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Sample records for redox responsive molecular

  1. Electrochemically controlled release of molecular guests from redox responsive polymeric multilayers and devices

    NARCIS (Netherlands)

    Song, J.; Janczewski, D.; Ma, Y.; Ingen, van L.; Ee Sim, C.; Goh, Q; Xu, J.; Vancso, G.J.

    2013-01-01

    A novel platform technology for a tunable molecular payload release, employing complex release profiles, from electrode surfaces is reported. Organometallic poly(ferrocenylsilanes) (PFSs), featuring redox responsive ferrocene units in their main chain, are used as a carrier medium to prepare thin fi

  2. Stimulus-Responsive Nanoporous System Based on a Redox-Active Molecular Self-Assembled Monolayer.

    Science.gov (United States)

    Abel, Annik; Wu, Yanlin; Bachmann, Julien

    2017-08-22

    Ordered arrays of electrically conducting cylindrical nanotubes are created by atomic layer deposition of a thin titanium dioxide layer onto the pore walls of an anodic alumina matrix. All geometric parameters (pore length and diameter and TiO2 layer thickness) are defined and tunable experimentally. The titanium dioxide surface is subsequently functionalized with ferrocenylacetic acid. The chemisorbed ferrocene moieties are oxidized chemically and electrochemically. Monitoring the redox chemistry by UV-visible absorption spectroscopy allows for the quantification of the total density of redox-active units grafted to the surface, as well as the fraction of them oxidized at a given applied potential. The capillary properties of the surface can be adjusted by the applied potential, as quantified by contact angle measurements.

  3. Engineering artificial redox chains by molecular 'Lego'.

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    Sadeghi, S J; Meharenna, Y T; Fantuzzi, A; Valetti, F; Gilardi, G

    2000-01-01

    This work reports on a novel approach for building artificial redox chains: the molecular 'Lego' approach. This exploits the scaffold of natural redox proteins by fusing together functional protein modules with the desired properties. The molecular 'Lego' mimics the natural molecular evolution that proceeded by modular assembly of genes/DNA segments. Non-physiological electron transfer partners, flavodoxin (fld) and cytochrome c553 (c553) from Desulfovibrio vulgaris and the haem domain of P450 BM3 (BMP) from Bacillus megaterium have been used as building blocks in different combinations to build artificial redox chains. The kinetic characterization of the electron transfer (ET) between the separate building blocks has been carried out. Under pseudo-first order conditions, a limiting ET rate, klim, of 0.48 +/- 0.05 s-1 and 43.77 +/- 2.18 s-1 and an apparent binding constant, Kapp, of 21 +/- 6 microM and 1.23 +/- 0.32 microM have been found for the fld/c553 and fld/BMP redox pairs, respectively. These results show that fld can be used as a module for transferring electrons to c553 and BMP. A 3D model of the fld/c553 and fld/BMP complexes was used to guide the construction of covalently linked assemblies via engineered disulfide bridges or by fusion of the relevant genes via an engineered loop. The first approach led to the construction, expression and characterization of the S35C and S64C mutants of fld and M23C and G51C mutants of c553. Although the redox potentials of the separate mutants were found to be the same as those of recombinant wild type proteins (-408 mV for the semiquinone/hydroquinone couple of fld and +32 mV for the c553), the c553 homo-dimers M23C-M23C and G51C-G51C were found to have redox potentials of +88 and +105 mV, respectively. These differences have been analysed in terms of exposure of the haem cofactors to the solvent, and these lead to some interesting questions on the redox potentials of the transient redox complexes in physiological

  4. Design of molecular scaffolds based on unusual geometries for magnetic modulation of spin-diverse complexes with selective redox response.

    Science.gov (United States)

    Lanznaster, Maurício; Heeg, Mary Jane; Yee, Gordon T; McGarvey, Bruce R; Verani, Claudio N

    2007-01-08

    A weakly coupled heterometallic [CuFe] complex has been prepared in which the metal centers are coordinated to a new electroactive ligand. The spin-diverse system delivers distinct ground states upon application of selective redox potentials. Ligand oxidation fosters radical generation, and the initial ground state associated with a weakly coupled [CuFe] core switches to a ground state associated with the [Fe-radical] coupling; the Cu(II) ion remains uncoupled. A third state is obtained upon reduction of the cupric center and in absence of the radical. The possibilities and limitations of these systems are discussed.

  5. Molecular analysis of Ku redox regulation

    Directory of Open Access Journals (Sweden)

    Shatilla Andrea

    2009-08-01

    Full Text Available Abstract Background DNA double-strand breaks (DSBs can occur in response to ionizing radiation (IR, radiomimetic agents and from endogenous DNA-damaging reactive oxygen metabolites. Unrepaired or improperly repaired DSBs are potentially the most lethal form of DNA damage and can result in chromosomal translocations and contribute to the development of cancer. The principal mechanism for the repair of DSBs in humans is non-homologous end-joining (NHEJ. Ku is a key member of the NHEJ pathway and plays an important role in the recognition step when it binds to free DNA termini. Ku then stimulates the assembly and activation of other NHEJ components. DNA binding of Ku is regulated by redox conditions and evidence from our laboratory has demonstrated that Ku undergoes structural changes when oxidized that results in a reduction in DNA binding activity. The C-terminal domain and cysteine 493 of Ku80 were investigated for their contribution to redox regulation of Ku. Results We effectively removed the C-terminal domain of Ku80 generating a truncation mutant and co-expressed this variant with wild type Ku70 in an insect cell system to create a Ku70/80ΔC heterodimer. We also generated two single amino acid variants of Cys493, replacing this amino acid with either an alanine (C493A or a serine (C493S, and over-expressed the variant proteins in SF9 insect cells in complex with wild type Ku70. Neither the truncation nor the amino acid substitutions alters protein expression or stability as determined by SDS-PAGE and Western blot analysis. We show that the C493 mutations do not alter the ability of Ku to bind duplex DNA in vitro under reduced conditions while truncation of the Ku80 C-terminus slightly reduced DNA binding affinity. Diamide oxidation of cysteines was shown to inhibit DNA binding similarly for both the wild-type and all variant proteins. Interestingly, differential DNA binding activity following re-reduction was observed for the Ku70/80

  6. Light and Redox Switchable Molecular Components for Molecular Electronics

    NARCIS (Netherlands)

    Browne, Wesley R.; Feringa, Bernard

    2010-01-01

    The field of molecular and organic electronics has seen rapid progress in recent years, developing from concept and design to actual demonstration devices in which both single molecules and self-assembled monolayers are employed as light-responsive components. Research in this field has seen

  7. Light and Redox Switchable Molecular Components for Molecular Electronics

    NARCIS (Netherlands)

    Browne, Wesley R.; Feringa, Bernard

    2010-01-01

    The field of molecular and organic electronics has seen rapid progress in recent years, developing from concept and design to actual demonstration devices in which both single molecules and self-assembled monolayers are employed as light-responsive components. Research in this field has seen numerou

  8. Molecular chaperones and proteostasis regulation during redox imbalance

    Directory of Open Access Journals (Sweden)

    Katerina Niforou

    2014-01-01

    Full Text Available Free radicals originate from both exogenous environmental sources and as by-products of the respiratory chain and cellular oxygen metabolism. Sustained accumulation of free radicals, beyond a physiological level, induces oxidative stress that is harmful for the cellular homeodynamics as it promotes the oxidative damage and stochastic modification of all cellular biomolecules including proteins. In relation to proteome stability and maintenance, the increased concentration of oxidants disrupts the functionality of cellular protein machines resulting eventually in proteotoxic stress and the deregulation of the proteostasis (homeostasis of the proteome network (PN. PN curates the proteome in the various cellular compartments and the extracellular milieu by modulating protein synthesis and protein machines assembly, protein recycling and stress responses, as well as refolding or degradation of damaged proteins. Molecular chaperones are key players of the PN since they facilitate folding of nascent polypeptides, as well as holding, folding, and/or degradation of unfolded, misfolded, or non-native proteins. Therefore, the expression and the activity of the molecular chaperones are tightly regulated at both the transcriptional and post-translational level at organismal states of increased oxidative and, consequently, proteotoxic stress, including ageing and various age-related diseases (e.g. degenerative diseases and cancer. In the current review we present a synopsis of the various classes of intra- and extracellular chaperones, the effects of oxidants on cellular homeodynamics and diseases and the redox regulation of chaperones.

  9. Picosecond time resolved conductance measurements of redox molecular junctions

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    Arielly, Rani; Nachman, Nirit; Zelinskyy, Yaroslav; May, Volkhard; Selzer, Yoram

    2017-03-01

    Due to bandwidth limitations of state of the art electronics, the transient transport properties of molecular junctions are experimentally a terra incognita, which can only be explored if novel picosecond current-probing techniques are developed. Here we demonstrate one such approach: the laser pulse-pair sequence scheme. The method is used to monitor in picosecond resolution the oxidation state of a redox molecule, 6-ferrocenyl-1-hexanethiol, within a junction and to quantify its redox rate constant, which is found to be (80 ps)-1.

  10. Molecular controls of the oxygenation and redox reactions of hemoglobin.

    Science.gov (United States)

    Bonaventura, Celia; Henkens, Robert; Alayash, Abdu I; Banerjee, Sambuddha; Crumbliss, Alvin L

    2013-06-10

    The broad classes of O(2)-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O(2)-binding functions. The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes.

  11. Multiple redox states of multiheme cytochromes may enable bacterial response to changing redox environments

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    Arbour, T.; Wrighton, K. C.; Mullin, S. W.; Castelle, C.; Luef, B.; Gilbert, B.; Banfield, J. F.

    2013-12-01

    Multiheme c-type cytochromes (MHCs) are key components in electron-transport pathways that enable some microorganisms to transfer electron byproducts of metabolism to a variety of minerals. As a response to changes in mineral redox potential, microbial communities may shift their membership, or individual organisms may adjust protein expression. Alternatively, the ability to respond may be conferred by the innate characteristics of certain electron-transport-chain components. Here, we used potentiostat-controlled microbial fuel cells (MFCs) to measure the timescale of response to imposed changes in redox conditions, thus placing constraints on the importance of these different mechanisms. In the experiments, a solid electrode acts as an electron-accepting mineral whose redox potential can be precisely controlled. We inoculated duplicate MFCs with a sediment/groundwater mixture from an aquifer at Rifle, Colorado, supplied acetate as an electron donor, and obtained stable, mixed-species biofilms dominated by Geobacter and a novel Geobacter-related family. We poised the anode at potentials spanning the range of natural Fe(III)-reduction, then performed cyclic voltammetry (CV) to characterize the overall biofilm redox signature. The apparent biofilm midpoint potential shifted directly with anode set potential when the latter was changed within the range from about -250 to -50 mV vs. SHE. Following a jump in set potential by 200 mV, the CV-midpoint shift by ~100 mV over a timescale of ~30 minutes to a few hours, depending on the direction of the potential change. The extracellular electron transfer molecules, whose overall CV signature is very similar to those of purified MHCs, appear to span a broad redox range (~200 mV), supporting the hypothesis that MHCs confer substantial redox flexibility. This flexibility may be a principle reason for the abundance of MHCs expressed by microorganisms capable of extracellular electron transfer to minerals.

  12. Friedreich Ataxia: Molecular Mechanisms, Redox Considerations, and Therapeutic Opportunities

    Science.gov (United States)

    Lefevre, Sophie; Sliwa, Dominika; Seguin, Alexandra; Camadro, Jean-Michel; Lesuisse, Emmanuel

    2010-01-01

    Abstract Mitochondrial dysfunction and oxidative damage are at the origin of numerous neurodegenerative diseases like Friedreich ataxia and Alzheimer and Parkinson diseases. Friedreich ataxia (FRDA) is the most common hereditary ataxia, with one individual affected in 50,000. This disease is characterized by progressive degeneration of the central and peripheral nervous systems, cardiomyopathy, and increased incidence of diabetes mellitus. FRDA is caused by a dynamic mutation, a GAA trinucleotide repeat expansion, in the first intron of the FXN gene. Fewer than 5% of the patients are heterozygous and carry point mutations in the other allele. The molecular consequences of the GAA triplet expansion is transcription silencing and reduced expression of the encoded mitochondrial protein, frataxin. The precise cellular role of frataxin is not known; however, it is clear now that several mitochondrial functions are not performed correctly in patient cells. The affected functions include respiration, iron–sulfur cluster assembly, iron homeostasis, and maintenance of the redox status. This review highlights the molecular mechanisms that underlie the disease phenotypes and the different hypothesis about the function of frataxin. In addition, we present an overview of the most recent therapeutic approaches for this severe disease that actually has no efficient treatment. Antioxid. Redox Signal. 13, 0000–0000. PMID:20156111

  13. Proteomics of Arabidopsis redox proteins in response to methyl jasmonate.

    Science.gov (United States)

    Alvarez, Sophie; Zhu, Mengmeng; Chen, Sixue

    2009-11-02

    Protein redox regulation is increasingly recognized as an important switch of protein activity in yeast, bacteria, mammals and plants. In this study, we identified proteins with potential thiol switches involved in jasmonate signaling, which is essential for plant defense. Methyl jasmonate (MeJA) treatment led to enhanced production of hydrogen peroxide in Arabidopsis leaves and roots, indicating in vivo oxidative stress. With monobromobimane (mBBr) labeling to capture oxidized sulfhydryl groups and 2D gel separation, a total of 35 protein spots that displayed significant redox and/or total protein expression changes were isolated. Using LC-MS/MS, the proteins in 33 spots were identified in both control and MeJA-treated samples. By comparative analysis of mBBr and SyproRuby gel images, we were able to determine many proteins that were redox responsive and proteins that displayed abundance changes in response to MeJA. Interestingly, stress and defense proteins constitute a large group that responded to MeJA. In addition, many cysteine residues involved in the disulfide dynamics were mapped based on tandem MS data. Identification of redox proteins and their cysteine residues involved in the redox regulation allows for a deeper understanding of the jasmonate signaling networks.

  14. Redox rhythm reinforces the circadian clock to gate immune response.

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    Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E; Dong, Xinnian

    2015-07-23

    Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.

  15. Sub-nanometer expansions of redox responsive polymer films monitored by imaging ellipsometry.

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    Cumurcu, Aysegul; Feng, Xueling; Ramos, Lionel Dos; Hempenius, Mark A; Schön, Peter; Vancso, G Julius

    2014-10-21

    We describe a novel approach to quantitatively visualize sub nm height changes occurring in thin films of redox active polymers upon reversible electrochemical oxidation/reduction in situ and in real-time with electrochemical imaging ellipsometry (EC-IE). Our approach is based on the utilization of a micro-patterned substrate containing circular patterns of passive (non-redox active) 11-mercapto-1-undecanol (MCU) within a redox-responsive oligoethylene sulfide end-functionalized poly(ferrocenyldimethylsilane) (ES-PFS) film on a gold substrate. The non-redox responsive MCU layer was used as a molecular reference layer for the direct visualization of the minute thickness variations of the ES-PFS film. The ellipsometric microscopy images were recorded in aqueous electrolyte solutions at potentials of -0.1 V and 0.6 V vs. Ag/AgCl corresponding to the reduced and oxidized redox states of ES-PFS, respectively. The ellipsometric contrast images showed a 37 (±2)% intensity increase in the ES-PFS layer upon oxidation. The thickness of the ES-PFS layer reversibly changed between 4.0 (±0.1) nm and 3.4 (±0.1) nm upon oxidation and reduction, respectively, as determined by IE. Additionally, electrochemical atomic force microscopy (EC-AFM) was used to verify the redox controlled thickness variations. The proposed method opens novel avenues to optically visualize minute and rapid height changes occurring e.g. in redox active (and other stimulus responsive) polymer films in a fast and non-invasive manner.

  16. The decay of Redox-stress Response Capacity is a substantive characteristic of aging: Revising the redox theory of aging.

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    Meng, Jiao; Lv, Zhenyu; Qiao, Xinhua; Li, Xiaopeng; Li, Yazi; Zhang, Yuying; Chen, Chang

    2017-04-01

    Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals. In response to paraquat stress, young individuals generated more ROS and activated signaling pathways including p-ERK, p-AKT and p-AMPKα/β. After the initial response, young individuals then promoted NRF2 translocation and induced additional antioxidant enzymes and higher expression of phase II enzymes, including SOD, CAT, GPX, HO-1, GSTP-1and others, to maintain redox homeostasis. Moreover, young individuals also demonstrated a better ability to degrade damaged proteins by up-regulating the expression of chaperones and improving proteasome activity. Based on these data, we propose a new concept "Redox-stress Response Capacity (RRC)", which suggests cells or organisms are capable of generating dynamic redox responses to activate cellular signaling and maintain cellular homeostasis. The decay of RRC is the substantive characteristic of aging, which gives a new understand of the redox theory of aging. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Redox control of GTPases: from molecular mechanisms to functional significance in health and disease.

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    Heo, Jongyun

    2011-02-15

    Small GTPases, including the proto-oncoprotein Ras and Rho GTPases, are involved in various cellular signaling events. Some of these small GTPases are redox sensitive, including Ras, Rho, Ran, Dexras1, and Rhes GTPases. Thus, the redox-mediated regulation of these GTPases often determines the course of their cellular signaling cascades. This article takes into consideration the application of Marcus theory to potential redox-based molecular mechanisms in the regulation of these redox-sensitive GTPases and the relevance of such mechanisms to a specific redox-sensitive motif. The discussion also takes into account various diseases, including cancers, heart, and neuronal disorders, that are often linked with the dysregulation of the redox signaling cascades associated with these redox-sensitive GTPases.

  18. Influence of Low Molecular Weight Fractions of Humic Substances on Their Reducing Capacities and Distribution of Redox Functional Groups.

    Science.gov (United States)

    Yang, Z.; Jiang, J.

    2015-12-01

    Humic substances (HS) are redox-active organic compounds and their reducing capacities depend on molecule structure and distribution of redox functional groups (RFG). During dialysis experiments, initial HS were separated into low molecular weight fractions (LMWF, molecular weight dialysis device were calculated for initial HA, retentate and LMWF in native and reduced state, and result suggests that releasing of LMWF leads to production and explosion of RFG. LWMF have great fluorescence intensities for protein-like fluorophores and humic acids-like fluorophores (quinone-like functional groups), where quinonoid π-π* transition is responsible for the great reducing capacities of LMWF. The 3,500 Da molecules (0.25 nm diameter) of HS are capable of stimulating transformation of redox-active metals or potential pollutants trapped in soil micropores (< 2 nm diameter). A development of relationship between reducing capacity and Ex / Em position provides a possibility to predicate relative reducing capacities of HS in treated raw water sample.

  19. Redox responsive nanotubes from organometallic polymers by template assisted layer by layer fabrication

    Science.gov (United States)

    Song, Jing; Jańczewski, Dominik; Guo, Yuanyuan; Xu, Jianwei; Vancso, G. Julius

    2013-11-01

    Redox responsive nanotubes were fabricated by the template assisted layer-by-layer (LbL) assembly method and employed as platforms for molecular payload release. Positively and negatively charged organometallic poly(ferrocenylsilane)s (PFS) were used to construct the nanotubes, in combination with other polyions. During fabrication, multilayers of these polyions were deposited onto the inner pores of template porous membranes, followed by subsequent removal of the template. Anodized porous alumina and track-etched polycarbonate membranes were used as templates. The morphology, electrochemistry, composition and other properties of the obtained tubular structure were characterized by fluorescence microscopy, scanning (SEM) and transmission electron microscopy (TEM) and energy-dispersive X-ray (EDX) spectroscopy. Composite nanotubes, consisting of poly(acrylic acid) anions with PFS+ and nanoparticles including fluorophore labelled dextran and decorated quantum dots, with PFS polyelectrolytes were also fabricated, broadening the scope of the structures. Cyclic voltammograms of PFS containing nanotubes showed similar redox responsive behaviour to thin LbL assembled films. Redox triggered release of labelled macromolecules from these tubular structures demonstrated application potential in controlled molecular delivery.Redox responsive nanotubes were fabricated by the template assisted layer-by-layer (LbL) assembly method and employed as platforms for molecular payload release. Positively and negatively charged organometallic poly(ferrocenylsilane)s (PFS) were used to construct the nanotubes, in combination with other polyions. During fabrication, multilayers of these polyions were deposited onto the inner pores of template porous membranes, followed by subsequent removal of the template. Anodized porous alumina and track-etched polycarbonate membranes were used as templates. The morphology, electrochemistry, composition and other properties of the obtained tubular

  20. Redox regulation of cancer metastasis: molecular signaling and therapeutic opportunities.

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    Yang, Wenyong; Zou, Linzhi; Huang, Canhua; Lei, Yunlong

    2014-08-01

    Cancer metastasis is the major cause of cancer-related mortality. Accumulated evidence has shown that high-metastasis potential cancer cells have more reactive oxygen species (ROS) accumulation compared with low-metastasis potential cancer cells. ROS can function as second messengers to regulate multiple cancer metastasis-related signaling pathways via reversible oxidative posttranslational modifications of cysteine in key redox-sensitive proteins, which leads to the structural and functional change of these proteins. Because ROS can promote cancer metastasis, therapeutic strategies aiming at inducing/reducing cellular ROS level or targeting redox sensors involved in metastasis hold great potential in developing new efficient approaches for anticancer therapy. In this review, we summarize recent findings on regulation of tumor metastasis by key redox sensors and describe the potential of targeting redox signaling pathways for cancer therapy.

  1. Polymeric redox-responsive delivery systems bearing ammonium salts cross-linked via disulfides

    Directory of Open Access Journals (Sweden)

    Christian Dollendorf

    2013-08-01

    Full Text Available A redox-responsive polycationic system was synthesized via copolymerization of N,N-diethylacrylamide (DEAAm and 2-(dimethylaminoethyl methacrylate (DMAEMA. N,N’-bis(4-chlorobutanoylcystamine was used as disulfide-containing cross-linker to form networks by the quaternization of tertiary amine groups. The insoluble cationic hydrogels become soluble by reduction of disulfide to mercaptanes by use of dithiothreitol (DTT, tris(2-carboxyethylphosphine (TCEP or cysteamine, respectively. The soluble polymeric system can be cross-linked again by using oxygen or hydrogen peroxide under basic conditions. The redox-responsive polymer networks can be used for molecular inclusion and controlled release. As an example, phenolphthalein, methylene blue and reactive orange 16 were included into the network. After treatment with DTT a release of the dye could be recognized. Physical properties of the cross-linked materials, e.g., glass transition temperature (Tg, swelling behavior and cloud points (Tc were investigated. Redox-responsive behavior was further analyzed by rheological measurements.

  2. Redox signaling: Potential arbitrator of autophagy and apoptosis in therapeutic response.

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    Zhang, Lu; Wang, Kui; Lei, Yunlong; Li, Qifu; Nice, Edouard Collins; Huang, Canhua

    2015-12-01

    Redox signaling plays important roles in the regulation of cell death and survival in response to cancer therapy. Autophagy and apoptosis are discrete cellular processes mediated by distinct groups of regulatory and executioner molecules, and both are thought to be cellular responses to various stress conditions including oxidative stress, therefore controlling cell fate. Basic levels of reactive oxygen species (ROS) may function as signals to promote cell proliferation and survival, whereas increase of ROS can induce autophagy and apoptosis by damaging cellular components. Growing evidence in recent years argues for ROS that below detrimental levels acting as intracellular signal transducers that regulate autophagy and apoptosis. ROS-regulated autophagy and apoptosis can cross-talk with each other. However, how redox signaling determines different cell fates by regulating autophagy and apoptosis remains unclear. In this review, we will focus on understanding the delicate molecular mechanism by which autophagy and apoptosis are finely orchestrated by redox signaling and discuss how this understanding can be used to develop strategies for the treatment of cancer.

  3. Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities

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    Jones, Dean P.; Brown, Lou Ann S.

    2012-01-01

    Abstract Asthma is a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness and airflow limitation in response to specific triggers. Whereas inflammation is important for tissue regeneration and wound healing, the profound and sustained inflammatory response associated with asthma may result in airway remodeling that involves smooth muscle hypertrophy, epithelial goblet-cell hyperplasia, and permanent deposition of airway extracellular matrix proteins. Although the specific mechanisms responsible for asthma are still being unraveled, free radicals such as reactive oxygen species and reactive nitrogen species are important mediators of airway tissue damage that are increased in subjects with asthma. There is also a growing body of literature implicating disturbances in oxidation/reduction (redox) reactions and impaired antioxidant defenses as a risk factor for asthma development and asthma severity. Ultimately, these redox-related perturbations result in a vicious cycle of airway inflammation and injury that is not always amenable to current asthma therapy, particularly in cases of severe asthma. This review will discuss disruptions of redox signaling and control in asthma with a focus on the thiol, glutathione, and reduced (thiol) form (GSH). First, GSH synthesis, GSH distribution, and GSH function and homeostasis are discussed. We then review the literature related to GSH redox balance in health and asthma, with an emphasis on human studies. Finally, therapeutic opportunities to restore the GSH redox balance in subjects with asthma are discussed. Antioxid. Redox Signal. 17, 375–408. PMID:22304503

  4. Novel Molecular Non-Volatile Memory: Application of Redox-Active Molecules

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    Hao Zhu

    2015-12-01

    Full Text Available This review briefly describes the development of molecular electronics in the application of non-volatile memory. Molecules, especially redox-active molecules, have become interesting due to their intrinsic redox behavior, which provides an excellent basis for low-power, high-density and high-reliability non-volatile memory applications. Recently, solid-state non-volatile memory devices based on redox-active molecules have been reported, exhibiting fast speed, low operation voltage, excellent endurance and multi-bit storage, outperforming the conventional floating-gate flash memory. Such high performance molecular memory will lead to promising on-chip memory and future portable/wearable electronics applications.

  5. A redox-assisted molecular assembly of molybdenum oxide amine composite nanobelts

    Energy Technology Data Exchange (ETDEWEB)

    Luo Haiyan [Institute of New Energy Technology and Nano-Materials, Fuzhou University, Fuzhou, Fujian 350002 (China); Wei Mingdeng, E-mail: wei-mingdeng@fzu.edu.cn [Institute of New Energy Technology and Nano-Materials, Fuzhou University, Fuzhou, Fujian 350002 (China); National Engineering Research Center for Chemical Fertilizer Catalyst, Fuzhou University, Fuzhou, Fujian 350002 (China); Wei Kemei [National Engineering Research Center for Chemical Fertilizer Catalyst, Fuzhou University, Fuzhou, Fujian 350002 (China)

    2011-01-21

    Research highlights: > Nanobelts of molybdenum oxide amine were first synthesized via a redox-assisted molecular assembly route. > These nanobelts are highly crystalline with a several tens of micrometers in length and 20-30 nm in thickness. - Abstract: In this paper, the nanobelts of molybdenum oxide amine composite were successfully synthesized via a redox-assisted molecular assembly route under the hydrothermal conditions. The synthesized nanobelts were characterized by XRD, SEM, TEM, TG and FT-IR measurements. The thickness of nanobelts is found to be ca. 20-30 nm and their lengths are up to several tens of micrometers. Based on a series of the experimental results, a possible model, redox-intercalation-exfoliation, was suggested for the formation of nanobelts of molybdenum oxide amine composite.

  6. Non-volatile memory devices with redox-active diruthenium molecular compound

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    Pookpanratana, S.; Zhu, H.; Bittle, E. G.; Natoli, S. N.; Ren, T.; Richter, C. A.; Li, Q.; Hacker, C. A.

    2016-03-01

    Reduction-oxidation (redox) active molecules hold potential for memory devices due to their many unique properties. We report the use of a novel diruthenium-based redox molecule incorporated into a non-volatile Flash-based memory device architecture. The memory capacitor device structure consists of a Pd/Al2O3/molecule/SiO2/Si structure. The bulky ruthenium redox molecule is attached to the surface by using a ‘click’ reaction and the monolayer structure is characterized by x-ray photoelectron spectroscopy to verify the Ru attachment and molecular density. The ‘click’ reaction is particularly advantageous for memory applications because of (1) ease of chemical design and synthesis, and (2) provides an additional spatial barrier between the oxide/silicon to the diruthenium molecule. Ultraviolet photoelectron spectroscopy data identified the energy of the electronic levels of the surface before and after surface modification. The molecular memory devices display an unsaturated charge storage window attributed to the intrinsic properties of the redox-active molecule. Our findings demonstrate the strengths and challenges with integrating molecular layers within solid-state devices, which will influence the future design of molecular memory devices.

  7. A nano switch mechanism for the redox-responsive sulfotransferase.

    Science.gov (United States)

    Lin, Chih-Heng; Lin, En-Shyh; Su, Tian-Mu; Hung, Kuo-Sheng; Yang, Yuh-Shyong

    2012-07-15

    Cellular redox signaling is important in diverse physiological and pathological processes. The activity of rat phenol sulfotransferase (rSULT1A1), which is important for the metabolism of hormone and drug, is subjected to redox regulation. Two cysteines, Cys232 and Cys66, nanometer away from each other and from the enzyme active site were proposed to form disulfide bond to regulate the activity of rSULT1A1. A nano switch, composed of a flexible loop from amino acid residues 59-70, explained how this long distance interaction between two cysteines can be achieved. The enzyme properties were investigated through site-directed muatagnesis, circular dichroism, enzyme kinetics and homologous modeling of the rSULT1A1 structures. We proposed that the formation of disulfide bond between Cys232 and Cys66 induced conformational changes of sulfotransferase, then in turn affected its nucleotide binding and enzyme activity. This discovery was extended to understand the possible redox regulation of other sulfotransferases from different organisms. The redox switch can be created in other redox-insensitive sulfotransferases, such as human phenol sulfotransferase (hSULT1A1) and human alcohol sulfotransferase (hSULT2A1), to produce mutant enzymes with redox regulation capacity. This study strongly suggested that redox regulation of drug and hormone metabolism can be significantly varied even though the sequence and structure of SULT1A1 of human and rat have a high degree of homology.

  8. Cyclic conductance switching in networks of redox-active molecular junctions.

    Science.gov (United States)

    Liao, Jianhui; Agustsson, Jon S; Wu, Songmei; Schönenberger, Christian; Calame, Michel; Leroux, Yann; Mayor, Marcel; Jeannin, Olivier; Ran, Ying-Fen; Liu, Shi-Xia; Decurtins, Silvio

    2010-03-10

    Redox-active dithiolated tetrathiafulvalene derivatives (TTFdT) were inserted in two-dimensional nanoparticle arrays to build interlinked networks of molecular junctions. Upon oxidation of the TTFdT to the dication state, we observed a conductance increase of the networks by up to 1 order of magnitude. Successive oxidation and reduction cycles demonstrated a clear switching behavior of the molecular junction conductance. These results show the potential of interlinked nanoparticle arrays as chemical sensors.

  9. E-tongue 2 REDOX response to heavy metals

    Science.gov (United States)

    Buehler, M. G.; Kuhlman, G. M.; Kounaves, S. P.

    2002-01-01

    E-Tongue 2 an array of electrochemical sensors including REDOX electrodes for Cylic Voltammetry and Anodic Stripping Voltammetry measurements, Galvanic cells for corrosion measurements, and Ion Selective Electrodes.

  10. Structure-redox-relaxivity relationships for redox responsive manganese-based magnetic resonance imaging probes.

    Science.gov (United States)

    Gale, Eric M; Mukherjee, Shreya; Liu, Cynthia; Loving, Galen S; Caravan, Peter

    2014-10-06

    A library of 10 Mn-containing complexes capable of switching reversibly between the Mn(II) and Mn(III) oxidation states was prepared and evaluated for potential usage as MRI reporters of tissue redox activity. We synthesized N-(2-hydroxybenzyl)-N,N',N'-ethylenediaminetriacetic acid (HBET) and N-(2-hydroxybenzyl-N,N',N'-trans-1,2-cyclohexylenediaminetriacetic acid (CyHBET) ligands functionalized (-H, -OMe, -NO2) at the 5-position of the aromatic ring. The Mn(II) complexes of all ligands and the Mn(III) complexes of the 5-H and 5-NO2 functionalized ligands were synthesized and isolated, but the Mn(III) complexes with the 5-OMe functionalized ligands were unstable. (1)H relaxivity of the 10 isolable complexes was measured at pH 7.4 and 37 °C, 1.4 T. Thermodynamic stability, pH-dependent complex speciation, hydration state, water exchange kinetics of the Mn(II) complexes, and pseudo-first order reduction kinetics of the Mn(III) complexes were studied using a combination of pH-potentiometry, UV-vis spectroscopy, and (1)H and (17)O NMR measurements. The effects of ligand structural and electronic modifications on the Mn(II/III) redox couple were studied by cyclic voltammetry. The Mn(II) complexes are potent relaxation agents as compared to the corresponding Mn(III) species with [Mn(II)(CyHBET)(H2O)](2-) exhibiting a 7.5-fold higher relaxivity (3.3 mM(-1) s(-1)) than the oxidized form (0.4 mM(-1) s(-1)). At pH 7.4, Mn(II) exists as a mixture of fully deprotonated (ML) and monoprotonated (HML) complexes and Mn(II) complex stability decreases as the ligands become more electron-releasing (pMn for 10 μM [Mn(II)(CyHBET-R')(H2O)](2-) decreases from 7.6 to 6.2 as R' goes from -NO2 to -OMe, respectively). HML speciation increases as the electron-releasing nature of the phenolato-O donor increases. The presence of a water coligand is maintained upon conversion from HML to ML, but the water exchange rate of ML is faster by up to 2 orders of magnitude (k(ex)(310) for H

  11. Nonlinear optical molecular imaging enables metabolic redox sensing in tissue-engineered constructs

    Science.gov (United States)

    Chen, Leng-Chun; Lloyd, William R.; Wilson, Robert H.; Kuo, Shiuhyang; Marcelo, Cynthia L.; Feinberg, Stephen E.; Mycek, Mary-Ann

    2011-07-01

    Tissue-engineered constructs require noninvasive monitoring of cellular viability prior to implantation. In a preclinical study on human Ex Vivo Produced Oral Mucosa Equivalent (EVPOME) constructs, nonlinear optical molecular imaging was employed to extract morphological and functional information from intact constructs. Multiphoton excitation fluorescence images were acquired using endogenous fluorescence from cellular nicotinamide adenine dinucleotide phosphate [NAD(P)H] and flavin adenine dinucleotide (FAD). The images were analyzed to report quantitatively on tissue structure and metabolism (redox ratio). Both thickness variations over time and cell distribution variations with depth were identified, while changes in redox were quantified. Our results show that nonlinear optical molecular imaging has the potential to visualize and quantitatively monitor the growth and viability of a tissue-engineered construct over time.

  12. Influence of low molecular weight fractions of humic substances on reducing capacities and distribution of redox functional groups

    Science.gov (United States)

    Yang, Zhen; Jiang, Jie

    2016-04-01

    Humic substances (HS) are redox-active organic compounds and their reducing capacities depend on their molecule structure and distribution of redox functional groups (RFG). During dialysis experiments, bulk humic acids (HA) were separated into low molecular weight fractions (LMWF) and retentate. LMWF account for only 2% of the total organic carbon content of HA molecules, however, their reducing capacities are up to 33 times greater than either those of the bulk HA or retentate. Furthermore, the total reducing capacity of the bulk HA accounts for less than 15% of the total reducing capacity of bulk HA, retentate and LMWF combined, suggesting that releasing of LMWF cannot reduce the number of RFG. RFG are neither in fixed amounts nor in uniformly distributed in bulk HA. LWMF have great fluorescence intensities for humic-like fluorophores (quinone-like functional groups), where quinonoid π-π* transition is responsible for the great reducing capacities of LMWF, and protein-like fluorophores. The 3,500 Da molecules (1.25 nm diameter) of HS could stimulate transformation of redox-active metals or potential pollutants trapped in soil micropores (< 2 nm diameter). A development of relationship between reducing capacity and Ex/Em position provides a possibility to predicate relative reducing capacities of HS in environmental samples.

  13. Redox-switchable second-order nonlinear optical responses of push-pull monotetrathiafulvalene-metalloporphyrins.

    Science.gov (United States)

    Liu, Chun-Guang; Guan, Wei; Song, Ping; Yan, Li-Kai; Su, Zhong-Min

    2009-07-20

    The redox-active tetrathiafulvalene (TTF) is a good electron donor, and porphyrin is highly delocalized in cyclic pi-conjugated systems. The direct combination of the two interesting building units into the same molecule provides an intriguing molecular system for designing nonlinear optical (NLO) molecular materials. In the present paper, the second-order NLO properties of a series of monoTTF-porphyrins and metalloporphyrins have been calculated by density functional theory (DFT) combined with the finite field (FF) method. Our calculations show that these compounds possess considerably large static first hyperpolarizabilities, approximately 400 x 10(-30) esu. Since the TTF unit is able to exist in three different stable redox states (TTF, TTF(*+), and TTF(2+)), the redox switching of the NLO response of the zinc(II) derivative of monoTTF-metalloporphyrin has been studied, and a substantial enhancement in static first hyperpolarizability has been obtained in its oxidized species according to our DFT-FF calculations. The beta values of one- and two-electron-oxidized species are 3.6 and 8.7 times as large as that of the neutral compound, especially for two-electron-oxidized species, with a value of 3384 x 10(-30) esu. This value is about 3 times that for a push-pull metalloporphyrin, which has an exceptionally large hyperpolarizability among reported organic NLO chromophores. Meanwhile, to give a more intuitive description of band assignments of the electron spectrum and trends in NLO behavior of these compounds, the time-dependent (TD)DFT method has been adopted to calculate the electron spectrum. The TDDFT calculations well-reproduce the soret band and Q-type bands of the monoTTF-porphyrin, and these absorption bands can be assigned to the pi --> pi* transition of the porphyrin core. On the other hand, the oxidized process significantly affects the geometrical structures of the TTF unit and porphyrin ring, and the two-electron-oxidized species has a planar TTF unit

  14. Redox regulation of antioxidants, autophagy, and the response to stress: implications for electrophile therapeutics.

    Science.gov (United States)

    Levonen, Anna-Liisa; Hill, Bradford G; Kansanen, Emilia; Zhang, Jianhua; Darley-Usmar, Victor M

    2014-06-01

    Redox networks in the cell integrate signaling pathways that control metabolism, energetics, cell survival, and death. The physiological second messengers that modulate these pathways include nitric oxide, hydrogen peroxide, and electrophiles. Electrophiles are produced in the cell via both enzymatic and nonenzymatic lipid peroxidation and are also relatively abundant constituents of the diet. These compounds bind covalently to families of cysteine-containing, redox-sensing proteins that constitute the electrophile-responsive proteome, the subproteomes of which are found in localized intracellular domains. These include those proteins controlling responses to oxidative stress in the cytosol-notably the Keap1-Nrf2 pathway, the autophagy-lysosomal pathway, and proteins in other compartments including mitochondria and endoplasmic reticulum. The signaling pathways through which electrophiles function have unique characteristics that could be exploited for novel therapeutic interventions; however, development of such therapeutic strategies has been challenging due to a lack of basic understanding of the mechanisms controlling this form of redox signaling. In this review, we discuss current knowledge of the basic mechanisms of thiol-electrophile signaling and its potential impact on the translation of this important field of redox biology to the clinic. Emerging understanding of thiol-electrophile interactions and redox signaling suggests replacement of the oxidative stress hypothesis with a new redox biology paradigm, which provides an exciting and influential framework for guiding translational research.

  15. Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

    KAUST Repository

    Liu, Pei

    2015-02-27

    Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response.

  16. Information processing through a bio-based redox capacitor: signatures for redox-cycling.

    Science.gov (United States)

    Liu, Yi; Kim, Eunkyoung; White, Ian M; Bentley, William E; Payne, Gregory F

    2014-08-01

    Redox-cycling compounds can significantly impact biological systems and can be responsible for activities that range from pathogen virulence and contaminant toxicities, to therapeutic drug mechanisms. Current methods to identify redox-cycling activities rely on the generation of reactive oxygen species (ROS), and employ enzymatic or chemical methods to detect ROS. Here, we couple the speed and sensitivity of electrochemistry with the molecular-electronic properties of a bio-based redox-capacitor to generate signatures of redox-cycling. The redox capacitor film is electrochemically-fabricated at the electrode surface and is composed of a polysaccharide hydrogel with grafted catechol moieties. This capacitor film is redox-active but non-conducting and can engage diffusible compounds in either oxidative or reductive redox-cycling. Using standard electrochemical mediators ferrocene dimethanol (Fc) and Ru(NH3)6Cl3 (Ru(3+)) as model redox-cyclers, we observed signal amplifications and rectifications that serve as signatures of redox-cycling. Three bio-relevant compounds were then probed for these signatures: (i) ascorbate, a redox-active compound that does not redox-cycle; (ii) pyocyanin, a virulence factor well-known for its reductive redox-cycling; and (iii) acetaminophen, an analgesic that oxidatively redox-cycles but also undergoes conjugation reactions. These studies demonstrate that the redox-capacitor can enlist the capabilities of electrochemistry to generate rapid and sensitive signatures of biologically-relevant chemical activities (i.e., redox-cycling).

  17. Early perturbation in mitochondria redox homeostasis in response to environmental stress predicts cell fate in diatoms.

    Science.gov (United States)

    van Creveld, Shiri Graff; Rosenwasser, Shilo; Schatz, Daniella; Koren, Ilan; Vardi, Assaf

    2015-02-01

    Diatoms are ubiquitous marine photosynthetic eukaryotes that are responsible for about 20% of global photosynthesis. Nevertheless, little is known about the redox-based mechanisms that mediate diatom sensing and acclimation to environmental stress. Here we used a redox-sensitive green fluorescent protein sensor targeted to various subcellular organelles in the marine diatom Phaeodactylum tricornutum, to map the spatial and temporal oxidation patterns in response to environmental stresses. Specific organelle oxidation patterns were found in response to various stress conditions such as oxidative stress, nutrient limitation and exposure to diatom-derived infochemicals. We found a strong correlation between the mitochondrial glutathione (GSH) redox potential (EGSH) and subsequent induction of cell death in response to the diatom-derived unsaturated aldehyde 2E,4E/Z-decadienal (DD), and a volatile halocarbon (BrCN) that mediate trophic-level interactions in marine diatoms. Induction of cell death in response to DD was mediated by oxidation of mitochondrial EGSH and was reversible by application of GSH only within a narrow time frame. We found that cell fate can be accurately predicted by a distinct life-death threshold of mitochondrial EGSH (-335 mV). We propose that compartmentalized redox-based signaling can integrate the input of diverse environmental cues and will determine cell fate decisions as part of algal acclimation to stress conditions.

  18. A chemically powered unidirectional rotary molecular motor based on a palladium redox cycle

    Science.gov (United States)

    Collins, Beatrice S. L.; Kistemaker, Jos C. M.; Otten, Edwin; Feringa, Ben L.

    2016-09-01

    The conversion of chemical energy to drive directional motion at the molecular level allows biological systems, ranging from subcellular components to whole organisms, to perform a myriad of dynamic functions and respond to changes in the environment. Directional movement has been demonstrated in artificial molecular systems, but the fundamental motif of unidirectional rotary motion along a single-bond rotary axle induced by metal-catalysed transformation of chemical fuels has not been realized, and the challenge is to couple the metal-centred redox processes to stepwise changes in conformation to arrive at a full unidirectional rotary cycle. Here, we present the design of an organopalladium-based motor and the experimental demonstration of a 360° unidirectional rotary cycle using simple chemical fuels. Exploiting fundamental reactivity principles in organometallic chemistry enables control of directional rotation and offers the potential of harnessing the wealth of opportunities offered by transition-metal-based catalytic conversions to drive motion and dynamic functions.

  19. Carotenoid responses to environmental stimuli: integrating redox and carbon controls into a fruit model.

    Science.gov (United States)

    Fanciullino, A L; Bidel, L P R; Urban, L

    2014-02-01

    Carotenoids play an important role in plant adaptation to fluctuating environments as well as in the human diet by contributing to the prevention of chronic diseases. Insights have been gained recently into the way individual factors, genetic, environmental or developmental, control the carotenoid biosynthetic pathway at the molecular level. The identification of the rate-limiting steps of carotenogenesis has paved the way for programmes of breeding, and metabolic engineering, aimed at increasing the concentration of carotenoids in different crop species. However, the complexity that arises from the interactions between the different factors as well as from the coordination between organs remains poorly understood. This review focuses on recent advances in carotenoid responses to environmental stimuli and discusses how the interactions between the modulation factors and between organs affect carotenoid build-up. We develop the idea that reactive oxygen species/redox status and sugars/carbon status can be considered as integrated factors that account for most effects of the major environmental factors influencing carotenoid biosynthesis. The discussion highlights the concept of carotenoids or carotenoid-derivatives as stress signals that may be involved in feedback controls. We propose a conceptual model of the effects of environmental and developmental factors on carotenoid build-up in fruits.

  20. Electrochemical reverse engineering: A systems-level tool to probe the redox-based molecular communication of biology.

    Science.gov (United States)

    Li, Jinyang; Liu, Yi; Kim, Eunkyoung; March, John C; Bentley, William E; Payne, Gregory F

    2016-12-29

    The intestine is the site of digestion and forms a critical interface between the host and the outside world. This interface is composed of host epithelium and a complex microbiota which is "connected" through an extensive web of chemical and biological interactions that determine the balance between health and disease for the host. This biology and the associated chemical dialogues occur within a context of a steep oxygen gradient that provides the driving force for a variety of reduction and oxidation (redox) reactions. While some redox couples (e.g., catecholics) can spontaneously exchange electrons, many others are kinetically "insulated" (e.g., biothiols) allowing the biology to set and control their redox states far from equilibrium. It is well known that within cells, such non-equilibrated redox couples are poised to transfer electrons to perform reactions essential to immune defense (e.g., transfer from NADH to O2 for reactive oxygen species, ROS, generation) and protection from such oxidative stresses (e.g., glutathione-based reduction of ROS). More recently, it has been recognized that some of these redox-active species (e.g., H2O2) cross membranes and diffuse into the extracellular environment including lumen to transmit redox information that is received by atomically-specific receptors (e.g., cysteine-based sulfur switches) that regulate biological functions. Thus, redox has emerged as an important modality in the chemical signaling that occurs in the intestine and there have been emerging efforts to develop the experimental tools needed to probe this modality. We suggest that electrochemistry provides a unique tool to experimentally probe redox interactions at a systems level. Importantly, electrochemistry offers the potential to enlist the extensive theories established in signal processing in an effort to "reverse engineer" the molecular communication occurring in this complex biological system. Here, we review our efforts to develop this

  1. Evolutionary Design of Low Molecular Weight Organic Anolyte Materials for Applications in Nonaqueous Redox Flow Batteries.

    Science.gov (United States)

    Sevov, Christo S; Brooner, Rachel E M; Chénard, Etienne; Assary, Rajeev S; Moore, Jeffrey S; Rodríguez-López, Joaquín; Sanford, Melanie S

    2015-11-18

    The integration of renewable energy sources into the electric grid requires low-cost energy storage systems that mediate the variable and intermittent flux of energy associated with most renewables. Nonaqueous redox-flow batteries have emerged as a promising technology for grid-scale energy storage applications. Because the cost of the system scales with mass, the electroactive materials must have a low equivalent weight (ideally 150 g/(mol·e(-)) or less), and must function with low molecular weight supporting electrolytes such as LiBF4. However, soluble anolyte materials that undergo reversible redox processes in the presence of Li-ion supports are rare. We report the evolutionary design of a series of pyridine-based anolyte materials that exhibit up to two reversible redox couples at low potentials in the presence of Li-ion supporting electrolytes. A combination of cyclic voltammetry of anolyte candidates and independent synthesis of their corresponding charged-states was performed to rapidly screen for the most promising candidates. Results of this workflow provided evidence for possible decomposition pathways of first-generation materials and guided synthetic modifications to improve the stability of anolyte materials under the targeted conditions. This iterative process led to the identification of a promising anolyte material, N-methyl 4-acetylpyridinium tetrafluoroborate. This compound is soluble in nonaqueous solvents, is prepared in a single synthetic step, has a low equivalent weight of 111 g/(mol·e(-)), and undergoes two reversible 1e(-) reductions in the presence of LiBF4 to form reduced products that are stable over days in solution.

  2. Role of redox environment on the oligomerization of higher molecular weight adiponectin

    Directory of Open Access Journals (Sweden)

    Nuñez Martha

    2011-05-01

    Full Text Available Abstract Background Adiponectin is an adipocyte-secreted hormone with insulin-sensitizing and anti-inflammatory actions. The assembly of trimeric, hexameric, and higher molecular weight (HMW species of adiponectin is a topic of significant interest because physiological actions of adiponectin are oligomer-specific. In addition, adiponectin assembly is an example of oxidative oligomerization of multi-subunit protein complexes in endoplasmic reticulum (ER. Results We previously reported that trimers assemble into HMW adiponectin via intermediates stabilized by disulfide bonds, and complete oxidation of available cysteines locks adiponectin in hexameric conformation. In this study, we examined the effects of redox environment on the rate of oligomer formation and the distribution of oligomers. Reassembly of adiponectin under oxidizing conditions accelerated disulfide bonding but favored formation of hexamers over the HMW species. Increased ratios of HMW to hexameric adiponectin could be achieved rapidly under oxidizing conditions by promoting disulfide rearrangement. Conclusions Based upon these observations, we propose oxidative assembly of multi-subunit adiponectin complexes in a defined and stable redox environment is favored under oxidizing conditions coupled with high rates of disulfide rearrangement.

  3. Redox-active cellulose Langmuir-Blodgett films containing beta-carotene as a molecular wire.

    Science.gov (United States)

    Sakakibara, Keita; Kamitakahara, Hiroshi; Takano, Toshiyuki; Nakatsubo, Fumiaki

    2007-05-01

    Redox-active Langmuir-Blodgett (LB) films containing dihydrophytyl ferrocenoate (DFc) and beta-carotene (betaC) were fabricated by use of 6-O-dihydrophytylcellulose (DHPC) as a matrix. A mixture of DFc-DHPC formed a stable monolayer. Atomic force microscopy images revealed that the DFc molecules were dispersed uniformly throughout the surface in the ratio DFc:DHPC = 2:8 at 30 mN m-1. The DFc-DHPC monolayer was transferred successfully onto a substrate, yielding Y-type LB films. Cyclic voltammograms for the DFc-DHPC LB films on an indium tin oxide (ITO) electrode exhibited a well-defined surface wave. The voltammograms of the DFc-DHPC LB films exhibited 60-40% redox-active ferrocene moieties, whereas those of the DFc-DHPC-betaC LB films exhibited 90-70%. X-ray diffraction patterns indicated that the distance between layers was independent of betaC molecules incorporated into the LB films. Consequently, these results suggested that betaC can function as a molecular wire.

  4. Parameterization of the prosthetic redox centers of the bacterial cytochrome bc(1) complex for atomistic molecular dynamics simulations

    DEFF Research Database (Denmark)

    Kaszuba, K.; Postila, P. A.; Cramariuc, O.

    2013-01-01

    -molecular interactions at different redox stages of the cyt bc(1) complex. Accordingly, here we present high-precision atomic point charges for the metal centers of the cyt bc(1) complex of Rhodobacter capsulatus derived from extensive density functional theory calculations, fitted using the restrained electrostatic......Cytochrome (cyt) bc(1) is a multi-subunit membrane protein complex that is a vital component of the respiratory and photosynthetic electron transfer chains both in bacteria and eukaryotes. Although the complex's dimer structure has been solved using X-ray crystallography, it has not yet been...... studied in large-scale classical molecular dynamics (MD) simulations. In part, this is due to lack of suitable force field parameters, centered atomic point charges in particular, for the complex's prosthetic redox centers. Accurate redox center charges are needed to depict realistically the inter...

  5. Molecular Engineering with Organic Carbonyl Electrode Materials for Advanced Stationary and Redox Flow Rechargeable Batteries.

    Science.gov (United States)

    Zhao, Qing; Zhu, Zhiqiang; Chen, Jun

    2017-04-03

    Organic carbonyl electrode materials that have the advantages of high capacity, low cost and being environmentally friendly, are regarded as powerful candidates for next-generation stationary and redox flow rechargeable batteries (RFBs). However, low carbonyl utilization, poor electronic conductivity and undesired dissolution in electrolyte are urgent issues to be solved. Here, we summarize a molecular engineering approach for tuning the capacity, working potential, concentration of active species, kinetics, and stability of stationary and redox flow batteries, which well resolves the problems of organic carbonyl electrode materials. As an example, in stationary batteries, 9,10-anthraquinone (AQ) with two carbonyls delivers a capacity of 257 mAh g(-1) (2.27 V vs Li(+) /Li), while increasing the number of carbonyls to four with the formation of 5,7,12,14-pentacenetetrone results in a higher capacity of 317 mAh g(-1) (2.60 V vs Li(+) /Li). In RFBs, AQ, which is less soluble in aqueous electrolyte, reaches 1 M by grafting -SO3 H with the formation of 9,10-anthraquinone-2,7-disulphonic acid, resulting in a power density exceeding 0.6 W cm(-2) with long cycling life. Therefore, through regulating substituent groups, conjugated structures, Coulomb interactions, and the molecular weight, the electrochemical performance of carbonyl electrode materials can be rationally optimized. This review offers fundamental principles and insight into designing advanced carbonyl materials for the electrodes of next-generation rechargeable batteries. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish.

    Science.gov (United States)

    Yoo, Sa Kan; Freisinger, Christina M; LeBert, Danny C; Huttenlocher, Anna

    2012-10-15

    Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H(2)O(2) at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immediate SFK and calcium signaling in epithelia was important for late epimorphic regeneration of amputated fins. Wound-induced activation of SFKs in epithelia was dependent on injury-generated H(2)O(2). A SFK member, Fynb, was responsible for fin regeneration. This work provides a new link between early wound responses and late regeneration and suggests that redox, SFK, and calcium signaling are immediate "wound signals" that integrate early wound responses and late epimorphic regeneration.

  7. A protective role for HIF-1 in response to redox manipulation and glucose deprivation: implications for tumorigenesis.

    NARCIS (Netherlands)

    Williams, K.J.; Telfer, B.A.; Airley, R.E.; Peters, J.P.W.; Sheridan, M.R.; Kogel, A.J. van der; Harris, A.L.; Stratford, I.J.

    2002-01-01

    We have investigated the role of HIF-1 in the cellular response to redox modulation via the inhibition of oxidative phosphorylation. We demonstrate that manipulation of redox in air, achieved by inhibiting cytochrome oxidase with cyanide, induces HIF-1 mediated transcription in wild-type CHO and HT1

  8. Redox-Responsive Porphyrin-Based Polysilsesquioxane Nanoparticles for Photodynamic Therapy of Cancer Cells

    Directory of Open Access Journals (Sweden)

    Daniel L. Vega

    2015-12-01

    Full Text Available The development of stimulus-responsive photosensitizer delivery systems that carry a high payload of photosensitizers is of great importance in photodynamic therapy. In this study, redox-responsive polysilsesquioxane nanoparticles (PSilQNPs built by a reverse microemulsion approach using 5,10,15,20-tetrakis(carboxyphenyl porphyrin (TCPP silane derivatives as building blocks, were successfully fabricated. The structural properties of TCPP-PSilQNPs were characterized by dynamic light scattering (DLS/ζ-potential, scanning electron microscopy (SEM and thermogravimetric analysis (TGA. The photophysical properties were determined by UV-vis and fluorescence spectroscopy. The quantity of singlet oxygen generated in solution was measured using 1,3-diphenylisobenzofuran. The redox-responsive release of TCPP molecules was successfully demonstrated in solution in the presence of a reducing agent. The internalization of TCPP-PSilQNPs in cancer cells was investigated using laser scanning confocal microscopy. Phototoxicity experiments in vitro showed that the redox-responsive TCPP-PSilQNPs exhibited an improved phototherapeutic effect on cervical cancer cells compared to a non-responsive TCPP-PSilQNP control material.

  9. Redox-Responsive Porphyrin-Based Polysilsesquioxane Nanoparticles for Photodynamic Therapy of Cancer Cells

    Science.gov (United States)

    Vega, Daniel L.; Lodge, Patrick; Vivero-Escoto, Juan L.

    2015-01-01

    The development of stimulus-responsive photosensitizer delivery systems that carry a high payload of photosensitizers is of great importance in photodynamic therapy. In this study, redox-responsive polysilsesquioxane nanoparticles (PSilQNPs) built by a reverse microemulsion approach using 5,10,15,20-tetrakis(carboxyphenyl) porphyrin (TCPP) silane derivatives as building blocks, were successfully fabricated. The structural properties of TCPP-PSilQNPs were characterized by dynamic light scattering (DLS)/ζ-potential, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The photophysical properties were determined by UV-vis and fluorescence spectroscopy. The quantity of singlet oxygen generated in solution was measured using 1,3-diphenylisobenzofuran. The redox-responsive release of TCPP molecules was successfully demonstrated in solution in the presence of a reducing agent. The internalization of TCPP-PSilQNPs in cancer cells was investigated using laser scanning confocal microscopy. Phototoxicity experiments in vitro showed that the redox-responsive TCPP-PSilQNPs exhibited an improved phototherapeutic effect on cervical cancer cells compared to a non-responsive TCPP-PSilQNP control material. PMID:26729110

  10. Improvement in the assessment of direct and facilitated ion transfers by electrochemically induced redox transformations of common molecular probes

    DEFF Research Database (Denmark)

    Zhou, Min; Gan, Shiyu; Zhong, Lijie;

    2012-01-01

    A new strategy based on a thick organic film modified electrode allowed us, for the first time, to explore the voltammetric processes for a series of hydrophilic ions by electrochemically induced redox transformations of common molecular probes. During the limited time available for voltammetry, ...

  11. pH and redox responsive polymer for antifouling surface coating

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kang Seok [Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju, 380-702 (Korea, Republic of); In, Insik, E-mail: in1@ut.ac.kr [Department of Polymer Science and Engineering, Korea National University of Transportation, Chungju, 380-702 (Korea, Republic of); Department of IT Convergence, Korea National University of Transportation, Chungju, 380-702 (Korea, Republic of); Park, Sung Young, E-mail: parkchem@ut.ac.kr [Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju, 380-702 (Korea, Republic of); Department of IT Convergence, Korea National University of Transportation, Chungju, 380-702 (Korea, Republic of)

    2014-09-15

    Graphical abstract: Dual responsive surface with highly fouling resistance with the formation of a pH-dependent benzoic imine and redox-sensitive disulfide bond has been developed using a catechol/benzoic acid conjugated polymer and disulfide containing amine end-capped Pluronic. - Highlights: • Stimuli-responsive antifouling surface was prepared by layer-by-layer method. • The surface contact angle showed responsive behavior via pH and redox environments. • Simply coated polymer completely prevented cell adhesion onto surfaces. - Abstract: A dual environmentally responsive polymer with a highly fouling-resistant surface has been developed using poly[(hydroxyethyl methacrylate-g-benzoic acid)-co-(dimethylaminoethyl methacrylate-g-2-chloro-3′, 4′-dihydroxyacetophenone)] [poly[(HEMA-BA)-co-(DMAEMA-CCDP)], P1] as a coating material. The redox-sensitive disulfide containing amine end-capped Pluronic [(Plu-S-S-NH{sub 2}), P2] was then introduced over the P1 surface via the formation of a pH-dependent benzoic imine bond, where the polyethylene glycol (PEG) acts as an antifouling agent. The successful adhesion of P1 and the deposition of P2 onto the P1-coated substrate were ascertained with X-ray photoelectron spectroscopy (XPS). In vitro cell adhesion followed by scanning electron microscopy (SEM) indicated an excellent antifouling nature of the P2 layer. Consequently, the reattachment of Hela cells was strongly observed when P2 layered on P1-coated substrates (P1–P2) was pretreated at lower pH and high redox conditions. The P1–P2 bilayer-coated substrate has exhibited a great advantage in its effective antifouling behaviors with well-tuned cell attachment and detachment.

  12. Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

    Directory of Open Access Journals (Sweden)

    S.F. Fonseca

    2016-03-01

    Full Text Available Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H and 8 normotensive (N subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively. They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity. Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS levels and ferric reducing ability of plasma (FRAP. Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05, although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1 and lower TBARS (P<0.01 and FRAP (P<0.05 levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors, present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

  13. Size-controlled and redox-responsive supramolecular nanoparticles

    Directory of Open Access Journals (Sweden)

    Raquel Mejia-Ariza

    2015-12-01

    Full Text Available Control over the assembly and disassembly of nanoparticles is pivotal for their use as drug delivery vehicles. Here, we aim to form supramolecular nanoparticles (SNPs by combining advantages of the reversible assembly properties of SNPs using host–guest interactions and of a stimulus-responsive moiety. The SNPs are composed of a core of positively charged poly(ethylene imine grafted with β-cyclodextrin (CD and a positively charged ferrocene (Fc-terminated poly(amidoamine dendrimer, with a monovalent stabilizer at the surface. Fc was chosen for its loss of CD-binding properties when oxidizing it to the ferrocenium cation. The ionic strength was shown to play an important role in controlling the aggregate growth. The attractive supramolecular and repulsive electrostatic interactions constitute a balance of forces in this system at low ionic strengths. At higher ionic strengths, the increased charge screening led to a loss of electrostatic repulsion and therefore to faster aggregate growth. A Job plot showed that a 1:1 stoichiometry of host and guest moieties gave the most efficient aggregate growth. Different stabilizers were used to find the optimal stopper to limit the growth. A weaker guest moiety was shown to be less efficient in stabilizing the SNPs. Also steric repulsion is important for achieving SNP stability. SNPs of controlled particle size and good stability (up to seven days were prepared by fine-tuning the ratio of multivalent and monovalent interactions. Finally, reversibility of the SNPs was confirmed by oxidizing the Fc guest moieties in the core of the SNPs.

  14. Size-controlled and redox-responsive supramolecular nanoparticles.

    Science.gov (United States)

    Mejia-Ariza, Raquel; Kronig, Gavin A; Huskens, Jurriaan

    2015-01-01

    Control over the assembly and disassembly of nanoparticles is pivotal for their use as drug delivery vehicles. Here, we aim to form supramolecular nanoparticles (SNPs) by combining advantages of the reversible assembly properties of SNPs using host-guest interactions and of a stimulus-responsive moiety. The SNPs are composed of a core of positively charged poly(ethylene imine) grafted with β-cyclodextrin (CD) and a positively charged ferrocene (Fc)-terminated poly(amidoamine) dendrimer, with a monovalent stabilizer at the surface. Fc was chosen for its loss of CD-binding properties when oxidizing it to the ferrocenium cation. The ionic strength was shown to play an important role in controlling the aggregate growth. The attractive supramolecular and repulsive electrostatic interactions constitute a balance of forces in this system at low ionic strengths. At higher ionic strengths, the increased charge screening led to a loss of electrostatic repulsion and therefore to faster aggregate growth. A Job plot showed that a 1:1 stoichiometry of host and guest moieties gave the most efficient aggregate growth. Different stabilizers were used to find the optimal stopper to limit the growth. A weaker guest moiety was shown to be less efficient in stabilizing the SNPs. Also steric repulsion is important for achieving SNP stability. SNPs of controlled particle size and good stability (up to seven days) were prepared by fine-tuning the ratio of multivalent and monovalent interactions. Finally, reversibility of the SNPs was confirmed by oxidizing the Fc guest moieties in the core of the SNPs.

  15. Investigation of multi-state charge-storage properties of redox-active organic molecules in silicon-molecular hybrid devices for DRAM and Flash applications

    Science.gov (United States)

    Gowda, Srivardhan Shivappa

    Molecular electronics has recently spawned a considerable amount of interest with several molecules possessing charge-conduction and charge-storage properties proposed for use in electronic devices. Hybrid silicon-molecular technology has the promise of augmenting the current silicon technology and provide for a transitional path to future molecule-only technology. The focus of this dissertation work has been on developing a class of hybrid silicon-molecular electronic devices for DRAM and Flash memory applications utilizing redox-active molecules. This work exploits the ability of molecules to store charges with single-electron precision at room temperature. The hybrid devices are fabricated by forming self-assembled monolayers of redox-active molecules on Si and oxide (SiO2 and HfO2) surfaces via formation of covalent linkages. The molecules possess discrete quantum states from which electrons can tunnel to the Si substrate at discrete applied voltages (oxidation process, cell write), leaving behind a positively charged layer of molecules. The reduction (erase) process, which is the process of electrons tunneling back from Si to the molecules, neutralizes the positively charged molecular monolayer. Hybrid silicon-molecular capacitor test structures were electrically characterized with an electrolyte gate using cyclic voltammetry (CyV) and impedance spectroscopy (CV) techniques. The redox voltages, kinetics (write/erase speeds) and charge-retention characteristics were found to be strongly dependent on the Si doping type and densities, and ambient light. It was also determined that the redox energy states in the molecules communicate with the valence band of the Si substrate. This allows tuning of write and read states by modulating minority carriers in n- and p-Si substrates. Ultra-thin dielectric tunnel barriers (SiO2, HfO2) were placed between the molecules and the Si substrate to augment charge-retention for Flash memory applications. The redox response was

  16. Redox regulation of T-cell function: from molecular mechanisms to significance in human health and disease.

    Science.gov (United States)

    Kesarwani, Pravin; Murali, Anuradha K; Al-Khami, Amir A; Mehrotra, Shikhar

    2013-04-20

    Reactive oxygen species (ROS) are thought to have effects on T-cell function and proliferation. Low concentrations of ROS in T cells are a prerequisite for cell survival, and increased ROS accumulation can lead to apoptosis/necrosis. The cellular redox state of a T cell can also affect T-cell receptor signaling, skewing the immune response. Various T-cell subsets have different redox statuses, and this differential ROS susceptibility could modulate the outcome of an immune response in various disease states. Recent advances in T-cell redox signaling reveal that ROS modulate signaling cascades such as the mitogen-activated protein kinase, phosphoinositide 3-kinase (PI3K)/AKT, and JAK/STAT pathways. Also, tumor microenvironments, chronic T-cell stimulation leading to replicative senescence, gender, and age affect T-cell susceptibility to ROS, thereby contributing to diverse immune outcomes. Antioxidants such as glutathione, thioredoxin, superoxide dismutase, and catalase balance cellular oxidative stress. T-cell redox states are also regulated by expression of various vitamins and dietary compounds. Changes in T-cell redox regulation may affect the pathogenesis of various human diseases. Many strategies to control oxidative stress have been employed for various diseases, including the use of active antioxidants from dietary products and pharmacologic or genetic engineering of antioxidant genes in T cells. Here, we discuss the existence of a complex web of molecules/factors that exogenously or endogenously affect oxidants, and we relate these molecules to potential therapeutics.

  17. Redox proteomics and the dynamic molecular landscape of the aging brain.

    Science.gov (United States)

    Perluigi, Marzia; Swomley, Aaron M; Butterfield, D Allan

    2014-01-01

    It is well established that the risk to develop neurodegenerative disorders increases with chronological aging. Accumulating studies contributed to characterize the age-dependent changes either at gene and protein expression level which, taken together, show that aging of the human brain results from the combination of the normal decline of multiple biological functions with environmental factors that contribute to defining disease risk of late-life brain disorders. Finding the "way out" of the labyrinth of such complex molecular interactions may help to fill the gap between "normal" brain aging and development of age-dependent diseases. To this purpose, proteomics studies are a powerful tool to better understand where to set the boundary line of healthy aging and age-related disease by analyzing the variation of protein expression levels and the major post translational modifications that determine "protein" physio/pathological fate. Increasing attention has been focused on oxidative modifications due to the crucial role of oxidative stress in aging, in addition to the fact that this type of modification is irreversible and may alter protein function. Redox proteomics studies contributed to decipher the complexity of brain aging by identifying the proteins that were increasingly oxidized and eventually dysfunctional as a function of age. The purpose of this review is to summarize the most important findings obtained by applying proteomics approaches to murine models of aging with also a brief overview of some human studies, in particular those related to dementia.

