) noise transmission through a panel. These devices use a combination of active, re-active, and passive technologies packaged into a single unit to control a broad frequency range utilizing the strength of each technology over its best suited frequency range. The RAP device uses passive constrained layer damping to cover the relatively high frequency range (>200 Hz), reactive distributed vibration absorber) to cover the medium frequency range (75 to 250 Hz), and active control for controlling low frequencies (<200 Hz). The device was applied to control noise transmission through a panel mounted in a transmission loss test facility. Experimental results are presented for the bare panel, and combinations of passive treatment, reactive treatment, and active control. Results indicate that three RAP devices were able to increase the overall broadband (15-1000 Hz) transmission loss by 9.4 dB. These three devices added a total of 285 grams to the panel mass of 6.0 kg, or approximately 5%, not including control electronics.

Tuning the Band Bending and Controlling the Surface Reactivity at Polar and Nonpolar Surfaces of ZnO through Phosphonic Acid Binding.

PubMed

McNeill, Alexandra R; Hyndman, Adam R; Reeves, Roger J; Downard, Alison J; Allen, Martin W

2016-11-16

ZnO is a prime candidate for future use in transparent electronics; however, development of practical materials requires attention to factors including control of its unusual surface band bending and surface reactivity. In this work, we have modified the O-polar (0001̅), Zn-polar (0001), and m-plane (101̅0) surfaces of ZnO with phosphonic acid (PA) derivatives and measured the effect on the surface band bending and surface sensitivity to atmospheric oxygen. Core level and valence band synchrotron X-ray photoemission spectroscopy was used to measure the surface band bending introduced by PA modifiers with substituents of opposite polarity dipole moment: octadecylphosphonic acid (ODPA) and 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctylphosphonic acid (F 13 OPA). Both PAs act as surface electron donors, increasing the downward band bending and the strength of the two-dimensional surface electron accumulation layer on all of the ZnO surfaces investigated. On the O-polar (0001̅) and m-plane (101̅0) surfaces, the ODPA modifier produced the largest increase in downward band bending relative to the hydroxyl-terminated unmodified surface of 0.55 and 0.35 eV, respectively. On the Zn-polar (0001) face, the F 13 OPA modifier gave the largest increase (by 0.50 eV) producing a total downward band bending of 1.00 eV, representing ∼30% of the ZnO band gap. Ultraviolet (UV) photoinduced surface wettability and photoconductivity measurements demonstrated that the PA modifiers are effective at decreasing the sensitivity of the surface toward atmospheric oxygen. Modification with PA derivatives produced a large increase in the persistence of UV-induced photoconductivity and a large reduction in UV-induced changes in surface wettability.

Depressive symptoms and attenuated physiological reactivity to laboratory stressors.

PubMed

Schwerdtfeger, Andreas; Rosenkaimer, Ann-Kathrin

2011-07-01

There is evidence that depressive symptoms are associated with attenuated physiological reactivity to active stressors. However, it is not known whether blunted reactivity in depressed individuals is stressor-specific. We examined cardiovascular and electrodermal reactivity in non-clinical participants with varying levels of depressive symptoms to different active and passive stressors. Depressive symptoms were inversely related to both blood pressure and skin conductance reactivity during a public speaking task and the viewing of the speech video. However, no effects were found during a cold pressor task. Together these findings suggest that depressive symptoms are related to attenuated sympathetic nervous system reactivity in response to self-relevant stressors. Copyright © 2011 Elsevier B.V. All rights reserved.

Extending the maximum operation time of the MNSR reactor.

PubMed

Dawahra, S; Khattab, K; Saba, G

2016-09-01

An effective modification to extend the maximum operation time of the Miniature Neutron Source Reactor (MNSR) to enhance the utilization of the reactor has been tested using the MCNP4C code. This modification consisted of inserting manually in each of the reactor inner irradiation tube a chain of three polyethylene-connected containers filled of water. The total height of the chain was 11.5cm. The replacement of the actual cadmium absorber with B(10) absorber was needed as well. The rest of the core structure materials and dimensions remained unchanged. A 3-D neutronic model with the new modifications was developed to compare the neutronic parameters of the old and modified cores. The results of the old and modified core excess reactivities (ρex) were: 3.954, 6.241 mk respectively. The maximum reactor operation times were: 428, 1025min and the safety reactivity factors were: 1.654 and 1.595 respectively. Therefore, a 139% increase in the maximum reactor operation time was noticed for the modified core. This increase enhanced the utilization of the MNSR reactor to conduct a long time irradiation of the unknown samples using the NAA technique and increase the amount of radioisotope production in the reactor. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vitro Reactivity to Implant Metals Demonstrates a Person Dependent Association with both T-Cell and B-Cell Activation

PubMed Central

Hallab, Nadim James; Caicedo, Marco; Epstein, Rachael; McAllister, Kyron; Jacobs, Joshua J

2009-01-01

Hypersensitivity to metallic implants remains relatively unpredictable and poorly understood. We initially hypothesized that metal-induced lymphocyte proliferation responses to soluble metal challenge (ions) are mediated exclusively by early T-cell activation (not B-cells), typical of a Delayed-Type-Hypersensitivity response. We tested this by comparing proliferation (6-days) of primary lymphocytes with early T-cell and B-cell activation (48-hours) in three groups of subjects likely to demonstrate elevated metal-reactivity: Group 1(n=12) history of metal-sensitivity with no implant; Group 2a(n=6) well performing metal-on-metal THRs, and Group 2b(n=20) subjects with poorly performing metal-on-polymer total joint arthroplasties (TJA). Group 1 showed 100%(12/12) metal reactivity (Stimulation Index>2) to Ni. Group 2a&2b were 83%(5/6) and 75%(15/22) metal reactive (to Co, Cr or Ni) respectively. Of the n=32 metal reactive subjects to Co, Cr or Ni (SI>2), n=22/32 demonstrated >2-fold elevations in % of T-cell or B-cell activation (CD25+,CD69+) to metal challenge compared to untreated control. 18/22 metal-activated subjects demonstrated an exclusively T-cell or B-cell activation response to metal challenge, where 6/18 demonstrated exclusively B-cell activation and 12/18 demonstrated a T-cell only response, as measured by surface activation markers CD25+ and CD69+. However, there was no direct correlation (R2<0.1) between lymphocyte proliferation and % T-cell or B-cell activation (CD25+:CD69+). Proliferation assays (LTT) showed greater ability to detect metal reactivity than did subject-dependent results of flow-cytometry analysis of T-cell or B-cell activation. The high incidence of lymphocyte reactivity and activation, indicate that more complex than initially hypothesized immune responses may contribute to the etiology of debris induced osteolysis in metal-sensitive individuals. PMID:19235773

Shaping memory consolidation via targeted memory reactivation during sleep.