  18. Genome-wide transcriptional response of a Saccharomyces cerevisiae strain with an altered redox metabolism.

    Science.gov (United States)

    Bro, Christoffer; Regenberg, Birgitte; Nielsen, Jens

    2004-02-05

    The genome-wide transcriptional response of a Saccharomyces cerevisiae strain deleted in GDH1 that encodes a NADP(+)-dependent glutamate dehydrogenase was compared to a wild-type strain under anaerobic steady-state conditions. The GDH1-deleted strain has a significantly reduced NADPH requirement, and therefore, an altered redox metabolism. Identification of genes with significantly changed expression using a t-test and a Bonferroni correction yielded only 16 transcripts when accepting two false-positives, and 7 of these were Open Reading Frames (ORFs) with unknown function. Among the 16 transcripts the only one with a direct link to redox metabolism was GND1, encoding phosphogluconate dehydrogenase. To extract additional information we analyzed the transcription data for a gene subset consisting of all known genes encoding metabolic enzymes that use NAD(+) or NADP(+). The subset was analyzed for genes with significantly changed expression again with a t-test and correction for multiple testing. This approach was found to enrich the analysis since GND1, ZWF1 and ALD6, encoding the most important enzymes for regeneration of NADPH under anaerobic conditions, were down-regulated together with eight other genes encoding NADP(H)-dependent enzymes. This indicates a possible common redox-dependent regulation of these genes. Furthermore, we showed that it might be necessary to analyze the expression of a subset of genes to extract all available information from global transcription analysis.

  19. Redox Stimulation of Human THP-1 Monocytes in Response to Cold Physical Plasma

    Directory of Open Access Journals (Sweden)

    Sander Bekeschus

    2016-01-01

    Full Text Available In plasma medicine, cold physical plasma delivers a delicate mixture of reactive components to cells and tissues. Recent studies suggested a beneficial role of cold plasma in wound healing. Yet, the biological processes related to the redox modulation via plasma are not fully understood. We here used the monocytic cell line THP-1 as a model to test their response to cold plasma in vitro. Intriguingly, short term plasma treatment stimulated cell growth. Longer exposure only modestly compromised cell viability but apparently supported the growth of cells that were enlarged in size and that showed enhanced metabolic activity. A significantly increased mitochondrial content in plasma treated cells supported this notion. On THP-1 cell proteome level, we identified an increase of protein translation with key regulatory proteins being involved in redox regulation (hypoxia inducible factor 2α, differentiation (retinoic acid signaling and interferon inducible factors, and cell growth (Yin Yang 1. Regulation of inflammation is a key element in many chronic diseases, and we found a significantly increased expression of the anti-inflammatory heme oxygenase 1 (HMOX1 and of the neutrophil attractant chemokine interleukin-8 (IL-8. Together, these results foster the view that cold physical plasma modulates the redox balance and inflammatory processes in wound related cells.

  20. Redox Modulation Matters: Emerging Functions for Glutaredoxins in Plant Development and Stress Responses

    Directory of Open Access Journals (Sweden)

    Shutian Li

    2014-11-01

    Full Text Available Glutaredoxins (GRXs are small ubiquitous glutathione (GSH-dependent oxidoreductases that catalyze the reversible reduction of protein disulfide bridges or protein-GSH mixed disulfide bonds via a dithiol or monothiol mechanism, respectively. Three major classes of GRXs, with the CPYC-type, the CGFS-type or the CC-type active site, have been identified in many plant species. In spite of the well-characterized roles for GRXs in Escherichia coli, yeast and humans, the biological functions of plant GRXs have been largely enigmatic. The CPYC-type and CGFS-type GRXs exist in all organisms, from prokaryotes to eukaryotes, whereas the CC-type class has thus far been solely identified in land plants. Only the number of the CC-type GRXs has enlarged dramatically during the evolution of land plants, suggesting their participation in the formation of more complex plants adapted to life on land. A growing body of evidence indicates that plant GRXs are involved in numerous cellular pathways. In this review, emphasis is placed on the recently emerging functions for GRXs in floral organ development and disease resistance. Notably, CC-type GRXs have been recruited to participate in these two seemingly unrelated processes. Besides, the current knowledge of plant GRXs in the assembly and delivery of iron-sulfur clusters, oxidative stress responses and arsenic resistance is also presented. As GRXs require GSH as an electron donor to reduce their target proteins, GSH-related developmental processes, including the control of flowering time and the development of postembryonic roots and shoots, are further discussed. Profiling the thiol redox proteome using high-throughput proteomic approaches and measuring cellular redox changes with fluorescent redox biosensors will help to further unravel the redox-regulated physiological processes in plants.

  1. A Redox-Controllable Molecular Switch Based on Weak Recognition of BPX26C6 at a Diphenylurea Station

    Directory of Open Access Journals (Sweden)

    Jia-Cheng Chang

    2015-01-01

    Full Text Available The Na+ ion–assisted recognition of urea derivatives by BPX26C6 has allowed the construction of a redox-controllable [2]rotaxane-type molecular switch based on two originally very weakly interacting host/guest systems. Using NOBF4 to oxidize the triarylamine terminus into a corresponding radical cation attracted the macrocyclic component toward its adjacent carbamate station; subsequent addition of Zn powder moved the macrocyclic component back to its urea station.

  2. Impact of redox-active polymer molecular weight on the electrochemical properties and transport across porous separators in nonaqueous solvents.

    Science.gov (United States)

    Nagarjuna, Gavvalapalli; Hui, Jingshu; Cheng, Kevin J; Lichtenstein, Timothy; Shen, Mei; Moore, Jeffrey S; Rodríguez-López, Joaquín

    2014-11-19

    Enhancing the ionic conductivity across the electrolyte separator in nonaqueous redox flow batteries (NRFBs) is essential for improving their performance and enabling their widespread utilization. Separating redox-active species by size exclusion without greatly impeding the transport of supporting electrolyte is a potentially powerful alternative to the use of poorly performing ion-exchange membranes. However, this strategy has not been explored possibly due to the lack of suitable redox-active species that are easily varied in size, remain highly soluble, and exhibit good electrochemical properties. Here we report the synthesis, electrochemical characterization, and transport properties of redox-active poly(vinylbenzyl ethylviologen) (RAPs) with molecular weights between 21 and 318 kDa. The RAPs reported here show very good solubility (up to at least 2.0 M) in acetonitrile and propylene carbonate. Ultramicroelectrode voltammetry reveals facile electron transfer with E1/2 ∼ -0.7 V vs Ag/Ag(+)(0.1 M) for the viologen 2+/+ reduction at concentrations as high as 1.0 M in acetonitrile. Controlled potential bulk electrolysis indicates that 94-99% of the nominal charge on different RAPs is accessible and that the electrolysis products are stable upon cycling. The dependence of the diffusion coefficient on molecular weight suggests the adequacy of the Stokes-Einstein formalism to describe RAPs. The size-selective transport properties of LiBF4 and RAPs across commercial off-the-shelf (COTS) separators such as Celgard 2400 and Celgard 2325 were tested. COTS porous separators show ca. 70 times higher selectivity for charge balancing ions (Li(+)BF4(-)) compared to high molecular weight RAPs. RAPs rejection across these separators showed a strong dependence on polymer molecular weight as well as the pore size; the rejection increased with both increasing polymer molecular weight and reduction in pore size. Significant rejection was observed even for rpoly/rpore (polymer

  3. Keap1 redox-dependent regulation of doxorubicin-induced oxidative stress response in cardiac myoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Nordgren, Kendra K.S., E-mail: knordgre@d.umn.edu; Wallace, Kendall B., E-mail: kwallace@d.umn.edu

    2014-01-01

    Doxorubicin (DOX) is a widely prescribed treatment for a broad scope of cancers, but clinical utility is limited by the cumulative, dose-dependent cardiomyopathy that occurs with repeated administration. DOX-induced cardiotoxicity is associated with the production of reactive oxygen species (ROS) and oxidation of lipids, DNA and proteins. A major cellular defense mechanism against such oxidative stress is activation of the Keap1/Nrf2-antioxidant response element (ARE) signaling pathway, which transcriptionally regulates expression of antioxidant genes such as Nqo1 and Gstp1. In the present study, we address the hypothesis that an initial event associated with DOX-induced oxidative stress is activation of the Keap1/Nrf2-dependent expression of antioxidant genes and that this is regulated through drug-induced changes in redox status of the Keap1 protein. Incubation of H9c2 rat cardiac myoblasts with DOX resulted in a time- and dose-dependent decrease in non-protein sulfhydryl groups. Associated with this was a near 2-fold increase in Nrf2 protein content and enhanced transcription of several of the Nrf2-regulated down-stream genes, including Gstp1, Ugt1a1, and Nqo1; the expression of Nfe2l2 (Nrf2) itself was unaltered. Furthermore, both the redox status and the total amount of Keap1 protein were significantly decreased by DOX, with the loss of Keap1 being due to both inhibited gene expression and increased autophagic, but not proteasomal, degradation. These findings identify the Keap1/Nrf2 pathway as a potentially important initial response to acute DOX-induced oxidative injury, with the primary regulatory events being the oxidation and autophagic degradation of the redox sensor Keap1 protein. - Highlights: • DOX caused a ∼2-fold increase in Nrf2 protein content. • DOX enhanced transcription of several Nrf2-regulated down-stream genes. • Redox status and total amount of Keap1 protein were significantly decreased by DOX. • Loss of Keap1 protein was due to

  4. HPLC analysis of nonprotein thiols in planktonic diatoms: Pool size, redox state and response to copper and cadmium exposure

    NARCIS (Netherlands)

    Rijstenbil, J.W.; Wijnholds, J.A.

    1996-01-01

    A sensitive method was developed to analyze low molecular weight thiols involved in metal homeostasis and detoxification in phytoplankton. The aims of this study were to (1) separate and measure all relevant thiols in a single HPLC run; (2) measure redox states of the thiols and (3) identify specifi

  5. Cyclophilin 20-3 relays a 12-oxo-phytodienoic acid signal during stress responsive regulation of cellular redox homeostasis.

    Science.gov (United States)

    Park, Sang-Wook; Li, Wei; Viehhauser, Andrea; He, Bin; Kim, Soonok; Nilsson, Anders K; Andersson, Mats X; Kittle, Joshua D; Ambavaram, Madana M R; Luan, Sheng; Esker, Alan R; Tholl, Dorothea; Cimini, Daniela; Ellerström, Mats; Coaker, Gitta; Mitchell, Thomas K; Pereira, Andy; Dietz, Karl-Josef; Lawrence, Christopher B

    2013-06-04

    The jasmonate family of phytohormones plays central roles in plant development and stress acclimation. However, the architecture of their signaling circuits remains largely unknown. Here we describe a jasmonate family binding protein, cyclophilin 20-3 (CYP20-3), which regulates stress-responsive cellular redox homeostasis. (+)-12-Oxo-phytodienoic acid (OPDA) binding promotes CYP20-3 to form a complex with serine acetyltransferase 1, which triggers the formation of a hetero-oligomeric cysteine synthase complex with O-acetylserine(thiol)lyase B in chloroplasts. The cysteine synthase complex formation then activates sulfur assimilation that leads to increased levels of thiol metabolites and the buildup of cellular reduction potential. The enhanced redox capacity in turn coordinates the expression of a subset of OPDA-responsive genes. Thus, we conclude that CYP20-3 is a key effector protein that links OPDA signaling to amino acid biosynthesis and cellular redox homeostasis in stress responses.

  6. Electrochemical Rectification of Redox Mediators Using Porphyrin-Based Molecular Multilayered Films on ITO Electrodes.

    Science.gov (United States)

    Civic, Marissa R; Dinolfo, Peter H

    2016-08-10

    Electrochemical charge transfer through multilayer thin films of zinc and nickel 5,10,15,20-tetra(4-ethynylphenyl) porphyrin constructed via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry was examined. Current rectification toward various outer-sphere redox probes is revealed with increasing numbers of layers, as these films possess insulating properties over the neutral potential range of the porphyrin, then become conductive upon reaching its oxidation potential. Interfacial electron transfer rates of mediator-dye interactions toward [Co(bpy)3](2+), [Co(dmb)3](2+), [Co(NO2-phen)3](2+), [Fe(bpy)3](2+), and ferrocene (Fc), all outer-sphere redox species, were measured by hydrodynamic methods. The ability to modify electroactive films' interfacial electron transfer rates, as well as current rectification toward redox species, has broad applicability in a number of devices, particularly photovoltaics and photogalvanics.

  7. Temperature, pH and redox responsive cellulose based hydrogels for protein delivery.

    Science.gov (United States)

    Dutta, Sujan; Samanta, Pousali; Dhara, Dibakar

    2016-06-01

    Cellulose based hydrogels are important due to their biocompatibility, non-toxicity and natural origin. In this work, a new set of pH, temperature and redox responsive hydrogels were prepared from carboxymethylcellulose (CMC) and poly(N-isopropylacrylamide). Copolymeric (CP) hydrogels were synthesized by copolymerizing N-isopropylacrylamide (NIPA) and methacrylated carboxymethylcellulose, semi-interpenetrating network (SIPN) hydrogels were prepared by polymerizing NIPA in presence of CMC. Two types of cross-linkers were used viz. N,N'-methylenebisacrylamide (BIS) and N,N'-bis(acryloyl)cystamine (CBA), a redox sensitive cross-linker. The structures of the hydrogels were characterized by FTIR and SEM studies. The CP hydrogels were found to be more porous than corresponding SIPNs which resulted in higher swelling for the CP hydrogels. Swelling for both the hydrogels were found to increase with CMC content. While the swelling of SIPN hydrogels showed discontinuous temperature dependency, CP hydrogels showed gradual decrease in water retention values with increase in temperature. CBA cross-linked hydrogels showed higher swelling in comparison to BIS cross-linked hydrogels. Additionally, lysozyme was loaded in the hydrogels and its in vitro release was studied in various pH, temperature and in presence of a reducing agent, glutathione (GSH). The release rate was found to be maximum at lower temperature, lower pH and in presence of GSH.

  8. Redox and pH dual-responsive PEG and chitosan-conjugated hollow mesoporous silica for controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Jian; Li, Xian; Zhang, Sha; Liu, Jie; Di, Donghua [Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016 (China); Zhang, Ying [School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, PR China. (China); Zhao, Qinfu, E-mail: zqf021110505@163.com [Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016 (China); Wang, Siling, E-mail: silingwang@syphu.edu.cn [Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016 (China)

    2016-10-01

    In this paper, a hollow mesoporous silica nanoparticles (HMSN) was used as the drug vehicle to develop the redox and pH dual stimuli-responsive delivery system, in which the chitosan (CS), a biodegradable cationic polymer, was grafted on the surface of HMSN via the cleavable disulfide bonds. CS was chosen as the gatekeeper mainly due to its appropriate molecular weight as well as possessing abundant amino groups which could be protonated in the acidic condition to achieve pH-responsive drug release. In addition, the PEG was further grafted on the surface of CS to increase the stability and biocompatibility under physiological conditions. The DOX loaded DOX/HMSN-SS-CS@PEG had a relatively high drug loading efficiency up to 32.8%. In vitro release results indicated that DOX was dramatically blocked within the mesopores of HMSN-SS-CS@PEG in pH 7.4 PBS without addition of GSH. However, the release rate of DOX was markedly increased after the addition of 10 mM GSH or in pH 5.0 release medium. Moreover, the release of DOX was further improved in pH 5.0 PBS with 10 mM GSH. The HMSN-SS-CS@PEG could markedly decrease the hemolysis percent and protein adsorption, and increase the biocompatibility and stability of HMSN compared with the HMSN-SS-CS and bare HMSN. This work suggested an exploration about HMSN based stimuli-responsive drug delivery and these results demonstrated that HMSN-SS-CS@PEG exhibited dual-responsive drug release property and could be used as a promising carrier for cancer therapy. - Highlights: • Hollow mesoporous silica nanoparticles (HMSN) were used as a drug carrier. • Chitosan (CS) and PEG were grafted on the surface of HMSN via disulfide bonds. • The DOX loaded DOX/HMSN-SS-CS@PEG had a high drug loading efficiency up to 32.8%. • DOX/HMSN-SS-CS@PEG showed redox/pH dual-responsive drug release property in vitro. • The grafted PEG could increase the biocompatibility and stability of HMSN.

  9. Nutrient and growth responses of cattail (Typha domingensis) to redox intensity and phosphate availability.

    Science.gov (United States)

    Li, Shuwen; Lissner, Jørgen; Mendelssohn, Irving A; Brix, Hans; Lorenzen, Bent; McKee, Karen L; Miao, Shili

    2010-01-01

    In the Florida Everglades, the expansion of cattail (Typha domingensis) into areas once dominated by sawgrass (Cladium jamaicense) has been attributed to altered hydrology and phosphorus (P) enrichment. The objective of this study was to quantify the interactive effects of P availability and soil redox potential (Eh) on the growth and nutrient responses of Typha, which may help to explain its expansion. The study examined the growth and nutrient responses of Typha to the interactive effects of P availability (10, 80 and 500 microg P L(-1)) and Eh level (-150, +150 and +600 mV). Plants were grown hydroponically in a factorial experiment using titanium (Ti(3+)) citrate as a redox buffer. Relative growth rate, elongation, root-supported tissue/root ratio, leaf length, lateral root length and biomass, as well as tissue nutrient concentrations, were all adversely affected by low Eh conditions. P availability compensated for the negative effect of low Eh for all these variables except that low P stimulated root length and nutrient use efficiency. The most growth-promoting treatment combination was 500 microg P L(-1)/ + 600 mV. These results, plus previous data on Cladium responses to P/Eh combinations, document that high P availability and low Eh should benefit Typha more than Cladium as the growth and tissue nutrients of the former species responded more to excess P, even under highly reduced conditions. Therefore, the interactive effects of P enrichment and Eh appear to be linked to the expansion of Typha in the Everglades Water Conservation Area 2A, where both low Eh and enhanced phosphate availability have co-occurred during recent decades.

  10. Copy number variations of genes involved in stress responses reflect the redox state and DNA damage in brewing yeasts.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Natkanska, Urszula; Kwiatkowska, Aleksandra; Rawska, Ewa; Potocki, Leszek; Kuna, Ewelina; Panek, Anita; Lewinska, Anna; Wnuk, Maciej

    2016-09-01

    The yeast strains of the Saccharomyces sensu stricto complex involved in beer production are a heterogeneous group whose genetic and genomic features are not adequately determined. Thus, the aim of the present study was to provide a genetic characterization of selected group of commercially available brewing yeasts both ale top-fermenting and lager bottom-fermenting strains. Molecular karyotyping revealed that the diversity of chromosome patterns and four strains with the most accented genetic variabilities were selected and subjected to genome-wide array-based comparative genomic hybridization (array-CGH) analysis. The differences in the gene copy number were found in five functional gene categories: (1) maltose metabolism and transport, (2) response to toxin, (3) siderophore transport, (4) cellular aldehyde metabolic process, and (5) L-iditol 2-dehydrogenase activity (p < 0.05). In the Saflager W-34/70 strain (Fermentis) with the most affected array-CGH profile, loss of aryl-alcohol dehydrogenase (AAD) gene dosage correlated with an imbalanced redox state, oxidative DNA damage and breaks, lower levels of nucleolar proteins Nop1 and Fob1, and diminished tolerance to fermentation-associated stress stimuli compared to other strains. We suggest that compromised stress response may not only promote oxidant-based changes in the nucleolus state that may affect fermentation performance but also provide novel directions for future strain improvement.

  11. Studies on Molecular and Ion Transport in Silicalite Membranes and Applications as Ion Separator for Redox Flow Battery

    Science.gov (United States)

    Yang, Ruidong

    Microporous zeolite membranes have been widely studied for molecular separations based on size exclusion or preferential adsorption-diffusion mechanisms. The MFI-type zeolite membranes were also demonstrated for brine water desalination by molecular sieving effect. In this research, the pure silica MFI-type zeolite (i.e. silicalite) membrane has been for the first time demonstrated for selective permeation of hydrated proton (i.e. H3O+) in acidic electrolyte solutions. The silicalite membrane allows for permeation of H 3O+ ions, but is inaccessible to the large hydrated multivalent vanadium ions due to steric effect. The silicalite membrane has been further demonstrated as an effective ion separator in the all-vanadium redox flow battery (RFB).The silicalite is nonionic and its proton conductivity relies on the electric field-driven H3O+ transport through the sub nanometer-sized pores under the RFB operation conditions. The silicalite membrane displayed a significantly reduced self-discharge rate because of its high proton-to-vanadium ion transport selectivity. However, the nonionic nature of the silicalite membrane and very small diffusion channel size render low proton conductivity and is therefore inefficient as ion exchange membranes (IEMs) for practical applications. The proton transport efficiency may be improved by reducing the membrane thickness. However, the zeolite thin films are extremely fragile and must be supported on mechanically strong and rigid porous substrates. In this work, silicalite-Nafion composite membranes were synthesized to achieve a colloidal silicalite skin on the Nafion thin film base. The "colloidal zeolite-ionic polymer" layered composite membrane combines the advantages of high proton-selectivity of the zeolite layer and the mechanical flexibility and low proton transport resistance of the ionic polymer membrane. The composite membrane exhibited higher proton/vanadium ion separation selectivity and lower electrical resistance than

  12. Selective redox-active molecular receptors for K+ and Ag+

    DEFF Research Database (Denmark)

    Larsen, Karina Riisom; Johnsen, Carsten; Hammerich, Ole;

    2013-01-01

    Two new tetrathiafulvalene based receptors in which the favorable redox properties of the tetrathiafulvalene unit are coupled to either a benzo-crown (X = O) or a dithiabenzo-crown (X = S) ether binding site were designed and synthesized as receptors for K(+) and Ag(+). The receptors display a go...

  13. Age affects the contraction-induced mitochondrial redox response in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Dennis R Claflin

    2015-02-01

    Full Text Available Compromised mitochondrial respiratory function is associated with advancing age. Damage due to an increase in reactive oxygen species (ROS with age is thought to contribute to the mitochondrial deficits. The coenzyme nicotinamide adenine dinucleotide in its reduced (NADH and oxidized (NAD+ forms plays an essential role in the cyclic sequence of reactions that result in the regeneration of ATP by oxidative phosphorylation in mitochondria. Monitoring mitochondrial NADH/NAD+ redox status during recovery from an episode of high energy demand thus allows assessment of mitochondrial function. NADH fluoresces when excited with ultraviolet light in the UV-A band and NAD+ does not, allowing NADH/NAD+ to be monitored in real time using fluorescence microscopy. Our goal was to assess mitochondrial function by monitoring the NADH fluorescence response following a brief period of high energy demand in muscle from adult and old wild-type (WT mice. This was accomplished by isolating whole lumbrical muscles from the hind paws of 7- and 28-month-old WT mice and making simultaneous measurements of force and NADH fluorescence responses during and after a 5 s maximum isometric contraction. All muscles exhibited fluorescence oscillations that were qualitatively similar and consisted of a brief transient increase followed by a longer transient period of reduced fluorescence and, finally, an increase that included an overshoot before recovering to resting level. Compared with the adult WT mice, muscles from the 28 mo WT mice exhibited a delayed peak during the first fluorescence transient and an attenuated recovery following the second transient. These findings indicate an impaired mitochondrial capacity to maintain NADH/NAD+ redox homeostasis during contractile activity in skeletal muscles of old mice.

  14. Redox regulation of water stress responses in field-grown plants. Role of hydrogen peroxide and ascorbate.

    Science.gov (United States)

    Jubany-Marí, T; Munné-Bosch, S; Alegre, L

    2010-05-01

    Abiotic stresses, such as drought, can increase the production of reactive oxygen species (ROS) in plants. An increase in ROS levels can provoke a partial or severe oxidation of cellular components inducing redox status changes, so continuous control of ROS and therefore of their metabolism is decisive under stress conditions. The present work focuses on the contribution of one pro-oxidant, hydrogen peroxide (H(2)O(2)) and one antioxidant, ascorbate (AA) and its redox status, in the control of plant responses to drought-oxidative stress in resistant plants growing in field conditions. After a general introduction to the concept of drought and oxidative stress and its relationship, we describe the role of H(2)O(2) in drought stress responses, emphasizing the importance of studies in H(2)O(2) subcellular localization, needed for a better understanding of its role in plant responses to stress. Although more studies are needed in the study of changes of redox status in plants subjected to stress, the AA pools and its redox status can be indicative of its involvement as a part of cellular mechanisms by which the plant respond to drought-induced oxidative stress. The mechanism of resistance and/or tolerance to drought-oxidative stress is complex, especially when studies are carried out in plants growing in field conditions, where an interaction of stresses occurs. This study sheds light on the mechanisms of plant responses to water-oxidative stress in plants growing in the field.

  15. Involvement of oxidative stress response genes in redox homeostasis, the level of reactive oxygen species, and ageing in Saccharomyces cerevisiae.

    Science.gov (United States)

    Drakulic, Tamara; Temple, Mark D; Guido, Ron; Jarolim, Stefanie; Breitenbach, Michael; Attfield, Paul V; Dawes, Ian W

    2005-12-01

    Saccharomyces cerevisiae mutants lacking oxidative stress response genes were used to investigate which genes are required under normal aerobic conditions to maintain cellular redox homeostasis, using intracellular glutathione redox potential (glutathione E(h)) to indicate the redox environment of the cells. Levels of reactive oxygen species (ROS) and mitochondrial membrane potentials (MMP) were also assessed by FACS using dihydroethidium and rhodamine 123 as fluorescent probes. Cells became more oxidised as strains shifted from exponential growth to stationary phase. During both phases the presence of reduced thioredoxin and the activity of glutathione reductase were important for redox homeostasis. Thioredoxin reductase contributed less during exponential phase when there was a strong requirement for active Yap1p transcription factor, but was critical during stationary phase. The absence of ROS detoxification systems, such as catalases or superoxide dismutases, had a lesser effect on glutathione E(h), but a more pronounced effect on ROS levels and MMP. These results reflect the major shift in ROS generation as cells switch from fermentative to respiratory metabolism and also showed that there was not a strong correlation between ROS production, MMP and cellular redox environment. Heterogeneity was detected in populations of strains with compromised anti-oxidant defences, and as cells aged they shifted from one cell type with low ROS content to another with much higher intracellular ROS.

  16. Dexamethasone improves redox state in ataxia telangiectasia cells by promoting an NRF2-mediated antioxidant response.

    Science.gov (United States)

    Biagiotti, Sara; Menotta, Michele; Orazi, Sara; Spapperi, Chiara; Brundu, Serena; Fraternale, Alessandra; Bianchi, Marzia; Rossi, Luigia; Chessa, Luciana; Magnani, Mauro

    2016-11-01

    Ataxia telangiectasia (A-T) is a rare incurable neurodegenerative disease caused by biallelic mutations in the gene for ataxia-telangiectasia mutated (ATM). The lack of a functional ATM kinase leads to a pleiotropic phenotype, and oxidative stress is considered to have a crucial role in the complex physiopathology. Recently, steroids have been shown to reduce the neurological symptoms of the disease, although the molecular mechanism of this effect is largely unknown. In the present study, we have demonstrated that dexamethasone treatment of A-T lymphoblastoid cells increases the content of two of the most abundant antioxidants [glutathione (GSH) and NADPH] by up to 30%. Dexamethasone promoted the nuclear accumulation of the transcription factor nuclear factor (erythroid-derived 2)-like 2 to drive expression of antioxidant pathways involved in GSH synthesis and NADPH production. The latter effect was via glucose 6-phosphate dehydrogenase activation, as confirmed by increased enzyme activity and enhancement of the pentose phosphate pathway rate. This evidence indicates that glucocorticoids are able to potentiate antioxidant defenses to counteract oxidative stress in ataxia telangiectasia, and also reveals an unexpected role for dexamethasone in redox homeostasis and cellular antioxidant activity. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  17. A redox responsive, fluorescent supramolecular metallohydrogel consists of nanofibers with single-molecule width

    KAUST Repository

    Zhang, Ye

    2013-04-03

    The integration of a tripeptide derivative, which is a versatile self-assembly motif, with a ruthenium(II)tris(bipyridine) complex affords the first supramolecular metallo-hydrogelator that not only self assembles in water to form a hydrogel but also exhibits gel-sol transition upon oxidation of the metal center. Surprisingly, the incorporation of the metal complex in the hydrogelator results in the nanofibers, formed by the self-assembly of the hydrogelator in water, to have the width of a single molecule of the hydrogelator. These results illustrate that metal complexes, besides being able to impart rich optical, electronic, redox, or magnetic properties to supramolecular hydrogels, also offer a unique geometrical control to prearrange the self-assembly motif prior to self-assembling. The use of metal complexes to modulate the dimensionality of intermolecular interactions may also help elucidate the interactions of the molecular nanofibers with other molecules, thus facilitating the development of supramolecular hydrogel materials for a wide range of applications. © 2013 American Chemical Society.

  18. Reversible Switching of Redox-Active Molecular Orbitals and Electron Transfer Pathways in Cu(A) Sites of Cytochrome c Oxidase.

    Science.gov (United States)

    Zitare, Ulises; Alvarez-Paggi, Damián; Morgada, Marcos N; Abriata, Luciano A; Vila, Alejandro J; Murgida, Daniel H

    2015-08-10

    The Cu(A) site of cytochrome c oxidase is a redox hub that participates in rapid electron transfer at low driving forces with two redox cofactors in nearly perpendicular orientations. Spectroscopic and electrochemical characterizations performed on first and second-sphere mutants have allowed us to experimentally detect the reversible switching between two alternative electronic states that confer different directionalities to the redox reaction. Specifically, the M160H variant of a native Cu(A) shows a reversible pH transition that allows to functionally probe both states in the same protein species. Alternation between states exerts a dramatic impact on the kinetic redox parameters, thereby suggesting this effect as the mechanism underlying the efficiency and directionality of Cu(A) electron transfer in vivo. These findings may also prove useful for the development of molecular electronics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. A dual pH/Redox responsive copper-ligand nanoliposome bioactive complex for the treatment of chronic inflammation.

    Science.gov (United States)

    Mavuso, Simphiwe; Choonara, Yahya E; Marimuthu, Thashree; Kumar, Pradeep; du Toit, Lisa C; Kondiah, Pierre P D; Pillay, Viness

    2016-07-25

    A novel dual pH/redox-responsive polymeric nanoliposome system (NLs) loaded with a copper-liganded bioactive complex was prepared and designed as a controlled delivery system for the management of inflammation. The NLs were synthesised after preparation of the copper-glyglycine-prednisolone succinate] ([(Cu(glygly)(PS)]) complex, and the dual pH/redox responsive biopolymer respectively. The methodology undertaken for the development of the drug delivery system involved coordination of the bioactive to Copper (II), preparation of dual pH/redox responsive biopolymer, and the synthesis of dual pH/redox nanoliposomes. Characterisations of the prepared copper-liganded bioactive [Copper-glyglycine-prednisolone succinate] ([(Cu(glygly)(PS)]) complex, dual pH/redox responsive biopolymer (Eudragit E100-cystamine) and [(Cu(glygly)(PS)]-loaded NLs were carried out using spectroscopic and physicochemical techniques. Results indicated a high inflammatory/oxidant inhibitory activity of [Cu(glygly)(PS)] in comparison to the free PS drug. The [Cu(glygly)(PS)] complex exhibited a significant free radical-scavenging activity (60.1±1.2%) and lipoxygenase (LOX-5) inhibitory activity (36.6±1.3%) in comparison to PS which resulted in activity of 4.4±1.4% and inhibition of 6.1±2.6% respectively. The [Cu(glygly)(PS)] loaded NLs demonstrated low release profiles of 22.9±5.4% in 6h at pH 7.4, in comparison to a significant accelerated release at pH 5 in a reducing environment of 75.9±3.7% over 6h duration. Results suggest that the novel copper-liganded bioactive delivery system with controlled drug release mechanism could serve as a potential drug delivery system candidate in the management of inflammation.

  20. Supramolecular PEGylated Dendritic Systems as pH/Redox Dual-Responsive Theranostic Nanoplatforms for Platinum Drug Delivery and NIR Imaging.

    Science.gov (United States)

    Li, Yunkun; Li, Yachao; Zhang, Xiao; Xu, Xianghui; Zhang, Zhijun; Hu, Cheng; He, Yiyan; Gu, Zhongwei

    2016-01-01

    Recently, self-assembling small dendrimers into supramolecular dendritic systems offers an alternative strategy to develop multifunctional nanoplatforms for biomedical applications. We herein report a dual-responsive supramolecular PEGylated dendritic system for efficient platinum-based drug delivery and near-infrared (NIR) tracking. With a refined molecular/supramolecular engineering, supramolecular dendritic systems were stabilized by bioreducible disulfide bonds and endowed with NIR fluorescence probes, and PEGylated platinum derivatives coordinated onto the abundant peripheral groups of supramolecular dendritic templates to generate pH/redox dual-responsive theranostic supramolecular PEGylated dendritic systems (TSPDSs). TSPDSs markedly improved the pharmacokinetics and biodistribution of platinum-based drugs, owing to their stable nanostructures and PEGylated shells during the blood circulation. Tumor intracellular environment (low pH value and high glutathione concentration) could trigger the rapid disintegration of TSPDSs due to acid-labile coordination bonds and redox-cleavable disulfide linkages, and then platinum-based drugs were delivered into the nuclei to exert antitumor activity. In vivo antitumor treatments indicated TSPDSs not only provided high antitumor efficiency which was comparable to clinical cisplatin, but also reduced renal toxicity of platinum-based drugs. Moreover, NIR fluorescence of TSPDSs successfully visualized in vitro and in vivo fate of nanoplatforms and disclosed the intracellular platinum delivery and pharmacokinetics. These results confirm tailor-made supramolecular dendritic system with sophisticated nanostructure and excellent performance is a promising candidate as smart theranostic nanoplatforms.

  1. Redox proteomics and physiological responses in Cistus albidus shrubs subjected to long-term summer drought followed by recovery.

    Science.gov (United States)

    Brossa, Ricard; Pintó-Marijuan, Marta; Francisco, Rita; López-Carbonell, Marta; Chaves, Maria Manuela; Alegre, Leonor

    2015-04-01

    The interaction between enzymatic and non-enzymatic antioxidants, endogenous levels of ABA and ABA-GE, the rapid recuperation of photosynthetic proteins under re-watering as well the high level of antioxidant proteins in previously drought-stressed plants under re-watering conditions, will contribute to drought resistance in plants subjected to a long-term drought stress under Mediterranean field conditions. This work provides an overview of the mechanisms of Cistus albidus acclimation to long-term summer drought followed by re-watering in Mediterranean field conditions. To better understand the molecular mechanisms of drought resistance in these plants, a proteomic study using 2-DE and MALDI-TOF/TOF MS/MS was performed on leaves from these shrubs. The analysis identified 57 differentially expressed proteins in water-stressed plants when contrasted to well watered. Water-stressed plants showed an increase, both qualitatively and quantitatively, in HSPs, and downregulation of photosynthesis and carbon metabolism enzymes. Under drought conditions, there was considerable upregulation of enzymes related to redox homeostasis, DHA reductase, Glyoxalase, SOD and isoflavone reductase. However, upregulation of catalase was not observed until after re-watering was carried out. Drought treatment caused an enhancement in antioxidant defense responses that can be modulated by ABA, and its catabolites, ABA-GE, as well as JA. Furthermore, quantification of protein carbonylation was shown to be a useful marker of the relationship between water and oxidative stress, and showed that there was only moderate oxidative stress in C. albidus plants subjected to water stress. After re-watering plants recovered although the levels of ABA-GE and antioxidant enzymes still remain higher than in well-watered plants. We expect that our results will provide new data on summer acclimation to drought stress in Mediterranean shrubs.

  2. Early osmotic, antioxidant, ionic, and redox responses to salinity in leaves and roots of Indian mustard (Brassica juncea L.).

    Science.gov (United States)

    Ranjit, Singh Laxmi; Manish, Pandey; Penna, Suprasanna

    2016-01-01

    Salt-stress-induced alterations in osmotic, ionic, and redox responses were studied in the early period of treatment (30 min to 5 days) in seedlings of Brassica juncea L. Roots and shoots under mild (50 mM) and severe (250 mM) NaCl stress were analyzed for growth, oxidative stress, osmolyte accumulation, antioxidant defense, and redox state. Growth reduction was less pronounced in the early time period of salt stress while oxidative damage increased linearly and in a sustained manner under severe stress up to 6 h. An early and transient reactive oxygen species (ROS) burst, as evidenced by superoxide and hydrogen peroxide level was observed, followed by activation of enzymatic antioxidant system (GPX, SOD, CAT, and GR) in both root and shoot. The enzymatic activity was not affected much under mild stress particularly at early phase; however, severe stress induced a significant increase in the activity of antioxidant enzymes. Root ascorbate was progressively accumulated, and its redox state maintained in the early time phase of treatment under mild stress while increase in root and shoot glutathione content was recorded under mild stress at 5 days when the active ascorbate pool decreased. While early period of salt stress showed significant Na(+) accumulation over control, plants subjected to mild stress measured less Na(+) accumulation up to 5 days compared to severely stressed plants. The results showed an early induction of differential responses to salt stress in roots and shoots of Brassica which include growth limitations, reduced relative water content, increased osmolytes, redox state, and antioxidant system, and a significant Na(+) increase. The results also indicate that roots and shoots may have distinct mechanisms of responses to salt stress.

  3. Experimental verification of regression to the mean in redox biology: differential responses to exercise.

    Science.gov (United States)

    Margaritelis, Nikos V; Theodorou, Anastasios A; Paschalis, Vassilis; Veskoukis, Aristidis S; Dipla, Konstantina; Zafeiridis, Andreas; Panayiotou, George; Vrabas, Ioannis S; Kyparos, Antonios; Nikolaidis, Michalis G

    2016-01-01

    An important methodological threat when selecting individuals based on initial values for a given trait is the "regression to the mean" artifact. This artifact appears when a group with an extreme mean value during a first measurement tends to obtain a less extreme value (i.e. tends toward the mean) on a subsequent measurement. The main aim was to experimentally confirm the presence of this artifact in the responses of the reference oxidative stress biomarker (F2-isoprostanes) after exercise. Urine samples were collected before and immediately following acute exercise in order to determine the level of exercise-induced oxidative stress. Afterwards, participants were arranged into three groups based on their levels of exercise-induced oxidative stress (low, moderate and high oxidative stress groups; n = 12 per group). In order to verify the existence of the regression to the mean artifact, the three groups were subjected to a second exercise trial one week after the first trial. This study confirmed the regression to the mean artifact in a redox biology context and showed that this artifact can be minimized by performing a duplicate pretreatment measurement after completing a nonrandom sorting based on the first assessment. This study also indicated that different individuals experience high oxidative stress or reductive stress (or no stress) to the same exercise stimulus even after adjusting for regression to the mean. This finding substantiates the methodological choice to divide individuals based on their degree of exercise-induced oxidative stress in future experiments to investigate the role of reactive species in exercise adaptations.

  4. Redox Mechanisms in Regulation of Adipocyte Differentiation: Beyond a General Stress Response

    Directory of Open Access Journals (Sweden)

    Fan Jiang

    2012-11-01

    Full Text Available In this review, we summarize advances in our understanding of redox-sensitive mechanisms that regulate adipogenesis. Current evidence indicates that reactive oxygen species may act to promote both the initiation of adipocyte lineage commitment of precursor or stem cells, and the terminal differentiation of preadipocytes to mature adipose cells. These can involve redox regulation of pathways mediated by receptor tyrosine kinases, peroxisome proliferator-activated receptor γ (PPARγ, PPARγ coactivator 1α (PGC-1α, AMP-activated protein kinase (AMPK, and CCAAT/enhancer binding protein β (C/EBPβ. However, the precise roles of ROS in adipogenesis in vivo remain controversial. More studies are needed to delineate the roles of reactive oxygen species and redox signaling mechanisms, which could be either positive or negative, in the pathogenesis of obesity and related metabolic disorders.

  5. The redox-associated adaptive response of brain to physical exercise.

    Science.gov (United States)

    Radak, Z; Ihasz, F; Koltai, E; Goto, S; Taylor, A W; Boldogh, I

    2014-01-01

    Reactive oxygen species (ROS) are continuously generated during metabolism. ROS are involved in redox signaling, but in significant concentrations they can greatly elevate oxidative damage leading to neurodegeneration. Because of the enhanced sensitivity of brain to ROS, it is especially important to maintain a normal redox state in brain and spinal cord cell types. The complex effects of exercise benefit brain function, including functional enhancement as well as its preventive and therapeutic roles. Exercise can induce neurogenesis via neurotrophic factors, increase capillarization, decrease oxidative damage, and enhance repair of oxidative damage. Exercise is also effective in attenuating age-associated loss in brain function, which suggests that physical activity-related complex metabolic and redox changes are important for a healthy neural system.

  6. Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

    Science.gov (United States)

    Shen, Lin; Yang, Weitao

    2016-04-12

    We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer.

  7. The Arabidopsis cysteine-rich protein GASA4 promotes GA responses and exhibits redox activity in bacteria and in planta.

    Science.gov (United States)

    Rubinovich, Lior; Weiss, David

    2010-12-01

    Although the gibberellin (GA) signaling pathway has been elucidated, very little is known about the steps linking first transcriptional activation to physiological responses. Among the few identified GA-induced genes are the plant-specific GAST1-like genes, which encode small proteins with a conserved cysteine-rich domain. The role of these proteins in plant development and GA responses is not yet clear. The Arabidopsis GAST1-like gene family consists of 14 members, GASA1-14. Here we show that over-expression of the GA-induced GASA4 gene in Arabidopsis promoted GA responses such as flowering and seed germination. Suppression of several GASA genes using synthetic microRNA (miR(GASA) ) also promoted seed germination. This was probably caused by suppression of GASA5, which acts as a repressor of GA responses. Previously, we proposed that GAST1-like proteins are involved in redox reactions via their cysteine-rich domain. The results of this study support this hypothesis, as over-expression of GASA4 suppressed ROS accumulation and the transgenic seeds were partially resistant to the NO donor sodium nitroprusside (SNP). Moreover, Escherichia coli expressing intact GASA4 or a truncated version containing only the cysteine-rich domain were resistant to SNP. Mutated GASA4, in which conserved cysteines were replaced by alanines, lost its redox activity and the ability to promote GA responses, suggesting that the two functions are linked. We propose that GA induces some GAST1-like genes and suppresses others to regulate its own responses. We also suggest that the encoded proteins regulate the redox status of specific components to promote or suppress these responses.

  8. Redox chemistry of the molecular interactions between tea catechins and human serum proteins under simulated hyperglycemic conditions.

    Science.gov (United States)

    Özyurt, Hazal; Luna, Carolina; Estévez, Mario

    2016-03-01

    Carbonylation is an irreversible modification in oxidized proteins that has been directly related to a number of health disorders including Type 2 diabetes. Dietary antioxidants have been proposed to counteract the oxidative stress occurring under hyperglycemic conditions. An understanding of the nature and consequences of the molecular interactions between phytochemicals and human plasma proteins is of utmost scientific interest. Three tea catechins namely epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG) were tested for (i) their affinity to bind to human serum albumin (HSA) and human hemoglobin (HH) and (ii) their ability to inhibit tryptophan (Trp) depletion and for the formation of specific protein carbonyls and pentosidine in the aforementioned proteins. Both proteins (20 mg mL(-1)) were allowed to react with postprandial plasmatic concentrations of the catechins (EC: 0.7 μM, EGC: 1.8 μM, and EGCG: 0.7 μM) under simulated hyperglycemic conditions (12 mM glucose/0.2 mM Fe(3+)/37 °C/10 days). The three catechins were able to inhibit Trp oxidation and protein carbonylation in both plasma proteins. Some anti-glycation properties were linked to their binding affinities. The molecular interactions reported in the present study may explain the alleged beneficial effects of tea catechins against the redox impairment linked to hyperglycemic conditions.

  9. Self-assembly, redox activity, and charge transport of functional surface nano-architectures by molecular design

    Science.gov (United States)

    Skomski, Daniel

    Surface-assisted molecular self-assembly is a promising strategy to program the structure and chemical state of atoms and molecules in nano-architectures to achieve a specific function. The experiments described in this thesis demonstrate that the design and programming of basic organic components leads to desired characteristics by self-assembly. The fabrication of uniform single-site metal centers at surfaces, important for high selectivity in next-generation catalysts, was accomplished by coordination to redox non-innocent phenanthroline and tetrazine-based ligands. These examples were the first demonstrating tuning of the metal oxidation state in surface coordination architectures through rational ligand design. The molecular-scale coordination architectures were the first formed from chromium and vanadium, and the first from platinum in a non-porphyrin system. The first mixed valence metal-ligand surface structure was fabricated that attained the same ligand coordination number for all metal sites. A new surface reaction method was demonstrated between an inexpensive sodium chloride reagent and carboxylate ligands. High-temperature, molecular-resolution microscopy and spectroscopy of the ordered metal-organic structures demonstrated thermal stability up to 300 °C, the highest molecular-level thermal stability in organic surface nanostructures yet achieved, making such systems potential candidates for moderate-temperature catalytic reactions. Molecular self-assembly was expanded into organic semiconductor thin films. In a two-component, bi-layered system, hydrogen bonding between carboxylates and carboxylic acid-substituted thiophenes was utilized, yielding the first real-space images of phenyl-thiophene stacking. In a one-component system, multiple donor-acceptor pi-pi contacts between phenyltriazole building blocks accomplished assembly of flat-lying molecules from a surface with molecular-scale precision through more than twenty molecular layers. Sufficient

  10. An important impact of the molecule-electrode couplings asymmetry on the efficiency of bias-driven redox processes in molecular junctions

    CERN Document Server

    Baldea, Ioan

    2015-01-01

    Two recent experimental (Li, J.~\\emphj{et al}, \\emph{Proc.\\ Natl.\\ Acad.\\ Sci.\\ U.~S.~A.} {\\bf 2014}, 111, 1282-1287) and theoretical studies (B\\^aldea, I, \\emph{Phys.\\ Chem.\\ Chem.\\ Phys.}\\ {\\bf 2014}, 16, 25942-25949) have addressed the problem of tuning molecular charge and vibrational properties of single molecules embedded in nanojunctions. These are molecular characteristics escaping so far to an efficient experimental control in broad ranges. Here, we present a general argument demonstrating why, out of various experimental platforms possible, those wherein active molecules are asymmetrically coupled to electrodes are to be preferred to those symmetrically coupled for achieving a(n almost) complete redox process, and why electrochemical environment has advantages over "dry" setups. This study aims at helping to nanofabricate molecular junctions using the most appropriate platforms enabling the broadest possible bias-driven control of the redox state and vibrational modes of single molecules linked to e...

  11. TOXICOLOGICAL HIGHLIGHT (REDOX REDUX: A CLOSER LOOK AT CONCEPTAL LOW MOLECULAR WEIGHT THIOLS)

    Science.gov (United States)

    Glutathione (GSH) is present as the most abundant low molecular weight thiol (LMWT) in virtually all mitochondria-bearing eucaryotic cells, often at millimolar concentrations (Meister, 1988). Functions of GSH include roles in DNA and protein synthesis, maintenance of cell membra...

  12. Electronic and Redox Properties of Stacked-Ring Silicon Phthalocyanines from Molecular Orbital Theory.

    Science.gov (United States)

    1984-10-19

    a molecular orbital approximation to the electron delocalization energy.1 8 The ASED theory is derived from the Hellmann- Feynman formula for...34 . . 4.•" " ., .7% . r .- - - . , .-. - . . _ .-.- :.- .- . v ._ . _ . " - . ’ " _ _ 12. Wheeler , B. L.; Nagasubramanian, G.; Bard, A. J

  13. Stimulus Responsive Poly(ferrocenylsilanes): Redox Chemistry of Iron in the Main Chain

    NARCIS (Netherlands)

    Giannotti, M.I.; Lv, H.; Ma, Y.; Steenvoorden, M.P.; Overweg, A.R.; Roerdink, M.; Hempenius, Mark A.; Vancso, Gyula J.

    2006-01-01

    Redox chemistry of organometallic poly(ferrocenylsilane) polymers (soluble in organic or aqueous environment) is discussed. Poly(ferrocenyldimethylsilane) (PFDMS) was oxidized in CH2Cl2 solution with different oxidants. Oxidation was accomplished with stepwise increasing amounts of ferric chloride

  14. Sub-nanometer expansions of redox responsive polymer films monitored by imaging ellipsometry

    NARCIS (Netherlands)

    Cumurcu, Aysegul; Feng, X.; Dos Ramos, L.; Hempenius, M.A.; Schon, P.M.; Vancso, G.J.

    2014-01-01

    We describe a novel approach to quantitatively visualize sub nm height changes occurring in thin films of redox active polymers upon reversible electrochemical oxidation/reduction in situ and in real-time with electrochemical imaging ellipsometry (EC-IE). Our approach is based on the utilization of

  15. Stimulus Responsive Poly(ferrocenylsilanes): Redox Chemistry of Iron in the Main Chain

    NARCIS (Netherlands)

    Giannotti, M.; Lv, H.; Ma, Y.; Steenvoorden, M.P.; Overweg, A.R.; Roerdink, M.; Hempenius, M.A.; Vancso, G.J.

    2006-01-01

    Redox chemistry of organometallic poly(ferrocenylsilane) polymers (soluble in organic or aqueous environment) is discussed. Poly(ferrocenyldimethylsilane) (PFDMS) was oxidized in CH2Cl2 solution with different oxidants. Oxidation was accomplished with stepwise increasing amounts of ferric chloride (

  16. Redox-responsive organometallic hydrogels for in situ metal nanoparticle synthesis

    NARCIS (Netherlands)

    Zoetebier, Bram; Hempenius, Mark A.; Vancso, Gyula J.

    2015-01-01

    A new class of redox active hydrogels composed of poly(ferrocenylsilane) polyanion and poly(ethylene glycol) chains was assembled, using a copper-free azide–alkyne Huisgen cycloaddition reaction. These organometallic hydrogels displayed reversible collapse and reswelling upon chemical oxidation and

  17. Stimulus Responsive Poly(ferrocenylsilanes): Redox Chemistry of Iron in the Main Chain

    NARCIS (Netherlands)

    Giannotti, M.I.; Lv, H.; Ma, Y.; Steenvoorden, M.P.; Overweg, A.R.; Roerdink, M.; Hempenius, Mark A.; Vancso, Gyula J.

    2006-01-01

    Redox chemistry of organometallic poly(ferrocenylsilane) polymers (soluble in organic or aqueous environment) is discussed. Poly(ferrocenyldimethylsilane) (PFDMS) was oxidized in CH2Cl2 solution with different oxidants. Oxidation was accomplished with stepwise increasing amounts of ferric chloride (

  18. The prognostic and predictive power of redox protein expression for anthracycline-based chemotherapy response in locally advanced breast cancer

    Science.gov (United States)

    Woolston, Caroline M; Zhang, Lei; Storr, Sarah J; Al-Attar, Ahmad; Shehata, Mohamed; Ellis, Ian O; Chan, Stephen Y; Martin, Stewart G

    2012-01-01

    Neoadjuvant chemotherapy has become the standard of care for locally advanced primary breast cancer. Anthracycline-based regimens have proven to be one of the most effective treatments in this setting. As certain cytotoxic antineoplastic agents, such as anthracyclines, generate reactive oxygen species as a by-product of their mechanism of action, we examined whether redox protein expression was involved in the response to anthracycline-based chemotherapy and with clinical outcome. Pre-treatment needle core biopsy and post-anthracycline treatment tumour sections were analysed from 98 cases. In all, 32 individuals had a complete clinical response and 17 had a complete pathological response. Immunohistochemical staining was performed for eight redox proteins: thioredoxin, thioredoxin reductase, thioredoxin interacting protein (TxNIP), glutathione S-transferase (GST) π, θ and α, catalase and manganese superoxide dismutase. GST π (P=0.05) and catalase (P=0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP (P=0.017) and thioredoxin reductase (P=0.022) were independent prognostic factors for distant metastasis-free survival and TxNIP for overall survival (P=0.014). In oestrogen receptor negative patients that are known to have a poor overall survival, a considerably worse prognosis was seen in cases that exhibited low expression of TxNIP (P=0.000003), stratifying patients into more defined groups. This study indicates the importance of redox regulation in determining breast cancer response to anthracycline-based chemotherapy and provides ways of further stratifying pre-chemotherapy patients to potentially allow more tailored treatments. PMID:22481283

  19. Circadian clock and photoperiodic response in Arabidopsis: from seasonal flowering to redox homeostasis.

    Science.gov (United States)

    Shim, Jae Sung; Imaizumi, Takato

    2015-01-20

    Many of the developmental responses and behaviors in plants that occur throughout the year are controlled by photoperiod; among these, seasonal flowering is the most characterized. Molecular genetic and biochemical analyses have revealed the mechanisms by which plants sense changes in day length to regulate seasonal flowering. In Arabidopsis thaliana, induction of the expression of a florigen, FLOWERING LOCUS T (FT) protein, is a major output of the photoperiodic flowering pathway. The circadian clock coordinates the expression profiles and activities of the components in this pathway. Light-dependent control of CONSTANS (CO) transcription factor activity is a crucial part of the induction of the photoperiodic expression of FT. CO protein is stabilized only in the long day afternoon, which is when FT is induced. In this review, we summarize recent progress in the determination of the molecular architecture of the circadian clock and mechanisms underlying photoperiodic flowering. In addition, we introduce the molecular mechanisms of other biological processes, such as hypocotyl growth and reactive oxygen species production, which are also controlled by alterations in photoperiod.

  20. Adaptive Redox Response of Mesenchymal Stromal Cells to Stimulation with Lipopolysaccharide Inflammagen: Mechanisms of Remodeling of Tissue Barriers in Sepsis

    Directory of Open Access Journals (Sweden)

    Nikolai V. Gorbunov

    2013-01-01

    Full Text Available Acute bacterial inflammation is accompanied by excessive release of bacterial toxins and production of reactive oxygen and nitrogen species (ROS and RNS, which ultimately results in redox stress. These factors can induce damage to components of tissue barriers, including damage to ubiquitous mesenchymal stromal cells (MSCs, and thus can exacerbate the septic multiple organ dysfunctions. The mechanisms employed by MSCs in order to survive these stress conditions are still poorly understood and require clarification. In this report, we demonstrated that in vitro treatment of MSCs with lipopolysaccharide (LPS induced inflammatory responses, which included, but not limited to, upregulation of iNOS and release of RNS and ROS. These events triggered in MSCs a cascade of responses driving adaptive remodeling and resistance to a “self-inflicted” oxidative stress. Thus, while MSCs displayed high levels of constitutively present adaptogens, for example, HSP70 and mitochondrial Sirt3, treatment with LPS induced a number of adaptive responses that included induction and nuclear translocation of redox response elements such as NFkB, TRX1, Ref1, Nrf2, FoxO3a, HO1, and activation of autophagy and mitochondrial remodeling. We propose that the above prosurvival pathways activated in MSCs in vitro could be a part of adaptive responses employed by stromal cells under septic conditions.

  1. High REDOX RESPONSIVE TRANSCRIPTION FACTOR1 Levels Result in Accumulation of Reactive Oxygen Species in Arabidopsis thaliana Shoots and Roots.

    Science.gov (United States)

    Matsuo, Mitsuhiro; Johnson, Joy Michal; Hieno, Ayaka; Tokizawa, Mutsutomo; Nomoto, Mika; Tada, Yasuomi; Godfrey, Rinesh; Obokata, Junichi; Sherameti, Irena; Yamamoto, Yoshiharu Y; Böhmer, Frank-D; Oelmüller, Ralf

    2015-08-01

    Redox Responsive Transcription Factor1 (RRTF1) in Arabidopsis is rapidly and transiently upregulated by H2O2, as well as biotic- and abiotic-induced redox signals. RRTF1 is highly conserved in angiosperms, but its physiological role remains elusive. Here we show that inactivation of RRTF1 restricts and overexpression promotes reactive oxygen species (ROS) accumulation in response to stress. Transgenic lines overexpressing RRTF1 are impaired in root and shoot development, light sensitive, and susceptible to Alternaria brassicae infection. These symptoms are diminished by the beneficial root endophyte Piriformospora indica, which reduces ROS accumulation locally in roots and systemically in shoots, and by antioxidants and ROS inhibitors that scavenge ROS. More than 800 genes were detected in mature leaves and seedlings of transgenic lines overexpressing RRTF1; ∼ 40% of them have stress-, redox-, ROS-regulated-, ROS-scavenging-, defense-, cell death- and senescence-related functions. Bioinformatic analyses and in vitro DNA binding assays demonstrate that RRTF1 binds to GCC-box-like sequences in the promoter of RRTF1-responsive genes. Upregulation of RRTF1 by stress stimuli and H2O2 requires WRKY18/40/60. RRTF1 is co-regulated with the phylogenetically related RAP2.6, which contains a GCC-box-like sequence in its promoter, but transgenic lines overexpressing RAP2.6 do not accumulate higher ROS levels. RRTF1 also stimulates systemic ROS accumulation in distal non-stressed leaves. We conclude that the elevated levels of the highly conserved RRTF1 induce ROS accumulation in response to ROS and ROS-producing abiotic and biotic stress signals.

  2. Redox regulation of human OGG1 activity in response to cellular oxidative stress.

    Science.gov (United States)

    Bravard, Anne; Vacher, Monique; Gouget, Barbara; Coutant, Alexandre; de Boisferon, Florence Hillairet; Marsin, Stéphanie; Chevillard, Sylvie; Radicella, J Pablo

    2006-10-01

    8-Oxoguanine (8-oxoG), a common and mutagenic form of oxidized guanine in DNA, is eliminated mainly through base excision repair. In human cells its repair is initiated by human OGG1 (hOGG1), an 8-oxoG DNA glycosylase. We investigated the effects of an acute cadmium exposure of human lymphoblastoid cells on the activity of hOGG1. We show that coinciding with alteration of the redox cellular status, the 8-oxoG DNA glycosylase activity of hOGG1 was nearly completely inhibited. However, the hOGG1 activity returned to normal levels once the redox cellular status was normalized. In vitro, the activity of purified hOGG1 was abolished by cadmium and could not be recovered by EDTA. In cells, however, the reversible inactivation of OGG1 activity by cadmium was strictly associated with reversible oxidation of the protein. Moreover, the 8-oxoG DNA glycosylase activity of purified OGG1 and that from crude extracts were modulated by cysteine-modifying agents. Oxidation of OGG1 by the thiol oxidant diamide led to inhibition of the activity and a protein migration pattern similar to that seen in cadmium-treated cells. These results suggest that cadmium inhibits hOGG1 activity mainly by indirect oxidation of critical cysteine residues and that excretion of the metal from the cells leads to normalization of the redox cell status and restoration of an active hOGG1. The results presented here unveil a novel redox-dependent mechanism for the regulation of OGG1 activity.

  3. Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish

    OpenAIRE

    Yoo, Sa Kan; Freisinger, Christina M.; LeBert, Danny C.; Huttenlocher, Anna

    2012-01-01

    Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H2O2 at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immedi...

  4. Physical Training Status Determines Oxidative Stress and Redox Changes in Response to an Acute Aerobic Exercise

    Directory of Open Access Journals (Sweden)

    Farnaz Seifi-skishahr

    2016-01-01

    Full Text Available Objective. To assess the influence of different physical training status on exercise-induced oxidative stress and changes in cellular redox state. Methods. Thirty male subjects participated in this study and were assigned as well-trained (WT, moderately trained (MT, and untrained (UT groups. The levels of cortisol, creatine kinase, plasma reduced glutathione to oxidized glutathione (GSH/GSSG, cysteine/cystine (Cys/CySS, and GSH/GSSG ratio in red blood cells (RBCs were measured immediately and 10 and 30 min after exercise. Results. Following the exercise, plasma GSH/GSSG (p=0.001 and Cys/CySS (p=0.005 were significantly reduced in all groups. Reduction in plasma GSH/GSSG ratio in all groups induced a transient shift in redox balance towards a more oxidizing environment without difference between groups (p=0.860, while RBCs GSH/GSSG showed significant reduction (p=0.003 and elevation (p=0.007 in UT and MT groups, respectively. The highest level of RBCs GSH/GSSG ratio was recorded in MT group, and the lowest one was recorded in the WT group. Conclusion. Long term regular exercise training with moderate intensity shifts redox balance towards more reducing environment, versus intensive exercise training leads to more oxidizing environment and consequently development of related diseases.

  5. Pyrite oxidation and reduction - Molecular orbital theory considerations. [for geochemical redox processes

    Science.gov (United States)

    Luther, George W., III

    1987-01-01

    In this paper, molecular orbital theory is used to explain a heterogeneous reaction mechanism for both pyrite oxidation and reduction. The mechanism demonstrates that the oxidation of FeS2 by Fe(3+) may occur as a result of three important criteria: (1) the presence of a suitable oxidant having a vacant orbital (in case of liquid phase) or site (solid phase) to bind to the FeS2 via sulfur; (2) the initial formation of a persulfido (disulfide) bridge between FeS2 and the oxidant, and (3) an electron transfer from a pi(asterisk) orbital in S2(2-) to a pi or pi(asterisk) orbital of the oxidant.

  6. A synthetic biochemistry molecular purge valve module that maintains redox balance.

    Science.gov (United States)

    Opgenorth, Paul H; Korman, Tyler P; Bowie, James U

    2014-06-17

    The greatest potential environmental benefit of metabolic engineering would be the production of high-volume commodity chemicals, such as biofuels. Yet, the high yields required for the economic viability of low-value chemicals is particularly hard to achieve in microbes owing to the myriad competing biochemical pathways. An alternative approach, which we call synthetic biochemistry, is to eliminate the organism by constructing biochemical pathways in vitro. Viable synthetic biochemistry, however, will require simple methods to replace the cellular circuitry that maintains cofactor balance. Here we design a simple purge valve module for maintaining NADP(+)/NADPH balance. We test the purge valve in the production of polyhydroxybutyryl bioplastic and isoprene--pathways where cofactor generation and utilization are unbalanced. We find that the regulatory system is highly robust to variations in cofactor levels and readily transportable. The molecular purge valve provides a step towards developing continuously operating, sustainable synthetic biochemistry systems.

  7. Highly Swellable, Dual-Responsive Hydrogels Based on PNIPAM and Redox Active Poly(ferrocenylsilane) Poly(ionic liquid)s: Synthesis, Structure, and Properties

    NARCIS (Netherlands)

    Feng, Xueling; Zhang, Kaihuan; Chen, Peng; Sui, Xiaofeng; Hempenius, Mark A.; Liedberg, Bo; Vancso, Gyula J.

    2016-01-01

    Highly swellable, dual-responsive hydrogels, consisting of thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) and redox-responsive poly(ferrocenylsilane) (PFS) based poly(ionic liquid)s (PILs) are formed by photo-polymerization. PFS chains bearing cross-linkable vinylimidazolium (VIm) side

  8. Retinal proteins associated with redox regulation and protein folding play central roles in response to high glucose conditions.

    Science.gov (United States)

    Wang, Ssu-Han; Lee, Wen-Chi; Chou, Hsiu-Chuan

    2015-03-01

    Diabetic retinopathy typically causes poor vision and blindness. A previous study revealed that a high blood glucose concentration induces glycoxidation and weakens the retinal capillaries. Nevertheless, the molecular mechanisms underlying the effects of high blood glucose induced diabetic retinopathy remain to be elucidated. In the present study, we cultured the retinal pigmented epithelial cell line ARPE-19 in mannitol-balanced 5.5, 25, and 100 mM glucose media and investigated protein level alterations. Proteomic analysis revealed significant changes in 137 protein features, of which 124 demonstrated changes in a glucose concentration dependent manner. Several proteins functionally associated with redox regulation, protein folding, or the cytoskeleton are affected by increased glucose concentrations. Additional analyses also revealed that cellular oxidative stress, including endoplasmic reticulum stress, was significantly increased after treatment with high glucose concentrations. However, the mitochondrial membrane potential and cell survival remained unchanged during treatment with high glucose concentrations. To summarize, in this study, we used a comprehensive retinal pigmented epithelial cell based proteomic approach for identifying changes in protein expression associated retinal markers induced by high glucose concentrations. Our results revealed that a high glucose condition can induce cellular oxidative stress and modulate the levels of proteins with functions in redox regulation, protein folding, and cytoskeleton regulation; however, cell viability and mitochondrial integrity are not significantly disturbed under these high glucose conditions.

  9. Redox-controlled interaction of biferrocenyl-terminated dendrimers with beta-cyclodextrin molecular printboards.

    Science.gov (United States)

    Nijhuis, Christian A; Dolatowska, Karolina A; Ravoo, Bart Jan; Huskens, Jurriaan; Reinhoudt, David N

    2007-01-01

    This paper describes the synthesis and electrochemistry of biferrocenyl-terminated dendrimers and their beta-cyclodextrin (beta-CD) inclusion complexes in aqueous solution and at surfaces. Three generations of poly(propylene imine) (PPI) dendrimers, decorated with 4, 8, and 16 biferrocenyl (BFc) units, respectively, were synthesized. A water-soluble BFc derivative forms stable inclusion complexes with beta-CD. The intrinsic binding constant is K(i)=2.5 x 10(4) M(-1). The BFc dendrimers were solubilized in water by complexation of the end groups with beta-CD, resulting in large water-soluble supramolecular assemblies. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) showed that all the end groups are complexed to beta-CD. Adsorption of the dendrimers at self-assembled monolayers (SAMs) of heptathioether-functionalized beta-CD on gold ("molecular printboards") resulted in stable monolayers of the dendrimers due to the formation of multivalent host-guest interactions between the BFc end groups of the dendrimers and the immobilized beta-CD molecules. The number of interacting end groups is 3, 4, and 4 for dendrimer generations 1, 2, and 3, respectively. The complexation of BFc to beta-CD is sensitive to the oxidation state of the BFc unit. Oxidation of neutral BFc-Fe(2) ((II,II)) to the cationic, mixed-valence biferrocenium BFc-Fe(2) ((II,III)+) resulted in dissociation of the host-guest complexes. Scan-rate-dependent CV and DPV analyses of the dendrimer-beta-CD assemblies immobilized at the beta-CD host surface and in solution revealed that the dendrimers are oxidized in three steps. First, the surface-beta-CD-bound BFc moieties are oxidized to the mixed-valence state, Fe(2) ((II,III)+), followed by the oxidation of the non-surface-interacting BFc groups to the Fe(2) ((II,III)+) state. The third step involves the oxidation of all the BFc moieties to the Fe(2) ((III,III)2+) state.

  10. Changes in low-molecular-weight thiol-disulphide redox couples are part of bread wheat seed germination and early seedling growth.

    Science.gov (United States)

    Gerna, Davide; Roach, Thomas; Stöggl, Wolfgang; Wagner, Johanna; Vaccino, Patrizia; Limonta, Margherita; Kranner, Ilse

    2017-06-01

    The tripeptide antioxidant glutathione (γ-l-glutamyl-l-cysteinyl-glycine; GSH) essentially contributes to thiol-disulphide conversions, which are involved in the control of seed development, germination, and seedling establishment. However, the relative contribution of GSH metabolism in different seed structures is not fully understood. We studied the GSH/glutathione disulphide (GSSG) redox couple and associated low-molecular-weight (LMW) thiols and disulphides related to GSH metabolism in bread wheat (Triticum aestivum L.) seeds, focussing on redox changes in the embryo and endosperm during germination. In dry seeds, GSH was the predominant LMW thiol and, 15 h after the onset of imbibition, embryos of non-germinated seeds contained 12 times more LMW thiols than the endosperm. In germinated seeds, the embryo contained 17 and 11 times more LMW thiols than the endosperm after 15 and 48 h, respectively. This resulted in the embryo having significantly more reducing half-cell reduction potentials of GSH/GSSG and cysteine (Cys)/cystine (CySS) redox couples (EGSSG/2GSH and ECySS/2Cys, respectively). Upon seed germination and early seedling growth, Cys and CySS concentrations significantly increased in both embryo and endosperm, progressively contributing to the cellular LMW thiol-disulphide redox environment (Ethiol-disulphide). The changes in ECySS/2Cys could be related to the mobilisation of storage proteins in the endosperm during early seedling growth. We suggest that EGSSG/2GSH and ECySS/2Cys can be used as markers of the physiological and developmental stage of embryo and endosperm. We also present a model of interaction between LMW thiols and disulphides with hydrogen peroxide (H2O2) in redox regulation of bread wheat germination and early seedling growth.

  11. Multi-stimuli responsive copper nanoclusters with bright red luminescence for quantifying acid phosphatase activity via redox-controlled luminescence switch.

    Science.gov (United States)

    Zhao, Meizhi; Feng, Hui; Han, Jiaonan; Ao, Hang; Qian, Zhaosheng

    2017-09-01

    Thiolate-protected copper nanoclusers (CuNCs) are emerging as a promising class of luminescent materials since its unique optical properties such as aggregation-induced emission (AIE) and intriguing molecular-like behavior have been explored for sensing application. In this work, multi-stimuli responsive property of CuNCs was first investigated in depth and further adopted to develop a reliable and sensitive ACP assay. Penicilamine-capped CuNCs from a facile one-pot synthesis possess bright red luminescence and distinctive multi-stimuli responsive behaviors. Its sensitive and reversible response in luminescence to pH and temperature is originated from its inherent AIE property, and can be constructed as luminescent nanoswitches controlled by these external stimuli for precisely monitoring the change of environmental pH or temperature. The specific redox-responsive behavior of CuNC aggregates is found from severe luminescence quenching in the presence of a small amount of ferric or silver ions, and this sensitive response in luminescence to the preceding species is proved to be due to the conversion of Cu(II) from copper atoms with lower valence inside CuNCs. The luminescence switch of CuNC aggregates controlled by specific external potentials is further utilized to design a novel detection strategy for ACP activity. The great difference in luminescence quenching of CuNCs induced by iron(III) pyrophosphate (FePPi2) complex and free ferric ions enables us to quantitatively monitor ACP level by the luminescence change as variation of ACP activity in the assay solution. This assay is able to detect ACP level as lower as 0.8 U/L, and covers a broad linear scope of 100.0 U/L. This work reports redox-responsive property of CuNCs and its underlying nature due to the oxidation of its interior copper atoms, and provides a sensitive assay method for ACP activity which is sufficiently sensitive for practical measurement in real samples. Copyright © 2017 Elsevier B.V. All

  12. Chloroplast Redox Poise

    DEFF Research Database (Denmark)

    Steccanella, Verdiana

    The redox state of the chloroplast is maintained by a delicate balance between energy production and consumption and is affected by the need to avoid increased production of reactive oxygen species (ROS). Redox power and ROS generated in the chloroplast are essential for maintaining physiological...... the redox status of the plastoquinone pool and chlorophyll biosynthesis. Furthermore, in the plant cell, the equilibrium between redox reactions and ROS signals is also maintained by various balancing mechanisms among which the thioredoxin reductase-thioredoxin system (TR-Trx) stands out as a mediator...... it lacks some of the key enzymes for ROS scavenging and it is the only, so far, known species to have two NTRC genes. Our aim was to elucidate the role of the two NTRC isoforms found in moss as an alternative system for protection against oxidative damage, providing the first partial attempt of a molecular...

  13. Dose-Response Analysis of Chemotactic Signaling Response in Salmonella typhimurium LT2 upon Exposure to Cysteine/Cystine Redox Pair.

    Science.gov (United States)

    Rosier, Bob T; Lazova, Milena D

    2016-01-01

    The chemotaxis system enables motile bacteria to search for an optimum level of environmental factors. Salmonella typhimurium senses the amino acid cysteine as an attractant and its oxidized dimeric form, cystine, as a repellent. We investigated the dose-response dependence of changes in chemotactic signaling activity upon exposure to cysteine and cystine of S. typhimurium LT2 using in vivo fluorescence resonance energy transfer (FRET) measurements. The dose-response curve of the attractant response to cysteine had a sigmoidal shape, typical for receptor-ligand interactions. However, in a knockout strain of the chemoreceptor genes tsr and tar, we detected a repellent response to cysteine solutions, scaling linearly with the logarithm of the cysteine concentration. Interestingly, the magnitude of the repellent response to cystine also showed linear dependence to the logarithm of the cystine concentration. This linear dependence was observed over more than four orders of magnitude, where detection started at nanomolar concentrations. Notably, low concentrations of another oxidized compound, benzoquinone, triggered similar responses. In contrast to S. typhimurium 14028, where no response to cystine was observed in a knockout strain of chemoreceptor genes mcpB and mcpC, here we showed that McpB/McpC-independent responses to cystine existed in the strain S. typhimurium LT2 even at nanomolar concentrations. Additionally, knocking out mcpB and mcpC did not affect the linear dose-response dependence, whereas enhanced responses were only observed to solutions that where not pH neutral (>100 μM cystine) in the case of McpC overexpression. We discuss that the linear dependence of the response on the logarithm of cystine concentrations could be a result of a McpB/C-independent redox-sensing pathway that exists in S. typhimurium LT2. We supported this hypothesis with experiments with defined cysteine/cystine mixed solutions, where a transition from repellent to attractant

  14. Extracellular superoxide production, viability and redox poise in response to desiccation in recalcitrant Castanea sativa seeds.

    Science.gov (United States)

    Roach, Thomas; Beckett, Richard P; Minibayeva, Farida V; Colville, Louise; Whitaker, Claire; Chen, Hongying; Bailly, Christophe; Kranner, Ilse

    2010-01-01

    Reactive oxygen species (ROS) are implicated in seed death following dehydration in desiccation-intolerant 'recalcitrant' seeds. However, it is unknown if and how ROS are produced in the apoplast and if they play a role in stress signalling during desiccation. We studied intracellular damage and extracellular superoxide (O(2)(.-)) production upon desiccation in Castanea sativa seeds, mechanisms of O(2)(.-) production and the effect of exogenously supplied ROS. A transient increase in extracellular O(2)(.-) production by the embryonic axes preceded significant desiccation-induced viability loss. Thereafter, progressively more oxidizing intracellular conditions, as indicated by a significant shift in glutathione half-cell reduction potential, accompanied cell and axis death, coinciding with the disruption of nuclear membranes. Most hydrogen peroxide (H(2)O(2))-dependent O(2)(.-) production was found in a cell wall fraction that contained extracellular peroxidases (ECPOX) with molecular masses of approximately 50 kDa. Cinnamic acid was identified as a potential reductant required for ECPOX-mediated O(2)(.-) production. H(2)O(2), applied exogenously to mimic the transient ROS burst at the onset of desiccation, counteracted viability loss of sub-lethally desiccation-stressed seeds and of excised embryonic axes grown in tissue culture. Hence, extracellular ROS produced by embryonic axes appear to be important signalling components involved in wound response, regeneration and growth.

  15. Identification of redox-sensitive cysteines in the arabidopsis proteome using OxiTRAQ, a quantitative redox proteomics method

    KAUST Repository

    Liu, Pei

    2014-01-28

    Cellular redox status plays a key role in mediating various physiological and developmental processes often through modulating activities of redox-sensitive proteins. Various stresses trigger over-production of reactive oxygen/nitrogen species which lead to oxidative modifications of redox-sensitive proteins. Identification and characterization of redox-sensitive proteins are important steps toward understanding molecular mechanisms of stress responses. Here, we report a high-throughput quantitative proteomic approach termed OxiTRAQ for identifying proteins whose thiols undergo reversible oxidative modifications in Arabidopsis cells subjected to oxidative stress. In this approach, a biotinylated thiol-reactive reagent is used for differential labeling of reduced and oxidized thiols. The biotin-tagged peptides are affinity purified, labeled with iTRAQ reagents, and analyzed using a paralleled HCD-CID fragmentation mode in an LTQ-Orbitrap. With this approach, we identified 195 cysteine-containing peptides from 179 proteins whose thiols underwent oxidative modifications in Arabidopsis cells following the treatment with hydrogen peroxide. A majority of those redox-sensitive proteins, including several transcription factors, were not identified by previous redox proteomics studies. This approach allows identification of the specific redox-regulated cysteine residues, and offers an effective tool for elucidation of redox proteomes. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Aptamer-Functionalized and Backbone Redox-Responsive Hyperbranched Polymer for Targeted Drug Delivery in Cancer Therapy.

    Science.gov (United States)

    Zhuang, Yuanyuan; Deng, Hongping; Su, Yue; He, Lin; Wang, Ruibin; Tong, Gangsheng; He, Dannong; Zhu, Xinyuan

    2016-06-13

    A novel type of backbone redox-responsive hyperbranched poly(2-((2-(acryloyloxy)ethyl)disulfanyl)ethyl 4-cyano-4-(((propylthio)carbonothioyl)-thio)-pentanoate-co-poly(ethylene glycol) methacrylate) (HPAEG) has been designed and prepared successfully via the combination of reversible addition-fragmentation chain-transfer (RAFT) polymerization and self-condensing vinyl polymerization (SCVP). Owing to the existence of surface vinyl groups, HPAEG could be efficiently functionalized by DNA aptamer AS1411 via Michael addition reaction to obtain an active tumor targeting drug delivery carrier (HPAEG-AS1411). The amphiphilic HPAEG-AS1411 could form nanoparticles by macromolecular self-assembly strategy. Cell Counting Kit-8 (CCK-8) assay illustrated that HPAEG-AS1411 nanoparticles had low cytotoxicity to normal cell line. Flow cytometry and confocal laser scanning microscopy (CLSM) results demonstrated that HPAEG-AS1411 nanoparticles could be internalized into tumor cells via aptamer-mediated endocytosis. Compared with pure HPAEG nanoparticles, HPAEG-AS1411 nanoparticles displayed enhanced tumor cell uptake. When the HPAEG-AS1411 nanoparticles loaded with anticancer drug doxorubicin (DOX) were internalized into tumor cells, the disulfide bonds in the backbone of HPAEG-AS1411 were cleaved by glutathione (GSH) in the cytoplasm, so that DOX was released rapidly. Therefore, DOX-loaded HPAEG-AS1411 nanoparticles exhibited a high tumor cellular proliferation inhibition rate and low cytotoxicity to normal cells. This aptamer-functionalized and backbone redox-responsive hyperbranched polymer provides a promising platform for targeted drug delivery in cancer therapy.

  17. HmsC Controls Yersinia pestis Biofilm Formation in Response to Redox Environment

    Directory of Open Access Journals (Sweden)

    Gai-Xian Ren

    2017-08-01

    Full Text Available Yersinia pestis biofilm formation, controlled by intracellular levels of the second messenger molecule cyclic diguanylate (c-di-GMP, is important for blockage-dependent plague transmission from fleas to mammals. HmsCDE is a tripartite signaling system that modulates intracellular c-di-GMP levels to regulate biofilm formation in Y. pestis. Previously, we found that Y. pestis biofilm formation is stimulated in reducing environments in an hmsCDE-dependent manner. However, the mechanism by which HmsCDE senses the redox state remains elusive. Using a dsbA mutant and the addition of Cu2+ to simulate reducing and oxidizing periplasmic environments, we found that HmsC protein levels are decreased and the HmsC-HmsD protein-protein interaction is weakened in a reducing environment. In addition, we revealed that intraprotein disulphide bonds are critical for HmsC since breakage lowers protein stability and diminishes the interaction with HmsD. Our results suggest that HmsC might play a major role in sensing the environmental changes.

  18. Combining sedimentological, trace metal (Mn, Mo) and molecular evidence for reconstructing past water-column redox conditions: The example of meromictic Lake Cadagno (Swiss Alps)

    DEFF Research Database (Denmark)

    Wirth, S. B.; Gilli, A.; Niemann, H.

    2013-01-01

    was investigated for concentration variations of the trace metals Mn and Mo (XRF core scanning and ICP-MS measurements), and for the presence of anoxygenic phototrophic sulfur bacteria (carotenoid pigment analysis and 16S rDNA real time PCR). Our trace metal analysis documents an oxic-intermediate-sulfidic redox...... in the sediments (up to 490 ppm), accompanied by an abrupt drop in Mn concentrations and the increase of molecular biomarkers that indicate the presence of anoxygenic photosynthetic bacteria in the water column. Persistently high Mo concentrations >80 ppm provide evidence that sulfidic conditions prevailed...

  19. Fabrication of Redox-Responsive Degradable Capsule Particles by a Shell-Selective Photoinduced Cross-Linking Approach from Spherical Polymer Particles.

    Science.gov (United States)

    Kitayama, Yukiya; Takeuchi, Toshifumi

    2017-09-18

    In this study, a fabrication route towards functional capsule particles was successfully developed by means of a self-templating shell-selective cross-linking strategy that enables us to prepare shell-cross-linked hollow polymer particles directly from homogeneous spherical polymer particles. To prepare redox-responsive degradable capsule particles, a newly designed monomer bearing a photoinduced post-cross-linking group (cinnamoyl group) and a redox-environment-responsive cleavable group (disulfide group), N-cinnamoyl-N'-methyacryloylcystamine (MCC), was synthesized. Redox-responsive degradable capsule particles were successfully prepared from homogeneous spherical poly(MCC)-based particles by a self-templating shell-selective photoinduced cross-linking approach. Moreover, the cargo loading capability of the shell-cross-linked hollow particles was confirmed through a solvent exchange procedure using dyes, polymer precursors and anticancer reagents. Furthermore, redox-responsive degradability of the capsule polymer particles was also confirmed by adding a reducing agent for cleavage of the disulfide linkage. We hope that the efficient fabrication route of functional capsule particles directly from spherical polymer particles opens efficient routes for the fabrication of a wide range of capsule particles; in particular, this technique is robust, productive, and facile because neither additional sacrificial template particles nor toxic solvents are required. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Multistimuli responsive organogels based on a new gelator featuring tetrathiafulvalene and azobenzene groups: reversible tuning of the gel-sol transition by redox reactions and light irradiation.

    Science.gov (United States)

    Wang, Cheng; Chen, Qun; Sun, Fei; Zhang, Deqing; Zhang, Guanxin; Huang, Yanyan; Zhao, Rui; Zhu, Daoben

    2010-03-10

    For the development of multistimuli responsive organogels, the new organic gelator LMWG 1, featuring electroactive TTF and photoresponsive azobenzene groups, was designed and studied. By manipulating the redox state of the TTF group in LMWG 1, the gel-sol transition for organogels with the LMWG 1 can be reversibly tuned by either chemical or electrochemical oxidation/reduction reactions. Alternatively, the photoisomerization of the azobenzene group in LMWG 1 can also trigger the gel-sol transition. Therefore, organogels with LMWG 1 respond not only to thermal stimuli but also to redox reactions and light irradiation.

  1. Force Spectroscopy of Individual Stimulus-Responsive Poly(ferrocenyldimethylsilane) Chains: Towards a Redox-Driven Macromolecular Motor

    NARCIS (Netherlands)

    Zou, Shan; Hempenius, Mark A.; Schönherr, Holger; Vancso, G. Julius

    2006-01-01

    Progress in the development of a redox-driven macromolecular motor and the characterization of its redox-mechanical cycle using electrochemical AFM-based single-molecule force spectroscopy (SMFS) is described. The elasticities of individual neutral and oxidized poly(ferrocenyldimethylsilane) (PFS) m

  2. Molecular Mechanisms Regulating Macrophage Response to Hypoxia

    Directory of Open Access Journals (Sweden)

    Michal Amit Rahat

    2011-09-01

    Full Text Available Monocytes and Macrophages (Mo/Mϕ exhibit great plasticity, as they can shift between different modes of activation and, driven by their immediate microenvironment, perform divergent functions. These include, among others, patrolling their surroundings and maintaining homeostasis (resident Mo/Mϕ, combating invading pathogens and tumor cells (classically activated or M1 Mo/Mϕ, orchestrating wound healing (alternatively activated or M2 Mo/Mϕ, and restoring homeostasis after an inflammatory response (resolution Mϕ. Hypoxia is an important factor in the Mϕ microenvironment, is prevalent in many physiological and pathological conditions, and is interdependent with the inflammatory response. Although Mo/Mϕ have been studied in hypoxia, the mechanisms by which hypoxia influences the different modes of their activation, and how it regulates the shift between them, remain unclear. Here we review the current knowledge about the molecular mechanisms that mediate this hypoxic regulation of Mϕ activation. Much is known about the hypoxic transcriptional regulatory network, which includes the master regulators HIF-1 and NF-κB, as well as other transcription factors (e.g. AP-1, Erg-1, but we also highlight the role of post-transcriptional and post-translational mechanisms. These mechanisms mediate hypoxic induction of Mϕ pro-angiogenic mediators, suppress M1 Mϕ by post-transcriptionally inhibiting pro-inflammatory mediators, and help shift the classically activated Mϕ into an activation state which approximate the alternatively activated or resolution Mϕ.

  3. A Redox-Active, Compact Molecule for Cross-Linking Amyloidogenic Peptides into Nontoxic, Off-Pathway Aggregates: In Vitro and In Vivo Efficacy and Molecular Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Derrick, Jeffrey S.; Kerr, Richard A.; Nam, Younwoo; Oh, Shin Bi; Lee, Hyuck Jin; Earnest, Kaylin G.; Suh, Nayoung; Peck, Kristy L.; Ozbil, Mehmet; Korshavn, Kyle J.; Ramamoorthy, Ayyalusamy; Prabhakar, Rajeev; Merino, Edward J.; Shearer, Jason; Lee, Joo-Yong; Ruotolo, Brandon T.; Lim, Mi Hee

    2015-11-25

    Chemical reagents targeting and controlling amyloidogenic peptides have received much attention for helping identify their roles in the pathogenesis of protein-misfolding disorders. Herein, we report a novel strategy for redirecting amyloidogenic peptides into nontoxic, off-pathway aggregates, which utilizes redox properties of a small molecule (DMPD, N,N-dimethyl-p-phenylenediamine) to trigger covalent adduct formation with the peptide. In addition, for the first time, biochemical, biophysical, and molecular dynamics simulation studies have been performed to demonstrate a mechanistic understanding for such an interaction between a small molecule (DMPD) and amyloid-β (Aβ) and its subsequent anti-amyloidogenic activity, which, upon its transformation, generates ligand–peptide adducts via primary amine-dependent intramolecular cross-linking correlated with structural compaction. Furthermore, in vivo efficacy of DMPD toward amyloid pathology and cognitive impairment was evaluated employing 5xFAD mice of Alzheimer’s disease (AD). Such a small molecule (DMPD) is indicated to noticeably reduce the overall cerebral amyloid load of soluble Aβ forms and amyloid deposits as well as significantly improve cognitive defects in the AD mouse model. Overall, our in vitro and in vivo studies of DMPD toward Aβ with the first molecular-level mechanistic investigations present the feasibility of developing new, innovative approaches that employ redox-active compounds without the structural complexity as next-generation chemical tools for amyloid management.

  4. Microarray meta-analysis focused on the response of genes involved in redox homeostasis to diverse abiotic stresses in rice

    Directory of Open Access Journals (Sweden)

    Joao eBraga De Abreu Neto

    2016-01-01

    Full Text Available Plants are exposed to a wide range of abiotic stresses, which often occur in combination. Because physiological investigations typically focus on one stress, our understanding of unspecific stress responses remains limited. The plant redox homeostasis, i.e. the production and removal of reactive oxygen species (ROS, may be involved in many environmental stress conditions. Therefore, this study intended to identify genes, which are activated in diverse abiotic stresses, focusing on ROS–related pathways. We conducted a meta-analysis (MA of microarray experiments, focusing on rice. Transcriptome data were mined from public databases and fellow researchers, which represented 36 different experiments and investigated diverse abiotic stresses, including ozone stress, drought, heat, cold, salinity, and mineral deficiencies/toxicities. To overcome the inherent artefacts of different MA methods, data were processed using Fisher, rOP, REM and product of rank (GeneSelector, and genes identified by most approaches were considered as shared differentially expressed genes (DEGs. Two MA strategies were adopted: first, datasets were separated into shoot, root and seedling experiments, and these tissues were analyzed separately to identify shared DEGs. Second, shoot and seedling experiments were classed into oxidative stress (OS, i.e. ozone and hydrogen peroxide treatments directly producing ROS in plant tissue, and other abiotic stresses (AS, in which ROS production is indirect. In all tissues and stress conditions, genes a priori considered as ROS-related were overrepresented among the DEGs, as they represented 4% of all expressed genes but 7-10% of the DEGs. The combined MA approach was substantially more conservative than individual MA methods and identified 1001 shared DEGs in shoots, 837 shared DEGs in root, and 1172 shared DEGs in seedlings. Within the OS and AS groups, 990 and 1727 shared DEGs were identified, respectively. In total, 311 genes were

  5. How the redox state of tobacco 'Bel-W3' is modified in response to ozone and other environmental factors in a sub-tropical area?

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Ana P.L.; Dafre, Marcelle; Rinaldi, Mirian C.S. [Instituto de Botanica, Caixa Postal 3005, 01061-970 Sao Paulo, SP (Brazil); Domingos, Marisa, E-mail: mmingos@superig.com.b [Instituto de Botanica, Caixa Postal 3005, 01061-970 Sao Paulo, SP (Brazil)

    2011-02-15

    This study intended to determine whether the redox state in plants of Nicotiana tabacum 'Bel-W3' fluctuates in response to the environmental factors in a sub-tropical area contaminated by ozone (Sao Paulo, SE - Brazil) and which environmental factors are related to this fluctuation, discussing their biomonitoring efficiency. We comparatively evaluated the indicators of redox state (ascorbic acid, glutathione, superoxide dismutase, ascorbate peroxidase, and glutathione reductase) and leaf injury in 17 field experiments performed in 2008. The redox state was explained by the combined effects of chronic levels of O{sub 3} and meteorological variables 4-6 days prior to the plant sampling. Moderate leaf injury was observed in most cases. The redox state of tobacco decreases few days after their placement in the sub-tropical environment, causing them to become susceptible to oxidative stress imposed by chronic doses of O{sub 3}. Its bioindicator efficiency would not be diminished in such levels of atmospheric contamination. - Research highlights: Nicotiana tabacum 'Bel-W3' is potentially a bioindicator of O{sub 3} in the sub-tropics. However, it is unknown if its redox state would affect its bioindicator performance under sub-tropical environmental conditions. This study revealed that the redox state of tobacco decreases few days after their placement in the sub-tropical environment, causing them to become susceptible to oxidative stress imposed by chronic doses of O{sub 3}. Therefore, its bioindicator efficiency would not be diminished in such levels of atmospheric contamination. However, the bioindicator efficiency N. tabacum 'Bel-W3' for biomonitoring O{sub 3} should be regionally modeled in the sub-tropics, based on both its redox state and on the flux of O{sub 3} through stomata, in response to the varying micro-meteorological conditions that govern both physiological processes. - The bioindicator efficiency of tobacco plants is not

  6. Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism

    DEFF Research Database (Denmark)

    Olsen, Rikke K J; Cornelius, Nanna; Gregersen, Niels

    2015-01-01

    Mitochondria play a key role in overall cell physiology and health by integrating cellular metabolism with cellular defense and repair mechanisms in response to physiological or environmental changes or stresses. In fact, dysregulation of mitochondrial stress responses and its consequences...... and directions that can be tested experimentally and used in the design of future new approaches for pre-symptomatic diagnosis and prognosis and perhaps more effective treatments of inborn errors of metabolism....

  7. OSTEOPOROSIS AND ALZHEIMER PATHOLOGY: ROLE OF CELLULAR STRESS RESPONSE AND HORMETIC REDOX SIGNALING IN AGING AND BONE REMODELING

    Directory of Open Access Journals (Sweden)

    Vittorio eCalabrese

    2014-06-01

    Full Text Available Alzheimer’s disease (AD as well as osteoporosis are multifactorial progressive degenerative disorders characterized by low parenchymal density and microarchitectural deterioration of tissue. Though not referred to as one of the major complications of AD, osteoporosis and hip fracture are commonly observed in patients with AD, however, the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS are generally recognized as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-kB ligand (RANKL-dependent osteoclast differentiation, but they also have cytotoxic effects that include peroxidation of lipids and oxidative damage to proteins and DNA. ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways which regulate life span across species including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–response, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in bone remodeling and activation of vitagenes resulting in enhanced defense against energy and stress resistance homeostasis dysruption with consequent impact on

  8. Genome-wide transcriptional response of a Saccharomyces cerevisiae strain with an altered redox metabolism

    DEFF Research Database (Denmark)

    Bro, Christoffer; Regenberg, Birgitte; Nielsen, Jens

    2004-01-01

    The genome-wide transcriptional response of a Saccharomyces cerevisiae strain deleted in GDH1 that encodes a NADP(+)-dependent glutamate dehydrogenase was compared to a wild-type strain under anaerobic steady-state conditions. The GDH1-deleted strain has a significantly reduced NADPH requirement...

  9. Targeting the oxidative stress response system of fungi with safe, redox-potent chemosensitizing agents

    Science.gov (United States)

    One mode of action of the antimycotics amphotericin B (AMB) or itraconazole (ITZ) against filamentous fungi involves cellular oxidative stress response. Aspergillus fumigatus sakA', a mitogen-activated protein kinase (MAPK) gene deletion mutant in the antioxidation system, was more sensitive to AMB ...

  10. Effect of extracorporeal liver support by molecular adsorbents recirculating system and Prometheus on redox state of albumin in acute-on-chronic liver failure.

    Science.gov (United States)

    Oettl, Karl; Stadlbauer, Vanessa; Krisper, Peter; Stauber, Rudolf E

    2009-10-01

    Oxidative stress is believed to play an important role in acute-on-chronic liver failure (AoCLF). Albumin, an important transport vehicle, was found to be severely oxidized in AoCLF patients. Extracorporeal liver support systems may exert beneficial effects in AoCLF via removal of albumin-bound toxins. At present, two systems are commercially available, the molecular adsorbents recirculating system (MARS) and fractionated plasma separation, adsorption and dialysis (FPAD, also known as Prometheus). The aim of this study was to compare the effect of MARS and Prometheus treatments on the redox state of human serum albumin. Eight patients with AoCLF underwent alternating treatments with either MARS or Prometheus in a randomized cross-over design. Sixteen treatments (eight MARS and eight Prometheus) were available for analysis. The fraction of human mercaptalbumin (HMA), human nonmercaptalbumin-1 (HNA1), and human nonmercaptalbumin-2 (HNA2) were measured before and after single MARS and Prometheus treatments and during follow-up. In AoCLF patients the oxidized fractions of albumin, HNA1, and HNA2 were markedly increased. Both MARS and Prometheus treatments resulted in a shift of HNA1 to HMA, while HNA2 was not significantly affected. This shift in albumin fractions was transient and disappeared within 24 h after treatment. There were no significant differences between MARS and Prometheus treatments with respect to the redox state of albumin. Both MARS and Prometheus treatments lead to transient improvements of the redox state of albumin, which could be beneficial in the treatment of AoCLF.

  11. The nitric oxide redox sibling nitroxyl partially circumvents impairment of platelet nitric oxide responsiveness.

    Science.gov (United States)

    Dautov, R F; Ngo, D T M; Licari, G; Liu, S; Sverdlov, A L; Ritchie, R H; Kemp-Harper, B K; Horowitz, J D; Chirkov, Y Y

    2013-11-30

    Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic heart disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and the NO donor sodium nitroprusside (SNP) were compared. While SNP (10μM) induced 29±3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10μM) caused 75±4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response ratio was markedly increased (p<0.01), consistent with partial circumvention of NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001) with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO, 200μM) inhibited SNP and IPA/NO responses by 92±7% and 17±4% respectively (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only partially NO-mediated. ODQ (10μM) inhibited IPA/NO responses by 36±8% (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of aggregation. There was no significant relationship between whole blood ROS content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents platelet NO resistance while acting, at least partially, as a haem-mediated sGC activator.

  12. Solvent Effects on the Electrochemical Behavior of TAPD-Based Redox-Responsive Probes for Cadmium(II

    Directory of Open Access Journals (Sweden)

    Rihab Sahli

    2014-01-01

    Full Text Available Two tetralkylated phenylenediamines (TAPD 1 and 2 have been prepared by reductive alkylation of para-dimethylaminoaniline with furfural or thiophene 2-carboxaldehyde, respectively. Their chelation ability has been evaluated as electrochemical guest-responsive chemosensors for Cd(II in acetonitrile (ACN, dimethylformamide (DMF, propylene carbonate (PC, and nitromethane (NM. The voltamperometric studies showed that these compounds are able to bind the Cd(II cation with strong affinities except in DMF. The redox features of the chemosensors changed drastically when they are bounded to Cd(II to undergo important anodic potential peak shifts comprised between ca. 500 and ca. 900 mV depending on the solvent. The addition of ∼4–10% molar triflic acid (TfOH was found to be necessary to achieve rapidly the cation chelation which is slow without the acid. The electrochemical investigations suggested the formation of 1 : 2 stoichiometry complexes [Cd(L2]2+. The results are discussed in terms of solvent effects as a competitive electron donating ligand to the cation. The reaction coupling efficiency (RCE values were determined and were also found to be solvent-dependent.

  13. Fifty hertz extremely low-frequency magnetic field exposure elicits redox and trophic response in rat-cortical neurons.

    Science.gov (United States)

    Di Loreto, Silvia; Falone, Stefano; Caracciolo, Valentina; Sebastiani, Pierluigi; D'Alessandro, Antonella; Mirabilio, Alessandro; Zimmitti, Vincenzo; Amicarelli, Fernanda

    2009-05-01

    Large research activity has raised around the mechanisms of interaction between extremely low-frequency magnetic fields (ELF-MFs) and biological systems. ELF-MFs may interfere with chemical reactions involving reactive oxygen species (ROS), thus facilitating oxidative damages in living cells. Cortical neurons are particularly susceptible to oxidative stressors and are also highly dependent on the specific factors and proteins governing neuronal development, activity and survival. The aim of the present work was to investigate the effects of exposures to two different 50 Hz sinusoidal ELF-MFs intensities (0.1 and 1 mT) in maturing rat cortical neurons' major anti-oxidative enzymatic and non-enzymatic cellular protection systems, membrane peroxidative damage, as well as growth factor, and cytokine expression pattern. Briefly, our results showed that ELF-MFs affected positively the cell viability and concomitantly reduced the levels of apoptotic death in rat neuronal primary cultures, with no significant effects on the main anti-oxidative defences. Interestingly, linear regression analysis suggested a positive correlation between reduced glutathione (GSH) and ROS levels in 1 mT MF-exposed cells. On this basis, our hypothesis is that GSH could play an important role in the antioxidant defence towards the ELF-MF-induced redox challenge. Moreover, the GSH-based cellular response was achieved together with a brain-derived neurotrophic factor over-expression as well as with the interleukin 1beta-dependent regulation of pro-survival signaling pathways after ELF-MF exposure.

  14. A novel membrane-anchored cytochrome c-550 of alkaliphilic Bacillus clarkii K24-1U: expression, molecular features and properties of redox potential.

    Science.gov (United States)

    Ogami, Shinichi; Hijikata, Shoichi; Tsukahara, Tamotsu; Mie, Yasuhiro; Matsuno, Toshihide; Morita, Naoki; Hara, Isao; Yamazaki, Koji; Inoue, Norio; Yokota, Atsushi; Hoshino, Tamotsu; Yoshimune, Kazuaki; Yumoto, Isao

    2009-05-01

    A membrane-anchored cytochrome c-550, which is highly expressed in obligately alkaliphilic Bacillus clarkii K24-1U, was purified and characterized. The protein contained a conspicuous sequence of Gly(22)-Asn(34), in comparison with the other Bacillus small cytochromes c. Analytical data indicated that the original and lipase-treated intermediate forms of cytochrome c-550 bind to fatty acids of C(15), C(16) and C(17) chain lengths and C(15) chain length, respectively, and it was considered that these fatty acids are bound to glycerol-Cys(18). Since there was a possibility that the presence of a diacylglycerol anchor contributed to the formation of dimeric states of this protein (20 and 17 kDa in SDS-PAGE), a C18M (Cys(18) --> Met)-cytochrome c-550 was constructed. The molecular mass of the C18M-cytochrome c-550 was determined as 15 and 10 kDa in SDS-PAGE and 23 kDa in blue native PAGE. The C18M-cytochrome c-550 bound with or without Triton X-100 formed a tetramer as the original cytochrome c-550 bound with Triton X-100, as determined by gel filtration. The midpoint redox potential of cytochrome c-550 as determined by redox titration was +83 mV, while that determined by cyclic voltammetric measurement was +7 mV. The above results indicate that cytochrome c-550 is a novel cytochrome c.

  15. Short-term cigarette smoke exposure induces reversible changes in energy metabolism and cellular redox status independent of inflammatory responses in mouse lungs.

    Science.gov (United States)

    Agarwal, Amit R; Zhao, Liqin; Sancheti, Harsh; Sundar, Isaac K; Rahman, Irfan; Cadenas, Enrique

    2012-11-15

    Cigarette smoking leads to alteration in cellular redox status, a hallmark in the pathogenesis of chronic obstructive pulmonary disease. This study examines the role of cigarette smoke (CS) exposure in the impairment of energy metabolism and, consequently, mitochondrial dysfunction. Male A/J mice were exposed to CS generated by a smoking machine for 4 or 8 wk. A recovery group was exposed to CS for 8 wk and allowed to recover for 2 wk. Acute CS exposure altered lung glucose metabolism, entailing a decrease in the rate of glycolysis and an increase in the pentose phosphate pathway, as evidenced by altered expression and activity of GAPDH and glucose-6-phosphate dehydrogenase, respectively. Impairment of GAPDH was found to be due to glutathionylation of its catalytic site cysteines. Metabolic changes were associated with changes in cellular and mitochondrial redox status, assessed in terms of pyridine nucleotides and glutathione. CS exposure elicited an upregulation of the expression of complexes II, III, IV, and V and of the activity of complexes II, IV, and V. Microarray analysis of gene expression in mouse lungs after exposure to CS for 8 wk revealed upregulation of a group of genes involved in metabolism, electron transfer chain, oxidative phosphorylation, mitochondrial transport and dynamics, and redox regulation. These changes occurred independently of inflammatory responses. These findings have implications for the early onset of alterations in energy and redox metabolism upon acute lung exposure to CS.

  16. Quantitative measures for redox signaling.

    Science.gov (United States)

    Pillay, Ché S; Eagling, Beatrice D; Driscoll, Scott R E; Rohwer, Johann M

    2016-07-01

    Redox signaling is now recognized as an important regulatory mechanism for a number of cellular processes including the antioxidant response, phosphokinase signal transduction and redox metabolism. While there has been considerable progress in identifying the cellular machinery involved in redox signaling, quantitative measures of redox signals have been lacking, limiting efforts aimed at understanding and comparing redox signaling under normoxic and pathogenic conditions. Here we have outlined some of the accepted principles for redox signaling, including the description of hydrogen peroxide as a signaling molecule and the role of kinetics in conferring specificity to these signaling events. Based on these principles, we then develop a working definition for redox signaling and review a number of quantitative methods that have been employed to describe signaling in other systems. Using computational modeling and published data, we show how time- and concentration- dependent analyses, in particular, could be used to quantitatively describe redox signaling and therefore provide important insights into the functional organization of redox networks. Finally, we consider some of the key challenges with implementing these methods. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. An intelligent nanotheranostic agent for targeting, redox-responsive ultrasound imaging, and imaging-guided high-intensity focused ultrasound synergistic therapy.

    Science.gov (United States)

    Wang, Xia; Chen, Hangrong; Zhang, Kun; Ma, Ming; Li, Faqi; Zeng, Deping; Zheng, Shuguang; Chen, Yu; Jiang, Lixin; Xu, Huixiong; Shi, Jianlin

    2014-04-09

    A novel multifunctional nanotheranostic agent with targeting, redox-responsive ultrasound imaging and ultrasound imaging-guided high-intensity focused ultrasound (HIFU) therapy (MSNC-PEG-HA(SS)-PFH, abbreviated as MPH(SS)-PFH) capabilities is developed. The redox-responsive guest molecule release and ultrasound imaging functions can be both integrated in such a "smart" theranostic agent, which is accomplished by the redox-triggered transition from the crosslinking state to retrocrosslinking state of the grafted polyethylene glycol-disulfide hyaluronic acid molecules on the particle surface when reaching a reducing environment in vitro. More importantly, under the tailored ultrasound imaging guiding, in vivo Hela tumor-bearing nude mice can be thoroughly and spatial-accurately ablated during HIFU therapy, due to the targeted accumulation, responsive ultrasound imaging guidance and the synergistic ablation functions of nanotheranostic agent MPH(SS)-PFH in the tumors. This novel multifunctional nano-platform can serve as a promising candidate for further studies on oncology therapy, due to its high stability, responsive and indicative ultrasound imaging of tumors, and enhanced HIFU therapeutic efficiency and spatial accuracy under ultrasound-guidance.

  18. Thioredoxin-dependent Redox Regulation of Cellular Signaling and Stress Response through Reversible Oxidation of Methionines

    Energy Technology Data Exchange (ETDEWEB)

    Bigelow, Diana J.; Squier, Thomas C.

    2011-06-01

    Generation of reactive oxygen species (ROS) is a common feature of many forms of stress to which plants are exposed. Successful adaptation to changing environmental conditions requires sensitive sensors of ROS such as protein-bound methionines that are converted to their corresponding methionine sulfoxides, which in turn can influence cellular signaling pathways. Such a signaling protein is calmodulin, which represents an early and central point in calcium signaling pathways important to stress response in plants. We describe recent work elucidating fundamental mechanisms of reversible methionine oxidation within calmodulin, including the sensitivity of individual methionines within plant and animal calmodulin to ROS, the structural and functional consequences of their oxidation, and the interactions of oxidized calmodulin with methionine sulfoxide reductase enzymes.

  19. Medical ozone increases methotrexate clinical response and improves cellular redox balance in patients with rheumatoid arthritis.

    Science.gov (United States)

    León Fernández, Olga Sonia; Viebahn-Haensler, Renate; Cabreja, Gilberto López; Espinosa, Irainis Serrano; Matos, Yanet Hernández; Roche, Liván Delgado; Santos, Beatriz Tamargo; Oru, Gabriel Takon; Polo Vega, Juan Carlos

    2016-10-15

    Medical ozone reduced inflammation, IL-1β, TNF-α mRNA levels and oxidative stress in PG/PS-induced arthritis in rats. The aim of this study was to investigate the medical ozone effects in patients with rheumatoid arthritis treated with methotrexate and methotrexate+ozone, and to compare between them. A randomized clinical study with 60 patients was performed, who were divided into two groups: one (n=30) treated with methotrexate (MTX), folic acid and Ibuprophen (MTX group) and the second group (n=30) received the same as the MTX group+medical ozone by rectal insufflation of the gas (MTX+ozone group). The clinical response of the patients was evaluated by comparing Disease Activity Score 28 (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), Anti-Cyclic Citrullinated (Anti-CCP) levels, reactants of acute phase and biochemical markers of oxidative stress before and after 20 days of treatment. MTX+ozone reduced the activity of the disease while MTX merely showed a tendency to decrease the variables. Reactants of acute phase displayed a similar picture. MTX+ozone reduced Anti-CCP levels as well as increased antioxidant system, and decreased oxidative damage whereas MTX did not change. Glutathione correlated with all clinical variables just after MTX+ozone. MTX+ozone increased the MTX clinical response in patients with rheumatoid arthritis. No side effects were observed. These results suggest that ozone can increase the efficacy of MTX probably because both share common therapeutic targets. Medical ozone treatment is capable of being a complementary therapy in the treatment of rheumatoid arthritis.

  20. The dynamic response of hyporheic zone redox zonation after surface flow perturbation

    Science.gov (United States)

    Kaufman, M.; Zheng, L.; Cardenas, M. B.

    2015-12-01

    As water in a stream or river flows over ripples and other bedforms, differential surface pressures create bedform-induced hyporheic exchange. The oxygen, carbon, and nutrients carried into the bed by the surface water as well as those already existing in the bed material form the basis for microbial communities in the sediment.The resulting dissolved oxygen conditions are a critical control on the ecological function of the hyporheic zone (HZ), from both micro- and macro-biological habitat perspectives. Because hyporheic exchange rates are controlled by surface flow velocity, variations in surface flow have significant impact on the subsurface oxygen conditions. Most rivers are subject to flow velocity variations due to natural forcing including precipitation and variations in evapotranspiration as well as anthropogenic forces like dam releases. We use a large (10m x 0.7m x 0.3m) programmable flume instrumented with a bedform-scale high-resolution planar optode dissolved oxygen imaging system to observe the distribution of oxygenated sediment within the HZ over time. Using this system we characterize the rate at which hyporheic oxygen conditions reconfigure in response to changes in the surface flow velocity, particularly the time it takes for conditions to recover after a pulse of increased flow velocity. In addition, we make use of numerical models to further identify critical response time drivers. With these tools, we develop equations to describe the post-disturbance recovery time as a function of relative pulse magnitude and duration. Using these equations we can predict the time scale over which the hyporheic zone will recover following both natural and anthropogenic flow regime disturbances. Being able to predict the magnitude and duration of dissolved oxygen changes in the wake of flow perturbing events allows us to better understand the impact these disturbances have on the ecology of the hyporheic zone.

  1. Functional role for redox in the epileptogenesis: molecular regulation of glutamate in the hippocampus of FeCl3-induced limbic epilepsy model.

    Science.gov (United States)

    Ueda, Yuto; Doi, Taku; Nagatomo, Keiko; Willmore, L James; Nakajima, Akira

    2007-08-01

    We used western blotting to measure the quantity of glutamate and gamma-aminobutyric acid (GABA) transporters proteins within hippocampal tissue obtained from rats who had undergone epileptogenesis. Chronic seizures were induced by amygdalar injection of FeCl(3). We found that the glial glutamate transporters GLAST and GLT-1 were down-regulated at 60 days after initiation of chronic and recurrent seizures. However, the neuronal glutamate transporter EAAC-1 and the GABA transporter GAT-3 were increased. We performed in vivo microdialysis in freely moving animals to estimate in vivo redox state. We found that the hippocampal tissues were oxidized, resulting in even further impairment of glutamate transport. Our data show that epileptogenesis in rats resulting in chronic and recurrent seizures is associated with collapse of glutamate regulation caused by both the molecular down-regulation of glial glutamate transporters combined with the functional failure due to oxidation.

  2. Redox-responsive repressor Rex modulates alcohol production and oxidative stress tolerance in Clostridium acetobutylicum.

    Science.gov (United States)

    Zhang, Lei; Nie, Xiaoqun; Ravcheev, Dmitry A; Rodionov, Dmitry A; Sheng, Jia; Gu, Yang; Yang, Sheng; Jiang, Weihong; Yang, Chen

    2014-11-01

    Rex, a transcriptional repressor that modulates its DNA-binding activity in response to NADH/NAD(+) ratio, has recently been found to play a role in the solventogenic shift of Clostridium acetobutylicum. Here, we combined a comparative genomic reconstruction of Rex regulons in 11 diverse clostridial species with detailed experimental characterization of Rex-mediated regulation in C. acetobutylicum. The reconstructed Rex regulons in clostridia included the genes involved in fermentation, hydrogen production, the tricarboxylic acid cycle, NAD biosynthesis, nitrate and sulfite reduction, and CO2/CO fixation. The predicted Rex-binding sites in the genomes of Clostridium spp. were verified by in vitro binding assays with purified Rex protein. Novel members of the C. acetobutylicum Rex regulon were identified and experimentally validated by comparing the transcript levels between the wild-type and rex-inactivated mutant strains. Furthermore, the effects of exposure to methyl viologen or H2O2 on intracellular NADH and NAD(+) concentrations, expression of Rex regulon genes, and physiology of the wild type and rex-inactivated mutant were comparatively analyzed. Our results indicate that Rex responds to NADH/NAD(+) ratio in vivo to regulate gene expression and modulates fermentation product formation and oxidative stress tolerance in C. acetobutylicum. It is suggested that Rex plays an important role in maintaining NADH/NAD(+) homeostasis in clostridia. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  3. Visible-light-responsive multielectron redox catalysis of lacunary polyoxometalates induced by substrate coordination to their lacuna.

    Science.gov (United States)

    Suzuki, Kosuke; Jeong, Jinu; Yamaguchi, Kazuya; Mizuno, Noritaka

    2015-01-01

    We describe herein the efficient visible-light-responsive polyoxometalate-based multielectron photoredox catalysis induced by in situ coordination of alcohols to the lacuna of TBA4 H4 [γ-SiW10 O36 ] (I, TBA=tetra-n-butylammonium). The coordination of alcohols to the lacuna of I generated a new highest occupied molecular orbital as the electron donor level and enabled the visible-light-responsive multielectron transfer from alcohols to I, which could be utilized for aerobic alcohol oxidation and one-pot synthesis of N-arylimines starting from nitroarenes and primary alcohols.

  4. Heme oxygenase-1: redox regulation and role in the hepatic response to oxidative stress.

    Science.gov (United States)

    Bauer, Michael; Bauer, Inge

    2002-10-01

    Heme oxygenase (HO) catalyzes the oxidative cleavage of the alpha-mesocarbon of Fe-protoporphyrin-IX yielding equimolar amounts of biliverdin-IXalpha, free divalent iron, and carbon monoxide (CO). Among the three isoenzymes cloned to date, only HO-1 can be induced by a variety of seemingly disparate stimuli, most of which are linked by their ability to provoke oxidative stress. Although constitutive expression of HO-1 in the liver is restricted to Kupffer cells, the gene is inducible in nonparenchymal as well as in parenchymal liver cells. HO-1 induction potentially confers protection against oxidative stress in a variety of experimental models, such as liver ischemia/reperfusion secondary to transplantation or hemorrhage/resuscitation. Induction of HO-1 may protect the cell against oxidative injury by (a) controlling intracellular levels of "free" heme (a prooxidant), (b) producing biliverdin (an antioxidant), (c) improving nutritive perfusion via CO release, and (d) fostering the synthesis of the Fe-binding protein ferritin. Although protective effects of up-regulation of the HO pathway--presumably through production of bile pigments and CO--have been reported for a variety of cells and tissues, including the liver, evidence suggests that the protective action might be restricted to a rather narrow threshold of overexpression. High levels of HO-1 may even sensitize the cell to oxidative stress, e.g., through release of reactive iron. Transcriptional activation of the HO-1 gene is an integral part of the cellular response to oxidative stress, but its induction seems to be neither exclusively cytoprotective nor exclusively cytotoxic.

  5. Cytochrome c end-capped mesoporous silica nanoparticles as redox-responsive drug delivery vehicles for liver tumor-targeted triplex therapy in vitro and in vivo.

    Science.gov (United States)

    Zhang, Beilu; Luo, Zhong; Liu, Junjie; Ding, Xingwei; Li, Jinghua; Cai, Kaiyong

    2014-10-28

    To develop carriers for efficient anti-cancer drug delivery with reduced side effects, a biocompatible and redox-responsive nanocontainer based on mesoporous silica nanoparticles (MSNs) for tumor-targeted triplex therapy was reported in this study. The nanocontainer was fabricated by immobilizing cytochrome c (CytC) onto the MSNs as sealing agent via intermediate linkers of disulfide bonds for redox-responsive intracellular drug delivery. AS1411 aptamer was further tailored onto MSNs for cell/tumor targeting. The successful construction of redox- responsive MSNs was confirmed by BET/BJH analysis, transmission electron microscopy, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermogravimetric analysis (TGA), respectively. Detailed investigations demonstrated that anticancer drug of doxorubicin (DOX) loaded nanocontainer could be triggered by reductant (e.g. glutathione) within cellular microenvironment and release DOX to induce tumor cell apoptosis in vitro. More importantly, the nanocontainer displayed great potential for tumor targeting and achieved triplex therapy effects on the tumor inhibition in vivo through the loading DOX, gatekeeper of CytC and AS1411 aptamer, which were reflected by the change of tumor size, TUNEL staining and HE staining assays.

  6. Probing the effect of the solution environment around redox-active moieties using rigid anthraquinone terminated molecular rulers.

    Science.gov (United States)

    Darwish, Nadim; Eggers, Paul K; Ciampi, Simone; Tong, Yujin; Ye, Shen; Paddon-Row, Michael N; Gooding, J Justin

    2012-11-07

    Herein, we report the influence of the position and the solution environment around surface-bound redox-active moieties on their redox reaction. The study was made possible by using rigid norbornylogous bridges, which possess anthraquinone (AQ) moieties. An L-shaped norbornylogous bridge (L-NB) and straight-shaped norbornylogous bridge (S-NB) were used to situate AQ moieties at well-defined position and environments above a mixed alkanethiol self-assembled monolayer (SAM) on Au (111) surfaces. Sum frequency generation (SFG) vibrational spectroscopy was employed to evaluate the interaction between the S-NB and L-NB with diluent molecules in the mixed SAMs. The SFG measurements demonstrated that hydrogen-bonding interactions were formed between AQ moieties of L-NB and diluent molecules terminated by hydroxyl group within a suitable separation. The SFG observations provided information about the relative position of the AQ moieties in each SAM, which significantly affects the thermodynamics and the kinetics of the electron transfer on the electrode/solution interface. The rate constant (k(et)) of the electron transfer between the AQ moiety and the gold surface and the apparent formal potential (E(0')) were studied using cyclic voltammetry (CV), alternating current voltammetry (ACV), and electrochemical impedance spectroscopy (EIS). It was found that the k(et) increases and E(0') shifts to more anodic values as the distance between the AQ moiety and the surface of the diluent was increased, for both methyl and hydroxyl terminated diluent. These results are discussed in relation to H-bonding interactions with water surrounding the AQ moieties.

  7. Electrochemical response of a biofilm community to changes in electron-acceptor redox potential elucidated using microbial fuel cells

    Science.gov (United States)

    Arbour, T.; Wrighton, K. C.; Mullin, S. W.; Luef, B.; Gilbert, B.; Banfield, J. F.

    2012-12-01

    Currently, we have limited insight into how mineral properties affect dissimilatory metal-reducing bacteria (DMRB) or the microbial communities that contain them. Advances in our understanding of DMRB metabolism have been achieved using microbial fuel cells (MFCs), which exploit the ability of these organisms to transfer electrons extracellularly. By replacing the mineral electron acceptor with a conductive electrode under potentiostat control, the activity of microorganisms capable of interfacial electron transfer can be quantified by the current flowing through the electrode and related to the thermodynamics of respiration. We seek to understand how communities and their individual members respond to changes in mineralogy, and expect mineral redox potential to be a primary control. The ability to precisely control the redox potential of the electron-accepting anodic electrode is our primary motivation for using MFCs. We inoculated duplicate MFCs containing 10 mM acetate in phosphate buffered media with a slurry of subsurface sediment and groundwater obtained from the Integrated Field-Scale Research Challenge Site at Rifle, CO. Electroactive biofilms were established on graphite anodes poised at a favorable potential (0.0 V vs. SHE) before poising at -0.2 V—a potential representative of natural iron reduction. The current was stable across both anodes over more than 100 days of operation, and the percentage of the electrons in acetate recovered as current ("Coulombic efficiency") was typically 70 to >90%. Current density reached 0.4 A/m2 at -0.2 V, to a max of over 1.0 A/m2 at or above ~0.0 V (based on geometric electrode surface area). Media exchanges and biofilm cyclic voltammetry (CV) experiments indicate that electrode-attached microbial communities were responsible for primary electron transfer. Cryo-electron and confocal fluorescence microscopies of the biofilm reveal numerous morphologies of viable microorganisms that are currently being characterized

  8. Deciphering the Transcriptional Response Mediated by the Redox-Sensing System HbpS-SenS-SenR from Streptomycetes

    Science.gov (United States)

    Busche, Tobias; Winkler, Anika; Wedderhoff, Ina; Rückert, Christian; Kalinowski, Jörn; Ortiz de Orué Lucana, Darío

    2016-01-01

    The secreted protein HbpS, the membrane-embedded sensor kinase SenS and the cytoplasmic response regulator SenR from streptomycetes have been shown to form a novel type of signaling pathway. Based on structural biology as well as different biochemical and biophysical approaches, redox stress-based post-translational modifications in the three proteins were shown to modulate the activity of this signaling pathway. In this study, we show that the homologous system, named here HbpSc-SenSc-SenRc, from the model species Streptomyces coelicolor A3(2) provides this bacterium with an efficient defense mechanism under conditions of oxidative stress. Comparative analyses of the transcriptomes of the Streptomyces coelicolor A3(2) wild-type and the generated hbpSc-senSc-senRc mutant under native and oxidative-stressing conditions allowed to identify differentially expressed genes, whose products may enhance the anti-oxidative defense of the bacterium. Amongst others, the results show an up-regulated transcription of genes for biosynthesis of cysteine and vitamin B12, transport of methionine and vitamin B12, and DNA synthesis and repair. Simultaneously, transcription of genes for degradation of an anti-oxidant compound is down-regulated in a HbpSc-SenSc-SenRc-dependent manner. It appears that HbpSc-SenSc-SenRc controls the non-enzymatic response of Streptomyces coelicolor A3(2) to counteract the hazardous effects of oxidative stress. Binding of the response regulator SenRc to regulatory regions of some of the studied genes indicates that the regulation is direct. The results additionally suggest that HbpSc-SenSc-SenRc may act in concert with other regulatory modules such as a transcriptional regulator, a two-component system and the Streptomyces B12 riboswitch. The transcriptomics data, together with our previous in vitro results, enable a profound characterization of the HbpS-SenS-SenR system from streptomycetes. Since homologues to HbpS-SenS-SenR are widespread in different

  9. Responsive molecular gels. : Surface Chemistry and Colloids

    NARCIS (Netherlands)

    de Jong, Jaap J. D.; Feringa, Bernard; van Esch, Jan

    2006-01-01

    A review discusses the chemo-responsive gels and physico-responsive gels. Phys. low mol. mass responsive gelators are interesting mols. with many potential applications in areas such as catalysis, sensor and sepn. technol., drug delivery, and biomedicine. In a relatively short period, a wide variety

  10. Responsive molecular gels. : Surface Chemistry and Colloids

    NARCIS (Netherlands)

    de Jong, Jaap J. D.; Feringa, Bernard; van Esch, Jan

    2006-01-01

    A review discusses the chemo-responsive gels and physico-responsive gels. Phys. low mol. mass responsive gelators are interesting mols. with many potential applications in areas such as catalysis, sensor and sepn. technol., drug delivery, and biomedicine. In a relatively short period, a wide variety

  11. Arabidopsis dehydroascorbate reductase 1 and 2 modulate redox states of ascorbate-glutathione cycle in the cytosol in response to photooxidative stress.

    Science.gov (United States)

    Noshi, Masahiro; Yamada, Hiroki; Hatanaka, Risa; Tanabe, Noriaki; Tamoi, Masahiro; Shigeoka, Shigeru

    2017-03-01

    Ascorbate and glutathione are indispensable cellular redox buffers and allow plants to acclimate stressful conditions. Arabidopsis contains three functional dehydroascorbate reductases (DHAR1-3), which catalyzes the conversion of dehydroascorbate into its reduced form using glutathione as a reductant. We herein attempted to elucidate the physiological role in DHAR1 and DHAR2 in stress responses. The total DHAR activities in DHAR knockout Arabidopsis plants, dhar1 and dhar2, were 22 and 92%, respectively, that in wild-type leaves. Under high light (HL), the levels of total ascorbate and dehydroascorbate were only reduced and increased, respectively, in dhar1. The oxidation of glutathione under HL was significantly inhibited in both dhar1 and dhar2, while glutathione contents were only enhanced in dhar1. The dhar1 showed stronger visible symptoms than the dhar2 under photooxidative stress conditions. Our results demonstrated a pivotal role of DHAR1 in the modulation of cellular redox states under photooxidative stress.

  12. Theoretical investigation on redox-switchable second-order nonlinear optical responses of push-pull Cp*CoEt2C2B4H3-expanded (metallo)porphyrins.

    Science.gov (United States)

    Ma, Nana; Liu, Chunguang; Qiu, Yongqing; Sun, Shiling; Su, Zhongmin

    2012-01-15

    The second-order nonlinear optical (NLO) properties of the Cp*Co(C(2)H(5))(2)C(2)B(4)H(3)-expanded (metallo)porphyrins (Cp* = C(5)Me(5)) have been investigated by using ab inito RHF and density functional theory (DFT) methods. The investigation shows that the compound with expand porphyrin possesses remarkable large molecular hyperpolarizability β(tot) value, ~414.1 × 10(-30) esu (at LC-ωPBE level), and might be an excellent second-order NLO material. From the character of charge transfer (CT) transition, it indicates that the -Cp*Co(C(2)H(5))(2)C(2)B(4)H(3) acts as an electron donor in this kind of systems. As a result of the redox behavior on expanded (metallo)porphyrin, the redox switching character of the NLO responses for the systems 2a-4a has also been studied. The results show that the β(tot) values of reduced forms are larger than that of neutral ones. Furthermore, the time-dependent DFT calculation illustrates that reduced forms have a significant difference on the CT patterns versus neutral ones. The present investigation provides insight into the comparison with DFT results on estimating first hyperpolarizability and the NLO properties of the series of push-pull compounds. Copyright © 2011 Wiley Periodicals, Inc.

  13. Divalent cations and redox conditions regulate the molecular structure and function of visinin-like protein-1.

    Directory of Open Access Journals (Sweden)

    Conan K Wang

    Full Text Available The NCS protein Visinin-like Protein 1 (VILIP-1 transduces calcium signals in the brain and serves as an effector of the non-retinal receptor guanylyl cyclases (GCs GC-A and GC-B, and nicotinic acetyl choline receptors (nAchR. Analysis of the quaternary structure of VILIP-1 in solution reveals the existence of monomeric and dimeric species, the relative contents of which are affected but not exclusively regulated by divalent metal ions and Redox conditions. Using small-angle X-ray scattering, we have investigated the low resolution structure of the calcium-bound VILIP-1 dimer under reducing conditions. Scattering profiles for samples with high monomeric and dimeric contents have been obtained. The dimerization interface involves residues from EF-hand regions EF3 and EF4.Using monolayer adsorption experiments, we show that myristoylated and unmyristoylated VILIP-1 can bind lipid membranes. The presence of calcium only marginally improves binding of the protein to the monolayer, suggesting that charged residues at the protein surface may play a role in the binding process.In the presence of calcium, VILIP-1 undergoes a conformational re-arrangement, exposing previously hidden surfaces for interaction with protein partners. We hypothesise a working model where dimeric VILIP-1 interacts with the membrane where it binds membrane-bound receptors in a calcium-dependent manner.

  14. Monitoring the redox cycle of low-molecular peptides using a modified target plate in MALDI-MS.

    Science.gov (United States)

    Borissova, Maria; Mahlapuu, Riina; Vaher, Merike

    2010-11-15

    A new method is being proposed for preparing MALDI target plates with a hydrophobic polymer coating and hydrophilic anchors. The particles of the MALDI matrix were pre-mixed with a poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole-co-tetrafluoroethylene] solution prior to their placement on a mass-spectrometric sample support. This technique led to the formation of matrix microspots with a diameter of less than 1mm inside the polymer. The polymer and matrix concentration as well as the amount of suspension placed on the target plate influenced the size and quality of microspots to a great extent. The sensitivity of the mass-spectrometric analysis was confirmed by obtaining the mass spectra of fmole concentrations of an apomyoglobin tryptic digest. The potential proteomic application of this type of MALDI surface preparation was demonstrated by performing the redox cycle using glutathione and its analogue. All reactions were carried out directly on a MALDI plate, which accommodates low volumes of reagents and prevents sample loss.

  15. Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress

    Science.gov (United States)

    Wang, Jie; Pareja, Kristeen A; Kaiser, Chris A; Sevier, Carolyn S

    2014-01-01

    Oxidative protein folding in the endoplasmic reticulum (ER) has emerged as a potentially significant source of cellular reactive oxygen species (ROS). Recent studies suggest that levels of ROS generated as a byproduct of oxidative folding rival those produced by mitochondrial respiration. Mechanisms that protect cells against oxidant accumulation within the ER have begun to be elucidated yet many questions still remain regarding how cells prevent oxidant-induced damage from ER folding events. Here we report a new role for a central well-characterized player in ER homeostasis as a direct sensor of ER redox imbalance. Specifically we show that a conserved cysteine in the lumenal chaperone BiP is susceptible to oxidation by peroxide, and we demonstrate that oxidation of this conserved cysteine disrupts BiP's ATPase cycle. We propose that alteration of BiP activity upon oxidation helps cells cope with disruption to oxidative folding within the ER during oxidative stress. DOI: http://dx.doi.org/10.7554/eLife.03496.001 PMID:25053742

  16. Age-Related Responses in Circulating Markers of Redox Status in Healthy Adolescents and Adults during the Course of a Training Macrocycle

    Directory of Open Access Journals (Sweden)

    Athanasios Zalavras

    2015-01-01

    Full Text Available Redox status changes during an annual training cycle in young and adult track and field athletes and possible differences between the two age groups were assessed. Forty-six individuals (24 children and 22 adults were assigned to four groups: trained adolescents, (TAD, N=13, untrained adolescents (UAD, N=11, trained adults (TA, N=12, and untrained adults (UA, N=10. Aerobic capacity and redox status related variables [total antioxidant capacity (TAC, glutathione (GSH, catalase activity, TBARS, protein carbonyls (PC, uric acid, and bilirubin] were assessed at rest and in response to a time-trial bout before training, at mid- and posttraining. TAC, catalase activity, TBARS, PC, uric acid, and bilirubin increased and GSH declined in all groups in response to acute exercise independent of training status and age. Training improved aerobic capacity, TAC, and GSH at rest and in response to exercise. Age affected basal and exercise-induced responses since adults demonstrated a greater TAC and GSH levels at rest and a greater rise of TBARS, protein carbonyls, and TAC and decline of GSH in response to exercise. Catalase activity, uric acid, and bilirubin responses were comparable among groups. These results suggest that acute exercise, age, and training modulate the antioxidant reserves of the body.

  17. Electrochemical atomic force microscopy reveals potential stimulated height changes of redox responsive Cu-azurin on gold

    NARCIS (Netherlands)

    Wu, Hairong; Feng, Xueling; Kieviet, B.D.; Zhang, K.; Zandvliet, H.J.W.; Canters, G.W.; Schon, P.M.; Vancso, G.J.

    2015-01-01

    The redox active metalloprotein Cu-azurin was directly chemisorbed on bare gold electrodes through disulfide forming groups (Cys3Cys26). Topological and electrochemical properties of the immobilized molecules were investigated by electrochemical atomic force microscopy (EC-AFM) in Peak Force Tapping

  18. Molecular events basic to cellular radiation response

    Energy Technology Data Exchange (ETDEWEB)

    Kolodny, G. M.

    1979-09-01

    The initiation and control of the division process in normal cells is studied to gain insight into changes in these regards caused by x-irradiation and neoplasia. The Primer Hypothesis for eukaryotic gene regulation proposes that small molecular weight RNA acts as primer for new RNA synthesis by hybridizing with DNA and there initiating the transcription of a new RNA chain. The experiments reported here indicate that small molecular weight RNA will induce the production of new proteins. These results are consistent with the Primer Hypothesis, and demonstrate that RNA can be taken up from the media by cells in culture and can induce in vitro the production of differentiated cell products. (ACR)

  19. Phenotypic Identification of the Redox Dye Methylene Blue as an Antagonist of Heat Shock Response Gene Expression in Metastatic Melanoma Cells

    Science.gov (United States)

    Davis, Angela L.; Cabello, Christopher M.; Qiao, Shuxi; Azimian, Sara; Wondrak, Georg T.

    2013-01-01

    Repurposing approved and abandoned non-oncological drugs is an alternative developmental strategy for the identification of anticancer therapeutics that has recently attracted considerable attention. Due to the essential role of the cellular heat shock response in cytoprotection through the maintenance of proteostasis and suppression of apoptosis, small molecule heat shock response antagonists can be harnessed for targeted induction of cytotoxic effects in cancer cells. Guided by gene expression array analysis and a phenotypic screen interrogating a collection of 3,7-diamino-phenothiazinium derivatives, we have identified the redox-drug methylene blue (MB), used clinically for the infusional treatment of methemoglobinemia, as a negative modulator of heat shock response gene expression in human metastatic melanoma cells. MB-treatment blocked thermal (43 °C) and pharmacological (celastrol, geldanamycin) induction of heat shock response gene expression, suppressing Hsp70 (HSPA1A) and Hsp27 (HSPB1) upregulation at the mRNA and protein level. MB sensitized melanoma cells to the apoptogenic activity of geldanamycin, an Hsp90 antagonist known to induce the counter-regulatory upregulation of Hsp70 expression underlying cancer cell resistance to geldanamycin chemotherapy. Similarly, MB-cotreatment sensitized melanoma cells to other chemotherapeutics (etoposide, doxorubicin). Taken together, these data suggest feasibility of repurposing the non-oncological redox drug MB as a therapeutic heat shock response antagonist for cancer cell chemosensitization. PMID:23429201

  20. Phenotypic Identification of the Redox Dye Methylene Blue as an Antagonist of Heat Shock Response Gene Expression in Metastatic Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Georg T. Wondrak

    2013-02-01

    Full Text Available Repurposing approved and abandoned non-oncological drugs is an alternative developmental strategy for the identification of anticancer therapeutics that has recently attracted considerable attention. Due to the essential role of the cellular heat shock response in cytoprotection through the maintenance of proteostasis and suppression of apoptosis, small molecule heat shock response antagonists can be harnessed for targeted induction of cytotoxic effects in cancer cells. Guided by gene expression array analysis and a phenotypic screen interrogating a collection of 3,7-diamino-phenothiazinium derivatives, we have identified the redox-drug methylene blue (MB, used clinically for the infusional treatment of methemoglobinemia, as a negative modulator of heat shock response gene expression in human metastatic melanoma cells. MB-treatment blocked thermal (43 °C and pharmacological (celastrol, geldanamycin induction of heat shock response gene expression, suppressing Hsp70 (HSPA1A and Hsp27 (HSPB1 upregulation at the mRNA and protein level. MB sensitized melanoma cells to the apoptogenic activity of geldanamycin, an Hsp90 antagonist known to induce the counter-regulatory upregulation of Hsp70 expression underlying cancer cell resistance to geldanamycin chemotherapy. Similarly, MB-cotreatment sensitized melanoma cells to other chemotherapeutics (etoposide, doxorubicin. Taken together, these data suggest feasibility of repurposing the non-oncological redox drug MB as a therapeutic heat shock response antagonist for cancer cell chemosensitization.