PubMed

Cellini, Nicola; Capuozzo, Alessandra

2018-05-15

Recent studies have shown that the reactivation of specific memories during sleep can be modulated using external stimulation. Specifically, it has been reported that matching a sensory stimulus (e.g., odor or sound cue) with target information (e.g., pairs of words, pictures, and motor sequences) during wakefulness, and then presenting the cue alone during sleep, facilitates memory of the target information. Thus, presenting learned cues while asleep may reactivate related declarative, procedural, and emotional material, and facilitate the neurophysiological processes underpinning memory consolidation in humans. This paradigm, which has been named targeted memory reactivation, has been successfully used to improve visuospatial and verbal memories, strengthen motor skills, modify implicit social biases, and enhance fear extinction. However, these studies also show that results depend on the type of memory investigated, the task employed, the sensory cue used, and the specific sleep stage of stimulation. Here, we present a review of how memory consolidation may be shaped using noninvasive sensory stimulation during sleep. © 2018 New York Academy of Sciences.

Comparative efficacy of intranasal and injectable vaccines in stimulating Bordetella bronchiseptica-reactive anamnestic antibody responses in household dogs

PubMed Central

Ellis, John A.; Gow, Sheryl P.; Lee, Lindsey B.; Lacoste, Stacey; Ball, Eileen C.

2017-01-01

In order to determine the comparative efficacy of injectable and intranasal vaccines to stimulate Bordetella bronchiseptica (Bb)-reactive anamnestic antibodies, a trial was conducted using 144 adult household dogs of various breeds and ages, which had been previously administered intranasal Bb vaccine approximately 12 months before enrollment. Dogs were randomized into 2 groups and blood, nasal swabs, and pharyngeal swabs were collected prior to the administration of single component Bb vaccines intranasally or parenterally. Ten to 14 days later all dogs were resampled to measure changes in systemic and local antibody to Bb. There were no differences in the changes in Bb-reactive serum IgG and nasal IgA between the groups, whereas intranasally vaccinated dogs had significantly higher Bb-reactive serum IgA. These data indicate that both of the current generation of intranasal (modified-live) and injectable (acellular) Bb vaccines can stimulate anamnestic local and systemic antibody responses in previously vaccinated, Bb-seropositive adult household dogs. PMID:28761185

Regulatory mechanisms of thiol-based redox sensors: lessons learned from structural studies on prokaryotic redox sensors.

PubMed

Lee, Sang Jae; Kim, Dong-Gyun; Lee, Kyu-Yeon; Koo, Ji Sung; Lee, Bong-Jin

2018-05-17

Oxidative stresses, such as reactive oxygen species, reactive electrophilic species, reactive nitrogen species, and reactive chlorine species, can damage cellular components, leading to cellular malfunction and death. In response to oxidative stress, bacteria have evolved redox-responsive sensors that enable them to simultaneously monitor and eradicate potential oxidative stress. Specifically, redox-sensing transcription regulators react to oxidative stress by means of modifying the thiol groups of cysteine residues, functioning as part of an efficient survival mechanism for many bacteria. In general, oxidative molecules can induce changes in the three-dimensional structures of redox sensors, which, in turn, affects the transcription of specific genes in detoxification pathways and defense mechanisms. Moreover, pathogenic bacteria utilize these redox sensors for adaptation and to evade subsequent oxidative attacks from host immune defense. For this reason, the redox sensors of pathogenic bacteria are potential antibiotic targets. Understanding the regulatory mechanisms of thiol-based redox sensors in bacteria will provide insight and knowledge into the discovery of new antibiotics.

Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions

PubMed Central

Jackson, Paul A.; Widen, John C.; Harki, Daniel A.; Brummond, Kay M.

2017-01-01

Although Michael acceptors display a potent and broad spectrum of bioactivity, they have largely been ignored in drug discovery because of their presumed indiscriminate reactivity. As such, a dearth of information exists relevant to the thiol reactivity of natural products and their analogs possessing this moiety. In the midst of recently approved acrylamide-containing drugs, it is clear that a good understanding of the hetero-Michael addition reaction and the relative reactivities of biological thiols with Michael acceptors under physiological conditions is needed for the design and use of these compounds as biological tools and potential therapeutics. This perspective provides information that will contribute to this understanding, such as kinetics of thiol addition reactions, bioactivities, as well as steric and electronic factors that influence the electrophilicity and reversibility of Michael acceptors. This perspective is focused on α,β-unsaturated carbonyls given their preponderance in bioactive natural products. PMID:27996267

Catalytic Role Of Palladium And Relative Reactivity Of Substituted Chlorines During Adsorption And Treatment Of PCBs On Reactive Activated Carbon

EPA Science Inventory

The adsorption-mediated dechlorination of polychlorinated biphenyls (PCBs) is a unique feature of reactive activated cabon (RAC). Here, we address the RAC system, containing a tunable amount of Fe as a primary electron donor coupled with Pd as an electrochemical catalyst to pote...

Transforming the Organic Chemistry Lab Experience: Design, Implementation, and Evaluation of Reformed Experimental Activities--REActivities

ERIC Educational Resources Information Center

Collison, Christina G.; Kim, Thomas; Cody, Jeremy; Anderson, Jason; Edelbach, Brian; Marmor, William; Kipsang, Rodgers; Ayotte, Charles; Saviola, Daniel; Niziol, Justin

2018-01-01

Reformed experimental activities (REActivities) are an innovative approach to the delivery of the traditional material in an undergraduate organic chemistry laboratory. A description of the design and implementation of REActivities at both a four- and two-year institution is discussed. The results obtained using a reformed teaching observational…

Nonquaternary Cholinesterase Reactivators.

DTIC Science & Technology

1982-08-30

c, a plot (not shown) of pKa versus Hammet substituent constant (a )42 is also linear and conforms p to equation (5) pKa - (7.63 ±0.02) - (.63 ±0.05...dissociates to the active oximate form, we have defined an effective bimolecular reactivation rate constant as in equation (6) keff ’ kb [1 + antilog(pKa...type 1 compounds generally exhibit low activity as reactivators. In terms of keff values [see equation (6)] for reactivation of ethyl methylphosphonyl

Regulation of protein activity with small-molecule-controlled inteins

PubMed Central

Skretas, Georgios; Wood, David W.