  1. Molecular and physiological responses to titanium dioxide ...

    Science.gov (United States)

    - Changes in tissue transcriptomes and productivity of Arabidopsis thaliana were investigated during exposure of plants to two widely-used engineered metal oxide nanoparticles, titanium dioxide (nano-titanium) and cerium dioxide (nano-cerium). Microarray analyses confirmed that exposure to either nanoparticle altered the transcriptomes of rosette leaves and roots, with comparatively larger numbers of differentially expressed genes (DEGs) found under nano-titania exposure. Nano-titania induced more DEGs in rosette leaves, whereas roots had more DEGs under nano-ceria exposure. MapMan analyses indicated that while nano-titania up-regulated overall and secondary metabolism in both tissues, metabolic processes under nano-ceria remained mostly unchanged. Gene enrichment analysis indicated that both nanoparticles mainly enriched ontology groups such as responses to stress (abiotic and biotic), and defense responses (pathogens), and responses to endogenous stimuli (hormones). Nano-titania specifically induced genes associated with photosynthesis, whereas nano-ceria induced expression of genes related to activating transcription factors, most notably those belonging to the ethylene responsive element binding protein family. Interestingly, there were also increased numbers of rosette leaves and plant biomass under nano-ceria exposure, but not under nano-titania. Other transcriptomic responses did not clearly relate to responses observed at the organism level. This may b

  2. Characterisation of the Redox Sensitive NMDA Receptor

    KAUST Repository

    Alzahrani, Ohood

    2016-05-01

    Glucose entry into the brain and its subsequent metabolism to L-lactate, regulated by astrocytes, plays a major role in synaptic plasticity and memory formation. A recent study has shown that L-lactate produced by the brain upon stimulation of glycolysis, and glycogen-derived L-lactate from astrocytes and its transport into neurons, is crucial for memory formation. A recent study revealed the molecular mechanisms that underlie the role of L-lactate in neuronal plasticity and long-term memory formation. L-lactate was shown to induce a cascade of molecular events via modulation of redox-sensitive N-Methyl-D-aspartate (NMDA) receptor activity that was mimicked by nicotinamide adenine dinucleotide hydride (NADH) co-enzyme. This indicated that changes in cellular redox state, following L-lactate transport inside the cells and its subsequent metabolism, production of NADH, and favouring a reduced state are the key effects of L-lactate. Therefore, we are investigating the role of L-lactate in modulating NMDA receptor function via redox modulatory sites. Accordingly, crucial redox-sensitive cysteine residues, Cys320 and Cys87, of the NR2A NMDA receptor subunit are mutated using site-directed mutation, transfected, and expressed in HEK293 cells. This cellular system will then be used to characterise and monitor its activity upon Llactate stimulation, compared to the wild type. This will be achieved by calcium imaging, using fluorescent microscopy. Our data shows that L-lactate potentiated NMDA receptor activity and increased intracellular calcium influx in NR1/NR2A wild type compared to the control condition (WT NR1/NR2A perfused with (1μM) glutamate and (1μM) glycine agonist only), showing faster response initiation and slower decay rate of the calcium signal to the baseline. Additionally, stimulating with L-lactate associated with greater numbers of cells having high fluorescent intensity (peak amplitude) compared to the control. Furthermore, L-lactate rescued the

  3. Optical redox ratio using endogenous fluorescence to assess the metabolic changes associated with treatment response of bioconjugated gold nanoparticles in streptozotocin-induced diabetic rats

    Science.gov (United States)

    Adavallan, K.; Gurushankar, K.; Nazeer, Shaiju S.; Gohulkumar, M.; Jayasree, Ramapurath S.; Krishnakumar, N.

    2017-06-01

    Fluorescence spectroscopic techniques have the potential to assess the metabolic changes during disease development and evaluation of treatment response in a non-invasive and label-free manner. The present study aims to evaluate the effect of mulberry-mediated gold nanoparticles (MAuNPs) in comparison with mulberry leaf extract alone (MLE) for monitoring endogenous fluorophores and to quantify the metabolic changes associated with mitochondrial redox states during streptozotocin-induced diabetic liver tissues using fluorescence spectroscopy. Two mitochondrial metabolic coenzymes, reduced nicotinamide dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD) are autofluorescent and are important optical biomarkers to estimate the redox state of a cell. Significant differences in the autofluorescence spectral signatures between the control and the experimental diabetic animals have been noticed under the excitation wavelength at 320 nm with emission ranging from 350-550 nm. A direct correlation between the progression of diabetes and the levels of collagen and optical redox ratio was observed. The results revealed that a significant increase in the emission of collagen in diabetic liver tissues as compared with the control liver tissues. Moreover, there was a significant decrease in the optical redox ratio (FAD/(FAD  +  NADH)) observed in diabetic control liver tissues, which indicates an increased oxidative stress compared to the liver tissues of control rats. Further, the extent of increased oxidative stress was confirmed by the reduced levels of reduced glutathione (GSH) in diabetic liver tissues. On a comparative basis, treatment with MAuNPs was found to be more effective than MLE for reducing the progression of diabetes and improving the optical redox ratio to a near normal range in streptozotocin-induced diabetic liver tissues. Furthermore, principal component analysis followed by linear discriminant analysis (PC-LDA) has been used to

  4. Molecular mechanisms in plant abiotic stress response

    Directory of Open Access Journals (Sweden)

    Poltronieri Palmiro

    2011-01-01

    Full Text Available Improved crop varieties are needed to sustain the food supply, to fight climate changes, water scarcity, temperature increase and a high variability of rainfalls. Variability of drought and increase in soil salinity have negative effects on plant growth and abiotic stresses seriously threaten sustainable agricultural production. To overcome the influence of abiotic stresses, new tolerant plant varieties and breeding techniques using assisted selection are sought. A deep understanding of the mechanisms that respond to stress and sustain stress resistance is required. Here is presented an overview of several mechanisms that interact in the stress response. Localised synthesis of plant hormones, second messengers and local effectors of abiotic stress response and survival, the signaling pathways regulated by plant hormones are today better understood. Metabolic networks in drought stress responses, long distance signaling, cross-talk between plant organs finalised to tissue-specific expression of abiotic stress relieving genes have been at the centre of most recent studies.

  5. Redox regulation of the Calvin-Benson cycle: something old, something new.

    Science.gov (United States)

    Michelet, Laure; Zaffagnini, Mirko; Morisse, Samuel; Sparla, Francesca; Pérez-Pérez, María Esther; Francia, Francesco; Danon, Antoine; Marchand, Christophe H; Fermani, Simona; Trost, Paolo; Lemaire, Stéphane D

    2013-11-25

    Reversible redox post-translational modifications such as oxido-reduction of disulfide bonds, S-nitrosylation, and S-glutathionylation, play a prominent role in the regulation of cell metabolism and signaling in all organisms. These modifications are mainly controlled by members of the thioredoxin and glutaredoxin families. Early studies in photosynthetic organisms have identified the Calvin-Benson cycle, the photosynthetic pathway responsible for carbon assimilation, as a redox regulated process. Indeed, 4 out of 11 enzymes of the cycle were shown to have a low activity in the dark and to be activated in the light through thioredoxin-dependent reduction of regulatory disulfide bonds. The underlying molecular mechanisms were extensively studied at the biochemical and structural level. Unexpectedly, recent biochemical and proteomic studies have suggested that all enzymes of the cycle and several associated regulatory proteins may undergo redox regulation through multiple redox post-translational modifications including glutathionylation and nitrosylation. The aim of this review is to detail the well-established mechanisms of redox regulation of Calvin-Benson cycle enzymes as well as the most recent reports indicating that this pathway is tightly controlled by multiple interconnected redox post-translational modifications. This redox control is likely allowing fine tuning of the Calvin-Benson cycle required for adaptation to varying environmental conditions, especially during responses to biotic and abiotic stresses.

  6. Diet affects the redox system in developing Atlantic cod (Gadus morhua larvae

    Directory of Open Access Journals (Sweden)

    Samuel Penglase

    2015-08-01

    Full Text Available The growth and development of marine fish larvae fed copepods is superior to those fed rotifers, but the underlying molecular reasons for this are unclear. In the following study we compared the effects of such diets on redox regulation pathways during development of Atlantic cod (Gadus morhua larvae. Cod larvae were fed a control diet of copepods or the typical rotifer/Artemia diet commonly used in commercial marine fish hatcheries, from first feeding until after metamorphosis. The oxidised and reduced glutathione levels, the redox potential, and the mRNA expression of 100 genes in redox system pathways were then compared between treatments during larval development. We found that rotifer/Artemia-fed cod larvae had lower levels of oxidised glutathione, a more reduced redox potential, and altered expression of approximately half of the redox system genes when compared to copepod-fed larvae. This rotifer/Artemia diet-induced differential regulation of the redox system was greatest during periods of suboptimal growth. Upregulation of the oxidative stress response transcription factor, nrf2, and NRF2 target genes in rotifer/Artemia fed larvae suggest this diet induced an NRF2-mediated oxidative stress response. Overall, the data demonstrate that nutritional intake plays a role in regulating the redox system in developing fish larvae. This may be a factor in dietary-induced differences observed in larval growth.

  7. Research Progress of Redox and Unfolded Protein Response%氧化还原状态与非折叠蛋白的研究进展

    Institute of Scientific and Technical Information of China (English)

    金海秀

    2016-01-01

    在许多生理过程中,细胞内的氧化还原状态(Redox)与非折叠蛋白反应(Unfolded protein response UPR)对于细胞的生存和死亡有着重要的意义.本文探讨了UPR的氧化还原机制,其中包括蛋白质二硫键异构酶与ER应激的直接相互作用,Redox与钙离子外流,细胞的氧化还原能力与UPR信号通路.

  8. ROS-mediated redox signaling during cell differentiation in plants.

    Science.gov (United States)

    Schmidt, Romy; Schippers, Jos H M

    2015-08-01

    Reactive oxygen species (ROS) have emerged in recent years as important regulators of cell division and differentiation. The cellular redox state has a major impact on cell fate and multicellular organism development. However, the exact molecular mechanisms through which ROS manifest their regulation over cellular development are only starting to be understood in plants. ROS levels are constantly monitored and any change in the redox pool is rapidly sensed and responded upon. Different types of ROS cause specific oxidative modifications, providing the basic characteristics of a signaling molecule. Here we provide an overview of ROS sensors and signaling cascades that regulate transcriptional responses in plants to guide cellular differentiation and organ development. Although several redox sensors and cascades have been identified, they represent only a first glimpse on the impact that redox signaling has on plant development and growth. We provide an initial evaluation of ROS signaling cascades involved in cell differentiation in plants and identify potential avenues for future studies. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Vegetarian diets and public health: biomarker and redox connections.

    Science.gov (United States)

    Benzie, Iris F F; Wachtel-Galor, Sissi

    2010-11-15

    Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.

  10. An All-or-None Response in the Release of Potassium by Yeast Cells Treated with Methylene Blue and Other Basic Redox Dyes

    Science.gov (United States)

    Passow, Hermann; Rothstein, Aser; Loewenstein, Barbara

    1959-01-01

    Basic redox dyes, such as methylene blue, induce a loss of K+ from yeast cells. The maximal loss, rather than the rate of loss, is related to the dye concentration, the response following a normal distribution on a plot of log-dose, versus percentage loss of K+. This fact taken together with the observed correlation between K+ loss and frequency of staining (as measured by microscopic observation), indicates that the response is all-or-none for individual cells. The response is produced by all the basic redox dyes tested (9), but by none of the acidic dyes (4). However, only the oxidized form of the dye is effective. Cations protect the cells from the basic dyes in a competitive manner, the bivalent cations (especially UO2++) being more effective than monovalent cations. It is suggested that the action of the dyes involves two steps, the first a binding to ribonucleic acid in the cell membrane (with competition from cations) and the second, an oxidation of neighboring sulfhydryl groups to the disulfide form. At a threshold level, unique for each cell, a generalized membrane breakdown occurs, resulting in the release of potassium and of other cytoplasmic constituents. PMID:14430753

  11. Ediacaran Redox Fluctuations

    Science.gov (United States)

    Sahoo, S. K.; Jiang, G.; Planavsky, N. J.; Kendall, B.; Owens, J. D.; Anbar, A. D.; Lyons, T. W.

    2013-12-01

    Evidence for pervasive oxic conditions, and likely even deep ocean oxygenation has been documented at three intervals in the lower (ca. 632 Ma), middle (ca. 580 Ma) and upper (ca. 551 Ma) Ediacaran. The Doushantuo Formation in South China hosts large enrichments of redox-sensitive trace element (e.g., molybdenum, vanadium and uranium) in anoxic shales, which are indicative of a globally oxic ocean-atmosphere system. However, ocean redox conditions between these periods continue to be a topic of debate and remain elusive. We have found evidence for widespread anoxic conditions through much of the Ediacaran in the deep-water Wuhe section in South China. During most of the Ediacaran-early Cambrian in basinal sections is characterized by Fe speciation data and pyrite morphologies that indicate deposition under euxinic conditions with near-crustal enrichments of redox-sensitive element and positive pyrite-sulfur isotope values, which suggest low levels of marine sulfate and widespread euxinia. Our work reinforces an emerging view that the early Earth, including the Ediacaran, underwent numerous rises and falls in surface oxidation state, rather than a unidirectional rise as originally imagined. The Ediacaran ocean thus experienced repetitive expansion and contraction of marine chalcophilic trace-metal levels that may have had fundamental impact on the slow evolution of early animals and ecosystems. Further, this framework forces us to re-examine the relationship between Neoproterozoic oxygenation and metazoan diversification. Varying redox conditions through the Cryogenian and Ediacaran may help explain molecular clock and biomarker evidence for an early appearance and initial diversification of metazoans but with a delay in the appearance of most major metazoan crown groups until close to Ediacaran-Cambrian boundary.

  12. A Redox-Active Fluorescent pH Indicator for Detecting Plasmodium falciparum Strains with Reduced Responsiveness to Quinoline Antimalarial Drugs.

    Science.gov (United States)

    Jida, Mouhamad; Sanchez, Cecilia P; Urgin, Karène; Ehrhardt, Katharina; Mounien, Saravanan; Geyer, Aurelia; Elhabiri, Mourad; Lanzer, Michael; Davioud-Charvet, Elisabeth

    2017-02-10

    Mutational changes in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) have been associated with differential responses to a wide spectrum of biologically active compounds including current and former quinoline and quinoline-like antimalarial drugs. PfCRT confers altered drug responsiveness by acting as a transport system, expelling drugs from the parasite's digestive vacuole where these drugs exert, at least part of, their antiplasmodial activity. To preserve the efficacy of these invaluable drugs, novel functional tools are required for epidemiological surveys of parasite strains carrying mutant PfCRT variants and for drug development programs aimed at inhibiting or circumventing the action of PfCRT. Here we report the synthesis and characterization of a pH-sensitive fluorescent chloroquine analogue consisting of 7-chloro-N-{2-[(propan-2-yl)amino]ethyl}quinolin-4-amine functionalized with the fluorochrome 7-nitrobenzofurazan (NBD) (henceforth termed Fluo-CQ). In the parasite, Fluo-CQ accumulates in the digestive vacuole, giving rise to a strong fluorescence signal but only in parasites carrying the wild type PfCRT. In parasites carrying the mutant PfCRT, Fluo-CQ does not accumulate. The differential handling of the fluorescent probe, combined with live cell imaging, provides a diagnostic tool for quick detection of those P. falciparum strains that carry a PfCRT variant associated with altered responsiveness to quinoline and quinoline-like antimalarial drugs. In contrast to the accumulation studies, chloroquine (CQ)-resistant parasites were observed cross-resistant to Fluo-CQ when the chemical probe was tested in various CQ-sensitive and -resistant parasite strains. NBD derivatives were found to act as redox cyclers of two essential targets, using a coupled assay based on methemoglobin and the NADPH-dependent glutathione reductase (GRs) from P. falciparum. This redox activity is proposed to contribute to the dual action of Fluo-CQ on redox

  13. Self-consistent parametrization of DFT + U framework using linear response approach: Application to evaluation of redox potentials of battery cathodes

    Science.gov (United States)

    Shishkin, Maxim; Sato, Hirofumi

    2016-02-01

    The accuracy of DFT +U calculations, applied to the study of electronic structure and energetics of strongly correlated materials, heavily depends on U parameters, chosen for adequate treatment of d and f states. Computational evaluation of U parameters, which does not require fitting to experimental measurements or results of computationally expensive schemes, is highly desirable for the study of novel materials and even more so for materials not yet synthesized to date. Within this work, we show that the linear response method could provide U parameters which can yield redox potentials of battery cathode materials in much better agreement with experiment than conventional density functional theory (DFT). In our approach, we evaluate U values self-consistently, ensuring agreement between U calculated using linear response with the value used for DFT +U calculations. We find that such self-consistency is necessary for determination of adequate values of U . We also studied the impact of using various PAW (projector augmented wave) potentials for transition-metal ions, that differ by the number of electrons treated as valence. We find that redox potentials are reasonably well reproduced for all cases, although a slightly higher degree of accuracy corresponds to PAW potentials with semicore electrons treated as valence. Importantly, we find that converged values of U are substantially different for various PAW potentials of transition-metal ions of the same material. Overall, we find that self-consistent DFT +U /linear response calculations provide quite accurate values of redox potentials for materials with purely ionic bonding (e.g., LiFePO4, LiCoPO4, LiCoO2, LiMnPO4, NaFePO4), whereas for materials with covalent p d hybridization (e.g., LiNiO2) or conducting materials (e.g., LiTiS2) the agreement with experimental redox voltage is lower. This emphasizes the need for application of more advanced techniques (e.g., DFT +U +V method) for accurate study of partially

  14. Redox theory of aging

    Directory of Open Access Journals (Sweden)

    Dean P. Jones

    2015-08-01

    Full Text Available Metazoan genomes encode exposure memory systems to enhance survival and reproductive potential by providing mechanisms for an individual to adjust during lifespan to environmental resources and challenges. These systems are inherently redox networks, arising during evolution of complex systems with O2 as a major determinant of bioenergetics, metabolic and structural organization, defense, and reproduction. The network structure decreases flexibility from conception onward due to differentiation and cumulative responses to environment (exposome. The redox theory of aging is that aging is a decline in plasticity of genome–exposome interaction that occurs as a consequence of execution of differentiation and exposure memory systems. This includes compromised mitochondrial and bioenergetic flexibility, impaired food utilization and metabolic homeostasis, decreased barrier and defense capabilities and loss of reproductive fidelity and fecundity. This theory accounts for hallmarks of aging, including failure to maintain oxidative or xenobiotic defenses, mitochondrial integrity, proteostasis, barrier structures, DNA repair, telomeres, immune function, metabolic regulation and regenerative capacity.

  15. Physiological, biochemical and molecular responses of the potato (Solanum tuberosum L.) plant to moderately elevated temperature.

    Science.gov (United States)

    Hancock, Robert D; Morris, Wayne L; Ducreux, Laurence J M; Morris, Jenny A; Usman, Muhammad; Verrall, Susan R; Fuller, John; Simpson, Craig G; Zhang, Runxuan; Hedley, Pete E; Taylor, Mark A

    2014-02-01

    Although significant work has been undertaken regarding the response of model and crop plants to heat shock during the acclimatory phase, few studies have examined the steady-state response to the mild heat stress encountered in temperate agriculture. In the present work, we therefore exposed tuberizing potato plants to mildly elevated temperatures (30/20 °C, day/night) for up to 5 weeks and compared tuber yield, physiological and biochemical responses, and leaf and tuber metabolomes and transcriptomes with plants grown under optimal conditions (22/16 °C). Growth at elevated temperature reduced tuber yield despite an increase in net foliar photosynthesis. This was associated with major shifts in leaf and tuber metabolite profiles, a significant decrease in leaf glutathione redox state and decreased starch synthesis in tubers. Furthermore, growth at elevated temperature had a profound impact on leaf and tuber transcript expression with large numbers of transcripts displaying a rhythmic oscillation at the higher growth temperature. RT-PCR revealed perturbation in the expression of circadian clock transcripts including StSP6A, previously identified as a tuberization signal. Our data indicate that potato plants grown at moderately elevated temperatures do not exhibit classic symptoms of abiotic stress but that tuber development responds via a diversity of biochemical and molecular signals.

  16. Synthesis, structure elucidation, and redox properties of 99Tc complexes of lacunary Wells-Dawson polyoxometalates: insights into molecular 99Tc-metal oxide interactions.

    Science.gov (United States)

    McGregor, Donna; Burton-Pye, Benjamin P; Howell, Robertha C; Mbomekalle, Israel M; Lukens, Wayne W; Bian, Fang; Mausolf, Edward; Poineau, Frederic; Czerwinski, Kenneth R; Francesconi, Lynn C

    2011-03-01

    The isotope (99)Tc (β(max), 293.7; half-life, 2.1 × 10(5) years) is an abundant product of uranium-235 fission in nuclear reactors and is present throughout the radioactive waste stored in underground tanks at the Hanford and Savannah River sites. Understanding and controlling the extensive redox chemistry of (99)Tc is important in identifying tunable strategies to separate (99)Tc from spent fuel and from waste tanks and, once separated, to identify and develop an appropriately stable waste form for (99)Tc. Polyoxometalates (POMs), nanometer-sized models for metal oxide solid-state materials, are used in this study to provide a molecular level understanding of the speciation and redox chemistry of incorporated (99)Tc. In this study, (99)Tc complexes of the (α(2)-P(2)W(17)O(61))(10-) and (α(1)-P(2)W(17)O(61))(10-) isomers were prepared. Ethylene glycol was used as a "transfer ligand" to minimize the formation of TcO(2)·xH(2)O. The solution structures, formulations, and purity of Tc(V)O(α(1)/α(2)-P(2)W(17)O(61))(7-) were determined by multinuclear NMR. X-ray absorption spectroscopy of the complexes is in agreement with the formulation and structures determined from (31)P and (183)W NMR. Preliminary electrochemistry results are consistent with the EXAFS results, showing a facile reduction of the Tc(V)O(α(1)-P(2)W(17)O(61))(7-) species compared to the Tc(V)O(α(2)-P(2)W(17)O(61))(7-) analog. The α(1) defect is unique in that a basic oxygen atom is positioned toward the α(1) site, and the Tc(V)O center appears to form a dative metal-metal bond with a framework W site. These attributes may lead to the assistance of protonation events that facilitate reduction. Electrochemistry comparison shows that the Re(V) analogs are about 200 mV more difficult to reduce in accordance with periodic trends.

  17. Synthesis, structure elucidation and redox properties of 99Tc complexes of lacunary Wells Dawson polyoxometalates: insights into molecular 99Tc - metal oxide interactions

    Energy Technology Data Exchange (ETDEWEB)

    McGregor, Donna; Burton-Pye, Benjamin P.; Howell, Robertha C.; Mbomekalle, Israel M.; Lukens Jr, Wayne W.; Bian, Fang; Mausolf, Edward; Poineau, Frederic; Czerwinski, Kenneth R; Francesconi, Lynn C.

    2011-01-10

    The isotope 99Tc (beta max: 250 keV, half-life: 2 x 105 year) is an abundant product of uranium-235 fission in nuclear reactors and is present throughout the radioactive waste stored in underground tanks at Hanford and Savannah River. Understanding and controlling the extensive redox chemistry of 99Tc is important to identify tunable strategies to separate 99Tc from spent fuel and from waste tanks and once separated, to identify and develop an appropriately stable waste-form for 99Tc. Polyoxometalates (POMs), nanometer sized models for metal oxide solid-state materials, are used in this study to provide a molecular level understanding of the speciation and redox chemistry of incorporated 99Tc. In this study, 99Tc complexes of the (alpha 2-P2W17O61)10- and (alpha 1-P2W17O61)10- isomers were prepared. Ethylene glycol was used as a"transfer ligand" to minimize the formation of TcO2 cdot xH2O. The solution structures, formulations, and purity of TcVO(alpha 1/alpha 2-P2W17O61)7- were determined by multinuclear NMR. X-ray Absorption Spectroscopy of the complexes are in agreement with the formulation and structures determined from 31P and 183W NMR. Preliminary electrochemistry results are consistent with the EXAFS results, showing a facile reduction of the TcVO(alpha 1-P2W17O61)7- species compared to the TcVO(alpha 2-P2W17O61)7- analog. The alpha1- defect is unique in that a basic oxygen atom is positioned toward the alpha1- site and the TcVO center appears to form a dative metal-metal bond with a framework W site. These attributes may lead to the assistance of protonation events that facilitate reduction. Electrochemistry comparison shows that the ReV analogs are about 200 mV more difficult to reduce in accordance with periodic trends.

  18. Early Biventricular Molecular Responses to an Acute Myocardial Infarction

    OpenAIRE

    Erdal, Cenk; Karakülah, Gökhan; Fermancı, Emel; Kunter, İmge; Silistreli, Erdem; Tülay CANDA; Erdal, Esra; Hepaguslar, Hasan

    2011-01-01

    Background: Acute myocardial infarction (AMI) remains as one of the most common lethal diseases in the world and therefore it is necessary to understand its effect on molecular basis. Genome-wide microarray analysis provides us to predict potential biomarkers and signaling pathways for this purpose. Objectives: The aim of this study is to understand the molecular basis of the immediate right ventricular cellular response to left ventricular AMI. Material and Methods: A rat model of left anter...

  19. NIR Light-, Temperature-, pH-, and Redox-Responsive Polymer-Modified Reduced Graphene Oxide/Mesoporous Silica Sandwich-Like Nanocomposites for Controlled Release.

    Science.gov (United States)

    Wang, Panjun; Chen, Shuo; Cao, Ziquan; Wang, Guojie

    2017-08-30

    Here a novel quadruple-responsive nanocarrier based on reduced graphene oxide/mesoporous silica sandwich-like nanocomposites (rGO@MS) modified by pH- and temperature-responsive poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) with a linker of disulfide was constructed via surface-initiated atom transfer radical polymerization. The polymer chains would be used as gatekeepers to control the release of the loaded cargo molecules under pH, temperature, NIR light and redox stimuli. The cargo molecules (rhodamine B) were demonstrated to release from the polymer-modified nanocomposites triggered by the quadruple-stimuli. It is noted that the release of the loaded rhodamine B from the nanocarriers could be enhanced greatly under the synergistic effect of multiple stimuli. The prepared quadruple-responsive polymer-modified nanocomposites show a bright prospect in the field of smart nanocarriers for controlled release.

  20. Redox and pH dual responsive poly(amidoamine) dendrimer-poly(ethylene glycol) conjugates for intracellular delivery of doxorubicin.

    Science.gov (United States)

    Hu, Wen; Qiu, Lipeng; Cheng, Liang; Hu, Qing; Liu, Yang; Hu, Ziyang; Chen, Dawei; Cheng, Lifang

    2016-05-01

    To solve the contradiction between long circulation time and effective intracellular drug release, redox and pH-responsive drug delivery system was developed by incorporated redox-sensitive disulfide linkage between poly(amidoamine) dendrimers (PAMAM) and poly(ethylene glycol) (PEG). Doxorubicin (DOX) was loaded into the hydrophobic core of the conjugates to prepare PAMAM-SS-PEG/DOX complexes (PSSP/DOX). In vitro release studies suggested that DOX release from PSSP/DOX complexes followed an redox and acid-triggered manner and increased with increasing PEGylation degree. In vitro cytotoxicity of PSSP/DOX complexes against B16 tumor cells increased with, while cellular uptake decreased with increasing PEGylation degree. Further, intracellular DOX release observation and measurement indicate that the intracellular DOX release played a critical role for the cytotoxicity of DOX-loaded PSSP conjugates. In addition, cellular entry mechanism of the PSSP/DOX study demonstrated that both clathrin- and caveolae-mediated endocytosis were the primary pathways for cellular entry of PSSP/DOX. Finally, in vivo study of PSSP/DOX complexes in B16 tumor-bearing mice indicate that PSSP/DOX could significantly improve antitumor efficiency and present a good safety. The redox and pH-responsive drug delivery system has been demonstrated to be a promising candidate for solid tumor therapy. In previous research, pH-sensitive diblock polymer of poly(ethylene glycol)-poly(2,4,6-trimethoxybenzylidene-pentaerythritol carbonate) (PEG-PTMBPEC) was synthesized to facilitate the intracellular anticancer drug release. However, the nanoparticles based on PEG-PTMBPEC get into the tumor cells just relying on the EPR-mediated passive targeting resulting in the low drug accumulation. Therefore, cRGD peptide modified PEG-PTMBPEC polymeric micelles were developed for specific targeted delivery of doxorubicin (DOX) to neovascular cells and tumor cells simultaneously. The precise intracellular target site

  1. Chloroplast Redox Status Modulates Genome-Wide Plant Responses during the Non-host Interaction of Tobacco with the Hemibiotrophic Bacterium Xanthomonas campestris pv. vesicatoria

    Directory of Open Access Journals (Sweden)

    Juan J. Pierella Karlusich

    2017-07-01

    Full Text Available Non-host resistance is the most ample and durable form of plant resistance against pathogen infection. It includes induction of defense-associated genes, massive metabolic reprogramming, and in many instances, a form of localized cell death (LCD at the site of infection, purportedly designed to limit the spread of biotrophic and hemibiotrophic microorganisms. Reactive oxygen species (ROS have been proposed to act as signals for LCD orchestration. They are produced in various cellular compartments including chloroplasts, mitochondria and apoplast. We have previously reported that down-regulation of ROS build-up in chloroplasts by expression of a plastid-targeted flavodoxin (Fld suppressed LCD in tobacco leaves inoculated with the non-host bacterium Xanthomonas campestris pv. vesicatoria (Xcv, while other defensive responses were unaffected, suggesting that chloroplast ROS and/or redox status play a major role in the progress of LCD. To better understand these effects, we compare here the transcriptomic alterations caused by Xcv inoculation on leaves of Fld-expressing tobacco plants and their wild-type siblings. About 29% of leaf-expressed genes were affected by Xcv and/or Fld. Surprisingly, 5.8% of them (1,111 genes were regulated by Fld in the absence of infection, presumably representing pathways responsive to chloroplast ROS production and/or redox status during normal growth conditions. While the majority (∼75% of pathogen-responsive genes were not affected by Fld, many Xcv responses were exacerbated, attenuated, or regulated in opposite direction by expression of this protein. Particularly interesting was a group of 384 genes displaying Xcv responses that were already triggered by Fld in the absence of infection, suggesting that the transgenic plants had a larger and more diversified suite of constitutive defenses against the attacking microorganism compared to the wild type. Fld modulated many genes involved in pathogenesis, signal

  2. Ero1-PDI interactions, the response to redox flux and the implications for disulfide bond formation in the mammalian endoplasmic reticulum.

    Science.gov (United States)

    Benham, Adam M; van Lith, Marcel; Sitia, Roberto; Braakman, Ineke

    2013-05-05

    The protein folding machinery of the endoplasmic reticulum (ER) ensures that proteins entering the eukaryotic secretory pathway acquire appropriate post-translational modifications and reach a stably folded state. An important component of this protein folding process is the supply of disulfide bonds. These are introduced into client proteins by ER resident oxidoreductases, including ER oxidoreductin 1 (Ero1). Ero1 is usually considered to function in a linear pathway, by 'donating' a disulfide bond to protein disulfide isomerase (PDI) and receiving electrons that are passed on to the terminal electron acceptor molecular oxygen. PDI engages with a range of clients as the direct catalyst of disulfide bond formation, isomerization or reduction. In this paper, we will consider the interactions of Ero1 with PDI family proteins and chaperones, highlighting the effect that redox flux has on Ero1 partnerships. In addition, we will discuss whether higher order protein complexes play a role in Ero1 function.

  3. In vivo monitoring of cellular energy metabolism using SoNar, a highly responsive sensor for NAD(+)/NADH redox state.

    Science.gov (United States)

    Zhao, Yuzheng; Wang, Aoxue; Zou, Yejun; Su, Ni; Loscalzo, Joseph; Yang, Yi

    2016-08-01

    NADH and its oxidized form NAD(+) have a central role in energy metabolism, and their concentrations are often considered to be among the most important readouts of metabolic state. Here, we present a detailed protocol to image and monitor NAD(+)/NADH redox state in living cells and in vivo using a highly responsive, genetically encoded fluorescent sensor known as SoNar (sensor of NAD(H) redox). The chimeric SoNar protein was initially developed by inserting circularly permuted yellow fluorescent protein (cpYFP) into the NADH-binding domain of Rex protein from Thermus aquaticus (T-Rex). It functions by binding to either NAD(+) or NADH, thus inducing protein conformational changes that affect its fluorescent properties. We first describe steps for how to establish SoNar-expressing cells, and then discuss how to use the system to quantify the intracellular redox state. This approach is sensitive, accurate, simple and able to report subtle perturbations of various pathways of energy metabolism in real time. We also detail the application of SoNar to high-throughput chemical screening of candidate compounds targeting cell metabolism in a microplate-reader-based assay, along with in vivo fluorescence imaging of tumor xenografts expressing SoNar in mice. Typically, the approximate time frame for fluorescence imaging of SoNar is 30 min for living cells and 60 min for living mice. For high-throughput chemical screening in a 384-well-plate assay, the whole procedure generally takes no longer than 60 min to assess the effects of 380 compounds on cell metabolism.

  4. Oxidative Stress Assessment in Response to Ultraendurance Exercise: Thiols Redox Status and ROS Production according to Duration of a Competitive Race

    Directory of Open Access Journals (Sweden)

    Alessandra Vezzoli

    2016-01-01

    Full Text Available Purpose. Response to an ultraendurance competitive race on thiols redox status, reactive oxygen species (ROS production, and oxidative stress (OxS was investigated according to duration. Methods. Twenty-four elite runners were examined: six completed 50 km and eighteen 100 km. Blood and urine samples were collected before and immediately after the race. Erythrocytes and plasma aminothiols by high-performance liquid chromatography, total antioxidant capacity (TAC, and OxS biomarkers (protein carbonyl (PC, thiobarbituric acid-reactive substances (TBARS, 8-isoprostane (8-iso-PGF2α, and 8-OH-2-deoxyguanosine (8-OH-dG by immunoenzymatic assays and ROS production by Electron Paramagnetic Resonance were assessed. Results. Significant increases (P between <0.05 and <0.0001 were recorded in plasma total and oxidized aminothiols concentration and TAC (P<0.0001 only after 100 km: plasmatic (ROS production (+12 versus +29%, PC (+54 versus +115%, and TBARS (+28 versus +55% and urinary (8-OH-dG.creatinine−1 (+71 versus +158% and 8-iso-PGF2α.creatinine−1 (+43 versus +135% concentrations for 50 and 100 km (duration 4 h 3′ versus 8 h 42′, respectively. Conclusion. Very prolonged ultraendurance exercise causes an increase in ROS production and OxS depending on specific biomarker examined but always linearly and directly related to exercise duration. Redox status of erythrocytes was preserved. A relationship between running performance and both prerace ROS production and antioxidant-redox status was found in 100 km race.

  5. A redox-sensitive yellow fluorescent protein sensor for monitoring nuclear glutathione redox dynamics.

    Science.gov (United States)

    Banach-Latapy, Agata; Dardalhon, Michèle; Huang, Meng-Er

    2015-01-01

    Intracellular redox homeostasis is crucial for many cellular functions, but accurate measurements of cellular compartment-specific redox states remain technically challenging. Genetically encoded biosensors, including the glutathione-specific redox-sensitive yellow fluorescent protein (rxYFP), provide an alternative approach to overcome the limitations of conventional glutathione/glutathione disulfide (GSH/GSSG) redox measurements. In this chapter we describe methods to measure the nuclear rxYFP redox state in human cells by a redox Western blot technique. A nucleus-targeted rxYFP sensor can be used to sense nuclear steady-state and dynamic redox changes in response to oxidative stress. Complementary to existing redox sensors and conventional redox measurements, nucleus-targeted rxYFP sensors provide a novel tool for examining nuclear redox homeostasis in mammalian cells, permitting high-resolution readout of steady glutathione state and dynamics of redox changes. The technique described may be used with minimal variations to study the effects of stress conditions which lead to glutathione redox changes.

  6. Nanocrystalline CePO(4):Tb as a novel oxygen sensing material on the basis of its redox responsive reversible luminescence.

    Science.gov (United States)

    Di, Weihua; Wang, Xiaojun; Ren, Xinguang

    2010-02-19

    This work reports for the first time on a new finding of luminescent CePO(4):Tb nanocrystals providing a novel oxygen sensing material on the basis of the redox responsive reversible luminescence in an oxidizing/reducing atmosphere. The origin of the luminescence quenching/recovery of nanocrystalline CePO(4):Tb was clearly demonstrated, from the surface chemistry of nanocrystals and the fluorescence decay dynamics of Tb(III). Our present work represents a preliminary demonstration of the feasibility of using nanocrystalline CePO(4):Tb as a novel oxygen sensing material since it yields several advantages including surfactant-free synthesis, dual detection functioning, rapid response, high sensitivity and good reproducibility.

  7. Molecular cloning of cecropin B responsive endonucleases in Yersinia ruckeri

    Science.gov (United States)

    We have previously demonstrated that Yersinia ruckeri resists cecropin B in an inducible manner. In this study, we sought to identify the molecular changes responsible for the inducible cecropin B resistance of Y. ruckeri. Differences in gene expression associated with the inducible resistance were ...

  8. Gold Nanocluster Decorated Polypeptide/DNA Complexes for NIR Light and Redox Dual-Responsive Gene Transfection.

    Science.gov (United States)

    Lei, Qi; Hu, Jing-Jing; Rong, Lei; Cheng, Han; Sun, Yun-Xia; Zhang, Xian-Zheng

    2016-08-20

    Endo/lysosomal escape and subsequent nuclear translocation are recognized as the two major challenges for efficient gene transfection. Herein, nuclear localization signal (NLS) peptide sequences and oligomeric lysine sequences were crosslinked via disulfide bonds to obtain glutathione (GSH) reducible polypeptide (pNLS). The pNLS could condense DNA into compact positive-charged complexes with redox sensitivity, and then gold nanoclusters (AuNC) were further decorated to the surface via electrostatic interactions obtaining versatile pNLS/DNA/AuNC complexes. The AuNC could generate reactive oxygen species (ROS) under NIR-irradiation and accelerate the endo/lysosomal escape of the complexes, and then the pNLS sequence degraded by GSH in cytoplasm would release the DNA and facilitate the subsequent nuclear translocation for enhanced gene transfection.

  9. Redox Homeostasis in Pancreatic Cells

    Directory of Open Access Journals (Sweden)

    Petr Ježek

    2012-01-01

    Full Text Available We reviewed mechanisms that determine reactive oxygen species (redox homeostasis, redox information signaling and metabolic/regulatory function of autocrine insulin signaling in pancreatic β cells, and consequences of oxidative stress and dysregulation of redox/information signaling for their dysfunction. We emphasize the role of mitochondrion in β cell molecular physiology and pathology, including the antioxidant role of mitochondrial uncoupling protein UCP2. Since in pancreatic β cells pyruvate cannot be easily diverted towards lactate dehydrogenase for lactate formation, the respiration and oxidative phosphorylation intensity are governed by the availability of glucose, leading to a certain ATP/ADP ratio, whereas in other cell types, cell demand dictates respiration/metabolism rates. Moreover, we examine the possibility that type 2 diabetes mellitus might be considered as an inevitable result of progressive self-accelerating oxidative stress and concomitantly dysregulated information signaling in peripheral tissues as well as in pancreatic β cells. It is because the redox signaling is inherent to the insulin receptor signaling mechanism and its impairment leads to the oxidative and nitrosative stress. Also emerging concepts, admiting participation of redox signaling even in glucose sensing and insulin release in pancreatic β cells, fit in this view. For example, NADPH has been firmly established to be a modulator of glucose-stimulated insulin release.

  10. Redox Active Polymers as Soluble Nanomaterials for Energy Storage.

    Science.gov (United States)

    Burgess, Mark; Moore, Jeffrey S; Rodríguez-López, Joaquín

    2016-11-15

    RAPs conveniently translate the redox properties of small molecules into a nanostructure, they give rise to charge transfer mechanisms and electrolyte interactions that elicit distinct electrochemical responses. To understand how the electrochemical characteristics of RAPs depend on molecular features, including redox moiety, macromolecular size, and backbone structure, a range of techniques has been employed by our groups, including voltammetry at macro- and microelectrodes, rotating disk electrode voltammetry, bulk electrolysis, and scanning electrochemical microscopy. RAPs rely on three-dimensional charge transfer within their inner bulk, which is an efficient process and allows quantitative electrolysis of particles of up to ∼800 nm in radius. Interestingly, we find that interactions between neighboring pendants create unique opportunities for fine-tuning their electrochemical reactivity. Furthermore, RAP interrogation toward the single particle limit promises to shed light on fundamental charge storage mechanisms.

  11. Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility

    Science.gov (United States)

    Wedege, Kristina; Dražević, Emil; Konya, Denes; Bentien, Anders

    2016-12-01

    Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined with single cell battery RFB tests on selected redox pairs. Data shows that both the solubility and redox potential are determined by the position of the side groups and only to a small extent by the number of side groups. Additionally, the chemical stability and possible degradation mechanisms leading to capacity loss over time are discussed. The main challenge for the development of all-organic RFBs is to identify a redox pair for the positive side with sufficiently high stability and redox potential that enables battery cell potentials above 1 V.

  12. Accumulation of mercury, selenium and PCBs in domestic duck brain, liver and egg from a contaminated area with an investigation of their redox responses.

    Science.gov (United States)

    Cheng, Jinping; Zhao, Wenchang; Wang, Qian; Liu, Xiaojie; Wang, Wenhua

    2013-05-01

    PCBs and methylmercury (MeHg) are two of the most ubiquitous contaminants in the Qingzhen (QZ) area of Guizhou province. The estimated tolerable daily intakes (TDIs) of total mercury (T-Hg), MeHg, PCBs and Se from contaminated rice, eggs and fish by Chinese people in QZ showed that both MeHg and PCBs exceeded the corresponding safety limits. Pearson's correlation analyses of mercury and Se in all duck tissues showed that there were high correlations with T-Hg or MeHg and Se in QZ samples. However, the molar ratio between T-Hg and Se in brain tissues was close to 1, suggesting that Se is antagonistic to mercury toxicity only in brain tissues. Biochemical analyses showed that both superoxide dismutase and glutathione peroxidase increased in the brain, whereas in the liver and egg these enzymes decreased. However, lipid peroxidation and H2O2 generation in liver and egg tissues showed contrary responses, where significant increases in these tissues were seen relative to controls. Mercury and PCBs co-accumulation in liver and egg tissues gave rise to large numbers of free radicals as well as aggravated alkyl free radicals, superoxide radical and nitric oxide, thereby resulting in oxidative stress in these tissues. It can be concluded that an adaptive response of the redox defense system is present in brain tissues, as opposed to a general break down of the redox defense system in liver and egg. The results obtained in this study will provide basic information on exposure and risk assessment in local residents.

  13. Pseudomonas aeruginosa Biofilm Response and Resistance to Cold Atmospheric Pressure Plasma Is Linked to the Redox-Active Molecule Phenazine.

    Directory of Open Access Journals (Sweden)

    Anne Mai-Prochnow

    Full Text Available Pseudomonas aeruginosa is an important opportunistic pathogen displaying high antibiotic resistance. Its resistance is in part due to its outstanding ability to form biofilms on a range of biotic and abiotic surfaces leading to difficult-to-treat, often long-term infections. Cold atmospheric plasma (CAP is a new, promising antibacterial treatment to combat antibiotic-resistant bacteria. Plasma is ionized gas that has antibacterial properties through the generation of a mix of reactive oxygen and nitrogen species (RONS, excited molecules, charged particles and UV photons. Our results show the efficient removal of P. aeruginosa biofilms using a plasma jet (kINPen med, with no viable cells detected after 5 min treatment and no attached biofilm cells visible with confocal microscopy after 10 min plasma treatment. Because of its multi-factorial action, it is widely presumed that the development of bacterial resistance to plasma is unlikely. However, our results indicate that a short plasma treatment (3 min may lead to the emergence of a small number of surviving cells exhibiting enhanced resistance to subsequent plasma exposure. Interestingly, these cells also exhibited a higher degree of resistance to hydrogen peroxide. Whole genome comparison between surviving cells and control cells revealed 10 distinct polymorphic regions, including four belonging to the redox active, antibiotic pigment phenazine. Subsequently, the interaction between phenazine production and CAP resistance was demonstrated in biofilms of transposon mutants disrupted in different phenazine pathway genes which exhibited significantly altered sensitivity to CAP.

  14. Pseudomonas aeruginosa Biofilm Response and Resistance to Cold Atmospheric Pressure Plasma Is Linked to the Redox-Active Molecule Phenazine.

    Science.gov (United States)

    Mai-Prochnow, Anne; Bradbury, Mark; Ostrikov, Kostya; Murphy, Anthony B

    2015-01-01

    Pseudomonas aeruginosa is an important opportunistic pathogen displaying high antibiotic resistance. Its resistance is in part due to its outstanding ability to form biofilms on a range of biotic and abiotic surfaces leading to difficult-to-treat, often long-term infections. Cold atmospheric plasma (CAP) is a new, promising antibacterial treatment to combat antibiotic-resistant bacteria. Plasma is ionized gas that has antibacterial properties through the generation of a mix of reactive oxygen and nitrogen species (RONS), excited molecules, charged particles and UV photons. Our results show the efficient removal of P. aeruginosa biofilms using a plasma jet (kINPen med), with no viable cells detected after 5 min treatment and no attached biofilm cells visible with confocal microscopy after 10 min plasma treatment. Because of its multi-factorial action, it is widely presumed that the development of bacterial resistance to plasma is unlikely. However, our results indicate that a short plasma treatment (3 min) may lead to the emergence of a small number of surviving cells exhibiting enhanced resistance to subsequent plasma exposure. Interestingly, these cells also exhibited a higher degree of resistance to hydrogen peroxide. Whole genome comparison between surviving cells and control cells revealed 10 distinct polymorphic regions, including four belonging to the redox active, antibiotic pigment phenazine. Subsequently, the interaction between phenazine production and CAP resistance was demonstrated in biofilms of transposon mutants disrupted in different phenazine pathway genes which exhibited significantly altered sensitivity to CAP.

  15. Investigate the variation in optical redox ratio of epicardial adipose tissue in patients with CAD through auto-fluorescence metabolic molecular image (Conference Presentation)

    Science.gov (United States)

    Guo, Lun-Zhang; Wang, Tzung-Dau; Lin, Jong-Wei; Liu, Tzu-Ming

    2016-04-01

    In recent years, it has been suggested that epicardial adipose tissue (EAT) plays an important role in development of coronary artery disease (CAD) and diabetes mellitus (DM). In this article, we used two-photon fluoresce microscope to measure the fluorescence metabolic image of EAT, which obtained from the patient with/without CAD/DM. We used 740nm and 890nm infrared light to excite the auto-fluorescence of metabolic molecules NADH and FAD respectively. We collected the fluorescence signal at wavelength 450nm to 500nm and 500nm to 550nm to obtain the metabolic image. Through the image, we computed the redox ratio (NADH/FAD) by analyzing the intensity. The preliminary result showed that the redox ratio increase in the patients with CAD. It indicates EAT adipocytes of patient with CAD have decreased cellular metabolic activity. But there were no significant variation of redox ratio in the patients with DM.

  16. Molecular modulation of airway epithelial ciliary response to sneezing.

    Science.gov (United States)

    Zhao, Ke-Qing; Cowan, Andrew T; Lee, Robert J; Goldstein, Natalia; Droguett, Karla; Chen, Bei; Zheng, Chunquan; Villalon, Manuel; Palmer, James N; Kreindler, James L; Cohen, Noam A

    2012-08-01

    Our purpose was to evaluate the effect of the mechanical force of a sneeze on sinonasal cilia function and determine the molecular mechanism responsible for eliciting the ciliary response to a sneeze. A novel model was developed to deliver a stimulation simulating a sneeze (55 mmHg for 50 ms) at 26°C to the apical surface of mouse and human nasal epithelial cells. Ciliary beating was visualized, and changes in ciliary beat frequency (CBF) were determined. To interrogate the molecular cascades driving sneeze-induced changes of CBF, pharmacologic manipulation of intra- and extracellular calcium, purinergic, PKA, and nitric oxide (NO) signaling were performed. CBF rapidly increases by ≥150% in response to a sneeze, which is dependent on the release of adenosine triphosphate (ATP), calcium influx, and PKA activation. Furthermore, apical release of ATP is independent of calcium influx, but calcium influx and subsequent increase in CBF are dependent on the ATP release. Lastly, we observed a blunted ciliary response in surgical specimens derived from patients with chronic rhinosinusitis compared to control patients. Apical ATP release with subsequent calcium mobilization and PKA activation are involved in sinonasal ciliary response to sneezing, which is blunted in patients with upper-airway disease.

  17. Redox regulation of mitochondrial biogenesis.

    Science.gov (United States)

    Piantadosi, Claude A; Suliman, Hagir B

    2012-12-01

    The cell renews, adapts, or expands its mitochondrial population during episodes of cell damage or periods of intensified energy demand by the induction of mitochondrial biogenesis. This bigenomic program is modulated by redox-sensitive signals that respond to physiological nitric oxide (NO), carbon monoxide (CO), and mitochondrial reactive oxygen species production. This review summarizes our current ideas about the pathways involved in the activation of mitochondrial biogenesis by the physiological gases leading to changes in the redox milieu of the cell, with an emphasis on the responses to oxidative stress and inflammation. The cell's energy supply is protected from conditions that damage mitochondria by an inducible transcriptional program of mitochondrial biogenesis that operates in large part through redox signals involving the nitric oxide synthase and the heme oxygenase-1/CO systems. These redox events stimulate the coordinated activities of several multifunctional transcription factors and coactivators also involved in the elimination of defective mitochondria and the expression of counterinflammatory and antioxidant genes, such as IL10 and SOD2, as part of a unified damage-control network. The redox-regulated mechanisms of mitochondrial biogenesis schematically outlined in the graphical abstract link mitochondrial quality control to an enhanced capacity to support the cell's metabolic needs while improving its resistance to metabolic failure and avoidance of cell death during periods of oxidative stress.

  18. Molecular Responses to Small Regulating Molecules against Huanglongbing Disease

    Science.gov (United States)

    Martinelli, Federico; Dolan, David; Fileccia, Veronica; Reagan, Russell L.; Phu, My; Spann, Timothy M.; McCollum, Thomas G.; Dandekar, Abhaya M.

    2016-01-01

    Huanglongbing (HLB; citrus greening) is the most devastating disease of citrus worldwide. No cure is yet available for this disease and infected trees generally decline after several months. Disease management depends on early detection of symptoms and chemical control of insect vectors. In this work, different combinations of organic compounds were tested for the ability to modulate citrus molecular responses to HLB disease beneficially. Three small-molecule regulating compounds were tested: 1) L-arginine, 2) 6-benzyl-adenine combined with gibberellins, and 3) sucrose combined with atrazine. Each treatment contained K-phite mineral solution and was tested at two different concentrations. Two trials were conducted: one in the greenhouse and the other in the orchard. In the greenhouse study, responses of 42 key genes involved in sugar and starch metabolism, hormone-related pathways, biotic stress responses, and secondary metabolism in treated and untreated mature leaves were analyzed. TGA5 was significantly induced by arginine. Benzyladenine and gibberellins enhanced two important genes involved in biotic stress responses: WRKY54 and WRKY59. Sucrose combined with atrazine mainly upregulated key genes involved in carbohydrate metabolism such as sucrose-phosphate synthase, sucrose synthase, starch synthase, and α-amylase. Atrazine also affected expression of some key genes involved in systemic acquired resistance such as EDS1, TGA6, WRKY33, and MYC2. Several treatments upregulated HSP82, which might help protect protein folding and integrity. A subset of key genes was chosen as biomarkers for molecular responses to treatments under field conditions. GPT2 was downregulated by all small-molecule treatments. Arginine-induced genes involved in systemic acquired resistance included PR1, WRKY70, and EDS1. These molecular data encourage long-term application of treatments that combine these regulating molecules in field trials. PMID:27459099

  19. Molecular Responses to Small Regulating Molecules against Huanglongbing Disease.

    Science.gov (United States)

    Martinelli, Federico; Dolan, David; Fileccia, Veronica; Reagan, Russell L; Phu, My; Spann, Timothy M; McCollum, Thomas G; Dandekar, Abhaya M

    2016-01-01

    Huanglongbing (HLB; citrus greening) is the most devastating disease of citrus worldwide. No cure is yet available for this disease and infected trees generally decline after several months. Disease management depends on early detection of symptoms and chemical control of insect vectors. In this work, different combinations of organic compounds were tested for the ability to modulate citrus molecular responses to HLB disease beneficially. Three small-molecule regulating compounds were tested: 1) L-arginine, 2) 6-benzyl-adenine combined with gibberellins, and 3) sucrose combined with atrazine. Each treatment contained K-phite mineral solution and was tested at two different concentrations. Two trials were conducted: one in the greenhouse and the other in the orchard. In the greenhouse study, responses of 42 key genes involved in sugar and starch metabolism, hormone-related pathways, biotic stress responses, and secondary metabolism in treated and untreated mature leaves were analyzed. TGA5 was significantly induced by arginine. Benzyladenine and gibberellins enhanced two important genes involved in biotic stress responses: WRKY54 and WRKY59. Sucrose combined with atrazine mainly upregulated key genes involved in carbohydrate metabolism such as sucrose-phosphate synthase, sucrose synthase, starch synthase, and α-amylase. Atrazine also affected expression of some key genes involved in systemic acquired resistance such as EDS1, TGA6, WRKY33, and MYC2. Several treatments upregulated HSP82, which might help protect protein folding and integrity. A subset of key genes was chosen as biomarkers for molecular responses to treatments under field conditions. GPT2 was downregulated by all small-molecule treatments. Arginine-induced genes involved in systemic acquired resistance included PR1, WRKY70, and EDS1. These molecular data encourage long-term application of treatments that combine these regulating molecules in field trials.

  20. Molecular Responses to Small Regulating Molecules against Huanglongbing Disease.

    Directory of Open Access Journals (Sweden)

    Federico Martinelli

    Full Text Available Huanglongbing (HLB; citrus greening is the most devastating disease of citrus worldwide. No cure is yet available for this disease and infected trees generally decline after several months. Disease management depends on early detection of symptoms and chemical control of insect vectors. In this work, different combinations of organic compounds were tested for the ability to modulate citrus molecular responses to HLB disease beneficially. Three small-molecule regulating compounds were tested: 1 L-arginine, 2 6-benzyl-adenine combined with gibberellins, and 3 sucrose combined with atrazine. Each treatment contained K-phite mineral solution and was tested at two different concentrations. Two trials were conducted: one in the greenhouse and the other in the orchard. In the greenhouse study, responses of 42 key genes involved in sugar and starch metabolism, hormone-related pathways, biotic stress responses, and secondary metabolism in treated and untreated mature leaves were analyzed. TGA5 was significantly induced by arginine. Benzyladenine and gibberellins enhanced two important genes involved in biotic stress responses: WRKY54 and WRKY59. Sucrose combined with atrazine mainly upregulated key genes involved in carbohydrate metabolism such as sucrose-phosphate synthase, sucrose synthase, starch synthase, and α-amylase. Atrazine also affected expression of some key genes involved in systemic acquired resistance such as EDS1, TGA6, WRKY33, and MYC2. Several treatments upregulated HSP82, which might help protect protein folding and integrity. A subset of key genes was chosen as biomarkers for molecular responses to treatments under field conditions. GPT2 was downregulated by all small-molecule treatments. Arginine-induced genes involved in systemic acquired resistance included PR1, WRKY70, and EDS1. These molecular data encourage long-term application of treatments that combine these regulating molecules in field trials.

  1. The responses of cytochrome redox state and energy metabolism to dehydration support a role for cytoplasmic viscosity in desiccation tolerance

    Science.gov (United States)

    Leprince; Hoekstra

    1998-12-01

    To characterize the depression of metabolism in anhydrobiotes, the redox state of cytochromes and energy metabolism were studied during dehydration of soaked cowpea (Vigna unguiculata) cotyledons and pollens of Typha latifolia and Impatiens glandulifera. Between water contents (WC) of 1.0 and 0.6 g H2O/g dry weight (g/g), viscosity as measured by electron spin resonance spectroscopy increased from 0.15 to 0.27 poise. This initial water loss was accompanied by a 50% decrease in respiration rates, whereas the adenylate energy charge remained constant at 0.8, and cytochrome c oxidase (COX) remained fully oxidized. From WC of 0.6 to 0.2 g/g, viscosity increased exponentially. The adenylate energy charge declined to 0.4 in seeds and 0.2 in pollen, whereas COX became progressively reduced. At WC of less than 0.2 g/g, COX remained fully reduced, whereas respiration ceased. When dried under N2, COX remained 63% reduced in cotyledons until WC was 0.7 g/g and was fully reduced at 0.2 g/g. During drying under pure O2, the pattern of COX reduction was similar to that of air-dried tissues, although the maximum reduction was 70% in dried tissues. Thus, at WC of less than 0.6 g/g, the reduction of COX probably originates from a decreased O2 availability as a result of the increased viscosity and impeded diffusion. We suggest that viscosity is a valuable parameter to characterize the relation between desiccation and decrease in metabolism. The implications for desiccation tolerance are discussed.

  2. Systemic Inflammatory Response Syndrome in End-Stage Heart Failure Patients Following Continuous-Flow Left Ventricular Assist Device Implantation: Differences in Plasma Redox Status and Leukocyte Activation.

    Science.gov (United States)

    Mondal, Nandan K; Sorensen, Erik N; Pham, Si M; Koenig, Steven C; Griffith, Bartley P; Slaughter, Mark S; Wu, Zhongjun J

    2016-05-01

    The role of oxidative stress and leukocyte activation has not been elucidated in developing systemic inflammatory response syndrome (SIRS) in heart failure (HF) patients after continuous-flow left ventricular assist device (CF-LVAD) implantation. The objective of this study was to investigate the change of plasma redox status and leukocyte activation in CF-LVAD implanted HF patients with or without SIRS. We recruited 31 CF-LVAD implanted HF patients (16 SIRS and 15 non-SIRS) and 11 healthy volunteers as the control. Pre- and postimplant blood samples were collected from the HF patients. Plasma levels of oxidized low-density lipoprotein (oxLDL), malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) in erythrocyte, myeloperoxidase (MPO), and polymorphonuclear elastase (PMN-elastase) were measured. The HF patients had a preexisting condition of oxidative stress than healthy controls as evident from the higher oxLDL and MDA levels as well as depleted SOD and TAC. Leukocyte activation in terms of higher plasma MPO and PMN-elastase was also prominent in HF patients than controls. Persistent oxidative stress and reduced antioxidant status were found to be more belligerent in HF patients with SIRS after the implantation of CF-LVAD when compared with non-SIRS patients. Similar to oxidative stress, the activation of blood leukocyte was significantly highlighted in SIRS patients after implantation compared with non-SIRS. We identified that the plasma redox status and leukocyte activation became more prominent in CF-LVAD implanted HF patients who developed SIRS. Our findings suggest that plasma biomarkers of oxidative stress and leukocyte activation may be associated with the development of SIRS after CF-LVAD implant surgery.

  3. Redox Signaling and CBF-Responsive Pathway are Involved in Salicylic Acid-Improved Photosynthesis and Growth under Chilling Stress in Watermelon

    Directory of Open Access Journals (Sweden)

    Fei Cheng

    2016-10-01

    Full Text Available Salicylic acid (SA plays an important role in plant response to abiotic stresses. This study investigated the potential role of SA in alleviating the adverse effects of chilling stress on photosynthesis and growth in watermelon (Citrullus lanatus. Chilling stress induced the simultaneous accumulation of free and conjugated SA in watermelon plants, and the chilling-induced SA production was attributed to the phenylalanine ammonia-lyase pathway. Applying SA at moderate concentrations induced chilling tolerance, whereas inhibition of SA biosynthesis by L-ɑ-aminooxy-β-phenylpropionic acid (AOPP increased the photooxidation of PS II under chilling stress in watermelon, resulting in reduced photosynthesis and growth. Chilling induced a transient increase in the ratios of reduced to oxidized glutathione and reduced ascorbate to dehydroascorbate. Then, the expression of antioxidant genes was upregulated, and the activities of antioxidant enzymes were enhanced. Furthermore, SA-induced chilling tolerance was associated with cellular glutathione and ascorbate homeostasis, which served as redox signals to regulate antioxidant metabolism under chilling stress. AOPP treatment stimulated the chilling-induced expression of cold-responsive genes, particularly via C-repeat binding factors CBF3 and CBF4. These results confirm the synergistic role of SA signaling and the CBF-dependent responsive pathway during chilling stress in watermelon.

  4. Redox Signaling and CBF-Responsive Pathway Are Involved in Salicylic Acid-Improved Photosynthesis and Growth under Chilling Stress in Watermelon

    Science.gov (United States)

    Cheng, Fei; Lu, Junyang; Gao, Min; Shi, Kai; Kong, Qiusheng; Huang, Yuan; Bie, Zhilong

    2016-01-01

    Salicylic acid (SA) plays an important role in plant response to abiotic stresses. This study investigated the potential role of SA in alleviating the adverse effects of chilling stress on photosynthesis and growth in watermelon (Citrullus lanatus). Chilling stress induced the simultaneous accumulation of free and conjugated SA in watermelon plants, and the chilling-induced SA production was attributed to the phenylalanine ammonia-lyase pathway. Applying SA at moderate concentrations induced chilling tolerance, whereas inhibition of SA biosynthesis by L-α-aminooxy-β-phenylpropionic acid (AOPP) increased the photooxidation of PS II under chilling stress in watermelon, resulting in reduced photosynthesis and growth. Chilling induced a transient increase in the ratios of reduced to oxidized glutathione and reduced ascorbate to dehydroascorbate. Then, the expression of antioxidant genes was upregulated, and the activities of antioxidant enzymes were enhanced. Furthermore, SA-induced chilling tolerance was associated with cellular glutathione and ascorbate homeostasis, which served as redox signals to regulate antioxidant metabolism under chilling stress. AOPP treatment stimulated the chilling-induced expression of cold-responsive genes, particularly via C-repeat binding factors CBF3 and CBF4. These results confirm the synergistic role of SA signaling and the CBF-dependent responsive pathway during chilling stress in watermelon. PMID:27777580

  5. Redox theory of aging.

    Science.gov (United States)

    Jones, Dean P

    2015-08-01

    Metazoan genomes encode exposure memory systems to enhance survival and reproductive potential by providing mechanisms for an individual to adjust during lifespan to environmental resources and challenges. These systems are inherently redox networks, arising during evolution of complex systems with O2 as a major determinant of bioenergetics, metabolic and structural organization, defense, and reproduction. The network structure decreases flexibility from conception onward due to differentiation and cumulative responses to environment (exposome). The redox theory of aging is that aging is a decline in plasticity of genome-exposome interaction that occurs as a consequence of execution of differentiation and exposure memory systems. This includes compromised mitochondrial and bioenergetic flexibility, impaired food utilization and metabolic homeostasis, decreased barrier and defense capabilities and loss of reproductive fidelity and fecundity. This theory accounts for hallmarks of aging, including failure to maintain oxidative or xenobiotic defenses, mitochondrial integrity, proteostasis, barrier structures, DNA repair, telomeres, immune function, metabolic regulation and regenerative capacity. Copyright © 2015. Published by Elsevier B.V.

  6. Insights into redox sensing metalloproteins in Mycobacterium tuberculosis.

    Science.gov (United States)

    Chim, Nicholas; Johnson, Parker M; Goulding, Celia W

    2014-04-01

    Mycobacterium tuberculosis, the pathogen that causes tuberculosis, has evolved sophisticated mechanisms for evading assault by the human host. This review focuses on M. tuberculosis regulatory metalloproteins that are sensitive to exogenous stresses attributed to changes in the levels of gaseous molecules (i.e., molecular oxygen, carbon monoxide and nitric oxide) to elicit an intracellular response. In particular, we highlight recent developments on the subfamily of Whi proteins, redox sensing WhiB-like proteins that contain iron-sulfur clusters, sigma factors and their cognate anti-sigma factors of which some are zinc-regulated, and the dormancy survival regulon DosS/DosT-DosR heme sensory system. Mounting experimental evidence suggests that these systems contribute to a highly complex and interrelated regulatory network that controls M. tuberculosis biology. This review concludes with a discussion of strategies that M. tuberculosis has developed to maintain redox homeostasis, including mechanisms to regulate endogenous nitric oxide and carbon monoxide levels.

  7. Plant redox proteomics

    DEFF Research Database (Denmark)

    Navrot, Nicolas; Finnie, Christine; Svensson, Birte

    2011-01-01

    In common with other aerobic organisms, plants are exposed to reactive oxygen species resulting in formation of post-translational modifications related to protein oxidoreduction (redox PTMs) that may inflict oxidative protein damage. Accumulating evidence also underscores the importance of redox...... PTMs in regulating enzymatic activities and controlling biological processes in plants. Notably, proteins controlling the cellular redox state, e.g. thioredoxin and glutaredoxin, appear to play dual roles to maintain oxidative stress resistance and regulate signal transduction pathways via redox PTMs....... To get a comprehensive overview of these types of redox-regulated pathways there is therefore an emerging interest to monitor changes in redox PTMs on a proteome scale. Compared to some other PTMs, e.g. protein phosphorylation, redox PTMs have received less attention in plant proteome analysis, possibly...

  8. UV radiation in marine ectotherms: Molecular effects and responses

    Energy Technology Data Exchange (ETDEWEB)

    Dahms, Hans-U. [National Research Lab of Marine Molecular and Environmental Bioscience, Department of Chemistry and the Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Green Life Science, College of Natural Science, Sangmyung University, Seoul 110-743 (Korea, Republic of); Lee, Jae-Seong, E-mail: jslee2@hanyang.ac.kr [National Research Lab of Marine Molecular and Environmental Bioscience, Department of Chemistry and the Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)

    2010-04-01

    This review summarizes current knowledge on ultraviolet radiation (UVR)-induced cellular and molecular damage in marine ectotherms (invertebrates and fish). UVR impairs sperm motility, reduces fertilization, and causes embryo malformation that in turn affects recruitment and therefore the sustainability of natural populations. The direct molecular effects of UVR are mediated by absorption of certain wavelengths by specific macromolecules and the dissipation of the absorbed energy via photochemical reactions. Most organisms have defense mechanisms that either prevent UVR-induced damage, or mechanisms that repair the damage. Photoprotective pigments, antioxidant defense compounds, and cell cycle development genes are some of the molecules involved in UVR defense. Photoenzymatic repair and nucleotide excision repair are the two primary DNA repair systems in marine ectotherms. We anticipate that toxicogenomic studies will gain importance in UVR research because they can elucidate the primary processes involved in UVR damage and the cellular response to this damage.