2005-01-01

Inteins are the protein analogs of self-splicing RNA introns, as they post-translationally excise themselves from a variety of protein hosts. Intein insertion abolishes, in general, the activity of its host protein, which is subsequently restored upon intein excision. These protein elements therefore have the potential to be used as general molecular “switches” for the control of arbitrary target proteins. Based on rational design, an intein-based protein switch has been constructed whose splicing activity is conditionally triggered in vivo by the presence of thyroid hormone or synthetic analogs. This modified intein was used in Escherichia coli to demonstrate that a number of different proteins can be inactivated by intein insertion and then reactivated by the addition of thyroid hormone via ligand-induced splicing. This conditional activation was also found to occur in a dose-dependent manner. Rational protein engineering was then combined with genetic selection to evolve an additional intein whose activity is controlled by the presence of synthetic estrogen ligands. The ability to regulate protein function post-translationally through the use of ligand-controlled intein splicing will most likely find applications in metabolic engineering, drug discovery and delivery, biosensing, molecular computation, as well as many additional areas of biotechnology. PMID:15632292

Assembling strategy to synthesize palladium modified kaolin nanocomposites with different morphologies

PubMed Central

Li, Xiaoyu; Ouyang, Jing; Zhou, Yonghua; Yang, Huaming

2015-01-01

Nanocomposites of aluminosilicate minerals, kaolins (kaolinite and halloysite) with natural different morphologies assembling with palladium (Pd) nanoparticles have been successfully synthesized through strong electrostatic adsorption and chemical bonding after surface modification with 3-aminopropyl triethoxysilane (APTES). Meanwhile, the influence of different morphologies supports on catalytic hydrogenation properties was explored. The surface concentration of amino groups on the kaolins was related to the morphology and surface nature. Electronmicroscopy revealed that the monodisperse Pd nanoparticles were uniformly deposited onto the surface of kaolins, ranging in diameter from 0.5 nm to 5.5 nm. The functional groups could not only improve the dispersion of kaolins with different morphologies in solution, but also enhance the interaction between Pd precursors and kaolins, thus preventing small Pd nanoparticles from agglomerating and leading to high activity for the catalytic hydrogenation of styrene. Pd-FK@APTES was more active compared to other samples. Selecting the kaolin morphology with a different surface nature allows the selective surface modification of a larger fraction of the reactive facets on which the active sites can be enriched and tuned. This desirable surface coordination of catalytically active atoms could substantially improve catalytic activity. PMID:26333629

Assembling strategy to synthesize palladium modified kaolin nanocomposites with different morphologies

NASA Astrophysics Data System (ADS)

Li, Xiaoyu; Ouyang, Jing; Zhou, Yonghua; Yang, Huaming

2015-09-01

Nanocomposites of aluminosilicate minerals, kaolins (kaolinite and halloysite) with natural different morphologies assembling with palladium (Pd) nanoparticles have been successfully synthesized through strong electrostatic adsorption and chemical bonding after surface modification with 3-aminopropyl triethoxysilane (APTES). Meanwhile, the influence of different morphologies supports on catalytic hydrogenation properties was explored. The surface concentration of amino groups on the kaolins was related to the morphology and surface nature. Electronmicroscopy revealed that the monodisperse Pd nanoparticles were uniformly deposited onto the surface of kaolins, ranging in diameter from 0.5 nm to 5.5 nm. The functional groups could not only improve the dispersion of kaolins with different morphologies in solution, but also enhance the interaction between Pd precursors and kaolins, thus preventing small Pd nanoparticles from agglomerating and leading to high activity for the catalytic hydrogenation of styrene. Pd-FK@APTES was more active compared to other samples. Selecting the kaolin morphology with a different surface nature allows the selective surface modification of a larger fraction of the reactive facets on which the active sites can be enriched and tuned. This desirable surface coordination of catalytically active atoms could substantially improve catalytic activity.

Assembling strategy to synthesize palladium modified kaolin nanocomposites with different morphologies.

PubMed

Li, Xiaoyu; Ouyang, Jing; Zhou, Yonghua; Yang, Huaming

2015-09-03

Nanocomposites of aluminosilicate minerals, kaolins (kaolinite and halloysite) with natural different morphologies assembling with palladium (Pd) nanoparticles have been successfully synthesized through strong electrostatic adsorption and chemical bonding after surface modification with 3-aminopropyl triethoxysilane (APTES). Meanwhile, the influence of different morphologies supports on catalytic hydrogenation properties was explored. The surface concentration of amino groups on the kaolins was related to the morphology and surface nature. Electronmicroscopy revealed that the monodisperse Pd nanoparticles were uniformly deposited onto the surface of kaolins, ranging in diameter from 0.5 nm to 5.5 nm. The functional groups could not only improve the dispersion of kaolins with different morphologies in solution, but also enhance the interaction between Pd precursors and kaolins, thus preventing small Pd nanoparticles from agglomerating and leading to high activity for the catalytic hydrogenation of styrene. Pd-FK@APTES was more active compared to other samples. Selecting the kaolin morphology with a different surface nature allows the selective surface modification of a larger fraction of the reactive facets on which the active sites can be enriched and tuned. This desirable surface coordination of catalytically active atoms could substantially improve catalytic activity.

Comparison of Hydrazone Heterobifunctional Crosslinking Agents for Reversible Conjugation of Thiol-Containing Chemistry

PubMed Central

Christie, R. James; Anderson, Diana J.; Grainger, David W.

2010-01-01

Reversible covalent conjugation chemistries that allow site- and condition-specific coupling and uncoupling reactions are attractive components in nanotechnologies, bioconjugation methods, imaging and drug delivery systems. Here, we compare three heterobifunctional crosslinkers, containing both thiol- and amine- reactive chemistry, to form pH-labile hydrazones with hydrazide derivatives of the known and often published water-soluble polymer, poly[N-(2-hydroxypropyl methacrylamide)] (pHPMA), while subsequently coupling thiol-containing molecules to the crosslinker via maleimide addition. Two novel crosslinkers were prepared from the popular heterobifunctional crosslinking agent, succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC), modified to contain either terminal aldehyde groups (i.e., 1-(N-3-propanal)-4-(N-maleimidomethyl) cyclohexane carboxamide, PMCA) or methylketone groups (i.e., 1-(N-3-butanone)-4-(N-maleimidomethyl) cyclohexane carboxamide, BMCA). A third crosslinking agent was the commercially available N-4-acetylphenyl maleimide (APM). PMCA and BMCA exhibited excellent reactivity towards hydrazide-derivatized pHPMA with essentially complete hydrazone conjugation to polymer reactive sites, while APM coupled only ~ 60% of available reactive sites on the polymer despite a 3-fold molar excess relative to polymer hydrazide groups. All polymer hydrazone conjugates bearing these bifunctional agents were then further reacted with thiol-modified tetramethylrhodamine dye, confirming crosslinker maleimide reactivity after initial hydrazone polymer conjugation. Incubation of dye-labeled polymer conjugates in phosphate buffered saline at 37°C showed that hydrazone coupling resulting from APM exhibited the greatest difference in stability between pH 7.4 and 5.0, with hydrolysis and dye release increased at pH 5.0 over a 24hr incubation period. Polymer conjugates bearing hydrazones formed from crosslinker BMCA exhibited intermediate stability with hydrolysis much greater at pH 5.0 at early time points, but hydrolysis at pH 7.4 was significant after 5 hrs. Hydrazones formed with the PMCA crosslinker showed no difference in release rates at pH 7.4 and 5.0. PMID:20695431