  9. Engineered Proteins: Redox Properties and Their Applications

    Science.gov (United States)

    Prabhulkar, Shradha; Tian, Hui; Wang, Xiaotang; Zhu, Jun-Jie

    2012-01-01

    Abstract Oxidoreductases and metalloproteins, representing more than one third of all known proteins, serve as significant catalysts for numerous biological processes that involve electron transfers such as photosynthesis, respiration, metabolism, and molecular signaling. The functional properties of the oxidoreductases/metalloproteins are determined by the nature of their redox centers. Protein engineering is a powerful approach that is used to incorporate biological and abiological redox cofactors as well as novel enzymes and redox proteins with predictable structures and desirable functions for important biological and chemical applications. The methods of protein engineering, mainly rational design, directed evolution, protein surface modifications, and domain shuffling, have allowed the creation and study of a number of redox proteins. This review presents a selection of engineered redox proteins achieved through these methods, resulting in a manipulation in redox potentials, an increase in electron-transfer efficiency, and an expansion of native proteins by de novo design. Such engineered/modified redox proteins with desired properties have led to a broad spectrum of practical applications, ranging from biosensors, biofuel cells, to pharmaceuticals and hybrid catalysis. Glucose biosensors are one of the most successful products in enzyme electrochemistry, with reconstituted glucose oxidase achieving effective electrical communication with the sensor electrode; direct electron-transfer-type biofuel cells are developed to avoid thermodynamic loss and mediator leakage; and fusion proteins of P450s and redox partners make the biocatalytic generation of drug metabolites possible. In summary, this review includes the properties and applications of the engineered redox proteins as well as their significance and great potential in the exploration of bioelectrochemical sensing devices. Antioxid. Redox Signal. 17, 1796–1822. PMID:22435347

  10. Transcriptional profiling of the PDR gene family in rice roots in response to plant growth regulators, redox perturbations and weak organic acid stresses.

    Science.gov (United States)

    Moons, Ann

    2008-12-01

    The role of plant pleiotropic drug resistance (PDR) type ATP-binding cassette (ABC) transporters remains poorly understood. We characterized the expression of the rice pleiotropic drug resistance (PDR) gene family in roots, where PDR transporters are believed to have major functions. A prototypical oligonucleotide array was developed containing 70-mers chosen in the gene-specific 3' untranslated regions of the rice PDR genes, other full-molecule rice ABC transporter genes and relevant marker genes. Jasmonates, which are involved in plant defense and secondary metabolism, proved major inducers of PDR gene expression. Over half of the PDR genes were JA-induced in roots of rice; OsPDR9 to the highest level. Salicylic acid, involved in plant pathogen defense, markedly induced the expression of OsPDR20. OsPDR20 was cDNA cloned and characterized. Abscisic acid, typically involved in water deficit responses, particularly induced OsPDR3 in roots and shoot and OsPDR6 in rice leaves. OsPDR9 and OsPDR20 were furthermore up-regulated in response to dithiothreitol- or glutathione-induced redox perturbations. Exogenous application of the weak organic acids lactic acid, malic acid, and citric acid differentially induced the expression of OsPDR3, OsPDR8, OsPDR9 and OsPDR20 in rice seedling roots. This transcriptional survey represents a guide for the further functional analysis of individual PDR transporters in roots of rice.

  11. Recent Molecular Advances on Downstream Plant Responses to Abiotic Stress

    Directory of Open Access Journals (Sweden)

    Cláudia Regina Batista de Souza

    2012-07-01

    Full Text Available Abiotic stresses such as extremes of temperature and pH, high salinity and drought, comprise some of the major factors causing extensive losses to crop production worldwide. Understanding how plants respond and adapt at cellular and molecular levels to continuous environmental changes is a pre-requisite for the generation of resistant or tolerant plants to abiotic stresses. In this review we aimed to present the recent advances on mechanisms of downstream plant responses to abiotic stresses and the use of stress-related genes in the development of genetically engineered crops.

  12. Molecular Responses of Groundnut (Arachis hypogea L. to Zinc Stress

    Directory of Open Access Journals (Sweden)

    A. John De Britto

    2013-08-01

    Full Text Available Heavy metals are important environmental pollutants and their toxicity is a problem of increasing significance for ecological, evolutionary and environmental reasons. The interference of germination related proteins by heavy metals has not been well documented at the proteomic and genomic level. In the current study, molecular responses of germinating groundnut seeds were investigated under Zinc stress. The SDS-PAGE showed the preliminary changes in the polypeptides patterns under Zinc stress. Restriction digestion banding pattern of EcoRI and Hind III enzymes showed distinct banding pattern in the treated plants.

  13. An overview of HCV molecular biology, replication and immune responses

    Directory of Open Access Journals (Sweden)

    Nawaz Zafar

    2011-04-01

    Full Text Available Abstract Hepatitis C virus (HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. In this review, we summarize molecular virology, replication and immune responses against HCV and discussed how HCV escape from adaptive and humoral immune responses. This advance knowledge will be helpful for development of vaccine against HCV and discovery of new medicines both from synthetic chemistry and natural sources.

  14. Controls on the redox potential of rainwater.

    Science.gov (United States)

    Willey, Joan D; Mullaugh, Katherine M; Kieber, Robert J; Avery, G Brooks; Mead, Ralph N

    2012-12-18

    Hydrogen peroxide acting as a reductant affects the redox potential of rainwater collected at the Bermuda Atlantic Time Series Station, the South Island of New Zealand, the contiguous USA, and the primary study site in Wilmington, NC. Analytical measurements of both halves of redox couples for dissolved iron, mercury, and the nitrate-nitrite-ammonium system can predict the rainwater redox potential measured directly by a platinum electrode. Measurements of these redox couples along with the pH in rain yields pe⁻ between 8 and 11; the half reaction for hydrogen peroxide acting as a reductant using typical rainwater conditions of 15 μM H₂O₂ at pH 4.7 gives pe⁻ = 9.12, where pe⁻ = negative log of the activity of hydrated electrons. Of the six rainwater redox systems investigated, only manganese speciation appeared to be controlled by molecular oxygen (pe⁻ = 15.90). Copper redox speciation was consistent with superoxide acting as a reductant (pe⁻ = 2.7). The concentration of H₂O₂ in precipitation has more than doubled over the preceding decade due to a decrease in SO₂ emissions, which suggests the redox chemistry of rainwater is dynamic and changing, potentially altering the speciation of many organic compounds and trace metals in atmospheric waters.

  15. Acupuncture mechanism and redox equilibrium.

    Science.gov (United States)

    Zeng, Xiang-Hong; Li, Qian-Qian; Xu, Qian; Li, Fang; Liu, Cun-Zhi

    2014-01-01

    Oxidative stress participates in the pathological process of various diseases. Acupuncture is a component of the health care system in China that can be traced back for at least 3000 years. Recently, increased evidences indicate that acupuncture stimulation could reduce oxidative damage in organisms under pathological state, but the exact mechanism remains unclear. This review focuses on the emerging links between acupuncture and redox modulation in various disorders, such as vascular dementia, Parkinson's disease, and hypertension, ranging from redox system, antioxidant system, anti-inflammatory system, and nervous system to signaling pathway. Although the molecular and cellular pathways studies of acupuncture effect on oxidative stress are preliminary, they represent an important step forward in the research of acupuncture antioxidative effect.

  16. Acupuncture Mechanism and Redox Equilibrium

    Directory of Open Access Journals (Sweden)

    Xiang-Hong Zeng

    2014-01-01

    Full Text Available Oxidative stress participates in the pathological process of various diseases. Acupuncture is a component of the health care system in China that can be traced back for at least 3000 years. Recently, increased evidences indicate that acupuncture stimulation could reduce oxidative damage in organisms under pathological state, but the exact mechanism remains unclear. This review focuses on the emerging links between acupuncture and redox modulation in various disorders, such as vascular dementia, Parkinson’s disease, and hypertension, ranging from redox system, antioxidant system, anti-inflammatory system, and nervous system to signaling pathway. Although the molecular and cellular pathways studies of acupuncture effect on oxidative stress are preliminary, they represent an important step forward in the research of acupuncture antioxidative effect.

  17. The ‘Goldilocks Zone’ from a redox perspective - Adaptive versus deleterious responses to oxidative stress in striated muscle

    Directory of Open Access Journals (Sweden)

    Rick J Alleman

    2014-09-01

    Full Text Available Consequences of oxidative stress may be beneficial or detrimental in physiological systems. An organ system’s position on the ‘hormetic curve’ is governed by the source and temporality of reactive oxygen species (ROS production, proximity of ROS to moieties most susceptible to damage, and the capacity of the endogenous cellular ROS scavenging mechanisms. Most importantly, the resilience of the tissue (the capacity to recover from damage is a decisive factor, and this is reflected in the disparate response to ROS in cardiac and skeletal muscle. In myocytes, a high oxidative capacity invariably results in a significant ROS burden which in homeostasis, is rapidly neutralized by the robust antioxidant network. The up-regulation of key pathways in the antioxidant network is a central component of the hormetic response to ROS. Despite such adaptations, persistent oxidative stress over an extended time-frame (e.g. months to years inevitably leads to cumulative damages, maladaptation and ultimately the pathogenesis of chronic diseases. Indeed, persistent oxidative stress in heart and skeletal muscle has been repeatedly demonstrated to have causal roles in the etiology of heart disease and insulin resistance, respectively. Deciphering the mechanisms that underlie the divergence between adaptive and maladaptive responses to oxidative stress remains an active area of research for basic scientists and clinicians alike, as this would undoubtedly lead to novel therapeutic approaches. Here, we provide an overview of major types of ROS in striated muscle and the divergent adaptations that occur in response to them. Emphasis is placed on highlighting newly uncovered areas of research on this topic, with particular focus on the mitochondria, and the diverging roles that ROS play in muscle health (e.g., exercise or preconditioning and disease (e.g., cardiomyopathy, ischemia, metabolic syndrome.

  18. pH/redox responsive core cross-linked nanoparticles from thiolated carboxymethyl chitosan for in vitro release study of methotrexate.

    Science.gov (United States)

    Gao, Cheng; Liu, Ting; Dang, Yinghua; Yu, Zhiyan; Wang, Wei; Guo, Jingjing; Zhang, Xueqiong; He, Guanghua; Zheng, Hua; Yin, Yihua; Kong, Xiangqi

    2014-10-13

    A novel amphiphilic thiolated carboxymethyl chitosan was synthesized. It self-assembled into disulfide bond cross-linked nanoparticles in deionized water. The TEM showed that these nanoparticles had a core-shell structure with an average diameter of 160 nm. Dynamic light scattering showed that the nanoparticles were stable in water solution. The particle size changed with pH values and GSH concentrations, and reached a maximum diameter at pH 7.0 and 20mM GSH respectively, exhibiting an obvious pH/redox responsibility. Methotrexate was encapsulated in nanoparticles reaching encapsulation efficiency as much as 43.4%. Release profiles of methotrexate showed a release rate of 19 wt% in pH 7.4 buffer containing 10 μM GSH, whereas as high as 93 wt% in pH 5.0 buffer containing 20mM GSH, indicating that the nanoparticles may be used for tumor-specific drug release. The anticancer activity test in vitro showed that the inhibition rate of methotrexate-loaded nanoparticles against HeLa cells reached 90%.

  19. Redox signaling in acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Salvador Pérez

    2015-08-01

    Full Text Available Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  20. Redox signaling in acute pancreatitis.

    Science.gov (United States)

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-08-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF-VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  1. Anchoring novel molecular biomarker responses to traditional responses in fish exposed to environmental contamination

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Patricia [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Department of Biology and Environmental Science, University of Sussex, Falmer, Brighton BN1 9QJ (United Kingdom); Pacheco, Mario [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Lourdes Pereira, M. [CICECO and Departamento de Biologia, Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Mendo, Sonia [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Rotchell, Jeanette M., E-mail: J.Rotchell@sussex.ac.u [Department of Biology and Environmental Science, University of Sussex, Falmer, Brighton BN1 9QJ (United Kingdom)

    2010-05-15

    The responses of Dicentrarchus labrax and Liza aurata to aquatic pollution were assessed in a contaminated coastal lagoon, using both traditional and novel biomarkers combined. DNA damage, assessed by comet assay, was higher in both fish species from the contaminated sites, whereas levels of cytochrome P450 1A1 gene expression were not significantly altered. The liver histopathological analysis also revealed significant lesions in fish from contaminated sites. Alterations in ras and xpf genes were analysed and additional pollutant-responsive genes were identified. While no alterations were found in ras gene, a downregulation of xpf gene was observed in D. labrax from a contaminated site. Suppression subtractive hybridization applied to D. labrax collected at a contaminated site, revealed altered expression in genes involved in energy metabolism, immune system activity and antioxidant response. The approach and results reported herein demonstrate the utility of anchoring traditional biomarker responses alongside novel biomarker responses. - Novel molecular biomarkers of aquatic environmental contamination in fish.

  2. The redox-sensing regulator Rex modulates central carbon metabolism, stress tolerance response and biofilm formation by Streptococcus mutans.

    Directory of Open Access Journals (Sweden)

    Jacob P Bitoun

    Full Text Available The Rex repressor has been implicated in regulation of central carbon and energy metabolism in gram-positive bacteria. We have previously shown that Streptococcus mutans, the primary causative agent of dental caries, alters its transcriptome upon Rex-deficiency and renders S. mutans to have increased susceptibility to oxidative stress, aberrations in glucan production, and poor biofilm formation. In this study, we showed that rex in S. mutans is co-transcribed as an operon with downstream guaA, encoding a putative glutamine amidotransferase. Electrophoretic mobility shift assays showed that recombinant Rex bound promoters of target genes avidly and specifically, including those down-regulated in response to Rex-deficiency, and that the ability of recombinant Rex to bind to selected promoters was modulated by NADH and NAD(+. Results suggest that Rex in S. mutans can function as an activator in response to intracellular NADH/NAD(+ level, although the exact binding site for activator Rex remains unclear. Consistent with a role in oxidative stress tolerance, hydrogen peroxide challenge assays showed that the Rex-deficient mutant, TW239, and the Rex/GuaA double mutant, JB314, were more susceptible to hydrogen peroxide killing than the wildtype, UA159. Relative to UA159, JB314 displayed major defects in biofilm formation, with a decrease of more than 50-fold in biomass after 48-hours. Collectively, these results further suggest that Rex in S. mutans regulates fermentation pathways, oxidative stress tolerance, and biofilm formation in response to intracellular NADH/NAD(+ level. Current effort is being directed to further investigation of the role of GuaA in S. mutans cellular physiology.

  3. Differential molecular responses of rapeseed cotyledons to light and dark reveal metabolic adaptations towards autotrophy establishment

    Directory of Open Access Journals (Sweden)

    Dongli He

    2016-07-01

    Full Text Available Photosynthesis competent autotrophy should be established during the postgerminative stage of plant growth. Among the multiple factors, light plays a decisive role in the switch from heterotrophic to autotrophic growth. Under dark condition, the rapeseed hypocotyl extends quickly with an apical hook, and the cotyledon is yellow and folded, and maintains high level of the isocitrate lyase (ICL. By contrast, in the light, the hypocotyl extends slowly, the cotyledon unfolds and turns green, the ICL content changes in parallel with the cotyledon greening. To reveal metabolic adaptations during the establishment of postgerminative autotrophy in rapeseed, we conducted comparative proteomic and metabolomic analyses of the cotyledons of seedlings grown under light versus dark conditions. Under both conditions, the increase of the protease, fatty acids β-oxidation and glyoxylate-cycle related proteins was accompanied with rapid degradation of the stored proteins and lipids with an accumulation of the amino acids, while light condition partially retarded these conversions. Light significantly induced the expression of chlorophyll-binding and photorespiration related proteins, resulting in an increase of the reducing-sugar. However, the levels of some chlide conversion, Calvin-cycle and photorespiration related proteins also accumulated in dark grown cotyledons, implying that the transition from heterotrophy to autotrophy is programmed in the seed rather than induced by light. Various anti-stress systems, e.g., redox related proteins, salicylic acid, proline and chaperones, were employed to release the oxidative stress, which was mainly derived from lipid oxidation or photorespiration, under both conditions. This study provides a comprehensive understanding of the differential molecular responses of rapeseed cotyledons to light and dark conditions, which will facilitate further study on the complex mechanism underlying the transition from heterotrophy to

  4. The Electrical Response to Injury: Molecular Mechanisms and Wound Healing

    Science.gov (United States)

    Reid, Brian; Zhao, Min

    2014-01-01

    Significance: Natural, endogenous electric fields (EFs) and currents arise spontaneously after wounding of many tissues, especially epithelia, and are necessary for normal healing. This wound electrical activity is a long-lasting and regulated response. Enhancing or inhibiting this electrical activity increases or decreases wound healing, respectively. Cells that are responsible for wound closure such as corneal epithelial cells or skin keratinocytes migrate directionally in EFs of physiological magnitude. However, the mechanisms of how the wound electrical response is initiated and regulated remain unclear. Recent Advances: Wound EFs and currents appear to arise by ion channel up-regulation and redistribution, which are perhaps triggered by an intracellular calcium wave or cell depolarization. We discuss the possibility of stimulation of wound healing via pharmacological enhancement of the wound electric signal by stimulation of ion pumping. Critical Issues: Chronic wounds are a major problem in the elderly and diabetic patient. Any strategy to stimulate wound healing in these patients is desirable. Applying electrical stimulation directly is problematic, but pharmacological enhancement of the wound signal may be a promising strategy. Future Directions: Understanding the molecular regulation of wound electric signals may reveal some fundamental mechanisms in wound healing. Manipulating fluxes of ions and electric currents at wounds might offer new approaches to achieve better wound healing and to heal chronic wounds. PMID:24761358

  5. Plant adaptation to low atmospheric pressures: potential molecular responses

    Science.gov (United States)

    Ferl, Robert J.; Schuerger, Andrew C.; Paul, Anna-Lisa; Gurley, William B.; Corey, Kenneth; Bucklin, Ray

    2002-01-01

    There is an increasing realization that it may be impossible to attain Earth normal atmospheric pressures in orbital, lunar, or Martian greenhouses, simply because the construction materials do not exist to meet the extraordinary constraints imposed by balancing high engineering requirements against high lift costs. This equation essentially dictates that NASA have in place the capability to grow plants at reduced atmospheric pressure. Yet current understanding of plant growth at low pressures is limited to just a few experiments and relatively rudimentary assessments of plant vigor and growth. The tools now exist, however, to make rapid progress toward understanding the fundamental nature of plant responses and adaptations to low pressures, and to develop strategies for mitigating detrimental effects by engineering the growth conditions or by engineering the plants themselves. The genomes of rice and the model plant Arabidopsis thaliana have recently been sequenced in their entirety, and public sector and commercial DNA chips are becoming available such that thousands of genes can be assayed at once. A fundamental understanding of plant responses and adaptation to low pressures can now be approached and translated into procedures and engineering considerations to enhance plant growth at low atmospheric pressures. In anticipation of such studies, we present here the background arguments supporting these contentions, as well as informed speculation about the kinds of molecular physiological responses that might be expected of plants in low-pressure environments.

  6. Characterization of a nif-regulated flavoprotein (FprA) from Rhodobacter capsulatus. Redox properties and molecular interaction with a [2Fe-2S] ferredoxin.

    Science.gov (United States)

    Jouanneau, Y; Meyer, C; Asso, M; Guigliarelli, B; Willison, J C

    2000-02-01

    A flavoprotein from Rhodobacter capsulatus was purified as a recombinant (His)6-tag fusion from an Escherichia coli clone over-expressing the fprA structural gene. The FprA protein is a homodimer containing one molecule of FMN per 48-kDa monomer. Reduction of the flavoprotein by dithionite showed biphasic kinetics, starting with a fast step of semiquinone (SQ) formation, and followed by a slow reduction of the SQ. This SQ was in the anionic form as shown by EPR and optical spectroscopies. Spectrophotometric titration gave a midpoint redox potential for the oxidized/SQ couple of Em1 = +20 mV (pH 8.0), whereas the SQ/hydroquinone couple could not be titrated due to the thermodynamic instability of SQ associated with its slow reduction process. The inability to detect the intermediate form, SQ, upon oxidative titration confirmed this instability and led to an estimate of Em2 - Em1 of > 80 mV. The reduction of SQ by dithionite was significantly accelerated when the [2Fe-2S] ferredoxin FdIV was used as redox mediator. The midpoint redox potential of this ferredoxin was determined to be -275 +/- 2 mV at pH 7.5, consistent with FdIV serving as electron donor to FprA in vivo. FdIV and FprA were found to cross-react when incubated together with the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, giving a covalent complex with an Mr of approximately 60 000. Formation of this complex was unaffected by the redox states of the two proteins. Other [2Fe-2S] ferredoxins, including FdV and FdVI from R. capsulatus, were ineffective as electron carriers to FprA, and cross-reacted poorly with the flavoprotein. The possible function of FprA with regard to nitrogen fixation was investigated using an fprA-deleted mutant. Although nitrogenase activity was significantly reduced in the mutant compared with the wild-type strain, nitrogen fixation was apparently unaffected by the fprA deletion even under iron limitation or microaerobic conditions.

  7. Formation of high-molecular-weight angiotensinogen during pregnancy is a result of competing redox reactions with the proform of eosinophil major basic protein

    DEFF Research Database (Denmark)

    Kløverpris, Søren; Skov, Louise Lind; Glerup, Simon

    2013-01-01

    compared to monomeric AGT and the proMBP-AGT complex. Furthermore, we have used recombinant proteins to analyse the formation of the proMBP-PAPP-A and the proMBP-AGT complexes, and we demonstrate that they are competing reactions, depending on the same cysteine residue of proMBP, but differentially...... on the redox potential, potentially important for the relative amounts of the complexes in vivo. These findings may be important physiologically, since the biochemical properties of the proteins change as a consequence of complex formation....

  8. Genetic inactivation of mitochondria-targeted redox enzyme p66ShcA preserves neuronal viability and mitochondrial integrity in response to oxidative challenges

    Directory of Open Access Journals (Sweden)

    Michael eForte

    2012-07-01

    Full Text Available Mitochondria are essential to neuronal viability and function due to their roles in ATP production, intracellular calcium regulation, and activation of apoptotic pathways. Accordingly, mitochondrial dysfunction has been indicated in a wide variety of neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, stroke and multiple sclerosis (MS. Recent evidence points to the permeability transition pore (PTP as a key player in mitochondrial dysfunction in these diseases, in which pathologic opening leads to mitochondrial swelling, rupture, release of cytochrome c, and neuronal death. Reactive oxygen species (ROS, which are inducers of PTP opening, have been prominently implicated in the progression of many of these neurodegenerative diseases. In this context, inactivation of a mitochondria-targeted redox enzyme p66ShcA (p66 has been recently shown to prevent the neuronal cell death leading to axonal severing in the murine model of MS, experimental autoimmune encephalomyelitis (EAE. To further characterize the response of neurons lacking p66, we assessed their reaction to treatment with oxidative stressors implicated in neurodegenerative pathways. Specifically, p66-knockout (p66-KO and wild-type (WT neurons were treated with hydrogen peroxide (H2O2 and nitric oxide (NO, and assessed for cell viability and changes in mitochondrial properties, including morphology and ROS production. The results showed that p66-KO neurons had greater survival following treatment with oxidative stressors and generated less ROS when compared to WT neurons. Correspondingly, mitochondria in p66-KO neurons showed diminished morphological changes in response to these challenges. Overall, these findings highlight the importance of developing mitochondria-targeted therapeutics for neurodegenerative disorders, and emphasize p66, mitochondrial ROS, and the PTP as key targets for maintaining mitochondrial and neuronal

  9. Molecular defense response of oil palm to Ganoderma infection.

    Science.gov (United States)

    Ho, C-L; Tan, Y-C

    2015-06-01

    Basal stem rot (BSR) of oil palm roots is due to the invasion of fungal mycelia of Ganoderma species which spreads to the bole of the stem. In addition to root contact, BSR can also spread by airborne basidiospores. These fungi are able to break down cell wall components including lignin. BSR not only decreases oil yield, it also causes the stands to collapse thus causing severe economic loss to the oil palm industry. The transmission and mode of action of Ganoderma, its interactions with oil palm as a hemibiotroph, and the molecular defence responses of oil palm to the infection of Ganoderma boninense in BSR are reviewed, based on the transcript profiles of infected oil palms. The knowledge gaps that need to be filled in oil palm-Ganoderma molecular interactions i.e. the associations of hypersensitive reaction (HR)-induced cell death and reactive oxygen species (ROS) kinetics to the susceptibility of oil palm to Ganoderma spp., the interactions of phytohormones (salicylate, jasmonate and ethylene) at early and late stages of BSR, and cell wall strengthening through increased production of guaiacyl (G)-type lignin, are also discussed.

  10. Shock responses of nanoporous aluminum by molecular dynamics simulations

    CERN Document Server

    Xiang, Meizhen; Yang, Yantao; Liao, Yi; Wang, Kun; Chen, Yun; Chen, Jun

    2016-01-01

    We present systematic investigations on the shock responses of nanoporous aluminum (np-Al) by nonequilibrium molecular dynamics simulations. The dislocation nucleation sites are found to concentrate in low latitude region near the equator of the spherical void surfaces. We propose a continuum wave reflection theory and a resolved shear stress model to explain the distribution of dislocation nucleation sites. The simulations reveals two mechanisms of void collapse: the plasticity mechanism and the internal jetting mechanism. The plasticity mechanism, which leads to transverse collapse of voids, prevails under relatively weaker shocks; while the internal jetting mechanism, which leads to longitudinal filling of the void vacuum, plays more significant role as the shock intensity increases. In addition, an abnormal thermodynamic phenomenon (i.e., arising of temperature with pressure dropping) in shocked np-Al is discovered. This phenomenon is incompatible with the conventional Rankine-Hugoniot theory, and is expl...

  11. Redox proteomics changes in the fungal pathogen Trichosporon asahii on arsenic exposure: identification of protein responses to metal-induced oxidative stress in an environmentally-sampled isolate.

    Directory of Open Access Journals (Sweden)

    Sidra Ilyas

    Full Text Available Trichosporon asahii is a yeast pathogen implicated in opportunistic infections. Cultures of an isolate collected from industrial wastewater were exposed for 2 days to 100 mg/L sodium arsenite (NaAsO2 and cadmium (CdCl2. Both metals reduced glutathione transferase (GST activity but had no effect on superoxide dismutase or catalase. NaAsO2 exposure increased glutathione reductase activity while CdCl2 had no effect. Protein thiols were labeled with 5-iodoacetamido fluorescein followed by one dimensional electrophoresis which revealed extensive protein thiol oxidation in response to CdCl2 treatment but thiol reduction in response to NaAsO2. Two dimensional electrophoresis analyses showed that the intensity of some protein spots was enhanced on treatment as judged by SameSpots image analysis software. In addition, some spots showed decreased IAF fluorescence suggesting thiol oxidation. Selected spots were excised and tryptic digested for identification by MALDI-TOF/TOF MS. Twenty unique T. asahii proteins were identified of which the following proteins were up-regulated in response to NaAsO2: 3-isopropylmalate dehydrogenase, phospholipase B, alanine-glyoxylate aminotransferase, ATP synthase alpha chain, 20S proteasome beta-type subunit Pre3p and the hypothetical proteins A1Q1_08001, A1Q2_03020, A1Q1_06950, A1Q1_06913. In addition, the following showed decreased thiol-associated fluorescence consistent with thiol oxidation; aconitase; aldehyde reductase I; phosphoglycerate kinase; translation elongation factor 2; heat shock protein 70 and hypothetical protein A1Q2_04745. Some proteins showed both increase in abundance coupled with decrease in IAF fluorescence; 3-hydroxyisobutyryl-CoA hydrolase; homoserine dehydrogenase Hom6 and hypothetical proteins A1Q2_03020 and A1Q1_00754. Targets implicated in redox response included 10 unique metabolic enzymes, heat shock proteins, a component of the 20S proteasome and translation elongation factor 2. These data

  12. Chloroplast Redox Poise

    DEFF Research Database (Denmark)

    Steccanella, Verdiana

    the redox status of the plastoquinone pool and chlorophyll biosynthesis. Furthermore, in the plant cell, the equilibrium between redox reactions and ROS signals is also maintained by various balancing mechanisms among which the thioredoxin reductase-thioredoxin system (TR-Trx) stands out as a mediator......The redox state of the chloroplast is maintained by a delicate balance between energy production and consumption and is affected by the need to avoid increased production of reactive oxygen species (ROS). Redox power and ROS generated in the chloroplast are essential for maintaining physiological...... metabolic pathways and for optimizing chloroplast functions. The redox poise of photosynthetic electron transport components like plastoquinone is crucial to initiate signaling cascades and might also be involved in key biosynthetic pathways such as chlorophyll biosynthesis. We, therefore, explored...

  13. Redox chemistry of green tea polyphenols: therapeutic benefits in neurodegenerative diseases.

    Science.gov (United States)

    Hügel, H M; Jackson, N

    2012-05-01

    Evidence for the medicinal and health benefits of polyphenols in green tea for the prevention of chronic diseases such as heart disease, various types of cancer and neurodegenerative diseases is advancing. Their in vivo effectiveness and molecular mechanisms are difficult to elucidate and remain a challenging task. We review the redox responsiveness and amyloid protein perturbation biophysical properties of the major green tea polyphenol constituent (-)- epigallocatechin-3-gallate [EGCG].

  14. Glucose-responsive insulin by molecular and physical design

    Science.gov (United States)

    Bakh, Naveed A.; Cortinas, Abel B.; Weiss, Michael A.; Langer, Robert S.; Anderson, Daniel G.; Gu, Zhen; Dutta, Sanjoy; Strano, Michael S.

    2017-10-01

    The concept of a glucose-responsive insulin (GRI) has been a recent objective of diabetes technology. The idea behind the GRI is to create a therapeutic that modulates its potency, concentration or dosing relative to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. From the perspective of the medicinal chemist, the GRI is also important as a generalized model of a potentially new generation of therapeutics that adjust potency in response to a critical therapeutic marker. The aim of this Perspective is to highlight emerging concepts, including mathematical modelling and the molecular engineering of insulin itself and its potency, towards a viable GRI. We briefly outline some of the most important recent progress toward this goal and also provide a forward-looking viewpoint, which asks if there are new approaches that could spur innovation in this area as well as to encourage synthetic chemists and chemical engineers to address the challenges and promises offered by this therapeutic approach.

  15. Hyaluronic acid functional amphipathic and redox-responsive polymer particles for the co-delivery of doxorubicin and cyclopamine to eradicate breast cancer cells and cancer stem cells

    Science.gov (United States)

    Hu, Kelei; Zhou, Huige; Liu, Ying; Liu, Zhu; Liu, Jing; Tang, Jinglong; Li, Jiayang; Zhang, Jiakun; Sheng, Wang; Zhao, Yuliang; Wu, Yan; Chen, Chunying

    2015-04-01

    Cancer stem cells (CSCs) have the ability to transform into bulk cancer cells, to promote tumor growth and establish tumor metastasis. To effectively inhibit tumor growth and prevent metastasis, treatments with conventional chemotherapy drugs should be combined with CSC targeted drugs. In this study, we describe the synthesis and characterization of a new amphiphilic polymer, hyaluronic acid-cystamine-polylactic-co-glycolic acid (HA-SS-PLGA), composed of a hydrophobic PLGA head and a hydrophilic HA segment linked by a bioreducible disulfide bond. With a double emulsion method, a nano delivery system was constructed to deliver doxorubicin (DOX) and cyclopamine (CYC, a primary inhibitor of the hedgehog signaling pathway of CSCs) to both a CD44-overexpressing breast CSC subpopulation and bulk breast cancer cells and allow an on-demand release. The resulting drug-loaded NPs exhibited a redox-responsive drug release profile. Dual drug-loaded particles potently diminished the number and size of tumorspheres and HA showed a targeting effect towards breast CSCs. In vivo combination therapy further demonstrated a remarkable synergistic anti-tumor effect and prolonged survival compared to mono-therapy using the orthotopic mammary fat pad tumor growth model. The co-delivery of drug and the CSC specific inhibitor towards targeted cancer chemotherapeutics provides an insight into anticancer strategy with facile control and high efficacy.Cancer stem cells (CSCs) have the ability to transform into bulk cancer cells, to promote tumor growth and establish tumor metastasis. To effectively inhibit tumor growth and prevent metastasis, treatments with conventional chemotherapy drugs should be combined with CSC targeted drugs. In this study, we describe the synthesis and characterization of a new amphiphilic polymer, hyaluronic acid-cystamine-polylactic-co-glycolic acid (HA-SS-PLGA), composed of a hydrophobic PLGA head and a hydrophilic HA segment linked by a bioreducible disulfide bond

  16. Plant genetic and molecular responses to water deficit

    Directory of Open Access Journals (Sweden)

    Silvio Salvi

    2011-02-01

    Full Text Available Plant productivity is severely affected by unfavourable environmental conditions (biotic and abiotic stresses. Among others, water deficit is the plant stress condition which mostly limits the quality and the quantity of plant products. Tolerance to water deficit is a polygenic trait strictly dependent on the coordinated expression of a large set of genes coding for proteins directly involved in stress-induced protection/repair mechanisms (dehydrins, chaperonins, enzymes for the synthesis of osmoprotectants and detoxifying compounds, and others as well as genes involved in transducing the stress signal and regulating gene expression (transcription factors, kinases, phosphatases. Recently, research activities in the field evolved from the study of single genes directly involved in cellular stress tolerance (functional genes to the identification and characterization of key regulatory genes involved in stress perception and transduction and able to rapidly and efficiently activate the complex gene network involved in the response to stress. The complexity of the events occurring in response to stress have been recently approached by genomics tools; in fact the analysis of transcriptome, proteome and metabolome of a plant tissue/cell in response to stress already allowed to have a global view of the cellular and molecular events occurring in response to water deficit, by the identification of genes activated and co-regulated by the stress conditions and the characterization of new signalling pathways. Moreover the recent application of forward and reverse genetic approaches, trough mutant collection development, screening and characterization, is giving a tremendous impulse to the identification of gene functions with key role in stress tolerance. The integration of data obtained by high-throughput genomic approaches, by means of powerful informatic tools, is allowing nowadays to rapidly identify of major genes/QTLs involved in stress tolerance

  17. Microglia antioxidant systems and redox signaling

    DEFF Research Database (Denmark)

    Vilhardt, F; Haslund-Vinding, J; Jaquet, V

    2017-01-01

    of protein thiolation of target redox proteins the necessity for tightly localized, timed, and confined oxidant production to work in concert with antioxidant proteins to promote redox signaling. NOX2-mediated redox signaling modulate the acquisition of the classical or alternative microglia activation...... of the antioxidant response in microglia will reveal antioxidant proteins as dynamic players in redox signaling, which in concert with NOX-derived oxidants fulfill important roles in the autocrine or paracrine regulation of essential enzymes or transcriptional programs. This article is protected by copyright. All......'t stand alone however, and are not always pernicious. We discuss in general terms, and where available in microglia, GSH synthesis and relation to cystine import and glutamate export, and the thioredoxin system as the most important antioxidative defense mechanism, and further, we discuss in the context...

  18. Molecular Dynamics of the Shewanella oneidensis Response to Chromate Stress

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Steven D [ORNL; Thompson, Melissa R [ORNL; Verberkmoes, Nathan C [ORNL; Chourey, Karuna [ORNL; Shah, Manesh B [ORNL; Zhou, Jizhong [ORNL; Hettich, Robert {Bob} L [ORNL; Thompson, Dorothea K [ORNL

    2006-01-01

    Temporal genomic profiling and whole-cell proteomic analyses were performed to characterize the dynamic molecular response of the metal-reducing bacterium Shewanella oneidensis MR-1 to an acute chromate shock. The complex dynamics of cellular processes demand the integration of methodologies that describe biological systems at the levels of regulation, gene and protein expression, and metabolite production. Genomic microarray analysis of the transcriptome dynamics of midexponential phase cells subjected to 1 mM potassium chromate (K2CrO4) at exposure time intervals of 5, 30, 60, and 90 min revealed 910 genes that were differentially expressed at one or more time points. Strongly induced genes included those encoding components of a TonB1 iron transport system (tonB1-exbB1-exbD1), hemin ATP-binding cassette transporters (hmuTUV), TonB-dependent receptors as well as sulfate transporters (cysP, cysW-2, and cysA-2), and enzymes involved in assimilative sulfur metabolism (cysC, cysN, cysD, cysH, cysI, and cysJ). Transcript levels for genes with annotated functions in DNA repair (lexA, recX, recA, recN, dinP, and umuD), cellular detoxification (so1756, so3585, and so3586), and two-component signal transduction systems (so2426) were also significantly upregulated (p < 0.05) in Cr(VI)-exposed cells relative to untreated cells. By contrast, genes with functions linked to energy metabolism, particularly electron transport (e.g. so0902-03-04, mtrA, omcA, and omcB), showed dramatic temporal alterations in expression with the majority exhibiting repression. Differential proteomics based on multidimensional HPLC-MS/MS was used to complement the transcriptome data, resulting in comparable induction and repression patterns for a subset of corresponding proteins. In total, expression of 2,370 proteins were confidently verified with 624 (26%) of these annotated as hypothetical or conserved hypothetical proteins. The initial response of S. oneidensis to chromate shock appears to

  19. Differential molecular response of monodehydroascorbate reductase and glutathione reductase by nitration and S-nitrosylation.

    Science.gov (United States)

    Begara-Morales, Juan C; Sánchez-Calvo, Beatriz; Chaki, Mounira; Mata-Pérez, Capilla; Valderrama, Raquel; Padilla, María N; López-Jaramillo, Javier; Luque, Francisco; Corpas, Francisco J; Barroso, Juan B

    2015-09-01

    The ascorbate-glutathione cycle is a metabolic pathway that detoxifies hydrogen peroxide and involves enzymatic and non-enzymatic antioxidants. Proteomic studies have shown that some enzymes in this cycle such as ascorbate peroxidase (APX), monodehydroascorbate reductase (MDAR), and glutathione reductase (GR) are potential targets for post-translational modifications (PMTs) mediated by nitric oxide-derived molecules. Using purified recombinant pea peroxisomal MDAR and cytosolic and chloroplastic GR enzymes produced in Escherichia coli, the effects of peroxynitrite (ONOO(-)) and S-nitrosoglutathione (GSNO) which are known to mediate protein nitration and S-nitrosylation processes, respectively, were analysed. Although ONOO(-) and GSNO inhibit peroxisomal MDAR activity, chloroplastic and cytosolic GR were not affected by these molecules. Mass spectrometric analysis of the nitrated MDAR revealed that Tyr213, Try292, and Tyr345 were exclusively nitrated to 3-nitrotyrosine by ONOO(-). The location of these residues in the structure of pea peroxisomal MDAR reveals that Tyr345 is found at 3.3 Å of His313 which is involved in the NADP-binding site. Site-directed mutagenesis confirmed Tyr345 as the primary site of nitration responsible for the inhibition of MDAR activity by ONOO(-). These results provide new insights into the molecular regulation of MDAR which is deactivated by nitration and S-nitrosylation. However, GR was not affected by ONOO(-) or GSNO, suggesting the existence of a mechanism to conserve redox status by maintaining the level of reduced GSH. Under a nitro-oxidative stress induced by salinity (150mM NaCl), MDAR expression (mRNA, protein, and enzyme activity levels) was increased, probably to compensate the inhibitory effects of S-nitrosylation and nitration on the enzyme. The present data show the modulation of the antioxidative response of key enzymes in the ascorbate-glutathione cycle by nitric oxide (NO)-PTMs, thus indicating the close involvement of

  20. Molecular and physiological responses of trees to waterlogging stress.

    Science.gov (United States)

    Kreuzwieser, Jürgen; Rennenberg, Heinz

    2014-10-01

    One major effect of global climate change will be altered precipitation patterns in many regions of the world. This will cause a higher probability of long-term waterlogging in winter/spring and flash floods in summer because of extreme rainfall events. Particularly, trees not adapted at their natural site to such waterlogging stress can be impaired. Despite the enormous economic, ecological and social importance of forest ecosystems, the effect of waterlogging on trees is far less understood than the effect on many crops or the model plant Arabidopsis. There is only a handful of studies available investigating the transcriptome and metabolome of waterlogged trees. Main physiological responses of trees to waterlogging include the stimulation of fermentative pathways and an accelerated glycolytic flux. Many energy-consuming, anabolic processes are slowed down to overcome the energy crisis mediated by waterlogging. A crucial feature of waterlogging tolerance is the steady supply of glycolysis with carbohydrates, particularly in the roots; stress-sensitive trees fail to maintain sufficient carbohydrate availability resulting in the dieback of the stressed tissues. The present review summarizes physiological and molecular features of waterlogging tolerance of trees; the focus is on carbon metabolism in both, leaves and roots of trees.

  1. Assessing coral stress responses using molecular biomarkers of gene transcription.

    Science.gov (United States)

    Morgan, M B; Vogelien, D L; Snell, T W

    2001-03-01

    We present a method for detecting rapid changes in coral gene expression at the messenger ribonucleic acid (mRNA) level. The staghorn coral Acropora cervicornis was exposed to 1 and 10 microg/L permethrin and 25 and 50 microg/L copper for 4 h. Using differential display polymerase chain reaction (PCR), mRNA associated with each toxicant exposure were reverse transcribed into complementary DNA (cDNA) fragments that were subsequently amplified and isolated. Six differentially expressed cDNA fragments were further developed into molecular probes that were used in Northern dot blots to determine the change in transcription levels of target transcripts. Changes in mRNA abundance were quantified by densitometry of chemiluminescence of digoxigenin-labeled probes hybridizing to target mRNA transcripts. The six gene probes showed varying degrees of sensitivity to the toxicants as well as specificity between toxicants. These probes were hybridized in Southern blots to genomic DNA from A. formosa sperm, which lacks zooxanthellae, to demonstrate that the genes coding for the mRNA transcripts produced are found within the coral genome. The gene probes developed in this study provide coral biologists with a new tool for coral assessment. Gene probes are sensitive, toxicant-specific biomarkers of coral stress responses with which gene sequence information can be obtained, providing a mechanism for identifying the stressor altering the gene expression.

  2. A robust molecular platform for non-volatile memory devices with optical and magnetic responses.

    Science.gov (United States)

    Simão, Cláudia; Mas-Torrent, Marta; Crivillers, Núria; Lloveras, Vega; Artés, Juan Manuel; Gorostiza, Pau; Veciana, Jaume; Rovira, Concepció

    2011-05-01

    Bistable molecules that behave as switches in solution have long been known. Systems that can be reversibly converted between two stable states that differ in their physical properties are particularly attractive in the development of memory devices when immobilized in substrates. Here, we report a highly robust surface-confined switch based on an electroactive, persistent organic radical immobilized on indium tin oxide substrates that can be electrochemically and reversibly converted to the anion form. This molecular bistable system behaves as an extremely robust redox switch in which an electrical input is transduced into optical as well as magnetic outputs under ambient conditions. The fact that this molecular surface switch, operating at very low voltages, can be patterned and addressed locally, and also has exceptionally high long-term stability and excellent reversibility and reproducibility, makes it a very promising platform for non-volatile memory devices.

  3. Electrochemistry of dithienylethenes and their application in electropolymer modified photo- and redox switchable surfaces

    NARCIS (Netherlands)

    Logtenberg, Hella; Browne, Wesley R.

    2013-01-01

    Diarylethenes have proven to be versatile responsive components in many applications due to their photochromic properties. In recent years their potential use as redox switchable components has become increasingly apparent. Applying dithienylethenes as redox switchable components requires their immo

  4. Electron paramagnetic resonance study of hydrogen peroxide/ascorbic acid ratio as initiator redox pair in the inulin-gallic acid molecular grafting reaction.

    Science.gov (United States)

    Arizmendi-Cotero, Daniel; Gómez-Espinosa, Rosa María; Dublán García, Octavio; Gómez-Vidales, Virginia; Dominguez-Lopez, Aurelio

    2016-01-20

    Gallic acid (GA) was grafted onto inulin using the free radicals method, generated by the hydrogen peroxide/ascorbic acid (H2O2/AA) redox pair. Molar ratios of H2O2/AA at 9, 20, 39 and 49 were evaluated by Electron Paramagnetic Resonance in order to find the effect of the oxidation of the inulin and the efficiency in the inulin-gallic acid grafting (IGA). The highest concentration of the inulin macro-radical was obtained with H2O2/AA molar ratios of 20 and 49 with the removal of a hydrogen atom from a methyl group of the inulin fructose monomers. The highest grafting ratio (30.4 mg GA eq/g IGA) was obtained at 9 M of H2O2/AA. UV-Vis, FT-IR-ATR and XDR results confirmed a successful IGA grafting. The efficiency of the grafting reaction depends on the concentration of the macro-radical, it depends on the molar ratio of H2O2/AA, being affected by simultaneous reactions between components of the mixture (H2O2, AA, inulin, GA and eventually atmospheric oxygen) as well.

  5. Investigation of the Molecular Response of Belugas to Stressors

    Science.gov (United States)

    2014-09-30

    described above were obtained from this related project. REFERENCES Denis, F., Archambault, D., 2001. Molecular cloning and characterization of...mRNA expression levels serve as indicators to assess stress? BMC Veterinary Research 9:145. St-Laurent, G. and Archambault, D., 2000. Molecular ... cloning , phylogenetic analysis and expression of beluga whale (Delphinapterus leucas) interleukin 6. Veterinary Immunology Immunopathology 73: 31-44

  6. Physiological response, molecular analysis and water use efficiency ...

    African Journals Online (AJOL)

    SAM

    2014-07-16

    Jul 16, 2014 ... Molecular analysis of three hybrids revealed the possibility of introgressing the ...... complex and depends on both biophysical and economic ... Grant RF, Jackson BS, Kiniry KR, Arkin GF (1989) Water deficit timing effects on ...

  7. Molecularly Imprinted Polymers with Stimuli-Responsive Affinity: Progress and Perspectives

    OpenAIRE

    Wei Chen; Yue Ma; Jianmin Pan; Zihui Meng; Guoqing Pan; Börje Sellergren

    2015-01-01

    Intelligent stimuli-responsive molecularly imprinted polymers (SR-MIPs) have attracted considerable research interest in recent years due to the potential applications in drug delivery, biotechnology and separation sciences. This review comprehensively summarizes various SR-MIPs, including the design and applications of thermo-responsive MIPs, pH-responsive MIPs, photo-responsive MIPs, biomolecule-responsive MIPs and ion-responsive MIPs. Besides the development of current SR-MIPs, the advanta...

  8. Redox control of teratogenesis.

    Science.gov (United States)

    Hansen, Jason M; Harris, Craig

    2013-01-01

    A number of human teratogens elicit their deleterious effects through mechanisms involving the generation of reactive oxygen species (ROS) and oxidative stress. However, classic definitions of oxidative stress do not fully coincide with basic fundamental principles of teratology. Newer definitions of oxidative stress focus on the targeted redox modification of cysteine/thiol functional groups found in the regulatory domains of critical signaling pathway proteins, suggesting that the targeted disruption of signaling through specific redox couples may account for the specificity of teratogen-induced malformations which previously could not be rationalized. Here, we review examples of teratogens that induce ROS and oxidative injury, describe oxidative stress-related teratogenic mechanisms, and provide rationale for developmental periods of sensitivity and species susceptibility. Understanding how chemicals disrupt redox status, induce oxidative stress leading to dysmorphogenesis becomes important to identify potential teratogens and develop therapeutic interventions for attenuation of harmful chemical effects in utero following exposure.

  9. Direct observation of bis(dicarbollyl)nickel conformers in solution by fluorescence spectroscopy: an approach to redox-controlled metallacarborane molecular motors.

    Science.gov (United States)

    Safronov, Alexander V; Shlyakhtina, Natalia I; Everett, Thomas A; VanGordon, Monika R; Sevryugina, Yulia V; Jalisatgi, Satish S; Hawthorne, M Frederick

    2014-10-06

    As a continuation of work on metallacarborane-based molecular motors, the structures of substituted bis(dicarbollyl)nickel complexes in Ni(III) and Ni(IV) oxidation states were investigated in solution by fluorescence spectroscopy. Symmetrically positioned cage-linked pyrene molecules served as fluorescent probes to enable the observation of mixed meso-trans/dl-gauche (pyrene monomer fluorescence) and dl-cis/dl-gauche (intramolecular pyrene excimer fluorescence with residual monomer fluorescence) cage conformations of the nickelacarboranes in the Ni(III) and Ni(IV) oxidation states, respectively. The absence of energetically disfavored conformers in solution--dl-cis in the case of nickel(III) complexes and meso-trans in the case of nickel(IV)--was demonstrated based on spectroscopic data and conformer energy calculations in solution. The conformational persistence observed in solution indicates that bis(dicarbollyl)nickel complexes may provide attractive templates for building electrically driven and/or photodriven molecular motors.

  10. Redox interplay between mitochondria and peroxisomes

    Directory of Open Access Journals (Sweden)

    Celien eLismont

    2015-05-01

    Full Text Available Reduction-oxidation or ‘redox’ reactions are an integral part of a broad range of cellular processes such as gene expression, energy metabolism, protein import and folding, and autophagy. As many of these processes are intimately linked with cell fate decisions, transient or chronic changes in cellular redox equilibrium are likely to contribute to the initiation and progression of a plethora of human diseases. Since a long time, it is known that mitochondria are major players in redox regulation and signaling. More recently, it has become clear that also peroxisomes have the capacity to impact redox-linked physiological processes. To serve this function, peroxisomes cooperate with other organelles, including mitochondria. This review provides a comprehensive picture of what is currently known about the redox interplay between mitochondria and peroxisomes in mammals. We first outline the pro- and antioxidant systems of both organelles and how they may function as redox signaling nodes. Next, we critically review and discuss emerging evidence that peroxisomes and mitochondria share an intricate redox-sensitive relationship and cooperate in cell fate decisions. Key issues include possible physiological roles, messengers, and mechanisms. We also provide examples of how data mining of publicly-available datasets from ‘omics’ technologies can be a powerful means to gain additional insights into potential redox signaling pathways between peroxisomes and mitochondria. Finally, we highlight the need for more studies that seek to clarify the mechanisms of how mitochondria may act as dynamic receivers, integrators, and transmitters of peroxisome-derived mediators of oxidative stress. The outcome of such studies may open up exciting new avenues for the community of researchers working on cellular responses to organelle-derived oxidative stress, a research field in which the role of peroxisomes is currently highly underestimated and an issue of

  11. Redox regulation of transient receptor potential channels.

    OpenAIRE

    2014-01-01

    Abstract Significance: Environmental and endogenous reactive species such as reactive oxygen species (ROS), reactive nitrogen species (RNS), and other electrophiles are not only known to exert toxic effects on organisms, but are also emerging as molecules that mediate cell signaling responses. However, the mechanisms underlying this cellular redox signaling by reactive species remains largely uncharacterized.

  12. Redox homeostasis: The Golden Mean of healthy living.

    Science.gov (United States)

    Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

    2016-08-01

    The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve "reactive oxygen species" rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary

  13. Redox homeostasis: The Golden Mean of healthy living

    Directory of Open Access Journals (Sweden)

    Fulvio Ursini

    2016-08-01

    Full Text Available The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve “reactive oxygen species” rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles

  14. Multi-stimuli-responsive organometallic gels based on ferrocene-linked poly(aryl ether) dendrons: reversible redox switching and Pb2+-ion sensing.

    Science.gov (United States)

    Lakshmi, Neelakandan Vidhya; Mandal, Dipendu; Ghosh, Sundargopal; Prasad, Edamana

    2014-07-14

    We describe the design, synthesis, and "stimuli-responsive" study of ferrocene-linked Fréchet-type [poly(aryl ether)]-dendron-based organometallic gels, in which the ferrocene moiety is attached to the dendron framework through an acyl hydrazone linkage. The low-molecular-weight gelators (LMWGs) form robust gels in both polar and non-polar solvent/solvent mixtures. The organometallic gels undergo stimuli-responsive behavior through 1) thermal, 2) chemical, and 3) electrochemical methods. Among them, conditions 1 and 3 lead to seamlessly reversible with repeated cycles of identical efficiency. Results indicate that the flexible nature of the poly(aryl ether) dendron framework plays a key role in retaining the reversible electrochemical behavior of ferrocene moiety in the LMWGs. Further, the organometallic gelators have exhibited unique selectivity towards Pb(2+) ions (detection limit ≈10(-8)  M). The metal ion-sensing results in a gel-sol phase transition associated with a color change visible to the naked eye. Most importantly, decomplexing the metal ion from the system leads to the regeneration of the initial gel morphology, indicating the restoring ability of the organometallic gel. The metal-ligand binding nature has been analyzed by using (1)H NMR spectroscopy, mass spectrometry, and DFT calculations.

  15. Maximizing the dielectric response of molecular thin films via quantum chemical design.

    Science.gov (United States)

    Heitzer, Henry M; Marks, Tobin J; Ratner, Mark A

    2014-12-23

    Developing high-capacitance organic gate dielectrics is critical for advances in electronic circuitry based on unconventional semiconductors. While high-dielectric constant molecular substances are known, the mechanism of dielectric response and the fundamental chemical design principles are not well understood. Using a plane-wave density functional theory formalism, we show that it is possible to map the atomic-scale dielectric profiles of molecule-based materials while capturing important bulk characteristics. For molecular films, this approach reveals how basic materials properties such as surface coverage density, molecular tilt angle, and π-system planarity can dramatically influence dielectric response. Additionally, relatively modest molecular backbone and substituent variations can be employed to substantially enhance film dielectric response. For dense surface coverages and proper molecular alignment, conjugated hydrocarbon chains can achieve dielectric constants of >8.0, more than 3 times that of analogous saturated chains, ∼2.5. However, this conjugation-related dielectric enhancement depends on proper molecular orientation and planarization, with enhancements up to 60% for proper molecular alignment with the applied field and an additional 30% for conformations such as coplanarity in extended π-systems. Conjugation length is not the only determinant of dielectric response, and appended polarizable high-Z substituents can increase molecular film response more than 2-fold, affording estimated capacitances of >9.0 μF/cm2. However, in large π-systems, polar substituent effects are substantially attenuated.

  16. Molecular responses to moderate endurance exercise in skeletal muscle

    Science.gov (United States)

    This study examined alterations in skeletal-muscle growth and atrophy-related molecular events after a single bout of moderate-intensity endurance exercise. Muscle biopsies were obtained from 10 men (23 +/- 1 yr, body mass 80 +/- 2 kg, and VO(2peak) 45 +/- 1 ml x kg'¹ x min'¹) immediately (0 hr) and...

  17. Radical polymer-wrapped SWNTs at a molecular level: High-rate redox mediation through a percolation network for a transparent charge-storage material

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Wonsung; Nishide, Hiroyuki [Department of Applied Chemistry, Waseda University, Tokyo 169-8555 (Japan); Department of Nanobio Materials and Electronics (WCU), Gwangju Institute of Science and Technology(GIST), Gwangju 500-712 (Korea, Republic of); Ohtani, Shota; Oyaizu, Kenichi [Department of Applied Chemistry, Waseda University, Tokyo 169-8555 (Japan); Geckeler, Kurt E. [Department of Nanobio Materials and Electronics (WCU), Gwangju Institute of Science and Technology(GIST), Gwangju 500-712 (Korea, Republic of)

    2011-10-11

    A transparent nanocomposite of a radical polymer, the poly(2,2,6,6-tetramethylpiperidine-1-oxy-4-yl methacrylate) (PTMA), and single-walled carbon nanotubes (SWNTs) display a reversible charging and discharging, allowing for full discharging in seconds. This is ascribed to the reversible electrochemical reaction of the pendant radical group in PTMA aided by both PTMA wrapping at a molecular level and the SWNT network for electrical conduction. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  18. The Yin and Yang of redox regulation.

    Science.gov (United States)

    Olsen, Lars Folke; Issinger, Olaf-Georg; Guerra, Barbara

    2013-01-01

    Mammalian cells produce reactive oxygen and nitrogen species (ROS/RNOS) in response to an oxidative environment. Powerful antioxidant mechanisms have been developed in order to avoid oxidative stress by contributing to the maintenance of redox homeostasis. Traditionally, accumulation of ROS/RNOS is considered deleterious for cells as it can lead to loss of cellular function, aging, and cell death. Consequently, ROS/RNOS imbalance has been implicated in the etiology and/or progression of numerous pathologies such as cardiovascular diseases, inflammation, and cancer. An interesting concept that has emerged more recently is that not only have cells developed efficient systems to cope with ROS/RNOS accumulation but they have also learned to profit of them under certain circumstances. This notion is supported by data showing that ROS/RNOS can act as signaling molecules affecting the function and activity of a multiplicity of protein kinases and phosphatases controlling cellular homeostasis. This review does not provide an exhaustive overview of molecular mechanisms linked to ROS/RNOS generation and processing but includes relevant examples highlighting the dichotomic nature of these small molecules and the multitude of effects elicited by their accumulation. This aspect of ROS/RNOS ought to be taken into account particularly in novel therapeutic setups that aim to achieve high efficiency and minimal or no side effects.

  19. Determination of the in vivo redox potential using roGFP and fluorescence spectra obtained from one-wavelength excitation

    Science.gov (United States)

    Wierer, S.; Elgass, K.; Bieker, S.; Zentgraf, U.; Meixner, A. J.; Schleifenbaum, F.

    2011-02-01

    The analysis of molecular processes in living (plant) cells such as signal transduction, DNA replication, carbon metabolism and senescence has been revolutionized by the use of green fluorescent protein (GFP) and its variants as specific cellular markers. Many cell biological processes are accompanied by changes in the intracellular redox potential. To monitor the redox potential, a redox-sensitive mutant of GFP (roGFP) was created, which shows changes in its optical properties in response to changes in the redox state of its surrounding medium. For a quantitative analysis in living systems, it is essential to know the optical properties of roGFP in vitro. Therefore, we applied spectrally resolved fluorescence spectroscopy on purified roGFP exposed to different redox potentials to determine shifts in both the absorption and the emission spectra of roGFP. Based on these in vitro findings, we introduce a new approach using one-wavelength excitation to use roGFP for the in vivo analysis of cell biological processes. We demonstrate the ability this technique by investigating chloroplast-located Grx1-roGFP2 expressing Arabidopsis thaliana cells as example for dynamically moving intracellular compartments. This is not possible with the two-wavelength excitation technique established so far, which hampers a quantitative analysis of highly mobile samples due to the time delay between the two measurements and the consequential displacement of the investigated area.

  20. Mono-functionalized glycosylated platinum(IV) complexes possessed both pH and redox dual-responsive properties: Exhibited enhanced safety and preferentially accumulated in cancer cells in vitro and in vivo.

    Science.gov (United States)

    Ma, Jing; Yang, Xiande; Hao, Wenpei; Huang, Zhonglv; Wang, Xin; Wang, Peng George

    2017-03-10

    A serious of carbohydrate-conjugated platinum(IV) complexes in the form Pt(L2)(A2)(OH)R based on the clinical drug cisplatin and oxaliplatin were designed, synthesized and evaluated as antitumor agents in vitro and in vivo. The conjugates possessing both pH and redox dual-responsive properties exhibited more potent cytotoxicity in seven different human cancer cell lines and lower toxicity to the normal 3T3 cells than cisplatin, oxaliplatin and even the reported bis-functionalized glycosylated platinum(IV) complexes indicating the enhanced safety of the sugar conjugates. Cellular drug uptake and DNA platination were also superior to cisplatin, oxaliplatin and the reported bis-functionalized ones. Peak current of B7 and B8 with the scan rate of 200mv/s at the concentration of 0.08 mM was 5-fold higher at pH 6.4 than the pH 7.4, indicating that carbohydrate-conjugated mono-functionalized platinum(IV) complexes possessed both pH and redox dual-responsive properties in the cancer cells. The in vivo assays demonstrated that the Pt(IV) compounds could inhibit the growth of MCF-7 tumour and exert more safety than oxaliplatin. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Redox Flow Batteries, a Review

    Energy Technology Data Exchange (ETDEWEB)

    Knoxville, U. Tennessee; U. Texas Austin; U, McGill; Weber, Adam Z.; Mench, Matthew M.; Meyers, Jeremy P.; Ross, Philip N.; Gostick, Jeffrey T.; Liu, Qinghua

    2011-07-15

    Redox flow batteries are enjoying a renaissance due to their ability to store large amounts of electrical energy relatively cheaply and efficiently. In this review, we examine the components of redox flow batteries with a focus on understanding the underlying physical processes. The various transport and kinetic phenomena are discussed along with the most common redox couples.

  2. Molecular communications between plant heat shock responses and disease resistance.

    Science.gov (United States)

    Lee, Jae-Hoon; Yun, Hye Sup; Kwon, Chian

    2012-08-01

    As sessile, plants are continuously exposed to potential dangers including various abiotic stresses and pathogen attack. Although most studies focus on plant responses under an ideal condition to a specific stimulus, plants in nature must cope with a variety of stimuli at the same time. This indicates that it is critical for plants to fine-control distinct signaling pathways temporally and spatially for simultaneous and effective responses to various stresses. Global warming is currently a big issue threatening the future of humans. Reponses to high temperature affect many physiological processes in plants including growth and disease resistance, resulting in decrease of crop yield. Although plant heat stress and defense responses share important mediators such as calcium ions and heat shock proteins, it is thought that high temperature generally suppresses plant immunity. We therefore specifically discuss on interactions between plant heat and defense responses in this review hopefully for an integrated understanding of these responses in plants.

  3. Changes in phosphorylation of adenosine phosphate and redox state of nicotinamide-adenine dinucleotide (phosphate) in Geobacter sulfurreducens in response to electron acceptor and anode potential variation.

    Science.gov (United States)

    Rose, Nicholas D; Regan, John M

    2015-12-01

    Geobacter sulfurreducens is one of the dominant bacterial species found in biofilms growing on anodes in bioelectrochemical systems. The intracellular concentrations of reduced and oxidized forms of nicotinamide-adenine dinucleotide (NADH and NAD(+), respectively) and nicotinamide-adenine dinucleotide phosphate (NADPH and NADP(+), respectively) as well as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were measured in G. sulfurreducens using fumarate, Fe(III)-citrate, or anodes poised at different potentials (110, 10, -90, and -190 mV (vs. SHE)) as the electron acceptor. The ratios of CNADH/CNAD+ (0.088±0.022) and CNADPH/CNADP+ (0.268±0.098) were similar under all anode potentials tested and with Fe(III)-citrate (reduced extracellularly). Both ratios significantly increased with fumarate as the electron acceptor (0.331±0.094 for NAD and 1.96±0.37 for NADP). The adenylate energy charge (the fraction of phosphorylation in intracellular adenosine phosphates) was maintained near 0.47 under almost all conditions. Anode-growing biofilms demonstrated a significantly higher molar ratio of ATP/ADP relative to suspended cultures grown on fumarate or Fe(III)-citrate. These results provide evidence that the cellular location of reduction and not the redox potential of the electron acceptor controls the intracellular redox potential in G. sulfurreducens and that biofilm growth alters adenylate phosphorylation.

  4. Changes in phosphorylation of adenosine phosphate and redox state of nicotinamide-adenine dinucleotide (phosphate) in Geobacter sulfurreducens in response to electron acceptor and anode potential variation

    KAUST Repository

    Rose, Nicholas D.

    2015-12-01

    © 2015 Elsevier B.V. Geobacter sulfurreducens is one of the dominant bacterial species found in biofilms growing on anodes in bioelectrochemical systems. The intracellular concentrations of reduced and oxidized forms of nicotinamide-adenine dinucleotide (NADH and NAD+, respectively) and nicotinamide-adenine dinucleotide phosphate (NADPH and NADP+, respectively) as well as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were measured in G. sulfurreducens using fumarate, Fe(III)-citrate, or anodes poised at different potentials (110, 10, -90, and -190mV (vs. SHE)) as the electron acceptor. The ratios of CNADH/CNAD+ (0.088±0.022) and CNADPH/CNADP+ (0.268±0.098) were similar under all anode potentials tested and with Fe(III)-citrate (reduced extracellularly). Both ratios significantly increased with fumarate as the electron acceptor (0.331±0.094 for NAD and 1.96±0.37 for NADP). The adenylate energy charge (the fraction of phosphorylation in intracellular adenosine phosphates) was maintained near 0.47 under almost all conditions. Anode-growing biofilms demonstrated a significantly higher molar ratio of ATP/ADP relative to suspended cultures grown on fumarate or Fe(III)-citrate. These results provide evidence that the cellular location of reduction and not the redox potential of the electron acceptor controls the intracellular redox potential in G. sulfurreducens and that biofilm growth alters adenylate phosphorylation.

  5. Molecular targeted therapy in modern oncology: Imaging assessment of treatment response and toxicities

    Energy Technology Data Exchange (ETDEWEB)

    Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; DiPiro, Pamela J.; Jagannathan, Jyothi P.; Shinagare, Atul B. [Dept. of of Imaging, Dana Farber Cancer Institute, Boston (United States)

    2017-01-15

    Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities.

  6. Molecular Cloning and Characterization of Genes Involved in Cotton (Gossypium barbadense L.) Response to Verticillium dahliae

    Institute of Scientific and Technical Information of China (English)

    XU Li; ZHANG Xian-long; ZHU Long-fu; TU Li-li

    2008-01-01

    @@ Verticillium dahliae Kleb.is a necrotrophic plant pathogen which causes serious soil borne vascular disease in cotton.The molecular basis the defense response of cotton to this pathogen is poorly understood.

  7. Transcriptome analysis of molecular mechanisms responsible for light-stress response in Mythimna separata (Walker)

    Science.gov (United States)

    Duan, Yun; Gong, ZhongJun; Wu, RenHai; Miao, Jin; Jiang, YueLi; Li, Tong; Wu, XiaoBo; Wu, YuQing

    2017-01-01

    Light is an important environmental signal for most insects. The Oriental Armyworm, Mythimna separata, is a serious pest of cereal crops worldwide, and is highly sensitive to light signals during its developmental and reproductive stages. However, molecular biological studies of its response to light stress are scarce, and related genomic information is not available. In this study, we sequenced and de novo assembled the transcriptomes of M. separata exposed to four different light conditions: dark, white light (WL), UV light (UVL) and yellow light (YL). A total of 46,327 unigenes with an average size of 571 base pairs (bp) were obtained, among which 24,344 (52.55%) matched to public databases. The numbers of genes differentially expressed between dark vs WL, dark vs UVL, dark vs YL, and UVL vs YL were 12,012, 12,950, 14,855, and 13,504, respectively. These results suggest that light exposure altered gene expression patterns in M. separata. Putative genes involved in phototransduction-fly, phototransduction, circadian rhythm-fly, olfactory transduction, and taste transduction were identified. This study thus identified a series of candidate genes and pathways potentially related to light stress in M. separata. PMID:28345615

  8. Electronic control of gene expression and cell behaviour in Escherichia coli through redox signalling

    Science.gov (United States)

    Tschirhart, Tanya; Kim, Eunkyoung; McKay, Ryan; Ueda, Hana; Wu, Hsuan-Chen; Pottash, Alex Eli; Zargar, Amin; Negrete, Alejandro; Shiloach, Joseph; Payne, Gregory F.; Bentley, William E.