The Dynamics of Memory: Context-Dependent Updating

ERIC Educational Resources Information Center

Hupbach, Almut; Hardt, Oliver; Gomez, Rebecca; Nadel, Lynn

2008-01-01

Understanding the dynamics of memory change is one of the current challenges facing cognitive neuroscience. Recent animal work on memory reconsolidation shows that memories can be altered long after acquisition. When reactivated, memories can be modified and require a restabilization (reconsolidation) process. We recently extended this finding to…

Production of hydroxyl fatty acids, polyol oils, and diacylglycerol by bioprocess

USDA-ARS?s Scientific Manuscript database

Hydroxy fatty acids (HFA), originally found in plant systems, are good examples of the structurally modified lipids, rendering special properties such as higher viscosity and reactivity compared to normal fatty acids. Based on these properties, HFAs possess high industrial potentials in a wide range...

Coordinated Excitation and Inhibition of Prefrontal Ensembles During Awake Hippocampal Sharp-Wave Ripple Events

PubMed Central

Jadhav, Shantanu P.; Rothschild, Gideon; Roumis, Demetris K.; Frank, Loren M.

2016-01-01

SUMMARY Interactions between the hippocampus and prefrontal cortex (PFC) are critical for learning and memory. Hippocampal activity during awake sharp wave ripple (SWR) events is important for spatial learning, and hippocampal SWR activity often represents past or potential future experiences. Whether or how this reactivation engages the PFC, and how reactivation might interact with ongoing patterns of PFC activity remains unclear. We recorded hippocampal CA1 and PFC activity in animals learning spatial tasks and found that many PFC cells showed spiking modulation during SWRs. Unlike in CA1, SWR-related activity in PFC comprised both excitation and inhibition of distinct populations. Within individual SWRs, excitation activated PFC cells with representations related to the concurrently reactivated hippocampal representation, while inhibition suppressed PFC cells with unrelated representations. Thus, awake SWRs mark times of strong coordination between hippocampus and PFC that reflects structured reactivation of representations related to ongoing experience. PMID:26971950

A Diversity-Oriented Library of Fluorophore-Modified Receptors Constructed from a Chemical Library of Synthetic Fluorophores.

PubMed

Nakano, Shun; Tamura, Tomoki; Das, Raj Kumar; Nakata, Eiji; Chang, Young-Tae; Morii, Takashi

2017-11-16

The practical application of biosensors can be determined by evaluating the sensing ability of fluorophore-modified derivatives of a receptor with appropriate recognition characteristics for target molecules. One of the key determinants for successfully obtaining a useful biosensor is wide variation in the fluorophores attached to a given receptor. Thus, using a larger fluorophore-modified receptor library provides a higher probability of obtaining a practically useful biosensor. However, no effective method has yet been developed for constructing such a diverse library of fluorophore-modified receptors. Herein, we report a method for constructing fluorophore-modified receptors by using a chemical library of synthetic fluorophores with a thiol-reactive group. This library was converted into a library of fluorophore-modified adenosine-binding ribonucleopeptide (RNP) receptors by introducing the fluorophores to the Rev peptide of the RNP complex by alkylation of the thiol group. This method enabled the construction of 263 fluorophore-modified ATP-binding RNP receptors and allowed the selection of suitable receptor-based fluorescent sensors that target ATP. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Zeppelin NT - Measurement Platform for the Exploration of Atmospheric Chemistry and Dynamics in the Planetary Boundary Layer

NASA Astrophysics Data System (ADS)

Hofzumahaus, Andreas; Holland, Frank; Oebel, Andreas; Rohrer, Franz; Mentel, Thomas; Kiendler-Scharr, Astrid; Wahner, Andreas; Brauchle, Artur; Steinlein, Klaus; Gritzbach, Robert

2014-05-01

The planetary boundary layer (PBL) is the chemically most active and complex part of the atmosphere where freshly emitted reactive trace gases, tropospheric radicals, atmospheric oxidation products and aerosols exhibit a large variability and spatial gradients. In order to investigate the chemical degradation of trace gases and the formation of secondary pollutants in the PBL, a commercial Zeppelin NT was modified to be used as an airborne measurement platform for chemical and physical observations with high spatial resolution. The Zeppelin NT was developed by Zeppelin Luftschifftechnik (ZLT) and is operated by Deutsche Zeppelin Reederei (DZR) in Friedrichshafen, Germany. The modification was performed in cooperation between Forschungszentrum Jülich and ZLT. The airship has a length of 75 m, can lift about 1 ton of scientific payload and can be manoeuvered with high precision by propeller engines. The modified Zeppelin can carry measurement instruments mounted on a platform on top of the Zeppelin, or inside the gondola beneath the airship. Three different instrument packages were developed to investigate a. gas-phase oxidation processes involving free radicals (OH, HO2) b. formation of secondary organic aerosols (SOA) c. new particle formation (nucleation) The presentation will describe the modified airship and provide an overview of its technical performance. Examples of its application during the recent PEGASOS flight campaigns in Europe will be given.

Benzoin Radicals as Reducing Agent for Synthesizing Ultrathin Copper Nanowires.

PubMed

Cui, Fan; Dou, Letian; Yang, Qin; Yu, Yi; Niu, Zhiqiang; Sun, Yuchun; Liu, Hao; Dehestani, Ahmad; Schierle-Arndt, Kerstin; Yang, Peidong

2017-03-01

In this work, we report a new, general synthetic approach that uses heat driven benzoin radicals to grow ultrathin copper nanowires with tunable diameters. This is the first time carbon organic radicals have been used as a reducing agent in metal nanowire synthesis. In-situ temperature dependent electron paramagnetic resonance (EPR) spectroscopic studies show that the active reducing agent is the free radicals produced by benzoins under elevated temperature. Furthermore, the reducing power of benzoin can be readily tuned by symmetrically decorating functional groups on the two benzene rings. When the aromatic rings are modified with electron donating (withdrawing) groups, the reducing power is promoted (suppressed). The controllable reactivity gives the carbon organic radical great potential as a versatile reducing agent that can be generalized in other metallic nanowire syntheses.

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

PubMed Central

Picard, Martin; Shirihai, Orian S.; Gentil, Benoit J.

2013-01-01

In response to cellular and environmental stresses, mitochondria undergo morphology transitions regulated by dynamic processes of membrane fusion and fission. These events of mitochondrial dynamics are central regulators of cellular activity, but the mechanisms linking mitochondrial shape to cell function remain unclear. One possibility evaluated in this review is that mitochondrial morphological transitions (from elongated to fragmented, and vice-versa) directly modify canonical aspects of the organelle's function, including susceptibility to mitochondrial permeability transition, respiratory properties of the electron transport chain, and reactive oxygen species production. Because outputs derived from mitochondrial metabolism are linked to defined cellular signaling pathways, fusion/fission morphology transitions could regulate mitochondrial function and retrograde signaling. This is hypothesized to provide a dynamic interface between the cell, its genome, and the fluctuating metabolic environment. PMID:23364527

Effects of Atmospheric Pressure Air Plasma Pretreatment on the Seed Germination and Early Growth of Andrographis paniculata

NASA Astrophysics Data System (ADS)

Tong, Jiayun; He, Rui; Zhang, Xiaoli; Zhan, Ruoting; Chen, Weiwen; Yang, Size

2014-03-01

The objective of this paper is to demonstrate whether air plasma can change the seed germination characteristics, seedling emergence, as well as biochemical reactivity, in Andrographis paniculata (A. paniculata) seedlings by modifying the seed coat and finding a beneficial treatment dose. Eight treatment doses and one control were used to conduct electrical conductivity determination, a germination test, a seedling emergence test and a biochemical assay. The results showed that after being treated with air plasma excited at 5950 V for 10 s, the permeability of the seeds was improved significantly, resulting in the acceleration of seed germination and seedling emergence. In the meantime, the catalase activity and catalase isoenzyme expression were also improved, while the malondialdehyde content in the seedlings was decreased (which means greater counteraction with environmental stress). After being treated with 4250 V for 10 s and 5950 V for 20 s, the seed germination was enhanced, but without an obvious change in seedling emergence. However, after treatment with 3400 V for 20 s and 5100 V for 10 s, the permeability of the seeds was decreased, resulting in a delay in seedling emergence. These results indicate that air plasma can change the physiological and biochemical characteristics of Andrographis paniculata seeds by modifying the seed coat, combined with the effects of the active plasma species, and that different treating doses have different effects.

Modified Epoxy Adhesives and Primers

DTIC Science & Technology

1992-06-30

Shear Stress max Bulk Resin (MPa) Control 66.52±3.1 100 67.84 ±23 +20 VCDHAA 79.59 ±2.8 120 78.18 ±2.6 +15 CTBN 51.81 ±3.8 78 53.88 ±2.4 +15 CTBN ...unlimited. 0 3. ABSTRACT (MaX,UM, wor At range of monepoxy additives for epoxy resins , and non-reactive additives for3 polyimides, have been examined...a modified failure mechanism. These properties of the bulk resin translate into modest improvements in adhesive bond performance, particularly for low

Rocket injector anomalies study. Volume 1: Description of the mathematical model and solution procedure

NASA Technical Reports Server (NTRS)

Przekwas, A. J.; Singhal, A. K.; Tam, L. T.

1984-01-01

The capability of simulating three dimensional two phase reactive flows with combustion in the liquid fuelled rocket engines is demonstrated. This was accomplished by modifying an existing three dimensional computer program (REFLAN3D) with Eulerian Lagrangian approach to simulate two phase spray flow, evaporation and combustion. The modified code is referred as REFLAN3D-SPRAY. The mathematical formulation of the fluid flow, heat transfer, combustion and two phase flow interaction of the numerical solution procedure, boundary conditions and their treatment are described.

Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

PubMed Central

Herbert, Martha

2017-01-01

Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH) receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw) and modified (cooked and roasted) foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease. PMID:28894619

Development of a novel monoclonal antibody against 4-hydroxy-2E,6Z-dodecadienal (4-HDDE)-protein adducts: Immunochemical application in quantitative and qualitative analyses of lipid peroxidation in vitro and ex vivo.

PubMed

Uchida, Koji; Shibata, Takahiro; Toyokuni, Shinya; Daniel, Bareket; Zarkovic, Kamelija; Zarkovic, Neven; Sasson, Shlomo

2018-05-25

Non-enzymatic peroxidation of polyunsaturated fatty acids (PUFA) results in the formation of various α,β-unsaturated aldehydes, of which 4-hydroxyalkenals are abundant. The propensity of n-6 PUFA, such as linoleic acid, γ-linolenic acid and arachidonic acid, to undergo radical-induced peroxidation and generate 4-hydroxy-2E-nonenal (4-HNE) has been widely demonstrated. The ability of the latter to form covalent adducts with macromolecules and modify cellular functions has been linked to numerous pathological processes. Concomitantly, evidence has accumulated on specific signaling properties of low concentrations of 4-HNE that may induce hormetic and protective responses to peroxidation stress in cells. It has long been known that peroxidation of PUFA, and particularly arachidonic acid, also give rise to 4-hydroxy-2E,6Z-dodecadienal (4-HDDE), which is more chemically reactive than 4-HNE. Few studies on 4-HDDE revealed its ability to avidly interact covalently with electronegative moieties in macromolecules and to its ability to selectively activate the transcriptional regulator Peroxisome Proliferator-Activated Receptor (PPAR)-β/δ. The research on 4-HDDE has been impeded due to the lack of available pure 4-HDDE and antibodies that recognize 4-HDDE-modified epitopes in proteins. The purpose of this study was to employ an established procedure to synthesize 4-HDDE and use it to create and characterize a monoclonal antibody against 4-HDDE-modified proteins and establish its application for ELISA and immunohistochemical analysis of cells and tissues and further expand lipid peroxidation research. Copyright © 2018 Elsevier Inc. All rights reserved.

Redox Proteomics: A Key Tool for New Insights into Protein Modification with Relevance to Disease.