    2017-01-01

    The ability to interconvert information between electronic and ionic modalities has transformed our ability to record and actuate biological function. Synthetic biology offers the potential to expand communication `bandwidth' by using biomolecules and providing electrochemical access to redox-based cell signals and behaviours. While engineered cells have transmitted molecular information to electronic devices, the potential for bidirectional communication stands largely untapped. Here we present a simple electrogenetic device that uses redox biomolecules to carry electronic information to engineered bacterial cells in order to control transcription from a simple synthetic gene circuit. Electronic actuation of the native transcriptional regulator SoxR and transcription from the PsoxS promoter allows cell response that is quick, reversible and dependent on the amplitude and frequency of the imposed electronic signals. Further, induction of bacterial motility and population based cell-to-cell communication demonstrates the versatility of our approach and potential to drive intricate biological behaviours.

  9. Mediated Electron Transfer at Redox Active Monolayers

    Directory of Open Access Journals (Sweden)

    Michael E.G. Lyons

    2001-12-01

    Full Text Available A theoretical model describing the transport and kinetic processes involved in heterogeneous redox catalysis of solution phase reactants at electrode surfaces coated with redox active monolayers is presented. Although the analysis presented has quite general applicability, a specific focus of the paper is concerned with the idea that redox active monolayers can be used to model an ensemble of individual molecular nanoelectrodes. Three possible rate determining steps are considered: heterogeneous electron transfer between immobilized mediator and support electrode ; bimolecular chemical reaction between redox mediator and reactant species in the solution phase, and diffusional mass transport of reactant in solution. A general expression for the steady state reaction flux is derived which is valid for any degree of reversibility of both the heterogeneous electron transfer reaction involving immobilized mediator species and of the bimolecular cross exchange reaction between immobilized mediator and solution phase reactant. The influence of reactant transport in solution is also specifically considered. Simplified analytical expressions for the net reaction flux are derived for experimentally reasonable situations and a kinetic case diagram is constructed outlining the relationships between the various approximate solutions. The theory enables simple diagnostic plots to be constructed which can be used to analyse experimental data.

  10. Calculation of Dielectric Response in Molecular Solids for High Capacitance Organic Dielectrics

    Science.gov (United States)

    Heitzer, Henry Matthew

    The dielectric response of a material is critically important in numerous scientific processes spanning the fields of biology, chemistry, materials science, and physics. While important across these fundamental disciplines, it remains difficult to determine theoretically the dielectric environment of a system. With recent advances in nanotechnology, biochemistry, and molecular electronics, it has become necessary to determine the dielectric response in molecular systems that are difficult to measure experimentally, such as nanoscale interfaces, highly disordered biological environments, or molecular materials that are difficult to synthesize. In these scenarios it is highly advantageous to determine the dielectric response through efficient and accurate calculations. A good example of where a theoretical prediction of dielectric response is critical is in the development of high capacitance molecular dielectrics. Molecular dielectrics offer the promise of cheap, flexible, and mass producible electronic devices when used in conjunction with organic semiconducting materials to form Organic Field Effect Transistors (OFETs). To date, molecular dielectrics suffer from poor dielectric properties resulting in low capacitances. A low capacitance dielectric material requires a much larger power source to operate the device in OFETs, leading to modest device performance. Development of better performing dielectric materials has been hindered due to the time it takes to synthesize and fabricate new molecular materials. An accurate and efficient theoretical technique could drastically decrease this time by screening potential dielectric materials and providing design rules for future molecular dielectrics. Here in, the methodology used to calculate dielectric properties of molecular materials is described. The validity of the technique is demonstrated on model systems, capturing the frequency dependence of the dielectric response and achieving quantitative accuracy compared

  11. Time-course profiling of molecular stress responses to silver nanoparticles in the earthworm Eisenia fetida

    DEFF Research Database (Denmark)

    Hayashi, Yuya; Heckmann, Lars-Henrik; Simonsen, Vibeke

    2013-01-01

    The molecular mechanism of silver nanoparticle (AgNP) toxicity, particularly its temporal aspect, is currently limited in the literature. This study seeks to identify and profile changes in molecular response patterns over time during soil exposure of the earthworm Eisenia fetida to AgNPs (82±27 nm......) with reference to dissolved silver salt (AgNO3). Principal component analysis of selected gene and enzyme response profiles revealed dissimilar patterns between AgNO3 and AgNP treatments and also over time. Despite the observed difference in molecular profiles, the body burdens of total Ag were within the same...

  12. Redox-capacitor to connect electrochemistry to redox-biology.

    Science.gov (United States)

    Kim, Eunkyoung; Leverage, W Taylor; Liu, Yi; White, Ian M; Bentley, William E; Payne, Gregory F

    2014-01-07

    It is well-established that redox-reactions are integral to biology for energy harvesting (oxidative phosphorylation), immune defense (oxidative burst) and drug metabolism (phase I reactions), yet there is emerging evidence that redox may play broader roles in biology (e.g., redox signaling). A critical challenge is the need for tools that can probe biologically-relevant redox interactions simply, rapidly and without the need for a comprehensive suite of analytical methods. We propose that electrochemistry may provide such a tool. In this tutorial review, we describe recent studies with a redox-capacitor film that can serve as a bio-electrode interface that can accept, store and donate electrons from mediators commonly used in electrochemistry and also in biology. Specifically, we (i) describe the fabrication of this redox-capacitor from catechols and the polysaccharide chitosan, (ii) discuss the mechanistic basis for electron exchange, (iii) illustrate the properties of this redox-capacitor and its capabilities for promoting redox-communication between biology and electrodes, and (iv) suggest the potential for enlisting signal processing strategies to "extract" redox information. We believe these initial studies indicate broad possibilities for enlisting electrochemistry and signal processing to acquire "systems level" redox information from biology.

  13. Microfluidic redox battery.

    Science.gov (United States)

    Lee, Jin Wook; Goulet, Marc-Antoni; Kjeang, Erik

    2013-07-01

    A miniaturized microfluidic battery is proposed, which is the first membraneless redox battery demonstrated to date. This unique concept capitalizes on dual-pass flow-through porous electrodes combined with stratified, co-laminar flow to generate electrical power on-chip. The fluidic design is symmetric to allow for both charging and discharging operations in forward, reverse, and recirculation modes. The proof-of-concept device fabricated using low-cost materials integrated in a microfluidic chip is shown to produce competitive power levels when operated on a vanadium redox electrolyte. A complete charge/discharge cycle is performed to demonstrate its operation as a rechargeable battery, which is an important step towards providing sustainable power to lab-on-a-chip and microelectronic applications.

  14. Meristem Plant Cells as a Sustainable Source of Redox Actives for Skin Rejuvenation.

    Science.gov (United States)

    Korkina, Liudmila G; Mayer, Wolfgang; de Luca, Chiara

    2017-05-12

    Recently, aggressive advertisement claimed a "magic role" for plant stem cells in human skin rejuvenation. This review aims to shed light on the scientific background suggesting feasibility of using plant cells as a basis of anti-age cosmetics. When meristem cell cultures obtained from medicinal plants are exposed to appropriate elicitors/stressors (ultraviolet, ultrasound ultraviolet (UV), ultrasonic waves, microbial/insect metabolites, heavy metals, organic toxins, nutrient deprivation, etc.), a protective/adaptive response initiates the biosynthesis of secondary metabolites. Highly bioavailable and biocompatible to human cells, low-molecular weight plant secondary metabolites share structural/functional similarities with human non-protein regulatory hormones, neurotransmitters, pigments, polyamines, amino-/fatty acids. Their redox-regulated biosynthesis triggers in turn plant cell antioxidant and detoxification molecular mechanisms resembling human cell pathways. Easily isolated in relatively large quantities from contaminant-free cell cultures, plant metabolites target skin ageing mechanisms, above all redox imbalance. Perfect modulators of cutaneous oxidative state via direct/indirect antioxidant action, free radical scavenging, UV protection, and transition-metal chelation, they are ideal candidates to restore photochemical/redox/immune/metabolic barriers, gradually deteriorating in the ageing skin. The industrial production of plant meristem cell metabolites is toxicologically and ecologically sustainable for fully "biological" anti-age cosmetics.

  15. Modelling sulfamethoxazole degradation under different redox conditions

    Science.gov (United States)

    Sanchez-Vila, X.; Rodriguez-Escales, P.

    2015-12-01

    Sulfamethoxazole (SMX) is a low adsorptive, polar, sulfonamide antibiotic, widely present in aquatic environments. Degradation of SMX in subsurface porous media is spatially and temporally variable, depending on various environmental factors such as in situ redox potential, availability of nutrients, local soil characteristics, and temperature. It has been reported that SMX is better degraded under anoxic conditions and by co-metabolism processes. In this work, we first develop a conceptual model of degradation of SMX under different redox conditions (denitrification and iron reducing conditions), and second, we construct a mathematical model that allows reproducing different experiments of SMX degradation reported in the literature. The conceptual model focuses on the molecular behavior and contemplates the formation of different metabolites. The model was validated using the experimental data from Barbieri et al. (2012) and Mohatt et al. (2011). It adequately reproduces the reversible degradation of SMX under the presence of nitrite as an intermediate product of denitrification. In those experiments degradation was mediated by the transient formation of a diazonium cation, which was considered responsible of the substitution of the amine radical by a nitro radical, forming the 4-nitro-SMX. The formation of this metabolite is a reversible process, so that once the concentration of nitrite was back to zero due to further advancement of denitrification, the concentration of SMX was fully recovered. The forward reaction, formation of 4-nitro SMX, was modeled considering a kinetic of second order, whereas the backward reaction, dissociation of 4-nitro-SMX back to the original compound, could be modeled with a first order degradation reaction. Regarding the iron conditions, SMX was degraded due to the oxidation of iron (Fe2+), which was previously oxidized from goethite due to the degradation of a pool of labile organic carbon. As the oxidation of iron occurred on the

  16. Natural Variation of Molecular and Morphological Gibberellin Responses1[OPEN

    Science.gov (United States)

    Herman, Dorota; Kojima, Mikiko; Van Daele, Twiggy; Sakakibara, Hitoshi

    2017-01-01

    Although phytohormones such as gibberellins are essential for many conserved aspects of plant physiology and development, plants vary greatly in their responses to these regulatory compounds. Here, we use genetic perturbation of endogenous gibberellin levels to probe the extent of intraspecific variation in gibberellin responses in natural accessions of Arabidopsis (Arabidopsis thaliana). We find that these accessions vary greatly in their ability to buffer the effects of overexpression of GA20ox1, encoding a rate-limiting enzyme for gibberellin biosynthesis, with substantial differences in bioactive gibberellin concentrations as well as transcriptomes and growth trajectories. These findings demonstrate a surprising level of flexibility in the wiring of regulatory networks underlying hormone metabolism and signaling. PMID:27879393

  17. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chuan-Yaun

    2009-01-27

    Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  18. Molecular and biochemical responses of Volvox carteri to oxidative stress

    Science.gov (United States)

    Lingappa, U.; Rankin-Gee, E. K.; Lera, M.; Bebour, B.; Marcu, O.

    2014-03-01

    Understanding the intracellular response to environmental stresses is a key aspect to understanding the limits of habitability for life as we know it. A wide range of relevant stressors, from heat shock to radiation, result in the intracellular production of reactive oxygen species (ROS). ROS are used physiologically as signaling molecules to cause changes in gene expression and metabolism. However, ROS, including superoxide (O2-) and peroxides, are also highly reactive molecules that cause oxidative damage to proteins, lipids and DNA. Here we studied stress response in the multicellular, eukaryotic green alga Volvox carteri, after exposure to heat shock conditions. We show that the ROS response to heat stress is paralleled by changes in photosynthetic metabolism, antioxidant enzyme activity and gene expression, and fluctuations in the elemental composition of cells. Metabolism, as measured by pulse amplitude modulated (PAM) fluorometry over two hours of heat stress, showed a linear decrease in the photosynthetic efficiency of Volvox. ROS quantification uncovered an increase in ROS in the culture medium, paralleled by a decrease in ROS within the Volvox colonies, suggesting an export mechanism is utilized to mitigate stress. Enzyme kinetics indicated an increase in superoxide dismutase (SOD) activity over the heat stress timecourse. Using X-ray fluorescence (XRF) at the Stanford Synchrotron Radiation Lightsource, we show that these changes coincide with cell-specific import/export and intracellular redistribution of transition elements and halides, suggesting that the cellular metallome is also engaged in mediating oxidative stress in Volvox.

  19. Redox alters yellow dragonflies into red.

    Science.gov (United States)

    Futahashi, Ryo; Kurita, Ryoji; Mano, Hiroaki; Fukatsu, Takema

    2012-07-31

    Body color change associated with sexual maturation--so-called nuptial coloration--is commonly found in diverse vertebrates and invertebrates, and plays important roles for their reproductive success. In some dragonflies, whereas females and young males are yellowish in color, aged males turn vivid red upon sexual maturation. The male-specific coloration plays pivotal roles in, for example, mating and territoriality, but molecular basis of the sex-related transition in body coloration of the dragonflies has been poorly understood. Here we demonstrate that yellow/red color changes in the dragonflies are regulated by redox states of epidermal ommochrome pigments. Ratios of reduced-form pigments to oxidized-form pigments were significantly higher in red mature males than yellow females and immature males. The ommochrome pigments extracted from the dragonflies changed color according to redox conditions in vitro: from red to yellow in the presence of oxidant and from yellow to red in the presence of reductant. By injecting the reductant solution into live insects, the yellow-to-red color change was experimentally reproduced in vivo in immature males and mature females. Discontinuous yellow/red mosaicism was observed in body coloration of gynandromorphic dragonflies, suggesting a cell-autonomous regulation over the redox states of the ommochrome pigments. Our finding extends the mechanical repertoire of pigment-based body color change in animals, and highlights an impressively simple molecular mechanism that regulates an ecologically important color trait.

  20. Acoustic response of cemented granular sedimentary rocks: molecular dynamics modeling.

    Science.gov (United States)

    García, Xavier; Medina, Ernesto

    2007-06-01

    The effect of cementation processes on the acoustical properties of sands is studied via molecular dynamics simulation methods. We propose numerical methods where the initial uncemented sand is built by simulating the settling process of sediments. Uncemented samples of different porosity are considered by emulating natural mechanical compaction of sediments due to overburden. Cementation is considered through a particle-based model that captures the underlying physics behind the process. In our simulations, we consider samples with different degrees of compaction and cementing materials with distinct elastic properties. The microstructure of cemented sands is taken into account while adding cement at specific locations within the pores, such as grain-to-grain contacts. Results show that the acoustical properties of cemented sands are strongly dependent on the amount of cement, its stiffness relative to the hosting medium, and its location within the pores. Simulation results are in good correspondence with available experimental data and compare favorably with some theoretical predictions for the sound velocity within a range of cement saturation, porosity, and confining pressure.

  1. Simulations of coherent nonlinear optical response of molecular vibronic dimers

    CERN Document Server

    Perlík, Václav

    2016-01-01

    We have implemented vibronic dynamics for simulations of the third order coherent response of electronic dimers. In the present communication we provide the full and detailed description of the dynamical model, recently used for simulations of chlorophyll-carotenoid dyads, terylene dimers, or hypericin. We allow for explicit vibronic level structure, by including selected vibrational modes into a "system". Bath dynamics include the Landau-Teller vibrational relaxation, electronic dephasing, and nonlinear vibronic (to bath) coupling. Simulations combine effects of transport and dephasing between vibronic levels. Transport is described by master equation within secular approximation, phase is accumulated in cumulants and its calculation follows the transport pathways during waiting time period.

  2. Marine molluscs in environmental monitoring. I. Cellular and molecular responses

    Science.gov (United States)

    Bresler, Vladimir; Abelson, Avigdor; Fishelson, Lev; Feldstein, Tamar; Rosenfeld, Michael; Mokady, Ofer

    2003-10-01

    levels of biological organization—the molecular and cellular level—the parameters measured may have the capacity not only for biomonitoring environmental quality, but also for early warning.

  3. Molecular signatures in response to Isoliquiritigenin in lymphoblastoid cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae-Eun; Hong, Eun-Jung; Nam, Hye-Young [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of); Hwang, Meeyul [Research Center for Biomedical Resource of Oriental Medicine, Daegu Haany University (Korea, Republic of); Kim, Ji-Hyun [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of); Han, Bok-Ghee, E-mail: bokghee@nih.go.kr [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of); Jeon, Jae-Pil, E-mail: jpjeon@cdc.go.kr [National Biobank of Korea, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention (Korea, Republic of)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer We identified the inhibitory effect of ISL on cell proliferation of LCLs. Black-Right-Pointing-Pointer We found ISL-induced genes and miRNAs through microarray approach. Black-Right-Pointing-Pointer ISL-treated LCLs represented gene expression changes in cell cycle and p53 pathway. Black-Right-Pointing-Pointer We revealed 12 putative mRNA-miRNA functional pairs associated with ISL effect. -- Abstract: Isoliquiritigenin (ISL) has been known to induce cell cycle arrest and apoptosis of various cancer cells. However, genetic factors regulating ISL effects remain unclear. The aim of this study was to identify the molecular signatures involved in ISL-induced cell death of EBV-transformed lymphoblastoid cell lines (LCLs) using microarray analyses. For gene expression and microRNA (miRNA) microarray experiments, each of 12 LCL strains was independently treated with ISL or DMSO as a vehicle control for a day prior to total RNA extraction. ISL treatment inhibited cell proliferation of LCLs in a dose-dependent manner. Microarray analysis showed that ISL-treated LCLs represented gene expression changes in cell cycle and p53 signaling pathway, having a potential as regulators in LCL survival and sensitivity to ISL-induced cytotoxicity. In addition, 36 miRNAs including five miRNAs with unknown functions were differentially expressed in ISL-treated LCLs. The integrative analysis of miRNA and gene expression profiles revealed 12 putative mRNA-miRNA functional pairs. Among them, miR-1207-5p and miR-575 were negatively correlated with p53 pathway- and cell cycle-associated genes, respectively. In conclusion, our study suggests that miRNAs play an important role in ISL-induced cytotoxicity in LCLs by targeting signaling pathways including p53 pathway and cell cycle.

  4. Molecular Control of Flowering in Response to Day Length in Rice (F)

    Institute of Scientific and Technical Information of China (English)

    Vittoria Brambilla; Fabio Fornara

    2013-01-01

    Flowering at the most appropriate times of the year requires careful monitoring of environmental conditions and correct integration of such information with an endogenous molecular network.Rice (Oryza sativa) is a facultative short day plant,and flowers quickly under short day lengths,as opposed to Arabidopsis thaliana whose flowering is accelerated by longer days.Despite these physiological differences,several genes controlling flowering in response to day length (or photoperiod) are conserved between rice and Arabidopsis,and the molecular mechanisms involved are similar.Inductive day lengths trigger expression of florigenic proteins in leaves that can move to the shoot apical meristem to induce reproductive development.As compared to Arabidopsis,rice also possesses unique factors that regulate expression of florigenic genes.Here,we discuss recent advances in understanding the molecular mechanisms involved in day length perception,production of florigenic signals,and molecular responses of the shoot apical meristem to florigenic proteins.

  5. Tuning of redox regulatory mechanisms, reactive oxygen species and redox homeostasis under salinity stress

    Directory of Open Access Journals (Sweden)

    Hossain eSazzad

    2016-05-01

    Full Text Available Soil salinity is a crucial environmental constraint which limits biomass production at many sites on a global scale. Saline growth conditions cause osmotic and ionic imbalances, oxidative stress and perturb metabolism, e.g. the photosynthetic electron flow. The plant ability to tolerate salinity is determined by multiple biochemical and physiological mechanisms protecting cell functions, in particular by regulating proper water relations and maintaining ion homeostasis. Redox homeostasis is a fundamental cell property. Its regulation includes control of reactive oxygen species (ROS generation, sensing deviation from and readjustment of the cellular redox state. All these redox related functions have been recognized as decisive factors in salinity acclimation and adaptation. This review focuses on the core response of plants to overcome the challenges of salinity stress through regulation of ROS generation and detoxification systems and to maintain redox homeostasis. Emphasis is given to the role of NADH oxidase (RBOH, alternative oxidase (AOX, the plastid terminal oxidase (PTOX and the malate valve with the malate dehydrogenase isoforms under salt stress. Overwhelming evidence assigns an essential auxiliary function of ROS and redox homeostasis to salinity acclimation of plants.

  6. Reciprocal Control of the Circadian Clock and Cellular Redox State - a Critical Appraisal.

    Science.gov (United States)

    Putker, Marrit; O'Neill, John Stuart

    2016-01-01

    Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation of redox-sensitive cysteines, many biological processes sense and respond to signals from the intracellular redox environment. Redox signals are therefore important regulators of cellular homeostasis. Recently, it has become apparent that the cellular redox state oscillates in vivo and in vitro, with a period of about one day (circadian). Circadian time-keeping allows cells and organisms to adapt their biology to resonate with the 24-hour cycle of day/night. The importance of this innate biological time-keeping is illustrated by the association of clock disruption with the early onset of several diseases (e.g. type II diabetes, stroke and several forms of cancer). Circadian regulation of cellular redox balance suggests potentially two distinct roles for redox signalling in relation to the cellular clock: one where it is regulated by the clock, and one where it regulates the clock. Here, we introduce the concepts of redox signalling and cellular timekeeping, and then critically appraise the evidence for the reciprocal regulation between cellular redox state and the circadian clock. We conclude there is a substantial body of evidence supporting circadian regulation of cellular redox state, but that it would be premature to conclude that the converse is also true. We therefore propose some approaches that might yield more insight into redox control of cellular timekeeping.

  7. Modulation of the matrix redox signaling by mitochondrial Ca(2.).

    Science.gov (United States)

    Santo-Domingo, Jaime; Wiederkehr, Andreas; De Marchi, Umberto

    2015-11-26

    Mitochondria sense, shape and integrate signals, and thus function as central players in cellular signal transduction. Ca(2+) waves and redox reactions are two such intracellular signals modulated by mitochondria. Mitochondrial Ca(2+) transport is of utmost physio-pathological relevance with a strong impact on metabolism and cell fate. Despite its importance, the molecular nature of the proteins involved in mitochondrial Ca(2+) transport has been revealed only recently. Mitochondrial Ca(2+) promotes energy metabolism through the activation of matrix dehydrogenases and down-stream stimulation of the respiratory chain. These changes also alter the mitochondrial NAD(P)H/NAD(P)(+) ratio, but at the same time will increase reactive oxygen species (ROS) production. Reducing equivalents and ROS are having opposite effects on the mitochondrial redox state, which are hard to dissect. With the recent development of genetically encoded mitochondrial-targeted redox-sensitive sensors, real-time monitoring of matrix thiol redox dynamics has become possible. The discoveries of the molecular nature of mitochondrial transporters of Ca(2+) combined with the utilization of the novel redox sensors is shedding light on the complex relation between mitochondrial Ca(2+) and redox signals and their impact on cell function. In this review, we describe mitochondrial Ca(2+) handling, focusing on a number of newly identified proteins involved in mitochondrial Ca(2+) uptake and release. We further discuss our recent findings, revealing how mitochondrial Ca(2+) influences the matrix redox state. As a result, mitochondrial Ca(2+) is able to modulate the many mitochondrial redox-regulated processes linked to normal physiology and disease.

  8. A two-component regulatory system in transcriptional control of photosystem stoichiometry: redox-dependent and sodium ion-dependent phosphoryl transfer from cyanobacterial histidine kinase Hik2 to response regulators Rre1 and RppA

    Directory of Open Access Journals (Sweden)

    Iskander Mohamed Ibrahim

    2016-02-01

    Full Text Available I hereby submit the above-titled manuscript for publication in Frontiers in Plant Science. The research reported is original and novel. No part of it is submitted for publication elsewhere.We report on regulation and interactions of a unique histidine sensor kinase, Hik2. Hik2 is found in all known cyanobacteria, but has no previously identified functional response regulator. Here we show that it transfers phosphate rapidly, in vitro, to two response regulators, termed Rre1 and RppA. Hik2 is of special importance in being indispensable to cyanobacteria, and in being the closest cyanobacterial homologue of the uniquely conserved Chloroplast Sensor Kinase (CSK, which couples photosynthetic electron transport to gene transcription. Hik2 function is so important that it has survived the transition from cyanobacterium to eukaryotic sub-cellular organelle. Hik2 is likely to be a redox sensor involved in adjustment of the stoichiometry of photosystems I and II of oxygenic photosynthesis. We show that Hik2 also responds to the specific presence of sodium ions. These regulatory controls and the bifurcated signal transduction pathway indicated by two response regulators lead to a proposal for integration of photosynthetic light-acclimation with response to salt stress.

  9. Alpha B-crystallin induction in skeletal muscle cells under redox imbalance is mediated by a JNK-dependent regulatory mechanism.

    Science.gov (United States)

    Fittipaldi, Simona; Mercatelli, Neri; Dimauro, Ivan; Jackson, Malcolm J; Paronetto, Maria Paola; Caporossi, Daniela

    2015-09-01

    The small heat shock protein α-B-crystallin (CRYAB) is critically involved in stress-related cellular processes such as differentiation, apoptosis, and redox homeostasis. The up-regulation of CRYAB plays a key role in the cytoprotective and antioxidant response, but the molecular pathway driving its expression in muscle cells during oxidative stress still remains unknown. Here we show that noncytotoxic exposure to sodium meta-arsenite (NaAsO2) inducing redox imbalance is able to increase the CRYAB content of C2C12 myoblasts in a transcription-dependent manner. Our in silico analysis revealed a genomic region upstream of the Cryab promoter containing two putative antioxidant-responsive elements motifs and one AP-1-like binding site. The redox-sensitive transcription factors Nrf2 and the AP-1 component c-Jun were found to be up-regulated in NaAsO2-treated cells, and we demonstrated a specific NaAsO2-mediated increase of c-Jun and Nrf2 binding activity to the genomic region identified, supporting their putative involvement in CRYAB regulation following a shift in redox balance. These changes also correlated with a specific phosphorylation of JNK and p38 MAPK kinases, the well-known molecular mediators of signaling pathways leading to the activation of these transcription factors. Pretreatment of C2C12 cells with the JNK inhibitor SP600125 induced a decrease in c-Jun and Nrf2 content and was able to counteract the NaAsO2-mediated increase in CRYAB expression. Thus these data show a direct role of JNK in CRYAB regulation under redox imbalance and also point to a previously unrecognized link between c-Jun and Nrf2 transcription factors and redox-induced CRYAB expression in muscle cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Redox mechanisms in hepatic chronic wound healing and fibrogenesis

    Directory of Open Access Journals (Sweden)

    Novo Erica

    2008-10-01

    Full Text Available Abstract Reactive oxygen species (ROS generated within cells or, more generally, in a tissue environment, may easily turn into a source of cell and tissue injury. Aerobic organisms have developed evolutionarily conserved mechanisms and strategies to carefully control the generation of ROS and other oxidative stress-related radical or non-radical reactive intermediates (that is, to maintain redox homeostasis, as well as to 'make use' of these molecules under physiological conditions as tools to modulate signal transduction, gene expression and cellular functional responses (that is, redox signalling. However, a derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, can play a significant role in the pathogenesis of major human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis. This review has been designed to first offer a critical introduction to current knowledge in the field of redox research in order to introduce readers to the complexity of redox signalling and redox homeostasis. This will include ready-to-use key information and concepts on ROS, free radicals and oxidative stress-related reactive intermediates and reactions, sources of ROS in mammalian cells and tissues, antioxidant defences, redox sensors and, more generally, the major principles of redox signalling and redox-dependent transcriptional regulation of mammalian cells. This information will serve as a basis of knowledge to introduce the role of ROS and other oxidative stress-related intermediates in contributing to essential events, such as the induction of cell death, the perpetuation of chronic inflammatory responses, fibrogenesis and much more, with a major focus on hepatic chronic wound healing and liver fibrogenesis.

  11. Molecular response functions for the polarizable continuum model physical basis and quantum mechanical formalism

    CERN Document Server

    Cammi, Roberto

    2013-01-01

    This Brief presents the main aspects of the response functions theory (RFT) for molecular solutes described within the framework of the Polarizable Continuum Model (PCM). PCM is a solvation model for a Quantum Mechanical molecular system in which the solvent is represented as a continuum distribution of matter. Particular attention is devoted to the description of the basic features of the PCM model, and to the problems characterizing the study of the response function theory for molecules in solution with respect to the analogous theory on isolated molecules.

  12. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Bjerrum, O W; Pallisgaard, N

    2008-01-01

    chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response....

  13. Gated supramolecular chemistry in hybrid mesoporous silica nanoarchitectures: controlled delivery and molecular transport in response to chemical, physical and biological stimuli.

    Science.gov (United States)

    Alberti, Sebastián; Soler-Illia, Galo J A A; Azzaroni, Omar

    2015-04-11

    This review presents and discusses recent advances in the emerging field of "gated nanochemistry", outlining the substantial progress made so far. The development of hybrid mesoporous silica with complex tailored pore nanoarchitectures bridges the gap between molecular materials and the requirements of nanodevices for controlled nanoscale chemistry. In the last decade, membranes, particles and thin film porous architectures have been designed, synthesized and selectively modified by molecular, polymeric, organometallic or biologically active groups. The exquisite manipulation of mesopore morphology and interconnection combined with molecular or supramolecular functionalities, and the intrinsic biological compatibility of silica have made these materials a potential platform for selective sensing and drug delivery. The wide répertoire of these hard-soft architectures permit us to envisage sophisticated intelligent nano-systems that respond to a variety of external stimuli such as pH, redox potential, molecule concentration, temperature, or light. Transduction of these stimuli into a predefined response implies exploiting spatial and physico-chemical effects such as charge distribution, steric constraints, equilibria displacements, or local changes in ionic concentration, just to name a few examples. As expected, this "positional mesochemistry" can be only attained through the concerted control of assembly, surface tailoring and, confinement conditions, thus giving birth to a new class of stimuli-responsive materials with modulable transport properties. As a guiding framework the emerging field of "gated nanochemistry" offers methodologies and tools for building up stimuli-sensitive porous architectures equipped with switchable entities whose transport properties can be triggered at will. The gated nanoscopic hybrid materials discussed here not only herald a new era in the integrative design of "smart" drug delivery systems, but also give the reader a perspective of

  14. Alternative Evaluation for the REDOX (202-S) Plutonium Loadout Hood

    Energy Technology Data Exchange (ETDEWEB)

    N. R. Kerr

    1999-09-20

    Located in the 200 Areas is the inactive 202-S Reduction Oxidation (REDOX) Facility, which is managed by the Bechtel Hanford, Inc. Surveillance/Maintenance and Transition project. This facility is contaminated from nuclear material processes related to nuclear material separation from Hanford Site facility operations. This alternative evaluation report describes the alternatives and selection criteria based on the necessary protective requirements to maintain the REDOX Plutonium Loadout Hood in a safe and stable condition awaiting a final waste response action.

  15. Bimetallic redox synergy in oxidative palladium catalysis.

    Science.gov (United States)

    Powers, David C; Ritter, Tobias

    2012-06-19

    Polynuclear transition metal complexes, which are embedded in the active sites of many metalloenzymes, are responsible for effecting a diverse array of oxidation reactions in nature. The range of chemical transformations remains unparalleled in the laboratory. With few noteworthy exceptions, chemists have primarily focused on mononuclear transition metal complexes in developing homogeneous catalysis. Our group is interested in the development of carbon-heteroatom bond-forming reactions, with a particular focus on identifying reactions that can be applied to the synthesis of complex molecules. In this context, we have hypothesized that bimetallic redox chemistry, in which two metals participate synergistically, may lower the activation barriers to redox transformations relevant to catalysis. In this Account, we discuss redox chemistry of binuclear Pd complexes and examine the role of binuclear intermediates in Pd-catalyzed oxidation reactions. Stoichiometric organometallic studies of the oxidation of binuclear Pd(II) complexes to binuclear Pd(III) complexes and subsequent C-X reductive elimination from the resulting binuclear Pd(III) complexes have confirmed the viability of C-X bond-forming reactions mediated by binuclear Pd(III) complexes. Metal-metal bond formation, which proceeds concurrently with oxidation of binuclear Pd(II) complexes, can lower the activation barrier for oxidation. We also discuss experimental and theoretical work that suggests that C-X reductive elimination is also facilitated by redox cooperation of both metals during reductive elimination. The effect of ligand modification on the structure and reactivity of binuclear Pd(III) complexes will be presented in light of the impact that ligand structure can exert on the structure and reactivity of binuclear Pd(III) complexes. Historically, oxidation reactions similar to those discussed here have been proposed to proceed via mononuclear Pd(IV) intermediates, and the hypothesis of mononuclear Pd

  16. Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-06-01

    Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

  17. Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.

    Science.gov (United States)

    Del Rio, M; Mollevi, C; Bibeau, F; Vie, N; Selves, J; Emile, J-F; Roger, P; Gongora, C; Robert, J; Tubiana-Mathieu, N; Ychou, M; Martineau, P

    2017-05-01

    Currently, metastatic colorectal cancer is treated as a homogeneous disease and only RAS mutational status has been approved as a negative predictive factor in patients treated with cetuximab. The aim of this study was to evaluate if recently identified molecular subtypes of colon cancer are associated with response of metastatic patients to first-line therapy. We collected and analysed 143 samples of human colorectal tumours with complete clinical annotations, including the response to treatment. Gene expression profiling was used to classify patients in three to six classes using four different molecular classifications. Correlations between molecular subtypes, response to treatment, progression-free and overall survival were analysed. We first demonstrated that the four previously described molecular classifications of colorectal cancer defined in non-metastatic patients also correctly classify stage IV patients. One of the classifications is strongly associated with response to FOLFIRI (P=0.003), but not to FOLFOX (P=0.911) and FOLFIRI + Bevacizumab (P=0.190). In particular, we identify a molecular subtype representing 28% of the patients that shows an exceptionally high response rate to FOLFIRI (87.5%). These patients have a two-fold longer overall survival (40.1 months) when treated with FOLFIRI, as first-line regimen, instead of FOLFOX (18.6 months). Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer and a strong impact of the first-line regimen on the overall survival of some patients. This however remains to be confirmed in a large prospective clinical trial. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Redox flow batteries: a review

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Adam Z. [Lawrence Berkeley National Laboratory (LBNL); Mench, Matthew M [ORNL; Meyers, Jeremy [University of Texas, Austin; Ross, Philip N. [Lawrence Berkeley National Laboratory (LBNL); Gostick, Jeffrey T. [McGill University, Montreal, Quebec; Liu, Qinghua [University of Tennessee, Knoxville (UTK)

    2011-01-01

    Redox flow batteries (RFBs) are enjoying a renaissance due to their ability to store large amounts of electrical energy relatively cheaply and efficiently. In this review, we examine the components of RFBs with a focus on understanding the underlying physical processes. The various transport and kinetic phenomena are discussed along with the most common redox couples.

  19. Direct electrochemistry of redox proteins.

    NARCIS (Netherlands)

    Heering, H.A.

    1995-01-01

    The goal of the project was to obtain more detailed insight in interactions between redox proteins and solid electrodes and the mechanisms of electron transfer. In addition to this, the influence of the protein environment on the redox properties of the active site and the possible influence of the

  20. Redox enzymes in the plant plasma membrane and their possible roles

    DEFF Research Database (Denmark)

    Berczi, A.; Møller, I.M.

    2000-01-01

    Purified plasma membrane (PM) vesicles from higher plants contain redox proteins with low-molecular-mass prosthetic groups such as flavins (both FMN and FAD), hemes, metals (Cu, Fe and Mn), thiol groups and possibly naphthoquinone (vitamin K-1), all of which are likely to participate in redox...

  1. Redox Regulation in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Parakh, Sonam; Spencer, Damian M.; Halloran, Mark A.; Soo, Kai Y.; Atkin, Julie D.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS. PMID:23533690

  2. Redox Regulation in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Sonam Parakh

    2013-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS.

  3. Redox regulation in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Parakh, Sonam; Spencer, Damian M; Halloran, Mark A; Soo, Kai Y; Atkin, Julie D

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS.

  4. X-ray voltabsorptometry on redox proteins

    Energy Technology Data Exchange (ETDEWEB)

    Ascone, Isabella [Dipartimento di Fisica, Universita di Roma ' La Sapienza' , P.le A. Moro 5, 00185 Rome (Italy) and LURE/CNRS Centre Universitaire Paris-Sud, bat. 209 D, B.P. 34, 91898 Orsay Cedex (France)]. E-mail: i.ascone@caspur.it; Zamponi, Silvia [Dipartimento di Scienze Chimiche, Universita di Camerino, Via S. Agostino 1, 62032 Camerino (Italy); Cognigni, Andrea [LURE/CNRS Centre Universitaire Paris-Sud, bat. 209 D, B.P. 34, 91898 Orsay Cedex (France); Marmocchi, Franco [Dipartimento di Biologia Molecolare, Cellulare e Animale, Universita di Camerino, Via Camerini, 1 Camerino (Italy); Marassi, Roberto [Dipartimento di Scienze Chimiche, Universita di Camerino, Via S. Agostino 1, 62032 Camerino (Italy)

    2005-04-15

    Biological X-ray absorption spectroscopy (BioXAS) is able to describe the metal environment in a metalloprotein and is sensitive to metal oxidation state. Coupling of BioXAS and electrochemistry permits the characterization of different oxidation states and avoids uncontrolled protein redox state changes due to X-ray beam irradiation. XAS spectroelectrochemistry requires electrochemical cells specifically designed to meet the requirements of both XAS measurements and electrochemical effectiveness in potential control. In this context, this paper describes a new cell tested with different types of working electrodes developed for BioXAS, in particular for in situ studies of redox proteins. The XAS electrochemical measurements of a relatively high-molecular-weight protein (Cu,Zn superoxide dismutase) for which it is difficult to observe direct electrochemistry have been achieved. New working electrodes, capable of fast and unmediated electron transfer, are described. The cell permits to isolate protein redox states and to measure X-ray absorption intensity during a potential scan (X-ray voltabsorptometry)

  5. DHEA attenuates PDGF-induced phenotypic proliferation of vascular smooth muscle A7r5 cells through redox regulation

    Energy Technology Data Exchange (ETDEWEB)

    Urata, Yoshishige; Goto, Shinji; Kawakatsu, Miho [Department of Biochemistry and Molecular Biology in Disease, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Medical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Yodoi, Junji [Department of Biological Responses, Institute for Viral Research, Graduate School of Medicine, Kyoto University, 53 Shogain, Kawahara-cho, Sakyo-ku, Kyoto 606-8397 (Japan); Eto, Masato [Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Akishita, Masahiro, E-mail: akishita-tky@umin.ac.jp [Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Kondo, Takahito [Department of Biochemistry and Molecular Biology in Disease, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Medical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2010-05-28

    It is known that dehydroepiandrosterone (DHEA) inhibits a phenotypic switch in vascular smooth muscle cells (VSMC) induced by platelet-derived growth factor (PDGF)-BB. However, the mechanism behind the effect of DHEA on VSMC is not clear. Previously we reported that low molecular weight-protein tyrosine phosphatase (LMW-PTP) dephosphorylates PDGF receptor (PDGFR)-{beta} via a redox-dependent mechanism involving glutathione (GSH)/glutaredoxin (GRX)1. Here we demonstrate that the redox regulation of PDGFR-{beta} is involved in the effect of DHEA on VSMC. DHEA suppressed the PDGF-BB-dependent phosphorylation of PDGFR-{beta}. As expected, DHEA increased the levels of GSH and GRX1, and the GSH/GRX1 system maintained the redox state of LMW-PTP. Down-regulation of the expression of LMW-PTP using siRNA restored the suppression of PDGFR-{beta}-phosphorylation by DHEA. A promoter analysis of GRX1 and {gamma}-glutamylcysteine synthetase ({gamma}-GCS), a rate-limiting enzyme of GSH synthesis, showed that DHEA up-regulated the transcriptional activity at the peroxisome proliferator-activated receptor (PPAR) response element, suggesting PPAR{alpha} plays a role in the induction of GRX1 and {gamma}-GCS expression by DHEA. In conclusion, the redox regulation of PDGFR-{beta} is involved in the suppressive effect of DHEA on VSMC proliferation through the up-regulation of GSH/GRX system.

  6. Donor/Acceptor Mixed Self-Assembled Monolayers for Realising a Multi-Redox-State Surface.

    Science.gov (United States)

    Casado-Montenegro, Javier; Marchante, Elena; Crivillers, Núria; Rovira, Concepció; Mas-Torrent, Marta

    2016-06-17

    Mixed molecular self-assembled monolayers (SAMs) on gold, based on two types of electroactive molecules, that is, electron-donor (ferrocene) and electron-acceptor (anthraquinone) molecules, are prepared as an approach to realise surfaces exhibiting multiple accessible redox states. The SAMs are investigated in different electrolyte media. The nature of these media has a strong impact on the types of redox processes that take place and on the redox potentials. Under optimised conditions, surfaces with three redox states are achieved. Such states are accessible in a relatively narrow potential window in which the SAMs on gold are stable. This communication elucidates the key challenges in fabricating bicomponent SAMs as electrochemical switches.

  7. Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion

    DEFF Research Database (Denmark)

    Santoni-Rugiu, Eric; Jelnes, Peter; Thorgeirsson, Snorri S

    2005-01-01

    Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injuries in order to restore the lost liver mass and ensure maintenance of the multiple liver functions. Major players in the regeneration process are mature residual cells...... cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment...... created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations...

  8. Molecular characterization of the submergence response of Arabidopsis thaliana ecotype Columbia

    DEFF Research Database (Denmark)

    Lee, S.C.; Mustroph, A.; Sasidaharan, R.

    2011-01-01

    A detailed description of the molecular response of Arabidopsis thaliana to submergence can aid the identification of genes that are critical to flooding survival. • Rosette-stage plants were fully submerged in complete darkness and shoot and root tissue was harvested separately after the O2...

  9. A discrete solvent reaction field model for calculating molecular linear response properties in solution

    NARCIS (Netherlands)

    Jensen, L; van Duijnen, PT; Snijders, JG

    2003-01-01

    A discrete solvent reaction field model for calculating frequency-dependent molecular linear response properties of molecules in solution is presented. The model combines a time-dependent density functional theory (QM) description of the solute molecule with a classical (MM) description of the discr

  10. Modeling of the Electro-Mechanical Response of Carbon Nanotubes: Molecular Dynamics and Transport Calculations

    Science.gov (United States)

    Svizhenko, Alexel; Anantram, M. P.; Maiti, Amitesh

    2003-01-01

    This paper presents viewgraphs on the modeling of the electromechanical response of carbon nanotubes, utilizing molecular dynamics and transport calculations. The topics include: 1) Simulations of the experiment; 2) Effect of diameter, length and temperature; and 3) Study of sp3 coordination-"The Table experiment".

  11. Dynamic molecular crystals with switchable physical properties.

    Science.gov (United States)

    Sato, Osamu

    2016-06-21

    The development of molecular materials whose physical properties can be controlled by external stimuli - such as light, electric field, temperature, and pressure - has recently attracted much attention owing to their potential applications in molecular devices. There are a number of ways to alter the physical properties of crystalline materials. These include the modulation of the spin and redox states of the crystal's components, or the incorporation within the crystalline lattice of tunable molecules that exhibit stimuli-induced changes in their molecular structure. A switching behaviour can also be induced by changing the molecular orientation of the crystal's components, even in cases where the overall molecular structure is not affected. Controlling intermolecular interactions within a molecular material is also an effective tool to modulate its physical properties. This Review discusses recent advances in the development of such stimuli-responsive, switchable crystalline compounds - referred to here as dynamic molecular crystals - and suggests how different approaches can serve to prepare functional materials.

  12. Redox therapy in neonatal sepsis: reasons, targets, strategy, and agents.

    Science.gov (United States)

    Bajčetić, Milica; Spasić, Snežana; Spasojević, Ivan

    2014-09-01

    Neonatal sepsis is one of the most fulminating conditions in neonatal intensive care units. Antipathogen and supportive care are administered routinely, but do not deliver satisfactory results. In addition, the efforts to treat neonatal sepsis with anti-inflammatory agents have generally shown to be futile. The accumulating data imply that intracellular redox changes intertwined into neonatal sepsis redox cycle represent the main cause of dysfunction of mitochondria and cells in neonatal sepsis. Our aim here is to support the new philosophy in neonatal sepsis treatment, which involves the integration of mechanisms that are responsible for cellular dysfunction and organ failure, the recognition of the most important targets, and the selection of safe agents that can stop the neonatal sepsis redox cycle by hitting the hot spots. Redox-active agents that could be beneficial for neonatal sepsis treatment according to these criteria include lactoferrin, interleukin 10, zinc and selenium supplements, ibuprofen, edaravone, and pentoxifylline.

  13. The roles of conditional disorder in redox proteins.

    Science.gov (United States)

    Reichmann, Dana; Jakob, Ursula

    2013-06-01

    Cells are constantly exposed to various oxidants, either generated endogenously due to metabolic activity or exogenously. One way that cells respond to oxidants is through the action of redox-regulated proteins. These proteins also play important roles in oxidant signaling and protein biogenesis events. The key sensors built into redox-regulated proteins are cysteines, which undergo reversible thiol oxidation in response to changes in the oxidation status of the cellular environment. In this review, we discuss three examples of redox-regulated proteins found in bacteria, mitochondria, and chloroplasts. These proteins use oxidation of their redox-sensitive cysteines to reversibly convert large structural domains into more disordered regions or vice versa. These massive structural rearrangements are directly implicated in the functions of these proteins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Modulation of the matrix redox signaling by mitochondrial Ca2+

    Institute of Scientific and Technical Information of China (English)

    Jaime; Santo-Domingo; Andreas; Wiederkehr; Umberto; De; Marchi

    2015-01-01

    Mitochondria sense,shape and integrate signals,and thus function as central players in cellular signal transduction. Ca2+ waves and redox reactions are two such intracellular signals modulated by mitochondria. Mitochondrial Ca2+ transport is of utmost physio-pathological relevance with a strong impact on metabolism and cell fate. Despite its importance,the molecular nature of the proteins involvedin mitochondrial Ca2+ transport has been revealed only recently. Mitochondrial Ca2+ promotes energy metabolism through the activation of matrix dehydrogenases and downstream stimulation of the respiratory chain. These changes also alter the mitochondrial NAD(P)H/NAD(P)+ ratio,but at the same time will increase reactive oxygen species(ROS) production. Reducing equivalents and ROS are having opposite effects on the mitochondrial redox state,which are hard to dissect. With the recent development of genetically encoded mitochondrial-targeted redoxsensitive sensors,real-time monitoring of matrix thiol redox dynamics has become possible. The discoveries of the molecular nature of mitochondrial transporters of Ca2+ combined with the utilization of the novel redox sensors is shedding light on the complex relation between mitochondrial Ca2+ and redox signals and their impact on cell function. In this review,we describe mitochondrial Ca2+ handling,focusing on a number of newly identified proteins involved in mitochondrial Ca2+ uptake and release. We further discuss our recent findings,revealing how mitochondrial Ca2+ influences the matrix redox state. As a result,mitochondrial Ca2+ is able to modulate the many mitochondrial redox-regulated processes linked to normal physiology and disease.

  15. Modulation of Chlamydomonas reinhardtii flagellar motility by redox poise

    Science.gov (United States)

    Wakabayashi, Ken-ichi; King, Stephen M.

    2006-01-01

    Redox-based regulatory systems are essential for many cellular activities. Chlamydomonas reinhardtii exhibits alterations in motile behavior in response to different light conditions (photokinesis). We hypothesized that photokinesis is signaled by variations in cytoplasmic redox poise resulting from changes in chloroplast activity. We found that this effect requires photosystem I, which generates reduced NADPH. We also observed that photokinetic changes in beat frequency and duration of the photophobic response could be obtained by altering oxidative/reductive stress. Analysis of reactivated cell models revealed that this redox poise effect is mediated through the outer dynein arms (ODAs). Although the global redox state of the thioredoxin-related ODA light chains LC3 and LC5 and the redox-sensitive Ca2+-binding subunit of the docking complex DC3 did not change upon light/dark transitions, we did observe significant alterations in their interactions with other flagellar components via mixed disulfides. These data indicate that redox poise directly affects ODAs and suggest that it may act in the control of flagellar motility. PMID:16754958

  16. Globin-based redox signaling.

    Science.gov (United States)

    De Henau, Sasha; Braeckman, Bart P

    2016-01-01

    In recent years, moderate levels of reactive oxygen species (ROS) have become recognized as signaling cues that participate at all levels of cellular organization. Globins, with their redox-active heme iron and ubiquitous presence, seem ideally suited to participate in ROS metabolism. Here we comment on our recent findings that show the participation of a globin, GLB-12, in a redox signaling pathway in Caenorhabditis elegans. We found that GLB-12 produces superoxide, a type of ROS, after which this is converted to what appears to be a hydrogen peroxide gradient over the plasma membrane by the activity of intracellular and extracellular superoxide dismutases. In the first part, we discuss in more detail the different regulatory mechanisms that increase the effectiveness of this redox signal. In the second part, we comment on how specific structural and biochemical properties allow this globin to perform redox reactions. Interestingly, these properties are also observed in 2 other C. elegans globins that appear to be involved in redox biology. We therefore hypothesize that globins involved in redox signaling display similar structural and biochemical characteristics and propose that a subgroup of globins can be added to the group of proteins that play a vital role in redox signaling.

  17. Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?

    Science.gov (United States)

    Toss, Angela; Venturelli, Marta; Peterle, Chiara; Piacentini, Federico; Cascinu, Stefano; Cortesi, Laura

    2017-01-04

    In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc.) significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.

  18. Antioxidant responses and cellular adjustments to oxidative stress

    Science.gov (United States)

    Espinosa-Diez, Cristina; Miguel, Verónica; Mennerich, Daniela; Kietzmann, Thomas; Sánchez-Pérez, Patricia; Cadenas, Susana; Lamas, Santiago

    2015-01-01

    Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases. PMID:26233704

  19. Antioxidant responses and cellular adjustments to oxidative stress.

    Science.gov (United States)

    Espinosa-Diez, Cristina; Miguel, Verónica; Mennerich, Daniela; Kietzmann, Thomas; Sánchez-Pérez, Patricia; Cadenas, Susana; Lamas, Santiago

    2015-12-01

    Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases.

  20. Non-equilibrium responses of PFPE lubricants with various atomistic/molecular architecture at elevated temperature

    Science.gov (United States)

    Chung, Pil Seung; Song, Wonyup; Biegler, Lorenz T.; Jhon, Myung S.

    2017-05-01

    During the operation of hard disk drive (HDD), the perfluoropolyether (PFPE) lubricant experiences elastic or viscous shear/elongation deformations, which affect the performance and reliability of the HDD. Therefore, the viscoelastic responses of PFPE could provide a finger print analysis in designing optimal molecular architecture of lubricants to control the tribological phenomena. In this paper, we examine the rheological responses of PFPEs including storage (elastic) and loss (viscous) moduli (G' and G″) by monitoring the time-dependent-stress-strain relationship via non-equilibrium molecular dynamics simulations. We analyzed the rheological responses by using Cox-Merz rule, and investigated the molecular structural and thermal effects on the solid-like and liquid-like behaviors of PFPEs. The temperature dependence of the endgroup agglomeration phenomena was examined, where the functional endgroups are decoupled as the temperature increases. By analyzing the relaxation processes, the molecular rheological studies will provide the optimal lubricant selection criteria to enhance the HDD performance and reliability for the heat-assisted magnetic recording applications.

  1. Non-equilibrium responses of PFPE lubricants with various atomistic/molecular architecture at elevated temperature

    Directory of Open Access Journals (Sweden)

    Pil Seung Chung

    2017-05-01

    Full Text Available During the operation of hard disk drive (HDD, the perfluoropolyether (PFPE lubricant experiences elastic or viscous shear/elongation deformations, which affect the performance and reliability of the HDD. Therefore, the viscoelastic responses of PFPE could provide a finger print analysis in designing optimal molecular architecture of lubricants to control the tribological phenomena. In this paper, we examine the rheological responses of PFPEs including storage (elastic and loss (viscous moduli (G′ and G″ by monitoring the time-dependent-stress-strain relationship via non-equilibrium molecular dynamics simulations. We analyzed the rheological responses by using Cox-Merz rule, and investigated the molecular structural and thermal effects on the solid-like and liquid-like behaviors of PFPEs. The temperature dependence of the endgroup agglomeration phenomena was examined, where the functional endgroups are decoupled as the temperature increases. By analyzing the relaxation processes, the molecular rheological studies will provide the optimal lubricant selection criteria to enhance the HDD performance and reliability for the heat-assisted magnetic recording applications.

  2. Metabolic and redox barriers in the skin exposed to drugs and xenobiotics.

    Science.gov (United States)

    Korkina, Liudmila

    2016-01-01

    Growing exposure of human skin to environmental and occupational hazards, to numerous skin care/beauty products, and to topical drugs led to a biomedical concern regarding sustainability of cutaneous chemical defence that is essential for protection against intoxication. Since skin is the largest extra-hepatic drug/xenobiotic metabolising organ where redox-dependent metabolic pathways prevail, in this review, publications on metabolic processes leading to redox imbalance (oxidative stress) and its autocrine/endocrine impact to cutaneous drug/xenobiotic metabolism were scrutinised. Chemical and photo-chemical skin barriers contain metabolic and redox compartments: their protective and homeostatic functions. The review will examine the striking similarity of adaptive responses to exogenous chemical/photo-chemical stressors and endogenous toxins in cutaneous metabolic and redox system; the role(s) of xenobiotics/drugs and phase II enzymes in the endogenous antioxidant defence and maintenance of redox balance; redox regulation of interactions between metabolic and inflammatory responses in skin cells; skin diseases sharing metabolic and redox problems (contact dermatitis, lupus erythematosus, and vitiligo) Due to exceptional the redox dependence of cutaneous metabolic pathways and interaction of redox active metabolites/exogenous antioxidants with drug/xenobiotic metabolism, metabolic tests of topical xenobiotics/drugs should be combined with appropriate redox analyses and performed on 3D human skin models.

  3. Regulating a benzodifuran single molecule redox switch via electrochemical gating and optimization of molecule/electrode coupling.

    Science.gov (United States)

    Li, Zhihai; Li, Hui; Chen, Songjie; Froehlich, Toni; Yi, Chenyi; Schönenberger, Christian; Calame, Michel; Decurtins, Silvio; Liu, Shi-Xia; Borguet, Eric

    2014-06-25

    We report a novel strategy for the regulation of charge transport through single molecule junctions via the combination of external stimuli of electrode potential, internal modulation of molecular structures, and optimization of anchoring groups. We have designed redox-active benzodifuran (BDF) compounds as functional electronic units to fabricate metal-molecule-metal (m-M-m) junction devices by scanning tunneling microscopy (STM) and mechanically controllable break junctions (MCBJ). The conductance of thiol-terminated BDF can be tuned by changing the electrode potentials showing clearly an off/on/off single molecule redox switching effect. To optimize the response, a BDF molecule tailored with carbodithioate (-CS2(-)) anchoring groups was synthesized. Our studies show that replacement of thiol by carbodithioate not only enhances the junction conductance but also substantially improves the switching effect by enhancing the on/off ratio from 2.5 to 8.

  4. Molecular mechanisms governing differential robustness of development and environmental responses in plants

    DEFF Research Database (Denmark)

    Lachowiec, Jennifer; Queitsch, Christine; Kliebenstein, Daniel James

    2016-01-01

    -level and molecular, that modulate robustness, and discusses their implications for the optimization of plant fitness. Robustness in living systems arises from the structure of genetic networks, the specific molecular functions of the underlying genes, and their interactions. This very same network responsible......-genome duplications, tandem gene duplication and hybridization are emerging as major regulators of robustness in development. Despite their obvious implications for plant evolution and plant breeding, the mechanistic underpinnings by which plants modulate precise levels of robustness, plasticity and evolvability...

  5. Towards a unifying theory for the first-, second-, and third-order molecular (non)linear optical response

    Science.gov (United States)

    Pérez-Moreno, Javier; Clays, Koen; Kuzyk, Mark G.

    2010-05-01

    We present a procedure for the modeling of the dispersion of the nonlinear optical response of complex molecular structures that is based strictly on the results from experimental characterization. We show how under some general conditions, the use of the Thomas-Kuhn sum-rules leads to a successful modeling of the nonlinear response of complex molecular structures.

  6. Molecular response properties from a Hermitian eigenvalue equation for a time-periodic Hamiltonian.

    Science.gov (United States)

    Pawłowski, Filip; Olsen, Jeppe; Jørgensen, Poul

    2015-03-21

    The time-dependent Schrödinger equation for a time-periodic perturbation is recasted into a Hermitian eigenvalue equation, where the quasi-energy is an eigenvalue and the time-periodic regular wave function an eigenstate. From this Hermitian eigenvalue equation, a rigorous and transparent formulation of response function theory is developed where (i) molecular properties are defined as derivatives of the quasi-energy with respect to perturbation strengths, (ii) the quasi-energy can be determined from the time-periodic regular wave function using a variational principle or via projection, and (iii) the parametrization of the unperturbed state can differ from the parametrization of the time evolution of this state. This development brings the definition of molecular properties and their determination on par for static and time-periodic perturbations and removes inaccuracies and inconsistencies of previous response function theory formulations. The development where the parametrization of the unperturbed state and its time evolution may differ also extends the range of the wave function models for which response functions can be determined. The simplicity and universality of the presented formulation is illustrated by applying it to the configuration interaction (CI) and the coupled cluster (CC) wave function models and by introducing a new model-the coupled cluster configuration interaction (CC-CI) model-where a coupled cluster exponential parametrization is used for the unperturbed state and a linear parametrization for its time evolution. For static perturbations, the CC-CI response functions are shown to be the analytical analogues of the static molecular properties obtained from finite field equation-of-motion coupled cluster (EOMCC) energy calculations. The structural similarities and differences between the CI, CC, and CC-CI response functions are also discussed with emphasis on linear versus non-linear parametrizations and the size-extensivity of the obtained

  7. Different response to neoadjuvant chemotherapy for different molecular subtypes in patients with locally advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Huafeng Kang; Zhijun Dai; Xiaobin Ma; Xing Bao; Shuai Lin; Hongbing Ma; Xiaoxu Liu; Xijing Wang

    2013-01-01

    Objective: The aim of this study was to evaluate the impact of different molecular subtypes defined by immunohistochemistry (IHC) staining on the response rate for patients with locally advanced breast cancer received neoadjuvant chemotherapy. Methods: One hundred and seven breast cancer patients admitted from 2007 to 2011 who received 4 cycles of docetaxel/epirubicin-combined (TE) neoadjuvant chemotherapy were retrospectively reviewed, the patients were classified into 4 subtypes: luminal A, luminal B, HER-2 and triple negative breast cancer (TNBC) according to different combination patterns of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor-2 (HER-2) expression defined by IHC method. The correlation between response rate and the molecular subtypes were analyzed. Results: The pathological complete response (PCR), clinical complete response (CCR), clinical partial response (CPR), and clinical stable disease (CSD) rate of whole group was 15.89% (17/107), 22.43% (24/107), 63.55% (68/107), 14.02% (15/107), respectively, and the overall response rate (ORR) was 85.98% (92/107). The PCR rate and ORR of luminal A, luminal B, HER-2 and TNBC subtypes was 4.76% and 73.81%; 16.67% and 83.33%;17.65% and 100.00%; 30.00% and 96.67%, respectively. The PCR and ORR rate of HER-2/TNBC subtypes was higher than that of luminal A/B subtypes (P = 0.019, P = 0.002, respectively). Conclusion: Different molecular subtypes display different response rate for patients with locally advanced breast cancer received neoadjuvant TE chemotherapy, HER-2/TNBC subtypes have a higher PCR and ORR rate than that of luminal A/B subtypes.

  8. Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation.

    Science.gov (United States)

    Tanaka, Leonardo Y; Laurindo, Francisco R M

    2017-01-18

    Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases.

  9. Redox Properties of Free Radicals.

    Science.gov (United States)

    Neta, P.

    1981-01-01

    Describes pulse radiolysis as a useful means in studing one-electron redox potentials. This method allows the production of radicals and the determination of their concentration and rates of reaction. (CS)

  10. Membrane development for vanadium redox flow batteries.

    Science.gov (United States)

    Schwenzer, Birgit; Zhang, Jianlu; Kim, Soowhan; Li, Liyu; Liu, Jun; Yang, Zhenguo

    2011-10-17

    Large-scale energy storage has become the main bottleneck for increasing the percentage of renewable energy in our electricity grids. Redox flow batteries are considered to be among the best options for electricity storage in the megawatt range and large demonstration systems have already been installed. Although the full technological potential of these systems has not been reached yet, currently the main problem hindering more widespread commercialization is the high cost of redox flow batteries. Nafion, as the preferred membrane material, is responsible for about 11% of the overall cost of a 1 MW/8 MWh system. Therefore, in recent years two main membrane related research threads have emerged: 1) chemical and physical modification of Nafion membranes to optimize their properties with regard to vanadium redox flow battery (VRFB) application; and 2) replacement of the Nafion membranes with different, less expensive materials. This review summarizes the underlying basic scientific issues associated with membrane use in VRFBs and presents an overview of membrane-related research approaches aimed at improving the efficiency of VRFBs and making the technology cost-competitive. Promising research strategies and materials are identified and suggestions are provided on how materials issues could be overcome.

  11. Bifunctional redox flow battery

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Y.H. [Research Institute of Chemical Defense, Beijing 100083 (China)], E-mail: wen_yuehua@126.com; Cheng, J. [Research Institute of Chemical Defense, Beijing 100083 (China); Beijing Science and Technology University, Beijing 100083 (China); Xun, Y. [Research Institute of Chemical Defense, Beijing 100083 (China); Ma, P.H. [Full Cell R and D Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023 (China); Yang, Y.S. [Research Institute of Chemical Defense, Beijing 100083 (China); Beijing Science and Technology University, Beijing 100083 (China)

    2008-08-20

    A new bifunctional redox flow battery (BRFB) system, V(III)/V(II)-L-cystine(O{sub 2}), was systematically investigated by using different separators. It is shown that during charge, water transfer is significantly restricted with increasing the concentration of HBr when the Nafion 115 cation exchange membrane is employed. The same result can be obtained when the gas diffusion layer (GDL) hot-pressed separator is used. The organic electro-synthesis is directly correlated with the crossover of vanadium. When employing the anion exchange membrane, the electro-synthesis efficiency is over 96% due to a minimal crossover of vanadium. When the GDL hot-pressed separator is applied, the crossover of vanadium and water transfer are noticeably prevented and the electro-synthesis efficiency of over 99% is obtained. Those impurities such as vanadium ions and bromine can be eliminated through the purification of organic electro-synthesized products. The purified product is identified to be L-cysteic acid by IR spectrum. The BRFB shows a favorable discharge performance at a current density of 20 mA cm{sup -2}. Best discharge performance is achieved by using the GDL hot-pressed separator. The coulombic efficiency of 87% and energy efficiency of about 58% can be obtained. The cause of major energy losses is mainly associated with the cross-contamination of anodic and cathodic active electrolytes.

  12. Globin-based redox signaling

    OpenAIRE

    De Henau, Sasha; Braeckman, Bart

    2016-01-01

    ABSTRACT In recent years, moderate levels of reactive oxygen species (ROS) have become recognized as signaling cues that participate at all levels of cellular organization. Globins, with their redox-active heme iron and ubiquitous presence, seem ideally suited to participate in ROS metabolism. Here we comment on our recent findings that show the participation of a globin, GLB-12, in a redox signaling pathway in Caenorhabditis elegans. We found that GLB-12 produces superoxide, a type of ROS, a...

  13. Transcriptional responses in Lactococcus lactis subsp. cremoris to the changes in oxygen and redox potential during milk acidification

    DEFF Research Database (Denmark)

    Larsen, Nadja; Werner, Birgit Brøsted; Jespersen, Lene

    2016-01-01

    genes were detected during aerobic reduction phase. Upregulated genes were implicated in lactose utilization, glycogen biosynthesis, amino sugar metabolism, oxidation-reduction, pyrimidine biosynthesis and DNA integration processes. Genes of purine nucleotide biosynthesis and genes encoding amino acid......, multidrug resistance and ion ABC transporters were mostly downregulated, while oligopeptide transporter genes were reduced during oxygen depletion and induced at minimum Eh7. Significance and Impact of the Study: Understanding of gene responses in starter cultures to the changes of oxidation-reduction state...

  14. Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches.

    Science.gov (United States)

    Denning, Denise; Roos, Wouter H

    2016-09-02

    The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a defined microenvironment has also garnered deep insight into the engineering mechanisms existing within the cell. This review presents recent experimental findings on the influence of several parameters of the extracellular environment on cell behavior and fate, such as substrate topography, stiffness, chemistry and charge. In addition, the use of synthetic environments to measure physical properties of the reconstituted cytoskeleton and their interaction with intracellular proteins such as molecular motors is discussed, which is relevant for understanding cell migration, division and structural integrity, as well as intracellular transport. Insight is provided regarding the next steps to be taken in this interdisciplinary field, in order to achieve the global aim of artificially directing cellular response.

  15. Real-Time Molecular Monitoring of Chemical Environment in ObligateAnaerobes during Oxygen Adaptive Response

    Energy Technology Data Exchange (ETDEWEB)

    Holman, Hoi-Ying N.; Wozei, Eleanor; Lin, Zhang; Comolli, Luis R.; Ball, David. A.; Borglin, Sharon; Fields, Matthew W.; Hazen, Terry C.; Downing, Kenneth H.

    2009-02-25

    Determining the transient chemical properties of the intracellular environment canelucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms which enable some obligate anaerobic bacteria to survive a sudden exposure to oxygen. Here we used high-resolution Fourier Transform Infrared (FTIR) spectromicroscopy to continuously follow cellular chemistry within living obligate anaerobes by monitoring hydrogen bonding in their cellular water. We observed a sequence of wellorchestrated molecular events that correspond to changes in cellular processes in those cells that survive, but only accumulation of radicals in those that do not. We thereby can interpret the adaptive response in terms of transient intracellular chemistry and link it to oxygen stress and survival. This ability to monitor chemical changes at the molecular level can yield important insights into a wide range of adaptive responses.

  16. Lengthening our perspective: morphological, cellular, and molecular responses to eccentric exercise.

    Science.gov (United States)

    Hyldahl, Robert D; Hubal, Monica J

    2014-02-01

    The response of skeletal muscle to unaccustomed eccentric exercise has been studied widely, yet it is incompletely understood. This review is intended to provide an up-to-date overview of our understanding of how skeletal muscle responds to eccentric actions, with particular emphasis on the underlying molecular and cellular mechanisms of damage and recovery. This review begins by addressing the question of whether eccentric actions result in physical damage to muscle fibers and/or connective tissue. We next review the symptomatic manifestations of eccentric exercise (i.e., indirect damage markers, such as delayed onset muscle soreness), with emphasis on their relatively poorly understood molecular underpinnings. We then highlight factors that potentially modify the muscle damage response following eccentric exercise. Finally, we explore the utility of using eccentric training to improve muscle function in populations of healthy and aging individuals, as well as those living with neuromuscular disorders. Copyright © 2013 Wiley Periodicals, Inc.