PubMed

Butterfield, D Allan; Perluigi, Marzia

2017-03-01

Oxidatively modified proteins are characterized by elevations in protein-resident carbonyls or 3-nitrotyrosine, measures of protein oxidation, or protein bound reactive alkenals such as 4-hydroxy-2-nonenal, a measure of lipid peroxidation. Oxidatively modified proteins nearly always have altered structure and function. Redox proteomics is that branch of proteomics used to identify oxidized proteins and determine the extent and location of oxidative modifications in the proteomes of interest. This technique nearly always employs mass spectrometry as the major platform to achieve the goals of identifying the target proteins. Once identified, oxidatively modified proteins can be placed in specific molecular pathways to provide insights into protein oxidation and human disease. Both original research and review articles are included in this Forum on Redox Proteomics. The topics related to redox proteomics range from basic chemistry of sulfur radical-induced redox modifications in proteins, to the thiol secretome and inflammatory network, to reversible thiol oxidation in proteomes, to the role of glutamine synthetase in peripheral and central environments on inflammation and insulin resistance, to bioanalytical aspects of tyrosine nitrated proteins, to protein oxidation in human smokers and models thereof, and to Alzheimer disease, including articles on the brain ubiquitinylome and the "triangle of death" composed of oxidatively modified proteins involved in energy metabolism, mammalian target of rampamycin activation, and the proteostasis network. This Forum on Redox Proteomics is both timely and a critically important resource to highlight one of the key tools needed to better understand protein structure and function in oxidative environments in health and disease. Antioxid. Redox Signal. 26, 277-279.

In vitro assessment of biopolymer-modified porous silicon microparticles for wound healing applications.

PubMed

Mori, Michela; Almeida, Patrick V; Cola, Michela; Anselmi, Giulia; Mäkilä, Ermei; Correia, Alexandra; Salonen, Jarno; Hirvonen, Jouni; Caramella, Carla; Santos, Hélder A

2014-11-01

The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan and a mixture of chondroitin sulfate/hyaluronic acid, and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behavior of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications. Copyright © 2014 Elsevier B.V. All rights reserved.

The Janus face of reactive oxygen species in resistance and susceptibility of plants to necrotrophic and biotrophic pathogens.

PubMed

Barna, B; Fodor, J; Harrach, B D; Pogány, M; Király, Z

2012-10-01

Plant pathogens can be divided into biotrophs and necrotrophs according to their different life styles; biotrophs prefer living, while necrotrophs prefer dead cells for nutritional purposes. Therefore tissue necrosis caused by reactive oxygen species (ROS) during pathogen infection increases host susceptibility to necrotrophic, but resistance to biotrophic pathogen. Consequently, elevation of antioxidant capacity of plants enhances their tolerance to development of necroses caused by necrotrophic pathogens. Plant hormones can strongly influence induction of ROS and antioxidants, thereby influencing susceptibility or resistance of plants to pathogens. Pathogen-induced ROS themselves are considered as signaling molecules. Generally, salicylic acid (SA) signaling induces defense against biotrophic pathogens, whereas jasmonic acid (JA) against necrotrophic pathogens. Furthermore pathogens can modify plant's defense signaling network for their own benefit by changing phytohormone homeostasis. On the other hand, ROS are harmful also to the pathogens, consequently they try to defend themselves by elevating antioxidant activity and secreting ROS scavengers in the infected tissue. The Janus face nature of ROS and plant cell death on biotrophic and on necrotrophic pathogens is also supported by the experiments with BAX inhibitor-1 and the mlo mutation of Mlo gene in barley. It was found that ROS and elevated plant antioxidant activity play an important role in systemic acquired resistance (SAR) and induced systemic resistance (ISR), as well as in mycorrhiza induced abiotic and biotic stress tolerance of plants. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Tumor suppression effects of bilberry extracts and enzymatically modified isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl butoxide promotion in a two-stage rat hepatocarcinogenesis model.

PubMed

Hara, Shintaro; Morita, Reiko; Ogawa, Takashi; Segawa, Risa; Takimoto, Norifumi; Suzuki, Kazuhiko; Hamadate, Naobumi; Hayashi, Shim-Mo; Odachi, Ayano; Ogiwara, Isao; Shibusawa, Sakae; Yoshida, Toshinori; Shibutani, Makoto

2014-08-01

To investigate the protective effect of bilberry extracts (BBE) and enzymatically modified isoquercitrin (EMIQ) on the hepatocarcinogenic process involving oxidative stress responses, we used a two-stage hepatocarcinogenesis model in N-diethylnitrosamine-initiated and piperonyl butoxide (PBO)-promoted rats. We examined the modifying effect of co-administration with BBE or EMIQ on the liver tissue environment including oxidative stress responses, cell proliferation and apoptosis, and phosphatase and tensin homolog (PTEN)/Akt and transforming growth factor (TGF)-β/Smad signalings on the induction mechanism of preneoplastic lesions during early stages of hepatocellular tumor promotion. PBO increased the numbers and area of glutathione S-transferase placental form (GST-P)(+) liver cell foci and the numbers of Ki-67(+) proliferating cells within GST-P(+) foci. Co-administration of BBE or EMIQ suppressed these effects with the reductions of GST-P(+) foci (area) to 48.9-49.4% and Ki-67(+) cells to 55.5-61.4% of the PBO-promoted cases. Neither BBE nor EMIQ decreased microsomal reactive oxygen species induced by PBO. However, only EMIQ suppressed the level of thiobarbituric acid-reactive substances to 78.4% of the PBO-promoted cases. PBO increased the incidences of phospho-PTEN(-) foci, phospho-Akt substrate(+) foci, phospho-Smad3(-) foci and Smad4(-) foci in GST-P(+) foci. Both BBE and EMIQ decreased the incidences of phospho-PTEN(-) foci in GST-P(+) foci to 59.8-72.2% and Smad4(-) foci to 62.4-71.5% of the PBO-promoted cases, and BBE also suppressed the incidence of phospho-Akt substrate(+) foci in GST-P(+) foci to 75.2-75.7% of the PBO-promoted cases. These results suggest that PBO-induced tumor promotion involves facilitation of PTEN/Akt and disruptive TGF-β/Smad signalings without relation to oxidative stress responses, but this promotion was suppressed by co-treatment with BBE or EMIQ through suppression of cell proliferation activity of preneoplastic liver cells. Copyright © 2014 Elsevier GmbH. All rights reserved.

ATOMIC-SCALE DESIGN OF IRON FISCHER-TROPSCH CATALYSTS: A COMBINED COMPUTATIONAL CHEMISTRY, EXPERIMENTAL, AND MICROKINETIC MODELING APPROACH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manos Mavrikakis; James A. Dumesic; Amit A. Gokhale

2005-03-22

Efforts during this first year focused on four areas: (1) searching/summarizing published FTS mechanistic and kinetic studies of FTS reactions on iron catalysts; (2) construction of mass spectrometer-TPD and Berty CSTR reactor systems; (3) preparation and characterization of unsupported iron and alumina-supported iron catalysts at various iron loadings (4) Determination of thermochemical parameters such as binding energies of reactive intermediates, heat of FTS elementary reaction steps, and kinetic parameters such as activation energies, and frequency factors of FTS elementary reaction steps on a number of model surfaces. Literature describing mechanistic and kinetic studies of Fischer-Tropsch synthesis on iron catalysts wasmore » compiled in a draft review. Construction of the mass spectrometer-TPD system is 90% complete and of a Berty CSTR reactor system 98% complete. Three unsupported iron catalysts and three alumina-supported iron catalysts were prepared by nonaqueous-evaporative deposition (NED) or aqueous impregnation (AI) and characterized by chemisorption, BET, extent-of-reduction, XRD, and TEM methods. These catalysts, covering a wide range of dispersions and metal loadings, are well-reduced and relatively thermally stable up to 500-600 C in H{sub 2}, thus ideal for kinetic and mechanistic studies. The alumina-supported iron catalysts will be used for kinetic and mechanistic studies. In the coming year, adsorption/desorption properties, rates of elementary steps, and global reaction rates will be measured for these catalysts, with and without promoters, providing a database for understanding effects of dispersion, metal loading, and support on elementary kinetic parameters and for validation of computational models that incorporate effects of surface structure and promoters. Furthermore, using state-of-the-art self-consistent Density Functional Theory (DFT) methods, we have extensively studied the thermochemistry and kinetics of various elementary steps on three different model surfaces: (1) Fe(110), (2) Fe(110) modified by subsurface C, and (3) Fe surface modified with Pt adatoms. These studies have yielded valuable insights into the reactivity of Fe surfaces for FTS, and provided accurate estimates for the effect of Fe modifiers such as subsurface C and surface Pt.« less

Persistent latent tuberculosis reactivation risk in United States immigrants.

PubMed

Walter, Nicholas D; Painter, John; Parker, Matthew; Lowenthal, Phillip; Flood, Jennifer; Fu, Yunxin; Asis, Redentor; Reves, Randall

2014-01-01

Current guidelines limit latent tuberculosis infection (LTBI) evaluation to persons in the United States less than or equal to 5 years based on the assumption that high TB rates among recent entrants are attributable to high LTBI reactivation risk, which declines over time. We hypothesized that high postarrival TB rates may instead be caused by imported active TB. Estimate reactivation and imported TB in an immigrant cohort. We linked preimmigration records from a cohort of California-bound Filipino immigrants during 2001-2010 with subsequent TB reports. TB was likely LTBI reactivation if the immigrant had no evidence of active TB at preimmigration examination, likely imported if preimmigration radiograph was abnormal and TB was reported less than or equal to 6 months after arrival, and likely reactivation of inactive TB if radiograph was abnormal but TB was reported more than 6 months after arrival. Among 123,114 immigrants, 793 TB cases were reported. Within 1 year of preimmigration examination, 85% of TB was imported; 6 and 9% were reactivation of LTBI and inactive TB, respectively. Conversely, during Years 2-9 after U.S. entry, 76 and 24% were reactivation of LTBI and inactive TB, respectively. The rate of LTBI reactivation (32 per 100,000) did not decline during Years 1-9. High postarrival TB rates were caused by detection of imported TB through active postarrival surveillance. Among immigrants without active TB at baseline, reported TB did not decline over 9 years, indicating sustained high risk of LTBI reactivation. Revised guidelines should support LTBI screening and treatment more than 5 years after U.S. arrival.

Low-valent group 14 element hydride chemistry: towards catalysis.

PubMed

Hadlington, Terrance J; Driess, Matthias; Jones, Cameron

2018-06-05

The chemistry of group 14 element(ii) hydride complexes has rapidly expanded since the first stable example of such a compound was reported in 2000. Since that time it has become apparent that these systems display remarkable reactivity patterns, in some cases mimicking those of late transition-metal (TM) hydride compounds. This is especially so for the hydroelementation of unsaturated organic substrates. Recently, this aspect of their reactivity has been extended to the use of group 14 element(ii) hydrides as efficient, "TM-like" catalysts in organic synthesis. This review will detail how the chemistry of these hydride compounds has advanced since their early development. Throughout, there is a focus on the importance of ligand effects in these systems, and how ligand design can greatly modify a coordinated complex's electronic structure, reactivity, and catalytic efficiency.

The hippocampal response to psychosocial stress varies with salivary uric acid level

PubMed Central

Goodman, Adam M.; Wheelock, Muriah D.; Harnett, Nathaniel G.; Mrug, Sylvie; Granger, Douglas A.; Knight, David C.

2016-01-01

Uric acid is a naturally occurring, endogenous compound that impacts mental health. In particular, uric acid levels are associated with emotion-related psychopathology (e.g., anxiety and depression). Therefore, understanding uric acid’s impact on the brain would provide valuable new knowledge regarding neural mechanisms that mediate the relationship between uric acid and mental health. Brain regions including the prefrontal cortex, amygdala, and hippocampus underlie stress reactivity and emotion regulation. Thus, uric acid may impact emotion by modifying the function of these brain regions. The present study used functional magnetic resonance imaging (fMRI) during a psychosocial stress task to investigate the relationship between baseline uric acid levels (in saliva) and brain function. Results demonstrate that activity within the bilateral hippocampal complex varied with uric acid concentrations. Specifically, activity within the hippocampus and surrounding cortex increased as a function of uric acid level. The current findings suggest that uric acid levels modulate stress-related hippocampal activity. Given that the hippocampus has been implicated in emotion regulation during psychosocial stress, the present findings offer a potential mechanism by which uric acid impacts mental health. PMID:27725214

Physical and biological properties of U. S. standard endotoxin EC after exposure to ionizing radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Csako, G.; Elin, R.J.; Hochstein, H.D.

Techniques that reduce the toxicity of bacterial endotoxins are useful for studying the relationship between structure and biological activity. We used ionizing radiation to detoxify a highly refined endotoxin preparation. U.S. standard endotoxin EC. Dose-dependent changes occurred by exposure to /sup 60/Co-radiation in the physical properties and biological activities of the endotoxin. Sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis showed gradual loss of the polysaccharide components (O-side chain and R-core) from the endotoxin molecules. In contrast, although endotoxin revealed a complex absorption pattern in the UV range, radiation treatment failed to modify that pattern. Dose-related destruction of the primary toxic component,more » lipid A, was suggested by the results of activity tests: both the pyrogenicity and limulus reactivity of the endotoxin were destroyed by increasing doses of radiation. The results indicate that the detoxification is probably due to multiple effects of the ionizing radiation on bacterial lipopolysaccharides, and the action involves (i) the destruction of polysaccharide moieties and possibly (ii) the alteration of lipid A component of the endotoxin molecule.« less

ENHANCEMENT OF REACTIVITY IN SURFACTANT-MODIFIED SORBENTS FOR SULFUR DIOXIDE CONTROL

EPA Science Inventory

Injection of calcium-based sorbents into the postflame zone of utility boilers is capable of achieving sulfur dioxide (SO2) captures of 50-60% at a stoichiometry of 2. Calcium hydroxide [Ca(OH)2] appears to be the most effective commercially available sorbent. Recent attempts to ...