  17. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, T.S.; Pallisgaard, N.; Andersen, M.T.

    2008-01-01

    Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia...... chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response Udgivelsesdato: 2008/10...

  18. Redox regulation of protein damage in plasma

    Directory of Open Access Journals (Sweden)

    Helen R. Griffiths

    2014-01-01

    In this review, we focus on redox regulatory control of those enzymes and processes which control protein maturation during synthesis, produce reactive species, repair and remove damaged plasma proteins. We have highlighted the potential for alterations in the extracellular redox compartment to regulate intracellular redox state and, conversely, for intracellular oxidative stress to alter the cellular secretome and composition of extracellular vesicles. Through secreted, redox-active regulatory molecules, changes in redox state may be transmitted to distant sites.

  19. Molecular Origins of Higher Harmonics in Large-Amplitude Oscillatory Shear Flow: Shear Stress Response

    Science.gov (United States)

    Gilbert, Peter; Giacomin, A. Jeffrey; Schmalzer, Andrew; Bird, R. B.

    Recent work has focused on understanding the molecular origins of higher harmonics that arise in the shear stress response of polymeric liquids in large-amplitude oscillatory shear flow. These higher harmonics have been explained using only the orientation distribution of a dilute suspension of rigid dumbbells in a Newtonian fluid, which neglects molecular interactions and is the simplest relevant molecular model of polymer viscoelasticity [R.B. Bird et al., J Chem Phys, 140, 074904 (2014)]. We explore these molecular interactions by examining the Curtiss-Bird model, a kinetic molecular theory that accounts for restricted polymer motions arising when chains are concentrated [Fan and Bird, JNNFM, 15, 341 (1984)]. For concentrated systems, the chain motion transverse to the chain axis is more restricted than along the axis. This anisotropy is described by the link tension coefficient, ɛ, for which several special cases arise: ɛ =0 corresponds to reptation, ɛ > 1 1 8 8 to rod-climbing, 1 1 2 2 >= ɛ >= 3 3 4 4 to reasonable shear-thinning predictions in steady simple shear flow, and ɛ =1 to a dilute solution of chains. We examine the shapes of the shear stress versus shear rate loops for the special cases, ɛ = 0 , 1 0 , 1 8 , 3 3 8 8 8 , 3 3 8 8 , 1 , of the Curtiss-Bird model, and we compare these with those of rigid dumbbell and reptation model predictions.

  20. Molecular and hormonal responses and adaptation to resistance and protein nutrition in young and older men

    OpenAIRE

    Hulmi, Juha

    2009-01-01

    The aim of the present study was to investigate the mechanisms leading to muscle hypertrophy in humans by studying local muscle molecular and systemic hormonal responses to a single bout of heavy resistance exercise (RE) and to long-term resistance training (RT) with or without protein supplementation in a randomized controlled double-blinded design. In line with earlier studies, heavy RT for 21 weeks led to muscle hypertrophy and an increase in muscle strength in both young and older men. Wh...

  1. Redox regulation by reversible protein S-thiolation in bacteria.

    Science.gov (United States)

    Loi, Vu Van; Rossius, Martina; Antelmann, Haike

    2015-01-01

    Low molecular weight (LMW) thiols function as thiol-redox buffers to maintain the reduced state of the cytoplasm. The best studied LMW thiol is the tripeptide glutathione (GSH) present in all eukaryotes and Gram-negative bacteria. Firmicutes bacteria, including Bacillus and Staphylococcus species utilize the redox buffer bacillithiol (BSH) while Actinomycetes produce the related redox buffer mycothiol (MSH). In eukaryotes, proteins are post-translationally modified to S-glutathionylated proteins under conditions of oxidative stress. S-glutathionylation has emerged as major redox-regulatory mechanism in eukaryotes and protects active site cysteine residues against overoxidation to sulfonic acids. First studies identified S-glutathionylated proteins also in Gram-negative bacteria. Advances in mass spectrometry have further facilitated the identification of protein S-bacillithiolations and S-mycothiolation as BSH- and MSH-mixed protein disulfides formed under oxidative stress in Firmicutes and Actinomycetes, respectively. In Bacillus subtilis, protein S-bacillithiolation controls the activities of the redox-sensing OhrR repressor and the methionine synthase MetE in vivo. In Corynebacterium glutamicum, protein S-mycothiolation was more widespread and affected the functions of the maltodextrin phosphorylase MalP and thiol peroxidase (Tpx). In addition, novel bacilliredoxins (Brx) and mycoredoxins (Mrx1) were shown to function similar to glutaredoxins in the reduction of BSH- and MSH-mixed protein disulfides. Here we review the current knowledge about the functions of the bacterial thiol-redox buffers glutathione, bacillithiol, and mycothiol and the role of protein S-thiolation in redox regulation and thiol protection in model and pathogenic bacteria.

  2. Redox regulation by reversible protein S-thiolation in bacteria

    Directory of Open Access Journals (Sweden)

    Vu Van Loi

    2015-03-01

    Full Text Available Low molecular weight (LMW thiols function as thiol-redox buffers to maintain the reduced state of the cytoplasm. The best studied LMW thiol is the tripeptide glutathione (GSH present in all eukaryotes and Gram-negative bacteria. Firmicutes bacteria, including Bacillus and Staphylococcus species utilize the redox buffer bacillithiol (BSH while Actinomycetes produce the related redox buffer mycothiol (MSH. In eukaryotes, proteins are post-translationally modified to S-glutathionylated proteins under conditions of oxidative stress. S-glutathionylation has emerged as major redox-regulatory mechanism in eukaryotes and protects active site cysteine residues against overoxidation to sulfonic acids. First studies identified S-glutathionylated proteins also in Gram-negative bacteria. Advances in mass spectrometry have further facilitated the identification of protein S-bacillithiolations and S-mycothiolation as BSH- and MSH-mixed protein disulfides formed under oxidative stress in Firmicutes and Actinomycetes, respectively. In Bacillus subtilis, protein S-bacillithiolation controls the activities of the redox-sensing OhrR repressor and the methionine synthase MetE in vivo. In Corynebacterium glutamicum, protein S-mycothiolation was more widespread and affected the functions of the maltodextrin phosphorylase MalP and thiol peroxidase (Tpx. In addition, novel bacilliredoxins (Brx and mycoredoxins (Mrx1 were shown to function similar to glutaredoxins in the reduction of BSH- and MSH-mixed protein disulfides. Here we review the current knowledge about the functions of the bacterial thiol-redox buffers glutathione, bacillithiol and mycothiol and the role of protein S-thiolation in redox regulation and thiol protection in model and pathogenic bacteria.

  3. Folate receptor-specific, redox-responsive mesoporous silica nanoparticles for the simultaneous delivery of cisplatin and gemcitabine to treat cancer

    Science.gov (United States)

    Fink, Eric Douglas

    Nanoparticles are an innovative platform for cancer treatment that reduces systemic toxicity and allows for active targeting of tumor sites to enhance the therapeutic efficacy. Mesoporous silica nanoparticles (MSNs) have emerged as an attractive drug delivery system due to their high surface area, vast functionalization potential, and biocompatibility. The main goal of this project is to develop a target-specific stimuli-responsive MSN based drug delivery system for the simultaneous delivery of cisplatin and gemcitabine. Both drugs were chemically attached to the MSNs via stimuli-responsive linkers that respond to the high reducing environment and low pH characteristic of cancer cells. The MSN materials fabricated in this work were successfully synthesized and characterized with a wide variety of spectroscopic and microscopic techniques. The loading of cisplatin and gemcitabine and their release profile under high reducing conditions were determined using atomic absorption (AA) and UV-vis spectroscopy, respectively. In vitro toxicity studies were performed on human cervical cancer (HeLa) cells in the presence of different ratios of cisplatin/gemcitabine drugs to determine the best ratio to kill HeLa cells. Based on this data, MSN materials carrying individual drugs and the corresponding combinatorial nanoparticles were fabricated and their in vitro cytotoxicity evaluated in HeLa and pancreatic cancer cells (AsPC1 and BxPC-3). The next step in this project was to further modify with folic acid to enhance its targeting ability toward cancer cells overexpressing folate receptors.

  4. Electrochemistry of dithienylethenes and their application in electropolymer modified photo- and redox switchable surfaces.

    Science.gov (United States)

    Logtenberg, Hella; Browne, Wesley R

    2013-01-14

    Diarylethenes have proven to be versatile responsive components in many applications due to their photochromic properties. In recent years their potential use as redox switchable components has become increasingly apparent. Applying dithienylethenes as redox switchable components requires their immobilisation on conducting substrates and hence electropolymerisation is a promising, albeit, challenging approach to developing such systems. In this review the electrochemical properties of dithienylethenes will be discussed together with a consideration of mechanistic aspects of the switching processes observed followed by a review of recent efforts to develop dithienylethene based redox and photoswitchable redox polymers through electropolymerisation.

  5. The redox-sensing protein Rex, a transcriptional regulator of solventogenesis in Clostridium acetobutylicum.

    Science.gov (United States)

    Wietzke, Mandy; Bahl, Hubert

    2012-11-01

    Solventogenic clostridia are characterised by their biphasic fermentative metabolism, and the main final product n-butanol is of particular industrial interest because it can be used as a superior biofuel. During exponential growth, Clostridium acetobutylicum synthesises acetic and butyric acids which are accompanied by the formation of molecular hydrogen and carbon dioxide. During the stationary phase, the solvents acetone, butanol and ethanol are produced. However, the molecular mechanisms of this metabolic switch are largely unknown so far. In this study, in silico, in vitro and in vivo analyses were performed to elucidate the function of the CAC2713-encoded redox-sensing transcriptional repressor Rex and its role in the solventogenic shift of C. acetobutylicum ATCC 824. Electrophoretic mobility shift assays showed that Rex controls the expression of butanol biosynthetic genes as a response to the cellular NADH/NAD(+) ratio. Interestingly, the Rex-negative mutant C. acetobutylicum rex::int(95) produced high amounts of ethanol and butanol, while hydrogen and acetone production were significantly reduced. Both ethanol and butanol (but not acetone) formation started clearly earlier than in the wild type. In addition, the rex mutant showed a de-repression of the bifunctional aldehyde/alcohol dehydrogenase 2 encoded by the adhE2 gene (CAP0035) as demonstrated by increased adhE2 expression as well as high NADH-dependent alcohol dehydrogenase activities. The results presented here clearly indicated that Rex is involved in the redox-dependent solventogenic shift of C. acetobutylicum.

  6. Thioredoxin/Txnip: Redoxisome, As a Redox Switch for the Pathogenesis of Diseases

    Directory of Open Access Journals (Sweden)

    Eiji eYoshihara

    2014-01-01

    Full Text Available During the past few decades, it has been widely recognized that reducing-oxidizing (Redox responses occurring at the intra- and extra-cellular levels are one of most important biological phenomena and dysregulated redox responses are involved in the initiation and progression of multiple diseases. Thioredoxin 1 (Trx1 and Thioredoxin 2 (Trx2, mainly located in the cytoplasm and mitochondria, respectively, are ubiquitously expressed in variety of cells and control cellular reactive oxygen species (ROS by reducing the disulfides into thiol groups. Thioredoxin interacting protein (Txnip/TBP-2/VDUP1 directly binds to Trx1 & Trx2 (Trx and inhibit the reducing activity of Trx through their disulfide exchange. Recent studies have revealed that Trx1 and Txnip are involved in some critical redox-dependent signal pathways including NLRP3 inflammasome activation in a redox-dependent manner. Therefore, Trx/Txnip, a redox-sensitive signaling complex is a regulator of cellular redox status and has emerged as a key component in the link between redox-regulation and the pathogenesis of diseases. Here, we review the novel functional concept of the redox-related protein complex, named Redoxisome, consisting of Trx/Txnip, as a critical regulator for intra- and extra-cellular redox signaling, involved in the pathogenesis of various diseases such as cancer, autoimmune disease, and diabetes.

  7. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Sebastian Weckbach

    2012-01-01

    Full Text Available Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group were anesthetized and exposed to chest trauma (ChT, closed head injury (CHI, or Tib/Fib fracture including a soft tissue trauma (Fx + STT or to the following combination of injuries: (1 ChT; (2 ChT + Fx + STT; (3 ChT + CHI; (4 CHI; (5 polytrauma (PT = ChT + CHI + Fx + STT. Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL fluid samples. Results. Polytraumatized (PT rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.

  8. Molecular mechanisms of the yeast adaptive response and tolerance to stresses encountered during ethanol fermentation.

    Science.gov (United States)

    Auesukaree, Choowong

    2017-08-01

    During ethanol fermentation, yeast cells encounter various stresses including sugar substrates-induced high osmolarity, increased ethanol concentration, oxygen metabolism-derived reactive oxygen species (ROS), and elevated temperature. To cope with these fermentation-associated stresses, appropriate adaptive responses are required to prevent stress-induced cellular dysfunctions and to acquire stress tolerances. This review will focus on the cellular effects of these stresses, molecular basis of the adaptive response to each stress, and the cellular mechanisms contributing to stress tolerance. Since a single stress can cause diverse effects, including specific and non-specific effects, both specific and general stress responses are needed for achieving comprehensive protection. For instance, the high-osmolarity glycerol (HOG) pathway and the Yap1/Skn7-mediated pathways are specifically involved in responses to osmotic and oxidative stresses, respectively. On the other hand, due to the common effect of these stresses on disturbing protein structures, the upregulation of heat shock proteins (HSPs) and trehalose is induced upon exposures to all of these stresses. A better understanding of molecular mechanisms underlying yeast tolerance to these fermentation-associated stresses is essential for improvement of yeast stress tolerance by genetic engineering approaches. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  9. Elucidation of the molecular responses to waterlogging in Jatropha roots by transcriptome profiling.

    Science.gov (United States)

    Juntawong, Piyada; Sirikhachornkit, Anchalee; Pimjan, Rachaneeporn; Sonthirod, Chutima; Sangsrakru, Duangjai; Yoocha, Thippawan; Tangphatsornruang, Sithichoke; Srinives, Peerasak

    2014-01-01

    Jatropha (Jatropha curcas) is a promising oil-seed crop for biodiesel production. However, the species is highly sensitive to waterlogging, which can result in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in Jatropha remain elusive. Here, the transcriptome adjustment of Jatropha roots to waterlogging was examined by high-throughput RNA-sequencing (RNA-seq). The results indicated that 24 h of waterlogging caused significant changes in mRNA abundance of 1968 genes. Comprehensive gene ontology and functional enrichment analysis of root transcriptome revealed that waterlogging promoted responses to hypoxia and anaerobic respiration. On the other hand, the stress inhibited carbohydrate synthesis, cell wall biogenesis, and growth. The results also highlighted the roles of ethylene, nitrate, and nitric oxide in waterlogging acclimation. In addition, transcriptome profiling identified 85 waterlogging-induced transcription factors including members of AP2/ERF, MYB, and WRKY families implying that reprogramming of gene expression is a vital mechanism for waterlogging acclimation. Comparative analysis of differentially regulated transcripts in response to waterlogging among Arabidopsis, gray poplar, Jatropha, and rice further revealed not only conserved but species-specific regulation. Our findings unraveled the molecular responses to waterlogging in Jatropha and provided new perspectives for developing a waterlogging tolerant cultivar in the future.

  10. Elucidation of the molecular responses to waterlogging in Jatropha roots by transcriptome profiling

    Directory of Open Access Journals (Sweden)

    Piyada eJuntawong

    2014-12-01

    Full Text Available Jatropha (Jatropha curcas is a promising oil-seed crop for biodiesel production. However, the species is highly sensitive to waterlogging, which can result in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in Jatropha remain elusive. Here, the transcriptome adjustment of Jatropha roots to waterlogging was examined by high-throughput RNA-sequencing (RNA-seq. The results indicated that 24 h of waterlogging caused significant changes in mRNA abundance of 1,968 genes. Comprehensive gene ontology and functional enrichment analysis of root transcriptome revealed that waterlogging promoted responses to hypoxia and anaerobic respiration. On the other hand, the stress inhibited carbohydrate synthesis, cell wall biogenesis, and growth. The results also highlighted the roles of ethylene, nitrate, and nitric oxide in waterlogging acclimation. In addition, transcriptome profiling identified 85 waterlogging-induced transcription factors including members of AP2/ERF, MYB, and WRKY families implying that reprogramming of gene expression is a vital mechanism for waterlogging acclimation. Comparative analysis of differentially regulated transcripts in response to waterlogging among Arabidopsis, gray poplar, Jatropha, and rice further revealed not only conserved but species-specific regulation. Our findings unraveled the molecular responses to waterlogging in Jatropha and provided new perspectives for developing a waterlogging tolerant cultivar in the future.

  11. Redox electrode materials for supercapatteries

    Science.gov (United States)

    Yu, Linpo; Chen, George Z.

    2016-09-01

    Redox electrode materials, including transition metal oxides and electronically conducting polymers, are capable of faradaic charge transfer reactions, and play important roles in most electrochemical energy storage devices, such as supercapacitor, battery and supercapattery. Batteries are often based on redox materials with low power capability and safety concerns in some cases. Supercapacitors, particularly those based on redox inactive materials, e.g. activated carbon, can offer high power output, but have relatively low energy capacity. Combining the merits of supercapacitor and battery into a hybrid, the supercapattery can possess energy as much as the battery and output a power almost as high as the supercapacitor. Redox electrode materials are essential in the supercapattery design. However, it is hard to utilise these materials easily because of their intrinsic characteristics, such as the low conductivity of metal oxides and the poor mechanical strength of conducting polymers. This article offers a brief introduction of redox electrode materials, the basics of supercapattery and its relationship with pseudocapacitors, and reviews selectively some recent progresses in the relevant research and development.

  12. Molecular signatures of transgenerational response to ocean acidification in a species of reef fish

    Science.gov (United States)

    Schunter, Celia; Welch, Megan J.; Ryu, Taewoo; Zhang, Huoming; Berumen, Michael L.; Nilsson, Göran E.; Munday, Philip L.; Ravasi, Timothy

    2016-11-01

    The impact of ocean acidification on marine ecosystems will depend on species capacity to adapt. Recent studies show that the behaviour of reef fishes is impaired at projected CO 2 levels; however, individual variation exists that might promote adaptation. Here, we show a clear signature of parental sensitivity to high CO 2 in the brain molecular phenotype of juvenile spiny damselfish, Acanthochromis polyacanthus, primarily driven by circadian rhythm genes. Offspring of CO 2-tolerant and CO 2-sensitive parents were reared at near-future CO 2 (754 μatm) or present-day control levels (414 μatm). By integrating 33 brain transcriptomes and proteomes with a de novo assembled genome we investigate the molecular responses of the fish brain to increased CO 2 and the expression of parental tolerance to high CO 2 in the offspring molecular phenotype. Exposure to high CO 2 resulted in differential regulation of 173 and 62 genes and 109 and 68 proteins in the tolerant and sensitive groups, respectively. Importantly, the majority of differences between offspring of tolerant and sensitive parents occurred in high CO 2 conditions. This transgenerational molecular signature suggests that individual variation in CO 2 sensitivity could facilitate adaptation of fish populations to ocean acidification.

  13. Molecular signatures of transgenerational response to ocean acidification in a species of reef fish

    KAUST Repository

    Schunter, Celia Marei

    2016-07-29

    The impact of ocean acidification on marine ecosystems will depend on species capacity to adapt. Recent studies show that the behaviour of reef fishes is impaired at projected CO levels; however, individual variation exists that might promote adaptation. Here, we show a clear signature of parental sensitivity to high CO in the brain molecular phenotype of juvenile spiny damselfish, Acanthochromis polyacanthus, primarily driven by circadian rhythm genes. Offspring of CO -tolerant and CO -sensitive parents were reared at near-future CO (754 μatm) or present-day control levels (414 μatm). By integrating 33 brain transcriptomes and proteomes with a de novo assembled genome we investigate the molecular responses of the fish brain to increased CO and the expression of parental tolerance to high CO in the offspring molecular phenotype. Exposure to high CO resulted in differential regulation of 173 and 62 genes and 109 and 68 proteins in the tolerant and sensitive groups, respectively. Importantly, the majority of differences between offspring of tolerant and sensitive parents occurred in high CO conditions. This transgenerational molecular signature suggests that individual variation in CO sensitivity could facilitate adaptation of fish populations to ocean acidification.

  14. Molecular Components of the Sporothrix schenckii Complex that Induce Immune Response.

    Science.gov (United States)

    Alba-Fierro, Carlos A; Pérez-Torres, Armando; Toriello, Conchita; Romo-Lozano, Yolanda; López-Romero, Everardo; Ruiz-Baca, Estela

    2016-08-01

    Sporotrichosis is a fungal disease caused by the Sporothrix schenckii complex that includes species such as S. brasiliensis, S. schenckii sensu stricto, S. globosa, S. luriei, S. mexicana, and S. pallida, which exhibit different potentially antigenic molecular components. The immune response of susceptible hosts to control infection and disease caused by these fungi has been little studied. Besides, the fungus-host interaction induces the activation of different types of immune response. This mini-review analyzes and discusses existing reports on the identification and functional characterization of molecules from species of the S. schenckii complex with clinical relevance, and the mechanisms that mediate the type and magnitude of the immune response in experimental models in vivo and in vitro. This knowledge is expected to contribute to the development of protective and therapeutic strategies against sporotrichosis and other mycoses.

  15. Why do we need three levels to understand the molecular optical response?

    Science.gov (United States)

    Perez-Moreno, Javier; Clays, Koen; Kuzyk, Mark G.

    2011-10-01

    Traditionally, the nonlinear optical response at the molecular level has been modeled using the two-level approximation, under the assumption that the behavior of the exact sum-over-states (SOS) expressions for the molecular polarizabilities is well represented by the contribution of only two levels. We show how, a rigorous application of the Thomas-Kuhn sum-rules over the SOS expression for the diagonal component of the first-hyperpolarziability proves that the two-level approximation is unphysical. In addition, we indicate how the contributions of potentially infinite number of states to the SOS expressions for the first-hyperpolarizability are well represented by the contributions of a generic three-level system. This explains why the analysis of the three-level model in conjugation with the sum rules has lead to successful paradigms for the optimization of organic chromophores.

  16. From protein-protein interaction to therapy response: Molecular imaging of heat shock proteins

    Energy Technology Data Exchange (ETDEWEB)

    Niu Gang [Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA 94305-5484 (United States); Chen Xiaoyuan [Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA 94305-5484 (United States)], E-mail: shawchen@stanford.edu

    2009-05-15

    HSP70 promoter-driven gene therapy and inhibition of HSP90 activity with small molecule inhibitors are two shining points in a newly developed cohort of cancer treatment. For HSP70 promoters, high efficiency and heat inducibility within a localized region make it very attractive to clinical translation. The HSP90 inhibitors exhibit a broad spectrum of anticancer activities due to the downstream effects of HSP90 inhibition, which interfere with a wide range of signaling processes that are crucial for the malignant properties of cancer cells. In this review article, we summarize exciting applications of newly emerged molecular imaging techniques as they relate to HSP, including protein-protein interactions of HSP90 complexes, therapeutic response of tumors to HSP90 inhibitors, and HSP70 promoters-controlled gene therapy. In the HSPs context, molecular imaging is expected to play a vital role in promoting drug development and advancing individualized medicine.

  17. Redox driven conductance changes for resistive memory

    Energy Technology Data Exchange (ETDEWEB)

    Shoute, Lian C.T.; McCreery, Richard L. [National Institute for Nanotechnology, Edmonton, Alberta (Canada); University of Alberta, Department of Chemistry, Edmonton, Alberta (Canada); Pekas, Nikola [National Institute for Nanotechnology, Edmonton, Alberta (Canada); Wu, Yiliang [Xerox Research Centre of Canada, Mississauga, Ontario (Canada)

    2011-03-15

    The relationship between bias-induced redox reactions and resistance switching is considered for memory devices containing TiO{sub 2} or a conducting polymer in ''molecular heterojunctions'' consisting of thin (2-25 nm) films of covalently bonded molecules, polymers, and oxides. Raman spectroscopy was used to monitor changes in the oxidation state of polythiophene in Au/P3HT/SiO{sub 2}/Au devices, and it was possible to directly determine the formation and stability of the conducting polaron state of P3HT by applied bias pulses [P3HT = poly(3-hexyl thiophene)]. Polaron formation was strongly dependent on junction composition, particularly on the interfaces between the polymer, oxide, and electrodes. In all cases, trace water was required for polaron formation, leading to the proposal that water reduction acts as a redox counter-reaction to polymer oxidation. Polaron stability was longest for the case of a direct contact between Au and SiO{sub 2}, implying that catalytic water reduction at the Au surface generated hydroxide ions which stabilized the cationic polaron. The spectroscopic information about the dependence of polaron stability on device composition will be useful for designing and monitoring resistive switching memory based on conducting polymers, with or without TiO{sub 2} present. (orig.)

  18. Redox driven conductance changes for resistive memory

    Science.gov (United States)

    Shoute, Lian C. T.; Pekas, Nikola; Wu, Yiliang; McCreery, Richard L.

    2011-03-01

    The relationship between bias-induced redox reactions and resistance switching is considered for memory devices containing TiO2 or a conducting polymer in "molecular heterojunctions" consisting of thin (2-25 nm) films of covalently bonded molecules, polymers, and oxides. Raman spectroscopy was used to monitor changes in the oxidation state of polythiophene in Au/P3HT/SiO2/Au devices, and it was possible to directly determine the formation and stability of the conducting polaron state of P3HT by applied bias pulses [P3HT = poly(3-hexyl thiophene)]. Polaron formation was strongly dependent on junction composition, particularly on the interfaces between the polymer, oxide, and electrodes. In all cases, trace water was required for polaron formation, leading to the proposal that water reduction acts as a redox counter-reaction to polymer oxidation. Polaron stability was longest for the case of a direct contact between Au and SiO2, implying that catalytic water reduction at the Au surface generated hydroxide ions which stabilized the cationic polaron. The spectroscopic information about the dependence of polaron stability on device composition will be useful for designing and monitoring resistive switching memory based on conducting polymers, with or without TiO2 present.

  19. Natural dietary anti-cancer chemopreventive compounds: redox-mediated differential signaling mechanisms in cytoprotection of normal cellsversus cytotoxicity in tumor cells

    Institute of Scientific and Technical Information of China (English)

    Sujit NAIR; Wenge LI; Ah-Ng Tony KONG

    2007-01-01

    Many dietary phytochemicals exhibit health-beneficial effects including preven-tion of diseases such as cancer, as well as neurological, cardiovascular, inflam-matory, and metabolic diseases. Evolutionarily, herbivorous and omnivorous animals have been ingesting plants. This interaction between "animal-plant"ecosystems has resulted in an elaborate system of detoxification and defense mechanisms evolved by animals including humans. Mammalian cells, including human cells, respond to these dietary phytochemicals by "non-classical receptor sensing" mechanisms of electrophilic chemical-stress typified by "thiol-modu-lated" cellular signaling events primarily leading to the gene expression of phar-macologically beneficial effects, but sometimes unwanted cytotoxicity also. Our laboratory has been studying two groups of dietary phytochemical cancer-chemopreventive compounds (isothiocyanates and polyphenols), which are effective in chemical-induced, as well as genetically-induced, animal carcinogen-esis models. These compounds typically generate "cellular stress" and modulate gene expression of phase Ⅱ detoxifying/antioxidant enzymes. Electrophiles, reac-tive oxygen species, and reactive nitrogen species are known to act as second messengers in the modulation of many cellular signaling pathways leading to gene expression changes and pharmacological responses. Redox-sensitive tran-scription factors such as nuclear factor-E2-related factor 2 (Nrf2), AP-1, NF-κB, to cite a few examples, sense and transduce changes in the cellular redox status and modulate gene expression responses to oxidative and electrophilic stresses, pre-sumably via sulfhydryl modification of critical cysteine residues found on these proteins and/or other upstream redox-sensitive molecular targets. In the current review, we will explore dietary cancer chemopreventive phytochemicals, discuss the link between oxidative/electrophilic stresses and the redox circuitry, and con-sider different redox

  20. Possible roles of transglutaminases in molecular mechanisms responsible for human neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Nicola Gaetano Gatta

    2016-11-01

    Full Text Available Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted/crosslinked adducts or –OH groups (to form ester linkages. In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological or pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s Disease, Parkinson’s Disease, supranuclear palsy, Huntington’s Disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This review describes the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.

  1. Cellular and molecular responses of E. fetida coelomocytes exposed to TiO{sub 2} nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Bigorgne, Emilie, E-mail: emilie.bigorgne@univ-lorraine.fr; Foucaud, Laurent [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France); Caillet, Celine [Universite de Lorraine-Laboratoire Environnement et Mineralurgie (LEM) CNRS UMR7569 (France); Giamberini, Laure; Nahmani, Johanne [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France); Thomas, Fabien [Universite de Lorraine-Laboratoire Environnement et Mineralurgie (LEM) CNRS UMR7569 (France); Rodius, Francois [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France)

    2012-07-15

    An in vitro approach using coelomocytes of Eisenia fetida was investigated to evaluate toxicity of TiO{sub 2} nanoparticles. Coelomocytes were exposed to well-dispersed suspension of small aggregates (130 nm) of TiO{sub 2} nanoparticles (1-25 {mu}g/ml) during 4, 12 and 24 h. Intracellular localisation suggested that the main route of uptake was endocytosis. Cellular responses showed that TiO{sub 2} nanoparticles were not cytotoxic and had no effect on phagocytosis at any of the four concentrations for each time tested. Concerning molecular responses, an increase of fetidin and metallothionein mRNA expression was observed starting from 4 h of exposure. In contrast, expression of coelomic cytolytic factor mRNA decreased for 10 and 25 {mu}g/ml after 4 h. Superoxide dismutase, catalase and glutathione-S-transferase expression were not modified suggesting that oxidative stress was not induced by TiO{sub 2} in our experimental conditions. This in vitro approach showed that TiO{sub 2} nanoparticles were taken up by coelomocytes and they could modify the molecular response of immune and detoxification system.

  2. A discrete solvent reaction field model for calculating molecular linear response properties in solution

    Science.gov (United States)

    Jensen, Lasse; van Duijnen, Piet Th.; Snijders, Jaap G.

    2003-08-01

    A discrete solvent reaction field model for calculating frequency-dependent molecular linear response properties of molecules in solution is presented. The model combines a time-dependent density functional theory (QM) description of the solute molecule with a classical (MM) description of the discrete solvent molecules. The classical solvent molecules are represented using distributed atomic charges and polarizabilities. All the atomic parameters have been chosen so as to describe molecular gas phase properties of the solvent molecule, i.e., the atomic charges reproduce the molecular dipole moment and the atomic polarizabilities reproduce the molecular polarizability tensor using a modified dipole interaction model. The QM/MM interactions are introduced into the Kohn-Sham equations and all interactions are solved self-consistently, thereby allowing for the solute to be polarized by the solvent. Furthermore, the inclusion of polarizabilities in the MM part allows for the solvent molecules to be polarized by the solute and by interactions with other solvent molecules. Initial applications of the model to calculate the vertical electronic excitation energies and frequency-dependent molecular polarizability of a water molecule in a cluster of 127 classical water molecules are presented. The effect of using different exchange correlation (xc)-potentials is investigated and the results are compared with results from wave function methods combined with a similar solvent model both at the correlated and uncorrelated level of theory. It is shown that accurate results in agreement with correlated wave function results can be obtained using xc-potentials with the correct asymptotic behavior.

  3. Redox Couples with Unequal Diffusion Coefficients: Effect on Redox Cycling

    NARCIS (Netherlands)

    Mampallil Augustine, Dileep; Mathwig, Klaus; Kang, Shuo; Lemay, Serge G.

    2013-01-01

    Redox cycling between two electrodes separated by a narrow gap allows dramatic amplification of the faradaic current. Unlike conventional electrochemistry at a single electrode, however, the mass-transport-limited current is controlled by the diffusion coefficient of both the reduced and oxidized fo

  4. Skeletal Muscle Remodeling in Response to Eccentric vs. Concentric Loading: Morphological, Molecular, and Metabolic Adaptations

    Science.gov (United States)

    Franchi, Martino V.; Reeves, Neil D.; Narici, Marco V.

    2017-01-01

    Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively); however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT) is assumed to produce greater hypertrophy than concentric resistance training (CON RT). Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood. Thus, the present review aims to, (a) critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b) clarify the molecular mechanisms that may regulate such adaptations. We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions. PMID:28725197

  5. Skeletal Muscle Remodeling in Response to Eccentric vs. Concentric Loading: Morphological, Molecular, and Metabolic Adaptations

    Directory of Open Access Journals (Sweden)

    Martino V. Franchi

    2017-07-01

    Full Text Available Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively; however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT is assumed to produce greater hypertrophy than concentric resistance training (CON RT. Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood.Thus, the present review aims to, (a critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b clarify the molecular mechanisms that may regulate such adaptations.We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions.

  6. Reversibly monitoring oxidation and reduction events in living biological systems: Recent development of redox-responsive reversible NIR biosensors and their applications in in vitro/in vivo fluorescence imaging.

    Science.gov (United States)

    Chu, Tian-Shu; Lü, Rui; Liu, Bai-Tong

    2016-12-15

    Reactive oxygen species (ROS) and changes in their redox cycles have great therapeutic potential for treating serious redox-related human diseases such as acute and chronic inflammation, diabetes, cancer and neurodegenerative disorders. This article presents a survey of the recently (2011-2016) developed NIR small-molecule biosensors for reversibly monitoring oxidation and reduction events in living cells and small animals through in vitro/in vivo fluorescence imaging. Emission and absorption profile, design strategy and fluorescence sensing mechanism, ROS selectivity and sensitivity, reversibility, ability of subcellular location and cytotoxicity are discussed for the NIR small-molecule biosensors capable of quantitatively, continuously and reversibly detecting transient ROS burst and redox changes at cellular level.

  7. Co-assembly of tetrapeptides into complex pH-responsive molecular hydrogel networks

    OpenAIRE

    Tena Solsona, Marta; Alonso de Castro, S.; Miravet Celades, Juan Felipe; Escuder Gil, Beatriu

    2014-01-01

    Here we prepare pH-responsive complex molecular hydrogels from oppositely charged tetrapeptidic components that can be pH-tuned resulting in interconversion between different networks. Two different systems are described based on tetrapeptides with an alternating sequence of non-polar (F) and polar (D or K) residues. Co-aggregated hydrogels are easily formed in situ at neutral pH whereas one-component networks are maintained after changing into acidic or basic pH. These systems have been appl...

  8. Molecular responses of plants to solar UV-B and UV-A radiation

    OpenAIRE

    Morales Suárez, Luis Orlando

    2014-01-01

    Plant responses to solar ultraviolet radiation (UV, 280-400 nm) were assessed at different molecular levels using Betula pendula Roth (silver birch) and Arabidopsis thaliana (Arabidopsis) as model species in outdoor experiments to assess the possibly interacting roles of the UV-B and UV-A wavebands in acclimation to sunlight. Solar UV-B (280-315 nm) and UV-A (315-400 nm) irradiance was attenuated with plastic films. Both solar UV-B and UV-A promoted the acclimation of silver birch and Arabido...

  9. Redox regulation of mammalian sperm capacitation

    Directory of Open Access Journals (Sweden)

    Cristian O′Flaherty

    2015-01-01

    Full Text Available Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P H for sperm capacitation. Peroxiredoxins (PRDXs are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility.

  10. Fusarium oxysporum f.sp. ciceri race 1 induced redox state alterations are coupled to downstream defense signaling in root tissues of chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Gupta, Sumanti; Bhar, Anirban; Chatterjee, Moniya; Das, Sampa

    2013-01-01

    Reactive oxygen species are known to play pivotal roles in pathogen perception, recognition and downstream defense signaling. But, how these redox alarms coordinate in planta into a defensive network is still intangible. Present study illustrates the role of Fusarium oxysporum f.sp ciceri Race1 (Foc1) induced redox responsive transcripts in regulating downstream defense signaling in chickpea. Confocal microscopic studies highlighted pathogen invasion and colonization accompanied by tissue damage and deposition of callose degraded products at the xylem vessels of infected roots of chickpea plants. Such depositions led to the clogging of xylem vessels in compatible hosts while the resistant plants were devoid of such obstructions. Lipid peroxidation assays also indicated fungal induced membrane injury. Cell shrinkage and gradual nuclear adpression appeared as interesting features marking fungal ingress. Quantitative real time polymerase chain reaction exhibited differential expression patterns of redox regulators, cellular transporters and transcription factors during Foc1 progression. Network analysis showed redox regulators, cellular transporters and transcription factors to coordinate into a well orchestrated defensive network with sugars acting as internal signal modulators. Respiratory burst oxidase homologue, cationic peroxidase, vacuolar sorting receptor, polyol transporter, sucrose synthase, and zinc finger domain containing transcription factor appeared as key molecular candidates controlling important hubs of the defense network. Functional characterization of these hub controllers may prove to be promising in understanding chickpea-Foc1 interaction and developing the case study as a model for looking into the complexities of wilt diseases of other important crop legumes.

  11. Fusarium oxysporum f.sp. ciceri race 1 induced redox state alterations are coupled to downstream defense signaling in root tissues of chickpea (Cicer arietinum L..

    Directory of Open Access Journals (Sweden)

    Sumanti Gupta

    Full Text Available Reactive oxygen species are known to play pivotal roles in pathogen perception, recognition and downstream defense signaling. But, how these redox alarms coordinate in planta into a defensive network is still intangible. Present study illustrates the role of Fusarium oxysporum f.sp ciceri Race1 (Foc1 induced redox responsive transcripts in regulating downstream defense signaling in chickpea. Confocal microscopic studies highlighted pathogen invasion and colonization accompanied by tissue damage and deposition of callose degraded products at the xylem vessels of infected roots of chickpea plants. Such depositions led to the clogging of xylem vessels in compatible hosts while the resistant plants were devoid of such obstructions. Lipid peroxidation assays also indicated fungal induced membrane injury. Cell shrinkage and gradual nuclear adpression appeared as interesting features marking fungal ingress. Quantitative real time polymerase chain reaction exhibited differential expression patterns of redox regulators, cellular transporters and transcription factors during Foc1 progression. Network analysis showed redox regulators, cellular transporters and transcription factors to coordinate into a well orchestrated defensive network with sugars acting as internal signal modulators. Respiratory burst oxidase homologue, cationic peroxidase, vacuolar sorting receptor, polyol transporter, sucrose synthase, and zinc finger domain containing transcription factor appeared as key molecular candidates controlling important hubs of the defense network. Functional characterization of these hub controllers may prove to be promising in understanding chickpea-Foc1 interaction and developing the case study as a model for looking into the complexities of wilt diseases of other important crop legumes.

  12. Redox Changes during the Legume-Rhizobium Symbiosis

    Institute of Scientific and Technical Information of China (English)

    Christine Chang; Isabelle Damiani; Alain Puppo; Pierre Frendol

    2009-01-01

    Reactive Oxygen Species (ROS) are continuously produced as a result of aerobic metabolism or in response to biotic and abiotic stresses.ROS are not only toxic by-products of aerobic metabolism,but are also signaling molecules involved in plant growth and environmental adaptation.Antioxidants can protect the cell from oxidative damage by scav-enging the ROS.Thus,they play an important role in optimizing cell function by regulating cellular redox state and mod-ifying gene expression.This article aims to review recent studies highlighting the role of redox signals in establishing and maintaining symbiosis between rhizobia and legumes.

  13. Nuclear Quantum Effects on Aqueous Electron Attachment and Redox Properties.

    Science.gov (United States)

    Rybkin, Vladimir V; VandeVondele, Joost

    2017-03-17

    Nuclear quantum effects (NQEs) on the reduction and oxidation properties of small aqueous species (CO2, HO2, and O2) are quantified and rationalized by first-principles molecular dynamics and thermodynamic integration. Vertical electron attachment, or electron affinity, and detachment energies (VEA and VDE) are strongly affected by NQEs, decreasing in absolute value by 0.3 eV going from a classical to a quantum description of the nuclei. The effect is attributed to NQEs that lessen the solvent response upon oxidation/reduction. The reduction of solvent reorganization energy is expected to be general for small solutes in water. In the thermodynamic integral that yields the free energy of oxidation/reduction, these large changes enter with opposite sign, and only a small net effect (0.1 eV) remains. This is not obvious for CO2, where the integrand is strongly influenced by NQEs due to the onset of interaction of the reduced orbital with the conduction band of the liquid during thermodynamic integration. We conclude that NQEs might not have to be included in the computation of redox potentials, unless high accuracy is needed, but are important for VEA and VDE calculations.

  14. [Experimental and clinical aspects of oxidative stress and redox regulation].

    Science.gov (United States)

    Nakamura, Hajime

    2003-02-01

    Although excess amounts of oxidative stress damage proteins and nucleotides, small amounts of oxidative stress transduce intracellular signals for cellular activation, differentiation and proliferation. Reduction/oxidation(redox) regulation is defined as a biological response to maintain homeostasis against oxidative stress. Thioredoxin, a 12 kD small protein with a redox-active dithiol/disulfide in the conserved active site: -Cys-Gly-Pro-Cys-, is a key molecule for redox regulation as well as glutathione(GSH). Thioredoxin is induced by a variety of oxidative stresses and secreted from cells. Thioredoxin plays crucial roles as a redox-regulator of intracellular signal transduction and as a radical scavenger. Plasma levels of thioredoxin are good biomarkers for oxidative stress. Thioredoxin-transgenic mice are more resistant to cerebral infarction, infection or inflammation and survive longer than control mice. Administration of thioredoxin may have a good potential for anti-aging and anti-stress effects. Redox regulation mechanisms by thioredoxin and other thioredoxin family members will clarify the pathophysiology of oxidative stress-associated disorders.

  15. A novel glucose/pH responsive low-molecular-weight organogel of easy recycling.

    Science.gov (United States)

    Zhou, Chaoyu; Gao, Wenxia; Yang, Kaiwen; Xu, Long; Ding, Jinchang; Chen, Jiuxi; Liu, Miaochang; Huang, Xiaobo; Wang, Shun; Wu, Huayue

    2013-11-05

    A new phenylboronic acid based gelator was developed to prepare low-molecular-weight organogel (LMOG), which could interact with several solvents to assemble into a three-dimensional nanofiber network. (1)H NMR spectroscopy study suggests that the driving force for the gelation includes hydrogen bonding and π-π stacking. Evaluated by UV-spectroscopy, the gel showed a prompt initial response to glucose at low concentration of 0.012 mmol/mL, which is a critical concentration of venous plasma glucose for diabetes. Significantly, this organogel exhibits excellent sensitivity to glucose among seven sugars tested (i.e., mannitol, galactose, lactose, maltose, sucrose, and fructose). The proposed formation of hydrogen-bonded complexes during the glucose sensing was supported by our energy calculation. Meanwhile, this organogel exhibits pH-response. Importantly, this LMOG could be conveniently recycled and thus be reused.

  16. Molecular mechanisms of Saccharomyces cerevisiae stress adaptation and programmed cell death in response to acetic acid

    Directory of Open Access Journals (Sweden)

    Sergio eGiannattasio

    2013-02-01

    Full Text Available Beyond its classical biotechnological applications such as food and beverage production or as a cell factory, the yeast Saccharomyces cerevisiae is a valuable model organism to study fundamental mechanisms of cell response to stressful environmental changes. Acetic acid is a physiological product of yeast fermentation and it is a well-known food preservative due to its antimicrobial action. Acetic acid has recently been shown to cause yeast cell death and aging. Here we shall focus on the molecular mechanisms of S. cerevisiae stress adaptation and programmed cell death in response to acetic acid. We shall elaborate on the intracellular signaling pathways involved in the cross-talk of pro-survival and pro-death pathways underlying the importance of understanding fundamental aspects of yeast cell homeostasis to improve the performance of a given yeast strain in biotechnological applications.

  17. Recovery of Cognitive Dysfunction via Orally Administered Redox-Polymer Nanotherapeutics in SAMP8 Mice.

    Directory of Open Access Journals (Sweden)

    Pennapa Chonpathompikunlert

    Full Text Available Excessively generated reactive oxygen species are associated with age-related neurodegenerative diseases. We investigated whether scavenging of reactive oxygen species in the brain by orally administered redox nanoparticles, prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals, facilitates the recovery of cognition in 17-week-old senescence-accelerated prone (SAMP8 mice. The redox polymer was delivered to the brain after oral administration of redox nanoparticles via a disintegration of the nanoparticles in the stomach and absorption of the redox polymer at small intestine to the blood. After treatment for one month, levels of oxidative stress in the brain of SAMP8 mice were remarkably reduced by treatment with redox nanoparticles, compared to that observed with low-molecular-weight nitroxide radicals, resulting in the amelioration of cognitive impairment with increased numbers of surviving neurons. Additionally, treatment by redox nanoparticles did not show any detectable toxicity. These findings indicate the potential of redox polymer nanotherapeutics for treatment of the neurodegenerative diseases.

  18. Constrained Molecular Dynamics Modeling of Dielectric Response in Polar Polyethylene Analogs and Poly(vinylidene flouride)

    Science.gov (United States)

    Calame, Jeffrey

    2013-03-01

    A simplified molecular dynamics formalism for polymers, having united atoms with constrained bond lengths and bond angles along the backbone but allowing torsional motion, has been developed to model the dielectric response and ferroelectricity in polymers with permanent dipoles. Analytic relations existing on the backbone geometry and associated dihedral motion allow elimination of many dot and cross product evaluations. Also, constraint error correcting forces, symplectic integration with velocity prediction, random force excitation with damping and a momentum-conserving thermostat, and rapid neighbor list and long range force computation allow efficient computation and time steps as large as 20 fs to enable the study of relatively long time scale dielectric phenomena. Studies are performed on non-polar polyethylene for benchmarking, followed by a model system (polar polyethylene) which retains the molecular structure, dihedral potentials, and non-bonded interactions of polyethylene, except artificial partial charges are placed on the united atoms. The modeling is extended to poly(vinylidene fluoride) by changes to the molecular structure, potentials, and charges. Heterogeneous systems containing crystalline and amorphous arrangements of polymer chains are studied. Work supported by the U.S. Office of Naval Research.

  19. Molecular characters of melon (Cucumismelo L. "Tacapa") in response to karst critical land

    Science.gov (United States)

    Rachmawati, Yuanita; Daryono, Budi Setiadi; Aristya, Ganies Riza

    2017-06-01

    Yogyakarta district has 158.600 ha critical land and spread off in three Agro Ecosystem zones. Two of them are karsts critical land. Critical lands which contain calcium carbonate in high concentration and water dehydration in upper surface give abiotic stress in wide range of plant. Melon cultivar TACAPA has superior characteristic derived from parental crossing, ♀ Action 434 and ♂ PI 371795 and potential to be developed in karsts critical land. Abscicic acid (ABA) is a phytohormone expressed by plant in abiotic stress condition. CmBG1 is a gene which regulate ABA hormone in melon. The purposes of this research were examining the molecular character of melon cultivar TACAPA in response to karsts critical land in order to study molecular characterization of CmBG1 gene. Analysis was done qualitatively by using Reverse Transcriptase-PCR (RT-PCR) and Electrophoresis, while quantitative analysis was conducted by observing absorbance score in spectrophotometer. CmBG1 gene expression is examined by using Real time PCR (qPCR). Molecular characters obtained are CmBG1 detected in size ±1258 bp, CmBG1 gene concentrations in melon which planted in control media are lower than melon in critical lands media. These results are similar with the real time quantitative analysis method. It also be revealed that melon TACAPA is more potential plant compared to another cultivar that can be developed in karst critical land area.

  20. Mitochondrially targeted fluorescent redox sensors.

    Science.gov (United States)

    Yang, Kylie; Kolanowski, Jacek L; New, Elizabeth J

    2017-04-06

    The balance of oxidants and antioxidants within the cell is crucial for maintaining health, and regulating physiological processes such as signalling. Consequently, imbalances between oxidants and antioxidants are now understood to lead to oxidative stress, a physiological feature that underlies many diseases. These processes have spurred the field of chemical biology to develop a plethora of sensors, both small-molecule and fluorescent protein-based, for the detection of specific oxidizing species and general redox balances within cells. The mitochondrion, in particular, is the site of many vital redox reactions. There is therefore a need to target redox sensors to this particular organelle. It has been well established that targeting mitochondria can be achieved by the use of a lipophilic cation-targeting group, or by utilizing natural peptidic mitochondrial localization sequences. Here, we review how these two approaches have been used by a number of researchers to develop mitochondrially localized fluorescent redox sensors that are already proving useful in providing insights into the roles of reactive oxygen species in the mitochondria.

  1. Methanol and ethanol modulate responses to danger- and microbe-associated molecular patterns

    Directory of Open Access Journals (Sweden)

    Claire T Hann

    2014-10-01

    Full Text Available Methanol is a byproduct of cell wall modification, released through the action of pectin methylesterases (PMEs, which demethylesterify cell wall pectins. Plant PMEs play not only a role in developmental processes but also in responses to herbivory and infection by fungal or bacterial pathogens. Molecular mechanisms that explain how methanol affects plant defenses are poorly understood. Here we show that exogenously supplied methanol alone has weak effects on defense signaling in three dicot species, however it profoundly alters signaling responses to danger- and microbe-associated molecular patterns (DAMPs, MAMPs such as the alarm hormone systemin, the bacterial flagellum-derived flg22 peptide, and the fungal cell wall-derived oligosaccharide chitosan. In the presence of methanol the kinetics and amplitudes of DAMP/MAMP-induced MAP kinase (MAPK activity and oxidative burst are altered in tobacco and tomato suspension-cultured cells, in Arabidopsis seedlings and tomato leaf tissue. As a possible consequence of altered DAMP/MAMP signaling, methanol suppressed the expression of the defense genes PR-1 and PI-1 in tomato. In cell cultures of the grass tall fescue (Festuca arundinacea, Poaceae, Monocots, methanol alone activates MAPKs and increases chitosan-induced MAPK activity, and in the darnel grass Lolium temulentum (Poaceae, it alters wound-induced MAPK signaling. We propose that methanol can be recognized by plants as a sign of the damaged self. In dicots, methanol functions as a DAMP-like alarm signal with little elicitor activity on its own, whereas it appears to function as an elicitor-active DAMP in monocot grasses. Ethanol had been implicated in plant stress responses, although the source of ethanol in plants is not well established. We found that it has a similar effect as methanol on responses to MAMPs and DAMPs.

  2. Proteomics reveals a core molecular response of Pseudomonas putida F1 to acute chromate challenge

    Directory of Open Access Journals (Sweden)

    McCarthy Andrea T

    2010-05-01

    Full Text Available Abstract Background Pseudomonas putida is a model organism for bioremediation because of its remarkable metabolic versatility, extensive biodegradative functions, and ubiquity in contaminated soil environments. To further the understanding of molecular pathways responding to the heavy metal chromium(VI [Cr(VI], the proteome of aerobically grown, Cr(VI-stressed P. putida strain F1 was characterized within the context of two disparate nutritional environments: rich (LB media and minimal (M9L media containing lactate as the sole carbon source. Results Growth studies demonstrated that F1 sensitivity to Cr(VI was impacted substantially by nutrient conditions, with a carbon-source-dependent hierarchy (lactate > glucose >> acetate observed in minimal media. Two-dimensional HPLC-MS/MS was employed to identify differential proteome profiles generated in response to 1 mM chromate under LB and M9L growth conditions. The immediate response to Cr(VI in LB-grown cells was up-regulation of proteins involved in inorganic ion transport, secondary metabolite biosynthesis and catabolism, and amino acid metabolism. By contrast, the chromate-responsive proteome derived under defined minimal growth conditions was characterized predominantly by up-regulated proteins related to cell envelope biogenesis, inorganic ion transport, and motility. TonB-dependent siderophore receptors involved in ferric iron acquisition and amino acid adenylation domains characterized up-regulated systems under LB-Cr(VI conditions, while DNA repair proteins and systems scavenging sulfur from alternative sources (e.g., aliphatic sulfonates tended to predominate the up-regulated proteome profile obtained under M9L-Cr(VI conditions. Conclusions Comparative analysis indicated that the core molecular response to chromate, irrespective of the nutritional conditions tested, comprised seven up-regulated proteins belonging to six different functional categories including transcription, inorganic ion

  3. Impact of Backbone Tether Length and Structure on the Electrochemical Performance of Viologen Redox Active Polymers

    Energy Technology Data Exchange (ETDEWEB)

    Burgess, Mark; Chénard, Etienne; Hernández-Burgos, Kenneth; Nagarjuna, Gavvalapalli; Assary, Rajeev S.; Hui, Jingshu; Moore, Jeffrey S.; Rodríguez-López, Joaquín

    2016-10-25

    The design of chemically stable and electrochemically reversible redox active polymers (RAPs) is of great interest for energy storage technologies. Particularly, RAPs are new players for flow batteries relying on a size-exclusion based mechanism of electrolyte separation, but few studies have provided detailed molecular understanding of redox polymers in solution. Here, we use a systematic molecular design approach to investigate the impact of linker and redox-pendant electronic interactions on the performance of viologen RAPs. We used scanning electrochemical microscopy, cyclic voltammetry, bulk electrolysis, temperature-dependent absorbance, and spectroelectrochemistry to study the redox properties, charge transfer kinetics, and self-exchange of electrons through redox active dimers and their equivalent polymers. Stark contrast was observed between the electrochemical properties of viologen dimers and their corresponding polymers. Electron self-exchange kinetics in redox active dimers that only differ by their tether length and rigidity influences their charge transfer properties. Predictions from the Marcus Hush theory were consistent with observations in redox active dimers, but they failed to fully capture the behavior of macromolecular systems. For example, polymer bound viologen pendants, if too close in proximity, do not retain chemical reversibility. In contrast to polymer films, small modifications to the backbone structure decisively impact the bulk electrolysis of polymer solutions. This first comprehensive study highlights the careful balance between electronic interactions and backbone rigidity required to design RAPs with superior electrochemical performance.

  4. Erv2p: characterization of the redox behavior of a yeast sulfhydryl oxidase

    DEFF Research Database (Denmark)

    Wang, Wenzhong; Winther, Jakob R; Thorpe, Colin

    2007-01-01

    centers that facilitate the transfer of reducing equivalents from the dithiol substrates of these oxidases to the isoalloxazine ring where the reaction with molecular oxygen occurs. The present study examines yeast Erv2p and compares the redox behavior of this ER luminal protein with the augmenter...... and with unfolded proteins. Rapid reaction studies confirm that reduction of the flavin center of Erv2p is rate-limiting during turnover with molecular oxygen. This comparison of the redox properties between members of the ERV/ALR family of sulfhydryl oxidases provides insights into their likely roles in oxidative......The FAD prosthetic group of the ERV/ALR family of sulfhydryl oxidases is housed at the mouth of a 4-helix bundle and communicates with a pair of juxtaposed cysteine residues that form the proximal redox active disulfide. Most of these enzymes have one or more additional distal disulfide redox...

  5. Bioelectrochemical probing of intracellular redox processes in living yeast cells—application of redox polymer wiring in a microfluidic environment

    DEFF Research Database (Denmark)

    Heiskanen, Arto; Coman, Vasile; Kostesha, Natalie

    2013-01-01

    utilizing a new double mediator system to map redox metabolism and screen for genetic modifications in Saccharomyces cerevisiae cells. The function of this new double mediator system based on menadione and osmium redox polymer (PVI-Os) is demonstrated. “Wiring” of S. cerevisiae cells using PVI-Os shows...... mutant EBY44, which lacks the enzyme phosphoglucose isomerase. The cellular responses to introduced glucose and fructose were recorded for the two S. cerevisiae strains, and the obtained results are compared with previously published work when using an electrochemical batch cell, indicating...

  6. Acute molecular responses to concurrent resistance and high-intensity interval exercise in untrained skeletal muscle.

    Science.gov (United States)

    Pugh, Jamie K; Faulkner, Steve H; Jackson, Andrew P; King, James A; Nimmo, Myra A

    2015-04-01

    Concurrent training involving resistance and endurance exercise may augment the benefits of single-mode training for the purpose of improving health. However, muscle adaptations, associated with resistance exercise, may be blunted by a subsequent bout of endurance exercise, via molecular interference. High-intensity interval training (HIIT), generating similar adaptations to endurance exercise, may offer an alternative exercise mode to traditional endurance exercise. This study examined the influence of an acute HIIT session on the molecular responses following resistance exercise in untrained skeletal muscle. Ten male participants performed resistance exercise (4 × 8 leg extensions, 70% 1RM, (RE)) or RE followed by HIIT (10 × 1 min at 90% HRmax, (RE+HIIT)). Muscle biopsies were collected from the vastus lateralis before, 2 and 6 h post-RE to determine intramuscular protein phosphorylation and mRNA responses. Phosphorylation of Akt (Ser(473)) decreased at 6 h in both trials (P HIIT (P HIIT with PGC-1α and PGC-1α-ex1b remaining elevated at 6 h, whereas RE-induced increases at 2 and 6 h for PGC-1α-ex1b only (P HIIT versus RE at 2 and 6 h (P HIIT may be an alternative to endurance exercise when performed after resistance exercise in the same training session to optimize adaptations.

  7. The physiological and molecular response of Aurelia sp.1 under hypoxia.

    Science.gov (United States)

    Wang, Guoshan; Zhen, Yu; Yu, Zhigang; Shi, Yan; Zhao, Qing; Wang, Jianyan; Mi, Tiezhu

    2017-05-08

    Few studies have been published on the mechanisms of hypoxia response and tolerance in jellyfish, especially with respect to the regulatory mechanism at the molecular level. In this study, Aurelia sp.1, which is frequently found in Chinese coastal waters, was cultivated in a hypoxic system to determine the molecular mechanisms underlying its hypoxic response by studying the physiological activity, gene expression and metabolite contents in the prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) oxygen-sensing system. Physiological activity; the expression of PHD, HIF, ALDO (fructose-bisphosphate aldolase), PDK (pyruvate dehydrogenase kinase), and LDH (lactate dehydrogenase) genes; and the lactic acid content in medusae were significantly affected by hypoxia. The up-regulation of ALDO, PDK and LDH, which was directly or indirectly induced by HIF, mediated the transition from aerobic respiration to anaerobic glycolysis in the medusae. In polyps, there was a slight increase in the expression of HIF, PHD and ALDO, no obvious change in that of PDK and a slight decrease in that of LDH throughout the experiment; however, these changes were insufficient to induce the shift. This study provides a scientific basis for elucidating the regulatory mechanism underlying the PHD-HIF oxygen-sensing system in Aurelia sp.1.

  8. Discrete molecular states in the brain accompany changing responses to a vocal signal

    Science.gov (United States)

    Dong, Shu; Replogle, Kirstin L.; Hasadsri, Linda; Imai, Brian S.; Yau, Peter M.; Rodriguez-Zas, Sandra; Southey, Bruce R.; Sweedler, Jonathan V.; Clayton, David F.

    2009-01-01

    New experiences can trigger changes in gene expression in the brain. To understand this phenomenon better, we studied zebra finches hearing playbacks of birdsong. Earlier research had shown that initial playbacks of a novel song transiently increase the ZENK (ZIF-268, EGR1, NGFIA, KROX-24) mRNA in the auditory forebrain, but the response selectively habituates after repetition of the stimulus. Here, using DNA microarray analysis, we show that novel song exposure induces rapid changes in thousands of RNAs, with even more RNAs decreasing than increasing. Habituation training leads to the emergence of a different gene expression profile a day later, accompanied by loss of essentially all of the rapid “novel” molecular responses. The novel molecular profile is characterized by increases in genes involved in transcription and RNA processing and decreases in ion channels and putative noncoding RNAs. The “habituated” profile is dominated by changes in genes for mitochondrial proteins. A parallel proteomic analysis [2-dimensional difference gel electrophoresis (2D-DIGE) and sequencing by mass spectrometry] also detected changes in mitochondrial proteins, and direct enzyme assay demonstrated changes in both complexes I and IV in the habituated state. Thus a natural experience, in this case hearing the sound of birdsong, can lead to major shifts in energetics and macromolecular metabolism in higher centers in the brain. PMID:19541599

  9. Polysaccharides As Viscosupplementation Agents: Structural Molecular Characteristics but Not Rheology Appear Crucial to the Therapeutic Response

    Directory of Open Access Journals (Sweden)

    Rita C. Machado

    2017-06-01

    Full Text Available IntroductionMost clinical studies and basic research document viscosupplementation (VS in terms of effectiveness and safety, but only a few highlight its molecular mechanisms of action. Besides, there is generally focus on hyaluronic acid (HA as being the most relevant polysaccharide to reach the clinical endpoints, attributing its effect mainly to its unique viscoelastic properties, related to a high-molecular weight and gel formulation. Usually, studies do not approach the possible biological pathways where HA may interfere, and there is a lack of reports on other biocompatible polysaccharides that could be of use in VS.AimWe briefly review the main proposed mechanisms of action of intra-articular hyaluronic acid (IA-HA treatment and discuss its effectiveness focusing on the role of rheological and intrinsic structural molecular properties of polysaccharides in providing a therapeutic effect.MethodsWe conducted a literature search using PubMed database to find articles dealing with the mechanisms of action of IA-HA treatment and/or emphasizing how the structural properties of the polysaccharide used influenced the clinical outcomes.Discussion/conclusionHA is involved in numerous biochemical interactions that may explain the clinical benefits of VS, most of them resulting from HA–cluster of differentiation 44 receptor interaction. There are other important aspects apart from the molecular size or the colloidal state of the IA-HA involved in VS efficiency that still need to be consolidated. Indeed, it seems that clinical response may be dependent on the intrinsic properties of the polysaccharide, regardless of being HA, rather than to rheology, posing some controversy to previous beliefs.

  10. Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions

    Directory of Open Access Journals (Sweden)

    Moritz Palmowski

    2009-09-01

    Full Text Available Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1 and of αvβ3-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of αvβ3-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of αvβ3-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and αvβ3-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.

  11. Molecular origins of higher harmonics in large-amplitude oscillatory shear flow: Shear stress response

    Science.gov (United States)

    Gilbert, P. H.; Giacomin, A. J.

    2016-10-01

    Recent work has focused on deepening our understanding of the molecular origins of the higher harmonics that arise in the shear stress response of polymeric liquids in large-amplitude oscillatory shear flow. For instance, these higher harmonics have been explained by just considering the orientation distribution of rigid dumbbells suspended in a Newtonian solvent. These dumbbells, when in dilute suspension, form the simplest relevant molecular model of polymer viscoelasticity, and this model specifically neglects interactions between the polymer molecules [R. B. Bird et al., "Dilute rigid dumbbell suspensions in large-amplitude oscillatory shear flow: Shear stress response," J. Chem. Phys. 140, 074904 (2014)]. In this paper, we explore these interactions by examining the Curtiss-Bird model, a kinetic molecular theory designed specifically to account for the restricted motions that arise when polymer chains are concentrated, thus interacting and specifically, entangled. We begin our comparison using a heretofore ignored explicit analytical solution [X.-J. Fan and R. B. Bird, "A kinetic theory for polymer melts. VI. Calculation of additional material functions," J. Non-Newtonian Fluid Mech. 15, 341 (1984)]. For concentrated systems, the chain motion transverse to the chain axis is more restricted than along the axis. This anisotropy is described by the link tension coefficient, ɛ, for which several special cases arise: ɛ = 0 corresponds to reptation, ɛ > 1/8 to rod-climbing, 1/5 ≤ ɛ ≤ 3/4 to reasonable predictions for shear-thinning in steady simple shear flow, and ɛ = 1 to the dilute solution without hydrodynamic interaction. In this paper, we examine the shapes of the shear stress versus shear rate loops for the special cases ɛ = (" separators=" 0 , 1 / 8 , 3 / 8 , 1 ) , and we compare these with those of rigid dumbbell and reptation model predictions.

  12. Molecular genetic response to varied wavelengths of light in Xiphophorus maculatus skin.

    Science.gov (United States)

    Chang, Jordan; Lu, Yuan; Boswell, William T; Boswell, Mikki; Caballero, Kaela L; Walter, Ronald B

    2015-12-01

    Xiphophorus fishes represent a model often utilized to study UVB induced tumorigenesis. Recently, varied genetic responses to UVB exposure have been documented in the skin of female and male Xiphophorus, as have differences in UVB response in the skin of different parental species and for interspecies hybrids produced from crossing them. Additionally, it has been shown that exposure to "cool white" fluorescent light induces a shift in the genetic profiles of Xiphophorus skin that is nearly as robust as the UVB response, but involves a fundamentally different set of genes. Given these results and the use of Xiphophorus interspecies hybrids as an experimental model for UVB inducible melanoma, it is of interest to characterize genes that may be transcriptionally modulated in a wavelength specific manner. The global molecular genetic response of skin upon exposure of the intact animal to specific wavelengths of light has not been investigated. Herein, we report results of RNA-Seq experiments from the skin of male Xiphophorus maculatus Jp 163 B following exposure to varied 50nm wavelengths of light ranging from 300-600nm. We identify two specific wavelength regions, 350-400nm (88 genes) and 500-550nm (276 genes), that exhibit transcriptional modulation of a significantly greater number of transcripts than any of the other 50nm regions in the 300-600nm range. Observed functional sets of genes modulated within these two transcriptionally active light regions suggest different mechanisms of gene modulation.

  13. Paraquat-Melanin Redox-Cycling: Evidence from Electrochemical Reverse Engineering.

    Science.gov (United States)

    Kim, Eunkyoung; Leverage, W Taylor; Liu, Yi; Panzella, Lucia; Alfieri, Maria Laura; Napolitano, Alessandra; Bentley, William E; Payne, Gregory F

    2016-08-17

    Parkinson's disease is a neurodegenerative disorder associated with oxidative stress and the death of melanin-containing neurons of the substantia nigra. Epidemiological evidence links exposure to the pesticide paraquat (PQ) to Parkinson's disease, and this link has been explained by a redox cycling mechanism that induces oxidative stress. Here, we used a novel electrochemistry-based reverse engineering methodology to test the hypothesis that PQ can undergo reductive redox cycling with melanin. In this method, (i) an insoluble natural melanin (from Sepia melanin) and a synthetic model melanin (having a cysteinyldopamine-melanin core and dopamine-melanin shell) were entrapped in a nonconducting hydrogel film adjacent to an electrode, (ii) the film-coated electrode was immersed in solutions containing PQ (putative redox cycling reductant) and a redox cycling oxidant (ferrocene dimethanol), (iii) sequences of input potentials (i.e., voltages) were imposed to the underlying electrode to systematically engage reductive and oxidative redox cycling, and (iv) output response currents were analyzed for signatures of redox cycling. The response characteristics of the PQ-melanin systems to various input potential sequences support the hypothesis that PQ can directly donate electrons to melanin. This observation of PQ-melanin redox interactions demonstrates an association between two components that have been individually linked to oxidative stress and Parkinson's disease. Potentially, melanin's redox activity could be an important component in understanding the etiology of neurological disorders such as Parkinson's disease.