Influence of acid functionalization on the cardio-pulmonary toxicity of carbon nanotubes and carbon black in mice

EPA Science Inventory

Engineered carbon nanotubes are being developed for a wide range of industrial and medical applications. Because of their unique properties, nanotubes can impose potentially toxic effects, particularly if they have been modified to express functionally reactive chemical groups o...

Children’s Patterns of Emotional Reactivity to Conflict as Explanatory Mechanisms in Links Between Interpartner Aggression and Child Physiological Functioning

PubMed Central

Davies, Patrick T.; Sturge-Apple, Melissa L.; Cicchetti, Dante; Manning, Liviah G.; Zale, Emily

2009-01-01

Background This paper examined children’s fearful, sad, and angry reactivity to interparental conflict as mediators of associations between their exposure to interparental aggression and physiological functioning. Methods Participants included 200 toddlers and their mothers. Assessments of interparental aggression and children’s emotional reactivity were derived from maternal surveys and a semi-structured interview. Cortisol levels and cardiac indices of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity were used to assess toddler physiological functioning. Results Results indicated that toddler exposure to interparental aggression was associated with greater cortisol levels and PNS activity and diminished SNS activity. Toddler angry emotional reactivity mediated associations between interparental aggression and cortisol and PNS functioning. Fearful emotional reactivity was a mediator of the link between interparental aggression and SNS functioning. Conclusions The results are interpreted within conceptualizations of how exposure and reactivity to family risk organizing individual differences in physiological functioning. PMID:19744183

Social Stress and the Reactivation of Latent Herpes Simplex Virus Type 1

NASA Astrophysics Data System (ADS)

Padgett, David A.; Sheridan, John F.; Dorne, Julianne; Berntson, Gary G.; Candelora, Jessica; Glaser, Ronald

1998-06-01

Psychological stress is thought to contribute to reactivation of latent herpes simplex virus (HSV). Although several animal models have been developed in an effort to reproduce different pathogenic aspects of HSV keratitis or labialis, until now, no good animal model existed in which application of a psychological laboratory stressor results in reliable reactivation of the virus. Reported herein, disruption of the social hierarchy within colonies of mice increased aggression among cohorts, activated the hypothalamic-pituitary-adrenal axis, and caused reactivation of latent HSV type 1 in greater than 40% of latently infected animals. However, activation of the hypothalamic-pituitary-adrenal axis using restraint stress did not activate the latent virus. Thus, the use of social stress in mice provides a good model in which to investigate the neuroendocrine mechanisms that underlie behaviorally mediated reactivation of latent herpes-viruses.

Structures of MART-1 26/27-35Peptide/HLA-A2 Complexes Reveal a Remarkable Disconnect between Antigen Structural Homology and T Cell Recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borbulevych, Oleg Y; Insaidoo, Francis K; Baxter, Tiffany K

2008-09-17

Small structural changes in peptides presented by major histocompatibility complex (MHC) molecules often result in large changes in immunogenicity, supporting the notion that T cell receptors are exquisitely sensitive to antigen structure. Yet there are striking examples of TCR recognition of structurally dissimilar ligands. The resulting unpredictability of how T cells will respond to different or modified antigens impacts both our understanding of the physical bases for TCR specificity as well as efforts to engineer peptides for immunomodulation. In cancer immunotherapy, epitopes and variants derived from the MART-1/Melan-A protein are widely used as clinical vaccines. Two overlapping epitopes spanning aminomore » acid residues 26 through 35 are of particular interest: numerous clinical studies have been performed using variants of the MART-1 26-35 decamer, although only the 27-35 nonamer has been found on the surface of targeted melanoma cells. Here, we show that the 26-35 and 27-35 peptides adopt strikingly different conformations when bound to HLA-A2. Nevertheless, clonally distinct MART-1{sub 26/27-35}-reactive T cells show broad cross-reactivity towards these ligands. Simultaneously, however, many of the cross-reactive T cells remain unable to recognize anchor-modified variants with very subtle structural differences. These dichotomous observations challenge our thinking about how structural information on unligated peptide/MHC complexes should be best used when addressing questions of TCR specificity. Our findings also indicate that caution is warranted in the design of immunotherapeutics based on the MART-1 26/27-35 epitopes, as neither cross-reactivity nor selectivity is predictable based on the analysis of the structures alone.« less

Structures of MART-126/27–35 Peptide/HLA-A2 Complexes Reveal a Remarkable Disconnect between Antigen Structural Homology and T Cell Recognition

PubMed Central

Borbulevych, Oleg Y.; Insaidoo, Francis K.; Baxter, Tiffany K.; Powell, Daniel J.; Johnson, Laura A.; Restifo, Nicholas P.; Baker, Brian M.

2007-01-01

Small structural changes in peptides presented by major histocompatibility complex (MHC) molecules often result in large changes in immunogenicity, supporting the notion that T cell receptors are exquisitely sensitive to antigen structure. Yet there are striking examples of TCR recognition of structurally dissimilar ligands. The resulting unpredictability of how T cells will respond to different or modified antigens impacts both our understanding of the physical bases for TCR specificity as well as efforts to engineer peptides for immunomodulation. In cancer immunotherapy, epitopes and variants derived from the MART-1/Melan-A protein are widely used as clinical vaccines. Two overlapping epitopes spanning amino acid residues 26 through 35 are of particular interest: numerous clinical studies have been performed using variants of the MART-1 26–35 decamer, although only the 27–35 nonamer has been found on the surface of targeted melanoma cells. Here, we show that the 26–35 and 27–35 peptides adopt strikingly different conformations when bound to HLA-A2. Nevertheless, clonally distinct MART-126/27–35-reactive T cells show broad cross-reactivity towards these ligands. Simultaneously, however, many of the cross-reactive T cells remain unable to recognize anchor-modified variants with very subtle structural differences. These dichotomous observations challenge our thinking about how structural information on unligated peptide/MHC complexes should be best used when addressing questions of TCR specificity. Our findings also indicate that caution is warranted in the design of immunotherapeutics based on the MART-1 26/27–35 epitopes, as neither cross-reactivity nor selectivity is predictable based on the analysis of the structures alone. PMID:17719062