  14. Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

    Science.gov (United States)

    Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

    2016-08-01

    Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

  15. Herbivore-induced chemical and molecular responses of the kelps Laminaria digitata and Lessonia spicata

    Science.gov (United States)

    Ritter, Andrés; Cabioch, Léa; Brillet-Guéguen, Loraine; Corre, Erwan; Cosse, Audrey; Dartevelle, Laurence; Duruflé, Harold; Fasshauer, Carina; Goulitquer, Sophie; Thomas, François; Correa, Juan A.; Potin, Philippe; Faugeron, Sylvain; Leblanc, Catherine

    2017-01-01

    Kelps are founding species of temperate marine ecosystems, living in intertidal coastal areas where they are often challenged by generalist and specialist herbivores. As most sessile organisms, kelps develop defensive strategies to restrain grazing damage and preserve their own fitness during interactions with herbivores. To decipher some inducible defense and signaling mechanisms, we carried out metabolome and transcriptome analyses in two emblematic kelp species, Lessonia spicata from South Pacific coasts and Laminaria digitata from North Atlantic, when challenged with their main specialist herbivores. Mass spectrometry based metabolomics revealed large metabolic changes induced in these two brown algae following challenges with their own specialist herbivores. Targeted metabolic profiling of L. spicata further showed that free fatty acid (FFA) and amino acid (AA) metabolisms were particularly regulated under grazing. An early stress response was illustrated by the accumulation of Sulphur containing amino acids in the first twelve hours of herbivory pressure. At latter time periods (after 24 hours), we observed FFA liberation and eicosanoid oxylipins synthesis likely representing metabolites related to stress. Global transcriptomic analysis identified sets of candidate genes specifically induced by grazing in both kelps. qPCR analysis of the top candidate genes during a 48-hours time course validated the results. Most of these genes were particularly activated by herbivore challenge after 24 hours, suggesting that transcriptional reprogramming could be operated at this time period. We demonstrated the potential utility of these genes as molecular markers for herbivory by measuring their inductions in grazed individuals of field harvested L. digitata and L. spicata. By unravelling the regulation of some metabolites and genes following grazing pressure in two kelps representative of the two hemispheres, this work contributes to provide a set of herbivore

  16. Plant-parasitic nematodes: towards understanding molecular players in stress responses.

    Science.gov (United States)

    Gillet, François-Xavier; Bournaud, Caroline; Antonino de Souza Júnior, Jose Dijair; Grossi-de-Sa, Maria Fatima

    2017-03-01

    Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1 , which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches.

  17. Redox Regulation in Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Shijie Ding

    2015-01-01

    Full Text Available Reactive oxygen species (ROS and ROS-dependent (redox regulation signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of cancer stem cells (CSCs has been gaining ground as the subpopulation of cancer cells with stem cell-like properties and characteristics have been identified in various cancers. CSCs possess low levels of ROS and are responsible for cancer recurrence after chemotherapy or radiotherapy. Unfortunately, how CSCs control ROS production and scavenging and how ROS-dependent signaling pathways contribute to CSCs function remain poorly understood. This review focuses on the role of redox balance, especially in ROS-dependent cellular processes in cancer stem cells (CSCs. We updated recent advances in our understanding of ROS generation and elimination in CSCs and their effects on CSC self-renewal and differentiation through modulating signaling pathways and transcriptional activities. The review concludes that targeting CSCs by manipulating ROS metabolism/dependent pathways may be an effective approach for improving cancer treatment.

  18. Distinct Redox Profiles of Selected Human Prostate Carcinoma Cell Lines: Implications for Rational Design of Redox Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chaiswing, Luksana [Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, 1111 Highland Ave., WIMR 7168, Madison, WI 53705 (United States); Zhong, Weixiong; Oberley, Terry D., E-mail: toberley@wisc.edu [Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, 1111 Highland Ave., WIMR 7168, Madison, WI 53705 (United States); Pathology and Laboratory Medicine Service, William S. Middleton Memorial Veterans Hospital, Rm A-35, 2500 Overlook Terrace, Madison, WI 53705 (United States)

    2011-09-13

    The effects of several cancer chemotherapeutic drugs and radiation are mediated, at least in part, by oxidative stress. To better understand this process, we analyzed certain biochemical properties affecting reduction-oxidation (redox) balance in normal prostate epithelial cells and several prostate cancer cell lines. Highly aggressive androgen-independent prostate cancer PC3 cells demonstrated significantly higher levels of total antioxidant capacity (AC) and intra- and extracellular glutathione (GSH)/glutathione disulfide (GSSG) ratios when compared with normal prostate epithelial PrEC cells. WPE1-NB26 cells, a prostate cancer cell line derived from immortalized RWPE1 human prostate epithelial cells, demonstrated significantly higher levels of total AC and intra- and extracellular GSH/GSSG ratios, but lower levels of intracellular reactive oxygen/nitrogen species and lipid peroxidation compared with RWPE1 cells. LNCaP-C4-2 cells, a more aggressive prostate cancer derived from less aggressive androgen-responsive LNCaP cells, exhibited higher levels of AC and extracellular GSH/GSSG ratio when compared to LNCaP cells. Specific cell types showed distinct cytotoxic responses to redox-modulating compounds. WPE1-NB26 cells were more sensitive to phenethyl isothiocyanate and tumor necrosis factor (TNF) than RWPE1 cells, while PC3 cells were more sensitive to TNF than PrEC cells. These results are consistent with the hypothesis that cancer cell redox state may modulate responses to redox-modulating therapeutic regimens.

  19. Distinct Redox Profiles of Selected Human Prostate Carcinoma Cell Lines: Implications for Rational Design of Redox Therapy

    Directory of Open Access Journals (Sweden)

    Luksana Chaiswing

    2011-09-01

    Full Text Available The effects of several cancer chemotherapeutic drugs and radiation are mediated, at least in part, by oxidative stress. To better understand this process, we analyzed certain biochemical properties affecting reduction-oxidation (redox balance in normal prostate epithelial cells and several prostate cancer cell lines. Highly aggressive androgen-independent prostate cancer PC3 cells demonstrated significantly higher levels of total antioxidant capacity (AC and intra- and extracellular glutathione (GSH/glutathione disulfide (GSSG ratios when compared with normal prostate epithelial PrEC cells. WPE1-NB26 cells, a prostate cancer cell line derived from immortalized RWPE1 human prostate epithelial cells, demonstrated significantly higher levels of total AC and intra- and extracellular GSH/GSSG ratios, but lower levels of intracellular reactive oxygen/nitrogen species and lipid peroxidation compared with RWPE1 cells. LNCaP-C4-2 cells, a more aggressive prostate cancer derived from less aggressive androgen-responsive LNCaP cells, exhibited higher levels of AC and extracellular GSH/GSSG ratio when compared to LNCaP cells. Specific cell types showed distinct cytotoxic responses to redox-modulating compounds. WPE1-NB26 cells were more sensitive to phenethyl isothiocyanate and tumor necrosis factor (TNF than RWPE1 cells, while PC3 cells were more sensitive to TNF than PrEC cells. These results are consistent with the hypothesis that cancer cell redox state may modulate responses to redox-modulating therapeutic regimens.

  20. Reductive stress after exercise: The issue of redox individuality

    Directory of Open Access Journals (Sweden)

    N.V. Margaritelis

    2014-01-01

    Full Text Available Exercise has been consistently used as an oxidant stimulus in redox biology studies. However, previous studies have focused on group differences and did not examine individual differences. As a result, it remains untested whether all individuals experience oxidative stress after acute exercise. Therefore, the main aim of the present study was to investigate whether some individuals exhibit unexpected responses after an acute eccentric (i.e., muscle-damaging exercise session. Ninety eight (N = 98 young men performed an isokinetic eccentric exercise bout with the knee extensors. Plasma, erythrocytes and urine samples were collected immediately before and 2 days post-exercise. Three commonly used redox biomarkers (F2-isoprostanes, protein carbonyls and glutathione were assayed. As expected, the two oxidant biomarkers (F2-isoprostanes and protein carbonyls significantly increased 2 days after exercise (46% and 61%, respectively; whereas a significant decrease in glutathione levels (by −21% was observed after exercise. A considerable number of the participants exhibited changes in the levels of biomarkers in the opposite, unexpected direction than the group average. More specifically, 13% of the participants exhibited a decrease in F2-isoprostanes and protein carbonyls and 10% of the participants exhibited an increase in glutathione levels. Furthermore, more than 1 out of 3 individuals exhibited either unexpected or negligible (from 0% to ± 5% responses to exercise in at least one redox biomarker. It was also observed that the initial values of redox biomarkers are important predictors of the responses to exercise. In conclusion, although exercise induces oxidative stress in the majority of individuals, it can induce reductive stress or negligible stress in a considerable number of people. The data presented herein emphasize that the mean response to a redox stimulus can be very misleading. We believe that the wide variability (including the

  1. Extracellular cysteine in connexins: role as redox sensors

    Directory of Open Access Journals (Sweden)

    Mauricio Antonio Retamal

    2016-01-01

    Full Text Available Connexin-based channels comprise hemichannels and gap junction channels. The opening of hemichannels allow for the flux of ions and molecules from the extracellular space into the cell and vice versa. Similarly, the opening of gap junction channels permits the diffusional exchange of ions and molecules between the cytoplasm and contacting cells. The controlled opening of hemichannels has been associated with several physiological cellular processes; thereby unregulated hemichannel activity may induce loss of cellular homeostasis and cell death. Hemichannel activity can be regulated through several mechanisms, such as phosphorylation, divalent cations and changes in membrane potential. Additionally, it was recently postulated that redox molecules could modify hemichannels properties in vitro. However, the molecular mechanism by which redox molecules interact with hemichannels is poorly understood. In this work, we discuss the current knowledge on connexin redox regulation and we propose the hypothesis that extracellular cysteine could be important for sensing changes in redox potential. Future studies on this topic will offer new insight into hemichannel function, thereby expanding the understanding of the contribution of hemichannels to disease progression.

  2. Cobaltocenium-functionalized poly(propylene imine) dendrimers: redox and electromicrogravimetric studies and AFM imaging.

    Science.gov (United States)

    Takada, K; Díaz, D J; Abruña, H D; Cuadrado, I; González, B; Casado, C M; Alonso, B; Morán, M; Losada, J

    2001-03-02

    The first four generations of cobaltocenium-functionalized, diaminobutane-based poly(propylene imine) dendrimers DAB-dend-Cb,(PFb)x (x = 4, 8, 16, and 32; Cb=[Co(eta5-C5H4CONH)(eta5-C5H5)] (1-4) have been synthesized and characterized. The redox activity of the cobaltocenium centers in 1-4 has been characterized by using cyclic voltammetry and the electrochemical quartz-crystal microbalance (EQCM). All of the dendrimers exhibit reversible redox chemistry associated with the cobaltocenium/cobaltocene redox couple. Upon reduction. the dendrimers exhibit a tendency to electrodeposit onto the electrode surface, which is more pronounced for the higher generations. Pt and glassy carbon electrodes could be modified with films derived from 1-4,exhibiting a well-defined and persistent electrochemical response. EQCM measurements show that the dendrimers adsorb, at open circuit, onto platinum surfaces at monolayer or submonolayer coverage. Cathodic potential scanning past -0.75 V at which the cobaltocenium sites are reduced, gave rise to the electrodeposition of multilayer equivalents of the dendrimers. The additional material gradually desorbs upon re-oxidation so that only a monolayer equivalent remains on the electrode surface. Changes in film morphology as a function of dendrimer generation and surface coverage were studied by using admittance measurements of the quartz-crystal resonator on the basis of its electrical equivalent circuit, especially in terms of its resistance parameter. In general, we find that films of the lower dendrimer generation 1 behave rigidly, whereas those of the higher generation 4 exhibit viscoelastic behavior with an intermediate behavior being exhibited by 2 and 3. Using tapping-mode atomic force microscopy (AFM). we have been able to obtain molecularly resolved images of dendrimer 4 adsorbed on a Pt(111) electrode.

  3. Nitric oxide, induced by wounding, mediates redox regulation in pelargonium leaves.

    Science.gov (United States)

    Arasimowicz, M; Floryszak-Wieczorek, J; Milczarek, G; Jelonek, T

    2009-09-01

    The subject of this study was the participation of nitric oxide (NO) in plant responses to wounding, promoted by nicking of pelargonium (Pelargonium peltatum L.) leaves. Bio-imaging with the fluorochrome 4,5-diaminofluorescein diacetate (DAF-2DA) and electrochemical in situ measurement of NO showed early (within minutes) and transient (2 h) NO generation after wounding restricted to the site of injury. In order to clarify the functional role of NO in relation to modulation of the redox balance during wounding, a pharmacological approach was used. A positive correlation was found between NO generation and regulation of the redox state. NO caused a slight restriction of post-wounded O(2) (-) production, in contrast to the periodic and marked increase in H(2)O(2) level. The observed changes were accompanied by time-dependent inhibition of catalase (CAT) and ascorbate peroxidase (APX) activity. The effect was specific to NO, since the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) reversed the inhibition of CAT and APX, as well as temporarily enhancing H(2)O(2) synthesis. Finally, cooperation of NO/H(2)O(2) restricted the depletion of the low-molecular weight antioxidant pool (i.e. ascorbic acid and thiols) was positively correlated with sealing and reconstruction changes in injured pelargonium leaves (i.e. lignin formation and callose deposition). The above results clearly suggest that NO may promote restoration of wounded tissue through stabilisation of the cell redox state and stimulation of the wound scarring processes.

  4. The role of pathogen-associated molecular patterns in inflammatory responses against alginate based microcapsules.

    Science.gov (United States)

    Paredes-Juarez, Genaro A; de Haan, Bart J; Faas, Marijke M; de Vos, Paul

    2013-12-28

    Alginate-based microcapsules are used for immunoisolation of cells to release therapeutics on a minute-to-minute basis. Unfortunately, alginate-based microcapsules are suffering from varying degrees of success, which is usually attributed to differences in tissue responses. This results in failure of the therapeutic cells. In the present study we show that commercial, crude alginates may contain pathogen-associated molecular patterns (PAMPs), which are recognized by the sensors of the innate immune system. Known sensors are Toll-like receptors (TLRs), NOD receptors, and C-type lectins. By using cell-lines with a non-functional adaptor molecule essential in Toll-like receptor signaling, i.e. MyD88, we were able to show that alginates signal mainly via MyD88. This was found for low-G, intermediate-G, and high-G alginates applied in calcium-beads, barium-beads as well as in alginate-PLL-alginate capsules. These alginates did stimulate TLRs 2, 5, 8, and 9 but not TLR4 (LPS receptor). Upon implantation in rats these alginates provoked a strong inflammatory response resulting in fibrosis of the capsules. Analysis demonstrated that commercial alginates contain the PAMPs peptidoglycan, lipoteichoic acid, and flagellin. By applying purification procedures, these PAMPs were largely removed. This was associated with deletion of the inflammatory tissue responses as confirmed by an implantation experiment in rats. Our data also show that alginate itself does not provoke TLR mediated responses. We were able to unravel the sensor mechanism by which contaminants in alginates may provoke inflammatory responses.

  5. Integrating the cell stress response: a new view of molecular chaperones as immunological and physiological homeostatic regulators.

    Science.gov (United States)

    Henderson, Brian

    2010-01-01

    The response of cells to stress was first documented in the 1960s and 1970s and the molecular nature of the families of proteins that subserve this vital response, the molecular chaperones, were identified and subjected to critical study in the period from the late 1980s. This resulted in the rapidly advancing new field of protein folding and its role in cellular function. Emerging at the same time, but initially largely ignored, were reports that molecular chaperones could be released by cells and exist on the outer plasma membrane or in the body fluids. These secreted molecular chaperones were found to have intercellular signalling functions. There is now a growing body of evidence to support the hypothesis that molecular chaperones have properties ascribed to the Roman god Janus, the god of gates, doors, beginnings and endings, whose two faces point in different directions. Molecular chaperones appear to have one set of key functions within the cell and, potentially, a separate set of functions when they exist on the cell surface or in the various fluid phases of the body. Thus, it is a likely hypothesis that secreted molecular chaperones act as an additional level of homeostatic control possibly linking cellular stress to physiological systems such as the immune system. This review concentrates on three key molecular chaperones: Hsp10, Hsp60 and the Hsp70 family for which most information is available. An important consideration is the role that these proteins may play in human disease and in the treatment of human disease.

  6. Cellular, physiological, and molecular adaptive responses of Erwinia amylovora to starvation.

    Science.gov (United States)

    Santander, Ricardo D; Oliver, James D; Biosca, Elena G

    2014-05-01

    Erwinia amylovora causes fire blight, a destructive disease of rosaceous plants distributed worldwide. This bacterium is a nonobligate pathogen able to survive outside the host under starvation conditions, allowing its spread by various means such as rainwater. We studied E. amylovora responses to starvation using water microcosms to mimic natural oligotrophy. Initially, survivability under optimal (28 °C) and suboptimal (20 °C) growth temperatures was compared. Starvation induced a loss of culturability much more pronounced at 28 °C than at 20 °C. Natural water microcosms at 20 °C were then used to characterize cellular, physiological, and molecular starvation responses of E. amylovora. Challenged cells developed starvation-survival and viable but nonculturable responses, reduced their size, acquired rounded shapes and developed surface vesicles. Starved cells lost motility in a few days, but a fraction retained flagella. The expression of genes related to starvation, oxidative stress, motility, pathogenicity, and virulence was detected during the entire experimental period with different regulation patterns observed during the first 24 h. Further, starved cells remained as virulent as nonstressed cells. Overall, these results provide new knowledge on the biology of E. amylovora under conditions prevailing in nature, which could contribute to a better understanding of the life cycle of this pathogen.

  7. Insights into molecular and metabolic events associated with fruit response to postharvest fungal pathogens

    Directory of Open Access Journals (Sweden)

    Noam eAlkan

    2015-10-01

    Full Text Available Due to postharvest losses more than 30% of harvested fruits will not reach the consumers’ plate. Fungal pathogens play a key role in those losses, as they cause most of the fruit rots and the customer complaints. Many of the fungal pathogens are already present in the unripe fruit but remain quiescent during fruit growth until a particular phase of fruit ripening and senescence. The pathogens sense the developmental change and switch into the devastating necrotrophic life style that causes fruit rotting. Colonization of unripe fruit by the fungus initiates defensive responses that limit fungal growth and development. However, during fruit ripening several physiological processes occur that correlate with increased fruit susceptibility. In contrast to plant defenses in unripe fruit, the defense posture of ripe fruit entails a different subset of defense responses that will end with fruit rotting and losses. This review will focus on several aspects of molecular and metabolic events associated with fleshy fruit responses induced by postharvest fungal pathogens during fruit ripening.

  8. Insights into molecular and metabolic events associated with fruit response to post-harvest fungal pathogens.

    Science.gov (United States)

    Alkan, Noam; Fortes, Ana M

    2015-01-01

    Due to post-harvest losses more than 30% of harvested fruits will not reach the consumers' plate. Fungal pathogens play a key role in those losses, as they cause most of the fruit rots and the customer complaints. Many of the fungal pathogens are already present in the unripe fruit but remain quiescent during fruit growth until a particular phase of fruit ripening and senescence. The pathogens sense the developmental change and switch into the devastating necrotrophic life style that causes fruit rotting. Colonization of unripe fruit by the fungus initiates defensive responses that limit fungal growth and development. However, during fruit ripening several physiological processes occur that correlate with increased fruit susceptibility. In contrast to plant defenses in unripe fruit, the defense posture of ripe fruit entails a different subset of defense responses that will end with fruit rotting and losses. This review will focus on several aspects of molecular and metabolic events associated with fleshy fruit responses induced by post-harvest fungal pathogens during fruit ripening.

  9. Molecular mechanism of immune response induced by foreign plasmid DNA after oral administration in mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To study immune response induced by foreign plasmid DNA after oral administration in mice.METHODS: Mice were orally administered with 200 μg of plasmid pcDNA3 once and spleen was isolated 4 h and 18 h after administration. Total RNA was extracted from spleen and gene expression profile of BALB/c mice spleen was analyzed by using Affymetrix oligonucleotide GeneChip. Functional cluster analysis was conducted by GenMAPP software.RESULTS: At 4 h and 18 h after oral plasmid pcDNA3 administration, a number of immune-related genes,including cytokine and cytokine receptors, chemokines and chemokine receptor, complement molecule,proteasome, histocompatibility molecule, lymphocyte antigen complex and apoptotic genes, were up-regulated. Moreover, MAPPFinder results also showed that numerous immune response processes were up-regulated. In contrast, the immunoglobulin genes were down-regulated.CONCLUSION: Foreign plasmid DNA can modulate the genes expression related to immune system via the gastrointestinal tract, and further analysis of the related immune process may help understand the molecular mechanisms of immune response induced by foreign plasmid via the gastrointestinal tract.

  10. Redox Entropy of Plastocyanin: Developing a Microscopic View of Mesoscopic Polar Solvation

    CERN Document Server

    LeBard, David N

    2007-01-01

    We report applications of analytical formalisms and Molecular Dynamics (MD) simulations to the calculation of redox entropy of plastocyanin metalloprotein in aqueous solution. The goal of our analysis is to establish critical components of the theory required to describe polar solvation at the mesoscopic scale. The analytical techniques include a microscopic formalism based on structure factors of the solvent dipolar orientations and density and continuum dielectric theories. The microscopic theory employs the atomistic structure of the protein with force-field atomic charges and solvent structure factors obtained from separate MD simulations of the homogeneous solvent. The MD simulations provide linear response solvation free energies and reorganization energies of electron transfer in the temperature range 280--310 K. We found that continuum models universally underestimate solvation entropies, and a more favorable agreement is reported between the microscopic calculations and MD simulations. The analysis o...

  11. S-Glutathionylation and Redox Protein Signaling in Drug Addiction.

    Science.gov (United States)

    Womersley, Jacqueline S; Uys, Joachim D

    2016-01-01

    Drug addiction is a chronic relapsing disorder that comes at a high cost to individuals and society. Therefore understanding the mechanisms by which drugs exert their effects is of prime importance. Drugs of abuse increase the production of reactive oxygen and nitrogen species resulting in oxidative stress. This change in redox homeostasis increases the conjugation of glutathione to protein cysteine residues; a process called S-glutathionylation. Although traditionally regarded as a protective mechanism against irreversible protein oxidation, accumulated evidence suggests a more nuanced role for S-glutathionylation, namely as a mediator in redox-sensitive protein signaling. The reversible modification of protein thiols leading to alteration in function under different physiologic/pathologic conditions provides a mechanism whereby change in redox status can be translated into a functional response. As such, S-glutathionylation represents an understudied means of post-translational protein modification that may be important in the mechanisms underlying drug addiction. This review will discuss the evidence for S-glutathionylation as a redox-sensing mechanism and how this may be involved in the response to drug-induced oxidative stress. The function of S-glutathionylated proteins involved in neurotransmission, dendritic spine structure, and drug-induced behavioral outputs will be reviewed with specific reference to alcohol, cocaine, and heroin. Copyright © 2016. Published by Elsevier Inc.

  12. Molecular determinants responsible for sedative and non-sedative properties of histamine H₁-receptor antagonists.

    Science.gov (United States)

    Uesawa, Yoshihiro; Hishinuma, Shigeru; Shoji, Masaru

    2014-01-01

    There is argument whether non-sedative properties of histamine H1-receptor antagonists (antihistamines) are determined by their active extrusions from the brain via P-glycoprotein or their restricted penetration through the blood-brain barrier. We have reported that sedative and non-sedative antihistamines can be well discriminated by measuring changes in their binding to H1 receptors upon receptor internalization in intact cells, which depends on their membrane-penetrating ability. In this study, molecular determinants responsible for sedative and non-sedative properties of antihistamines were evaluated by quantitative structure-activity relationship (QSAR) analyses. Multiple regression analyses were applied to construct a QSAR model, taking internalization-mediated changes in the binding of antihistamines as objective variables and their structural descriptors as explanatory variables. The multiple regression model was successfully constructed with two explanatory variables, i.e., lipophilicity of the compounds at physiological pH (logD) and mean information content on the distance degree equality (IDDE) (r(2) = 0.753). The constructed model discriminated between sedative and non-sedative antihistamines with 94% accuracy for external validation. These results suggest that logD and IDDE concerning lipophilicity and molecular shapes of compounds, respectively, predominantly determine the membrane-penetrating ability of antihistamines for their side effects on the central nervous system.

  13. Molecular and physiological responses to abiotic stress in forest trees and their relevance to tree improvement.

    Science.gov (United States)

    Harfouche, Antoine; Meilan, Richard; Altman, Arie

    2014-11-01

    Abiotic stresses, such as drought, salinity and cold, are the major environmental stresses that adversely affect tree growth and, thus, forest productivity, and play a major role in determining the geographic distribution of tree species. Tree responses and tolerance to abiotic stress are complex biological processes that are best analyzed at a systems level using genetic, genomic, metabolomic and phenomic approaches. This will expedite the dissection of stress-sensing and signaling networks to further support efficient genetic improvement programs. Enormous genetic diversity for stress tolerance exists within some forest-tree species, and due to advances in sequencing technologies the molecular genetic basis for this diversity has been rapidly unfolding in recent years. In addition, the use of emerging phenotyping technologies extends the suite of traits that can be measured and will provide us with a better understanding of stress tolerance. The elucidation of abiotic stress-tolerance mechanisms will allow for effective pyramiding of multiple tolerances in a single tree through genetic engineering. Here we review recent progress in the dissection of the molecular basis of abiotic stress tolerance in forest trees, with special emphasis on Populus, Pinus, Picea, Eucalyptus and Quercus spp. We also outline practices that will enable the deployment of trees engineered for abiotic stress tolerance to land owners. Finally, recommendations for future work are discussed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Acupuncture Mechanism and Redox Equilibrium

    OpenAIRE

    Xiang-Hong Zeng; Qian-Qian Li; Qian Xu; Fang Li; Cun-Zhi Liu

    2014-01-01

    Oxidative stress participates in the pathological process of various diseases. Acupuncture is a component of the health care system in China that can be traced back for at least 3000 years. Recently, increased evidences indicate that acupuncture stimulation could reduce oxidative damage in organisms under pathological state, but the exact mechanism remains unclear. This review focuses on the emerging links between acupuncture and redox modulation in various disorders, such as vascular dementi...

  15. Soybean Hydrophobic Protein Response to External Electric Field: A Molecular Modeling Approach

    Directory of Open Access Journals (Sweden)

    Vijaya Raghavan

    2013-02-01

    Full Text Available The molecular dynamic (MD modeling approach was applied to evaluate the effect of an external electric field on soybean hydrophobic protein and surface properties. Nominal electric field strengths of 0.002 V/nm and 0.004 V/nm had no major effect on the structure and surface properties of the protein isolate but the higher electric field strength of 3 V/nm significantly affected the protein conformation and solvent accessible surface area. The response of protein isolate to various external field stresses demonstrated that it is necessary to gain insight into protein dynamics under electromagnetic fields in order to be able to develop the techniques utilizing them for food processing and other biological applications.

  16. Pulmonary fibrosis in response to environmental cues and molecular targets involved in its pathogenesis.

    Science.gov (United States)

    Yoshida, Toshinori; Ohnuma, Aya; Horiuchi, Haruka; Harada, Takanori

    2011-03-01

    Chronic lung injury resulting from a variety of different causes is frequently associated with the develop ment of pulmonary fibrosis in humans. Although the etiology of pulmonary fibrosis is generally unknown, several sources of evidence support the hypothesis that a number of environmental and occupational agents play an etiologic role in the pathogenesis of this disease. The agents discussed in this review include beryllium, nylon flock, textile printing aerosols, polyvinyl chloride and didecyldimethylammonium chloride. The authors also describe a variety of animal models, including genetically modified mice, in order to investigate the molecular mechanism of pulmonary fibrosis, focusing on chemokine receptors, regulatory T cells and transforming growth factor-β and bone morphogenetic protein signaling. Overall, we propose the concept of toxicological pulmonary fibrosis as a lung disease induced in response to environmental cues.

  17. Exploiting naturally occurring DNA variation and molecular profiling data to dissect disease and drug response traits.

    Science.gov (United States)

    Schadt, Eric E

    2005-12-01

    Identifying the key drivers of common human diseases and associated signaling pathways remains one of the primary objectives in the biomedical and life sciences. In this respect, common inbred strains of mice have played a crucial role, and recent advances in the development of genomics and bioinformatics tools have significantly enhanced their utility for this purpose. These advances have enabled a more holistic, network-oriented view of biological systems that facilitates elucidation of the underlying causes of disease and the best ways to target them. Success in reconstructing gene networks underlying disease traits (or other complex traits like drug response) and identifying the key drivers of these traits now largely rests on integrative approaches that combine data from multiple different sources. Such integrative genomics approaches that take into account genotypic, molecular profiling and clinical data in segregating mouse populations have recently been developed. Key to this integration has been the development and application of sophisticated algorithms to mine the diversity of data.

  18. Concurrent material point method and molecular dynamics approach for simulating transient responses

    Science.gov (United States)

    Chen, Zhen; Su, Yu-Chen; Zhang, Hetao; Jiang, Shan; Sewell, Thomas D.

    2017-01-01

    To effectively simulate multiscale transient responses such as impact and penetration without the need to invoke a master/slave treatment, the multiscale material point method (Multi-MPM) is being developed wherein molecular dynamics (MD) at the nanoscale or dissipative particle dynamics (DPD) at the mesoscale are handled concurrently within the framework of the original MPM (continuum scale). The proposed numerical scheme for concurrently linking different scales is described here along with a preliminary error analysis. Representative examples for concurrent MPM and DPD and concurrent MPM and MD simulations were presented at SCCM-2015. Because the original MPM is an extension from computational fluid dynamics to solid dynamics, the proposed Multi-MPM might also become robust for dealing with multiphase interactions involving failure evolution.

  19. Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes

    Directory of Open Access Journals (Sweden)

    Gina Manda

    2015-01-01

    Full Text Available This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation, and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators. Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy.

  20. Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes.

    Science.gov (United States)

    Manda, Gina; Checherita, Alexandru-Ionel; Comanescu, Maria Victoria; Hinescu, Mihail Eugen

    2015-01-01

    This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation), and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators). Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy.

  1. Contrasting impacts of ocean acidification and warming on the molecular responses of CO2-resilient oysters.

    Science.gov (United States)

    Goncalves, Priscila; Thompson, Emma L; Raftos, David A

    2017-06-02

    This study characterises the molecular processes altered by both elevated CO2 and increasing temperature in oysters. Differences in resilience of marine organisms against the environmental stressors associated with climate change will have significant implications for the sustainability of coastal ecosystems worldwide. Some evidence suggests that climate change resilience can differ between populations within a species. B2 oysters represent a unique genetic resource because of their capacity to better withstand the impacts of elevated CO2 at the physiological level, compared to non-selected oysters from the same species (Saccostrea glomerata). Here, we used proteomic and transcriptomic analysis of gill tissue to evaluate whether the differential response of B2 oysters to elevated CO2 also extends to increased temperature. Substantial and distinctive effects on protein concentrations and gene expression were evident among B2 oysters responding to elevated CO2 or elevated temperature. The combination of both stressors also altered oyster gill proteomes and gene expression. However, the impacts of elevated CO2 and temperature were not additive or synergistic, and may be antagonistic. The data suggest that the simultaneous exposure of CO2-resilient oysters to near-future projected ocean pH and temperature results in complex changes in molecular processes in order to prevent stress-induced cellular damage. The differential response of B2 oysters to the combined stressors also indicates that the addition of thermal stress may impair the resilience of these oysters to decreased pH. Overall, this study reveals the intracellular mechanisms that might enable marine calcifiers to endure the emergent, adverse seawater conditions resulting from climate change.

  2. Microsecond molecular dynamics simulations of intrinsically disordered proteins involved in the oxidative stress response.

    Directory of Open Access Journals (Sweden)

    Elio A Cino

    Full Text Available Intrinsically disordered proteins (IDPs are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTα and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2, with a common binding partner, Kelch-like ECH-associated protein 1(Keap1, are essential for regulating cellular response to oxidative stress. Misregulation of this pathway can lead to neurodegenerative diseases, premature aging and cancer. In order to understand the mechanisms these two disordered proteins employ to bind to Keap1, we performed extensive 0.5-1.0 microsecond atomistic molecular dynamics (MD simulations and isothermal titration calorimetry experiments to investigate the structure/dynamics of free-state ProTα and Neh2 and their thermodynamics of bindings. The results show that in their free states, both ProTα and Neh2 have propensities to form bound-state-like β-turn structures but to different extents. We also found that, for both proteins, residues outside the Keap1-binding motifs may play important roles in stabilizing the bound-state-like structures. Based on our findings, we propose that the binding of disordered ProTα and Neh2 to Keap1 occurs synergistically via preformed structural elements (PSEs and coupled folding and binding, with a heavy bias towards PSEs, particularly for Neh2. Our results provide insights into the molecular mechanisms Neh2 and ProTα bind to Keap1, information that is useful for developing therapeutics to enhance the oxidative stress response.

  3. Ground-state kinetics of bistable redox-active donor-acceptor mechanically interlocked molecules.

    Science.gov (United States)

    Fahrenbach, Albert C; Bruns, Carson J; Li, Hao; Trabolsi, Ali; Coskun, Ali; Stoddart, J Fraser

    2014-02-18

    The ability to design and confer control over the kinetics of theprocesses involved in the mechanisms of artificial molecular machines is at the heart of the challenge to create ones that can carry out useful work on their environment, just as Nature is wont to do. As one of the more promising forerunners of prototypical artificial molecular machines, chemists have developed bistable redox-active donor-acceptor mechanically interlocked molecules (MIMs) over the past couple of decades. These bistable MIMs generally come in the form of [2]rotaxanes, molecular compounds that constitute a ring mechanically interlocked around a dumbbell-shaped component, or [2]catenanes, which are composed of two mechanically interlocked rings. As a result of their interlocked nature, bistable MIMs possess the inherent propensity to express controllable intramolecular, large-amplitude, and reversible motions in response to redox stimuli. In this Account, we rationalize the kinetic behavior in the ground state for a large assortment of these types of bistable MIMs, including both rotaxanes and catenanes. These structures have proven useful in a variety of applications ranging from drug delivery to molecular electronic devices. These bistable donor-acceptor MIMs can switch between two different isomeric states. The favored isomer, known as the ground-state co-conformation (GSCC) is in equilibrium with the less favored metastable state co-conformation (MSCC). The forward (kf) and backward (kb) rate constants associated with this ground-state equilibrium are intimately connected to each other through the ground-state distribution constant, KGS. Knowing the rate constants that govern the kinetics and bring about the equilibration between the MSCC and GSCC, allows researchers to understand the operation of these bistable MIMs in a device setting and apply them toward the construction of artificial molecular machines. The three biggest influences on the ground-state rate constants arise from

  4. High-capacity thermo-responsive magnetic molecularly imprinted polymers for selective extraction of curcuminoids.

    Science.gov (United States)

    You, Qingping; Zhang, Yuping; Zhang, Qingwen; Guo, Junfang; Huang, Weihua; Shi, Shuyun; Chen, Xiaoqin

    2014-08-08

    Thermo-responsive magnetic molecularly imprinted polymers (TMMIPs) for selective recognition of curcuminoids with high capacity and selectivity have firstly been developed. The resulting TMMIPs were characterized by TEM, FT-IR, TGA, VSM and UV, which indicated that TMMIPs showed thermo-responsiveness [lower critical solution temperature (LCST) at 33.71°C] and rapid magnetic separation (5s). The polymerization, adsorption and release conditions were optimized in detail to obtain the highest binding capacity, selectivity and release ratio. We found that the adopted thermo-responsive monomer [N-isopropylacrylamide (NIPAm)] could be considered not only as inert polymer backbone for thermo-responsiveness but also as functional co-monomers combination with basic monomer (4-VP) for more specific binding sites when ethanol was added in binding solution. The maximum adsorption capacity with highest selectivity of curcumin was 440.3μg/g (1.93 times that on MMIPs with no thermosensitivity) at 45°C (above LCST) in 20% (v/v) ethanol solution on shrunk TMMIPs, and the maximum release proportion was about 98% at 20°C (below LCST) in methanol-acetic acid (9/1, v/v) solution on swelled TMMIPs. The adsorption process between curcumin and TMMIPs followed Langumuir adsorption isotherm and pseudo-first-order reaction kinetics. The prepared TMMIPs also showed high reproducibility (RSD<6% for batch-to-batch evaluation) and stability (only 7% decrease after five cycles). Subsequently, the TMMIPs were successfully applied for selective extraction of curcuminoids from complex natural product, Curcuma longa.

  5. Low molecular weight heparin alters porcine neutrophil responses to platelet-activating factor.

    Science.gov (United States)

    Kruse-Elliott, K T; Chaban, K; Grossman, J E; Tomasko, S; Kamke, C; Darien, B

    1998-09-01

    Because platelet-activating factor (PAF) is an important mediator of inflammation and heparin has anti-inflammatory effects, we hypothesized that low molecular weight heparin (LMWH) would inhibit PAF-induced activation and chemotaxis in porcine neutrophils. Citrated blood was obtained from pentobarbital-anesthetized pigs, and neutrophils were isolated over a 55%/65% Percoll gradient. The effect of LMWH on basal phorbol myristate acetate (PMA)-induced superoxide (SO) release, as well as its effect on PAF priming for PMA-induced SO release, were investigated. Additionally, the effect of LMWH on PAF-induced chemotaxis of neutrophils across transwell membranes was evaluated. Baseline SO release in response to PMA was .351+/-.046 nmol/10(6) cells/min, and this was decreased to .289+/-.034 nmol/10(6) cells/min by pretreatment with 50 U/mL LMWH. PMA-induced SO production was increased by .240+/-.042 nmol/10(6) cells/min when cells were primed with 10 microM PAF. This priming effect of PAF was reduced significantly by pretreatment of neutrophils with LMWH at 10 and 50 U/mL. Chemotaxis of neutrophils in response to 100 microM PAF was significantly decreased to 70.02+/-6.4% (n = 8) of the control response by pretreatment of cells with 50 U/mL LMWH. We conclude that LMWH has anti-inflammatory effects on porcine neutrophils, which includes attenuation of cell activation and chemotaxis in response to the lipid-derived inflammatory mediator, PAF.

  6. Redox signaling in pathophysiology of hypertension.

    Science.gov (United States)

    Majzunova, Miroslava; Dovinova, Ima; Barancik, Miroslav; Chan, Julie Y H

    2013-09-18

    Reactive oxygen species (ROS) are products of normal cellular metabolism and derive from various sources in different cellular compartments. Oxidative stress resultant from imbalance between ROS generation and antioxidant defense mechanisms is important in pathogenesis of cardiovascular diseases, such as hypertension, heart failure, atherosclerosis, diabetes, and cardiac hypertrophy. In this review we focus on hypertension and address sources of cellular ROS generation, mechanisms involved in regulation of radical homeostasis, superoxide dismutase isoforms in pathophysiology of hypertension; as well as radical intracellular signaling and phosphorylation processes in proteins of the affected cardiovascular tissues. Finally, we discuss the transcriptional factors involved in redox-sensitive gene transcription and antioxidant response, as well as their roles in hypertension.

  7. Redox regulation of autophagy in healthy brain and neurodegeneration.

    Science.gov (United States)

    Hensley, Kenneth; Harris-White, Marni E

    2015-12-01

    Autophagy and redox biochemistry are two major sub disciplines of cell biology which are both coming to be appreciated for their paramount importance in the etiology of neurodegenerative diseases including Alzheimer's disease (AD). Thus far, however, there has been relatively little exploration of the interface between autophagy and redox biology. Autophagy normally recycles macro-molecular aggregates produced through oxidative-stress mediated pathways, and also may reduce the mitochondrial production of reactive oxygen species through recycling of old and damaged mitochondria. Conversely, dysfunction in autophagy initiation, progression or clearance is evidenced to increase aggregation-prone proteins in neural and extraneural tissues. Redox mechanisms of autophagy regulation have been documented at the level of cross-talk between the Nrf2/Keap1 oxidant and electrophilic defense pathway and p62/sequestosome-1 (SQSTM1)-associated autophagy, at least in extraneural tissue; but other mechanisms of redox autophagy regulation doubtless remain to be discovered and the relevance of such processes to maintenance of neural homeostasis remains to be determined. This review summarizes current knowledge regarding the relationship of redox signaling, autophagy control, and oxidative stress as these phenomena relate to neurodegenerative disease. AD is specifically addressed as an example of the theme and as a promising indication for new therapies that act through engagement of autophagy pathways. To exemplify one such novel therapeutic entity, data is presented that the antioxidant and neurotrophic agent lanthionine ketimine-ethyl ester (LKE) affects autophagy pathway proteins including beclin-1 in the 3xTg-AD model of Alzheimer's disease where the compound has been shown to reduce pathological features and cognitive dysfunction.

  8. LDFF, the large molecular weight DNA fragmentation factor, is responsible for the large molecular weight DNA degradation during apoptosis in Xenopus egg extracts

    Institute of Scientific and Technical Information of China (English)

    Zhi Gang LU; Chuan Mao ZHANG; Zhong He ZHAI

    2004-01-01

    DNA degradation is a biochemical hallmark in apoptosis. It has been demonstrated in many cell types that there are two stages of DNA fragmentation during the apoptotic execution. In the early stage, chromatin DNA is cut into large molecular weight DNA fragments, although the responsible nuclease(s) has not been recognized. In the late stage, the chromatin DNA is cleaved further into short oligonucleosomal fragments by a well-characterized nuclease in apoptosis,the caspase-activated DNase (CAD/DFF40). In this study, we demonstrate that large molecular weight DNA fragmentation also occurs in Xenopus egg extracts in apoptosis. We show that the large molecular weight DNA fragmentation factor (LDFF) is not the Xenopus CAD homolog XCAD. LDFF is activated by caspase-3. The large molecular weight DNA fragmentation activity of LDFF is Mg2+-dependent and Ca2+-independent, can occur in both acidic and neutral pH conditions and can tolerate 45℃ treatment. These results indicate that LDFF in Xenopus egg extracts might be a new DNase (or DNases) responsible for the large DNA fragmentation.

  9. Molecular deconstruction, detection, and computational prediction of microenvironment-modulated cellular responses to cancer therapeutics.

    Science.gov (United States)

    Labarge, Mark A; Parvin, Bahram; Lorens, James B

    2014-04-01

    The field of bioengineering has pioneered the application of new precision fabrication technologies to model the different geometric, physical or molecular components of tissue microenvironments on solid-state substrata. Tissue engineering approaches building on these advances are used to assemble multicellular mimetic-tissues where cells reside within defined spatial contexts. The functional responses of cells in fabricated microenvironments have revealed a rich interplay between the genome and extracellular effectors in determining cellular phenotypes and in a number of cases have revealed the dominance of microenvironment over genotype. Precision bioengineered substrata are limited to a few aspects, whereas cell/tissue-derived microenvironments have many undefined components. Thus, introducing a computational module may serve to integrate these types of platforms to create reasonable models of drug responses in human tissues. This review discusses how combinatorial microenvironment microarrays and other biomimetic microenvironments have revealed emergent properties of cells in particular microenvironmental contexts, the platforms that can measure phenotypic changes within those contexts, and the computational tools that can unify the microenvironment-imposed functional phenotypes with underlying constellations of proteins and genes. Ultimately we propose that a merger of these technologies will enable more accurate pre-clinical drug discovery. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Molecular responses of mouse macrophages to copper and copper oxide nanoparticles inferred from proteomic analyses.

    Science.gov (United States)

    Triboulet, Sarah; Aude-Garcia, Catherine; Carrière, Marie; Diemer, Hélène; Proamer, Fabienne; Habert, Aurélie; Chevallet, Mireille; Collin-Faure, Véronique; Strub, Jean-Marc; Hanau, Daniel; Van Dorsselaer, Alain; Herlin-Boime, Nathalie; Rabilloud, Thierry

    2013-11-01

    The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins (especially oxidative phosphorylation complex subunits). Validation studies employing functional analyses showed that the increases in glutathione biosynthesis and in mitochondrial complexes observed in the proteomic screen were critical to cell survival upon stress with copper-based nanoparticles; pharmacological inhibition of these two pathways enhanced cell vulnerability to copper-based nanoparticles, but not to copper ions. Furthermore, functional analyses using primary macrophages derived from bone marrow showed a decrease in reduced glutathione levels, a decrease in the mitochondrial transmembrane potential, and inhibition of phagocytosis and of lipopolysaccharide-induced nitric oxide production. However, only a fraction of these effects could be obtained with copper ions. In conclusion, this study showed that macrophage functions are significantly altered by copper-based nanoparticles. Also highlighted are the cellular pathways modulated by cells for survival and the exemplified cross-toxicities that can occur between copper-based nanoparticles and pharmacological agents.

  11. Innate immune memory: Implications for host responses to damage-associated molecular patterns.

    Science.gov (United States)

    Crișan, Tania O; Netea, Mihai G; Joosten, Leo A B

    2016-04-01

    Cells of the innate immune system build immunological memory via epigenetic reprogramming after stimulations with microbial ligands. This functional readjustment allows for enhanced nonspecific inflammatory responses upon secondary challenges, a process termed "trained immunity." The epigenomic blueprint of trained monocytes has been recently reported, which revealed several important immunologic and metabolic mechanisms that underlie these changes. Interestingly, similar long-term reprogramming of cytokine production has also been described to be induced by endogenous damage-associated molecular patterns (DAMPs). Here, we present an overview of the novel data showing that endogenous alarm signals associated with tissue damage and sterile inflammation can induce trained immunity through epigenetic regulation of transcriptional programs. We describe new and old evidence of persistent effects of DAMPs in driving inflammation and enforce the concept that the influence of tissue-derived signals is critical in adjusting the magnitude and type of immune response built by the host. The better characterization of trained immunity for the persistence of inflammation induced by DAMPs would provide new possibilities for intervention in aging and autoinflammatory disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. A Quick-responsive DNA Nanotechnology Device for Bio-molecular Homeostasis Regulation.

    Science.gov (United States)

    Wu, Songlin; Wang, Pei; Xiao, Chen; Li, Zheng; Yang, Bing; Fu, Jieyang; Chen, Jing; Wan, Neng; Ma, Cong; Li, Maoteng; Yang, Xiangliang; Zhan, Yi

    2016-08-10

    Physiological processes such as metabolism, cell apoptosis and immune responses, must be strictly regulated to maintain their homeostasis and achieve their normal physiological functions. The speed with which bio-molecular homeostatic regulation occurs directly determines the ability of an organism to adapt to conditional changes. To produce a quick-responsive regulatory system that can be easily utilized for various types of homeostasis, a device called nano-fingers that facilitates the regulation of physiological processes was constructed using DNA origami nanotechnology. This nano-fingers device functioned in linked open and closed phases using two types of DNA tweezers, which were covalently coupled with aptamers that captured specific molecules when the tweezer arms were sufficiently close. Via this specific interaction mechanism, certain physiological processes could be simultaneously regulated from two directions by capturing one biofactor and releasing the other to enhance the regulatory capacity of the device. To validate the universal application of this device, regulation of the homeostasis of the blood coagulant thrombin was attempted using the nano-fingers device. It was successfully demonstrated that this nano-fingers device achieved coagulation buffering upon the input of fuel DNA. This nano-device could also be utilized to regulate the homeostasis of other types of bio-molecules.

  13. The emerging roles of microRNAs in the molecular responses of metabolic rate depression

    Institute of Scientific and Technical Information of China (English)

    Kyle K. Biggar; Kenneth B. Storey

    2011-01-01

    Metabolic rate depression is an important survival strategy for many animal species and a common element of hibernation, torpor,estivation, anoxia and diapause. Studies of the molecular mechanisms that regulate reversible transitions to and from hypometabolic states have identified principles of regulatory control. These control mechanisms are conserved among biologically diverse organisms and include the coordinated reduction of specific groups of key regulatory enzymes or proteins in the cell, a process likely driven by microRNA target repression/degradation. The present review focuses on a growing area of research in hypometabolism and mechanisms involving the rapid and reversible control of translation facilitated by microRNAs. The analysis draws primarily from current research on three animal models: hibernating mammals, anoxic turtles and freeze-tolerant frogs (with selected examples from multiple other sources). Here, we demonstrate a link between metabolic rate depression, a well-documented response to periods of environmental stress, and microRNA expression. Microarray-based expression profiles and PCR-driven studies have revealed that specific microRNAs are induced in response to environmental stress. Selected members of this group decrease pro-apeptotic signaling,reduce muscle wasting and reduce protein translation, whereas other members contribute to cell cycle arrest and mitogen-activated protein kinase signaling. Many of the same microRNAs are frequently deregulated in numerous disease pathologies and, hence, the hypometabolism model could provide a novel approach for the treatment of stroke and heart attack in humans.

  14. Molecular mechanism of dehydrin in response to environmental stress in plant

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yuxiu; WANG Zi; XU Jin

    2007-01-01

    Dehydrins, known as the D-11 subgroup of late embryogenesis abundant (LEA) protein, are an immunologically distinct family of proteins, which typically accumulate in desiccation-tolerant seed embryo or in vegetative tissues in response to various environmental stresses such as drought, salinity and freezing. The existence of conservative sequences designated as K, S, and Y segments is a structural feature of dehydrins, and the K segment found in all dehydrins represents a highly conserved 15 amino acid motif (EKKGIMDKIKEKLPG) and forms an amphiphilic a-helix. According to the arrangement of these domains and clustering analysis, dehydrins are subdivided into 5 subtypes: YnSK, Kn, KnS, SKn and YnK. Different types of dehydrins are induced by different environmental stress in plants. Study results showed that dehydrins might play important protective roles under abiotic stress via a number of different mechanisms, including improving or protecting enzyme activities by the cryoprotective activity in responding to freeze/thaw or dehydration; stabilizing vesicles or other endomembrane structures by function as the membrane stabilizer during freeze induced dehydration,and preventing the membrane system from the oxidative damage induced by reactive oxygen radicals as the radical scavenger. Here, the gene expression and molecular mechanisms of dehydrin in response to stress in plants are discussed.

  15. Frictional Response of Molecularly Thin Liquid Polymer Films Subject to Constant Shear Stress

    Science.gov (United States)

    Tschirhart, Charles; Troian, Sandra

    2014-03-01

    Measurements of the frictional response of nanoscale viscous films are typically obtained using the surface force apparatus in which a fluid layer is confined between smooth solid substrates approaching at constant speed or force. The squeezing pressure causes lateral flow from which the shear viscosity can be deduced. Under these conditions however, molecularly thin films tend to solidify wholly or partially and estimates of the shear viscosity can exceed those in macroscale films by many orders of magnitude. This problem can be avoided altogether by examining the response of an initially flat, supported, free surface film subject to comparable values of surface shear stress by application of an external inert gas stream. This method was first conceived by Derjaguin in 1944; more recent studies by Mate et al. at IBM Almaden on complex polymeric systems have uncovered fluid layering and other interesting behaviors. The only drawback is that this alternative technique requires an accurate model for interface distortion. We report on ellipsometric measurements of ultrathin polymeric films in efforts to determine whether the usual interface equations for free surface films based purely on continuum models can be properly extended to nanoscale films. Supported by a Fred and Jean Felberg Fellowship and G. W. Housner Student Discovery Fund.

  16. Molecular Responses of Mouse Macrophages to Copper and Copper Oxide Nanoparticles Inferred from Proteomic Analyses*

    Science.gov (United States)

    Triboulet, Sarah; Aude-Garcia, Catherine; Carrière, Marie; Diemer, Hélène; Proamer, Fabienne; Habert, Aurélie; Chevallet, Mireille; Collin-Faure, Véronique; Strub, Jean-Marc; Hanau, Daniel; Van Dorsselaer, Alain; Herlin-Boime, Nathalie; Rabilloud, Thierry

    2013-01-01

    The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins (especially oxidative phosphorylation complex subunits). Validation studies employing functional analyses showed that the increases in glutathione biosynthesis and in mitochondrial complexes observed in the proteomic screen were critical to cell survival upon stress with copper-based nanoparticles; pharmacological inhibition of these two pathways enhanced cell vulnerability to copper-based nanoparticles, but not to copper ions. Furthermore, functional analyses using primary macrophages derived from bone marrow showed a decrease in reduced glutathione levels, a decrease in the mitochondrial transmembrane potential, and inhibition of phagocytosis and of lipopolysaccharide-induced nitric oxide production. However, only a fraction of these effects could be obtained with copper ions. In conclusion, this study showed that macrophage functions are significantly altered by copper-based nanoparticles. Also highlighted are the cellular pathways modulated by cells for survival and the exemplified cross-toxicities that can occur between copper-based nanoparticles and pharmacological agents. PMID:23882024

  17. EFFECTS OF MOLECULAR WEIGHT ON THERMAL RESPONSIVE PROPERTY OF PEGYLATED POLY-L-GLUTAMATES

    Institute of Scientific and Technical Information of China (English)

    Shusheng Zhang; Chongyi Chen; Zhibo Li

    2013-01-01

    We investigated the ring opening polymerization (ROP) of di-and tri-ethylene glycol monomethyl ether functionalized L-glutamate N-carboxyanhydrides (NCAs) using hexamethyldisilazane (HMDS) as primary initiator and 1,5,7-triazabicyclo-[4.4.0]dec-5-ene (TBD) as co-initiator.The binary initiator system afforded a living ROP for these pegylated NCAs,and a series of homopolypeptides with controlled molecular weight (MW) and low polydispersity were obtained.We then systematically studied the helical content and clouding point (CP) dependence on polypeptide MW using circular dichroism (CD) spectroscopy and turbidity measurements,respectively.We found that the helical content of both homopolypeptides increased with MW,but the triethylene glycol functionalized poly-L-glutamate (poly-L-EG3Glu) intended to form more stable α-helical structure than diethylene glycol functionalized counterpart (poly-L-EG2Glu) at similar MW.Accordingly,the CP of poly-L-EG2Glu with known end group has strong dependence on its helical content,which is essentially determined by MW.Our results suggested that the thermal responsive properties of these unique pegylated poly-L-glutamates not only rely on their chemical structure but also on their secondary structures,which is different from conventional thermal responsive polymers.

  18. Current-voltage characteristics and transition voltage spectroscopy of individual redox proteins.

    Science.gov (United States)

    Artés, Juan M; López-Martínez, Montserrat; Giraudet, Arnaud; Díez-Pérez, Ismael; Sanz, Fausto; Gorostiza, Pau

    2012-12-19

    Understanding how molecular conductance depends on voltage is essential for characterizing molecular electronics devices. We reproducibly measured current-voltage characteristics of individual redox-active proteins by scanning tunneling microscopy under potentiostatic control in both tunneling and wired configurations. From these results, transition voltage spectroscopy (TVS) data for individual redox molecules can be calculated and analyzed statistically, adding a new dimension to conductance measurements. The transition voltage (TV) is discussed in terms of the two-step electron transfer (ET) mechanism. Azurin displays the lowest TV measured to date (0.4 V), consistent with the previously reported distance decay factor. This low TV may be advantageous for fabricating and operating molecular electronic devices for different applications. Our measurements show that TVS is a helpful tool for single-molecule ET measurements and suggest a mechanism for gating of ET between partner redox proteins.

  19. Mouse redox histology using genetically encoded probes.

    Science.gov (United States)

    Fujikawa, Yuuta; Roma, Leticia P; Sobotta, Mirko C; Rose, Adam J; Diaz, Mauricio Berriel; Locatelli, Giuseppe; Breckwoldt, Michael O; Misgeld, Thomas; Kerschensteiner, Martin; Herzig, Stephan; Müller-Decker, Karin; Dick, Tobias P

    2016-03-15

    Mapping the in vivo distribution of endogenous oxidants in animal tissues is of substantial biomedical interest. Numerous health-related factors, including diet, physical activity, infection, aging, toxins, or pharmacological intervention, may cause redox changes. Tools are needed to pinpoint redox state changes to particular organs, tissues, cell types, and subcellular organelles. We describe a procedure that preserves the in vivo redox state of genetically encoded redox biosensors within histological tissue sections, thus providing "redox maps" for any tissue and comparison of interest. We demonstrate the utility of the technique by visualizing endogenous redox differences and changes in the context of tumor growth, inflammation, embryonic development, and nutrient starvation. Copyright © 2016, American Association for the Advancement of Science.

  20. Late-onset running biphasically improves redox balance, energy- and methylglyoxal-related status, as well as SIRT1 expression in mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Stefano Falone

    Full Text Available Despite the active research in this field, molecular mechanisms underlying exercise-induced beneficial effects on brain physiology and functions are still matter of debate, especially with regard to biological processes activated by regular exercise affecting the onset and progression of hippocampal aging in individuals unfamiliar with habitual physical activity. Since such responses seem to be mediated by changes in antioxidative, antiglycative and metabolic status, a possible exercise-induced coordinated response involving redox, methylglyoxal- and sirtuin-related molecular networks may be hypothesized. In this study, hippocampi of CD1 mice undergoing the transition from mature to middle age were analyzed for redox-related profile, oxidative and methylglyoxal-dependent damage patterns, energy metabolism, sirtuin1 and glyoxalase1 expression after a 2- or 4-mo treadmill running program. Our findings suggested that the 4-mo regular running lowered the chance of dicarbonyl and oxidative stress, activated mitochondrial catabolism and preserved sirtuin1-related neuroprotection. Surprisingly, the same cellular pathways were negatively affected by the first 2 months of exercise, thus showing an interesting biphasic response. In conclusion, the duration of exercise caused a profound shift in the response to regular running within the rodent hippocampus in a time-dependent fashion. This research revealed important details of the interaction between exercise and mammal hippocampus during the transition from mature to middle age, and this might help to develop non-pharmacological approaches aimed at retarding brain senescence, even in individuals unfamiliar with habitual exercise.

  1. Transcriptomic analysis of molecular responses in Malus domestica 'M26' roots affected by apple replant disease.

    Science.gov (United States)

    Weiß, Stefan; Bartsch, Melanie; Winkelmann, Traud

    2017-06-01

    Gene expression studies in roots of apple replant disease affected plants suggested defense reactions towards biotic stress to occur which did not lead to adequate responses to the biotic stressors. Apple replant disease (ARD) leads to growth inhibition and fruit yield reduction in replanted populations and results in economic losses for tree nurseries and fruit producers. The etiology is not well understood on a molecular level and causal agents show a great diversity indicating that no definitive cause, which applies to the majority of cases, has been found out yet. Hence, it is pivotal to gain a better understanding of the molecular and physiological reactions of the plant when affected by ARD and later to overcome the disease, for example by developing tolerant rootstocks. For the first time, gene expression was investigated in roots of ARD affected plants employing massive analysis of cDNA ends (MACE) and RT-qPCR. In reaction to ARD, genes in secondary metabolite production as well as plant defense, regulatory and signaling genes were upregulated whereas for several genes involved in primary metabolism lower expression was detected. For internal verification of MACE data, candidate genes were tested via RT-qPCR and a strong positive correlation between both datasets was observed. Comparison of apple 'M26' roots cultivated in ARD soil or γ-irradiated ARD soil suggests that typical defense reactions towards biotic stress take place in ARD affected plants but they did not allow responding to the biotic stressors attack adequately, leading to the observed growth depressions in ARD variants.

  2. Listeria monocytogenes meningoencephalitis: molecular methods for diagnosis and for monitoring the response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Andrea Piana

    2005-03-01

    Full Text Available

    Background. Listeria monocytogenes is one of the most important human foodborne pathogens; it may be responsible for several disorders, like meningoencephalitis. Listerial isolation in cerebrospinal fluid (CSF is often difficult using microbiologic traditional assays. The aim of this study is to evaluate the reliability of molecular techniques as an alternative tool in order to identify Listeria monocytogenes meningitis and in particular, to evaluate a real-time PCR and a conventional PCR for the target hlyA gene.

    Methods. In 2000-2004, 145 patients, without T-cell immunodeficiency, affected by meningoencephalitis of unknown origin were admitted to the Infectious Diseases Institute of Sassari, Italy; a lumbar puncture was performed at the time of hospital admission. Two different PCR techniques, i.e. RT-PCR and a conventional PCR, were performed in order to detect CNS listerial infection, in conjunction with traditional microbiologic assays.

    Results. We identified fourteen patients affected by listerial meningitis using RT-PCR and conventional PCR. All but one of the CSF cultures were negative for L. monocytogenes. Molecular techniques were performed on the CSF samples collected during follow-up revealing that signal intensity decreased by 40%, 80% and 100% at day 15, 30 and 55 respectively, from the start of antibiotic treatment.

    Conclusions. Considering the seriousness of CNS involvement caused by L. monocytogenes infection, prompt diagnosis is necessary in order to rapidly start specific treatment. Conventional PCR and RT-PCR are rapid assays for L. monocytogenes diagnosis and they might be useful for monitoring the efficacy of antibiotic therapy

  3. Membranes for Redox Flow Battery Applications

    OpenAIRE

    Maria Skyllas-Kazacos; Aishwarya Parasuraman; Tuti Mariana Lim; Suminto Winardi; Helen Prifti

    2012-01-01

    The need for large scale energy storage has become a priority to integrate renewable energy sources into the electricity grid. Redox flow batteries are considered the best option to store electricity from medium to large scale applications. However, the current high cost of redox flow batteries impedes the wide spread adoption of this technology. The membrane is a critical component of redox flow batteries as it determines the performance as well as the economic viability of the batteries. Th...

  4. Roles of oxidative stress and redox regulation in atherosclerosis.

    Science.gov (United States)

    Kondo, Takahito; Hirose, Makoto; Kageyama, Kan

    2009-10-01

    Oxidative stress is believed to be a cause of aging and cardiovascular disorders. In response to inflam-mation or endothelial cell injury, production of reactive oxygen species (ROS) is enhanced in vascular cells. These changes contribute to the initiation of atherosclerosis. Vascular cells possess anti-oxidant systems to protect against oxidative stress, in addition to the redox system. The redox status of pro-tein thiols is important for cellular functions. The Akt signaling pathway exerts effects on survival and apoptosis, and is regulated by the glutathione (GSH)/glutaredoxin (GRX)-dependent redox sys-tem. Sex hormones such as estrogens protect against oxidative stress by protecting the Akt signaling pathway but the physiological role of the extracellular GSH/GRX system has not been clarified, although found an increase in the levels of S-glutathionylated serum proteins in patients with athero-sclerosis obliterans. The results suggested that impaired serum redox potential is a marker of the development vascular dysfunction and estrogen has a possible role in the prevention of atherosclerosis.

  5. Redox regime shifts in microbially-mediated biogeochemical cycles

    Science.gov (United States)

    Bush, T.; Butler, I. B.; Free, A.; Allen, R. J.

    2015-02-01

    Understanding how the Earth's biogeochemical cycles respond to environmental change is a prerequisite for the prediction and mitigation of the effects of anthropogenic perturbations. Microbial populations mediate key steps in these cycles, yet are often crudely represented in biogeochemical models. Here, we show that microbial population dynamics can qualitatively affect the response of biogeochemical cycles to environmental change. Using simple and generic mathematical models, we find that nutrient limitations on microbial population growth can lead to regime shifts, in which the redox state of a biogeochemical cycle changes dramatically as the availability of a redox-controlling species, such as oxygen or acetate, crosses a threshold (a "tipping point"). These redox regime shifts occur in parameter ranges that are relevant to the sulfur and nitrogen cycles in the present-day natural environment, and may also have relevance to iron cycling in the iron-containing Proterozoic and Archean oceans. We show that redox regime shifts also occur in models with physically realistic modifications, such as additional terms, chemical states, or microbial populations. Our work reveals a possible new mechanism by which regime shifts can occur in nutrient-cycling ecosystems and biogeochemical cycles, and highlights the importance of considering microbial population dynamics in models of biogeochemical cycles.

  6. Redox regime shifts in microbially mediated biogeochemical cycles

    Science.gov (United States)

    Bush, T.; Butler, I. B.; Free, A.; Allen, R. J.

    2015-06-01

    Understanding how the Earth's biogeochemical cycles respond to environmental change is a prerequisite for the prediction and mitigation of the effects of anthropogenic perturbations. Microbial populations mediate key steps in these cycles, yet they are often crudely represented in biogeochemical models. Here, we show that microbial population dynamics can qualitatively affect the response of biogeochemical cycles to environmental change. Using simple and generic mathematical models, we find that nutrient limitations on microbial population growth can lead to regime shifts, in which the redox state of a biogeochemical cycle changes dramatically as the availability of a redox-controlling species, such as oxygen or acetate, crosses a threshold (a "tipping point"). These redox regime shifts occur in parameter ranges that are relevant to the present-day sulfur cycle in the natural environment and the present-day nitrogen cycle in eutrophic terrestrial environments. These shifts may also have relevance to iron cycling in the iron-containing Proterozoic and Archean oceans. We show that redox regime shifts also occur in models with physically realistic modifications, such as additional terms, chemical states, or microbial populations. Our work reveals a possible new mechanism by which regime shifts can occur in nutrient-cycling ecosystems and biogeochemical cycles, and highlights the importance of considering microbial population dynamics in models of biogeochemical cycles.

  7. Redox conditions for mantle plumes

    Science.gov (United States)

    Heister, L. E.; Lesher, C. E.

    2005-12-01

    The vanadium to scandium ratio (V/Sc) for basalts from mid-ocean ridge (MOR) and arc environments has been proposed as a proxy for fO2 conditions during partial melting (e.g. [1] and [2]). Contrary to barometric measurements of the fO2 of primitive lavas, the V/Sc ratio of the upper mantle at mid-ocean ridges and arcs is similar, leading previous authors to propose that the upper mantle has uniform redox potential and is well-buffered. We have attempted to broaden the applicability of the V/Sc parameter to plume-influenced localities (both oceanic and continental), where mantle heterogeneities associated with recycled sediments, mafic crust, and metasomatized mantle, whether of shallow or deep origin, exist. We find that primitive basalts from the North Atlantic Igneous Province (NAIP), Hawaii (both the Loa and Kea trends), Deccan, Columbia River, and Siberian Traps show a range of V/Sc ratios that are generally higher (average ~9) than those for MOR (average ~ 6.7) or arc (average ~7) lavas. Based on forward polybaric decompression modeling, we attribute these differences to polybaric melting and melt segregation within the garnet stability field rather than the presence of a more oxidized mantle in plume-influenced settings. Like MORB, the V/Sc ratios for plume-influenced basalts can be accounted for by an oxidation state approximately one log unit below the Ni-NiO buffer (NNO-1). Our analysis suggests that source heterogeneities have little, if any, resolvable influence on mantle redox conditions, although they have significant influence on the trace element and isotopic composition of mantle-derived melts. We suggest that variations in the redox of erupted lavas is largely a function of shallow lithospheric processes rather than intrinsic to the mantle source, regardless of tectonic setting. [1] Li and Lee (2004) EPSL, [2] Lee et al. (2005) J. of Petrology

  8. Marsh plant response to metals: Exudation of aliphatic low molecular weight organic acids (ALMWOAs)

    Science.gov (United States)

    Rocha, A. Cristina S.; Almeida, C. Marisa R.; Basto, M. Clara P.; Vasconcelos, M. Teresa S. D.

    2016-03-01

    Metal exposure is known to induce the production and secretion of substances, such as aliphatic low molecular weight organic acids (ALMWOAs), into the rhizosphere by plant roots. Knowledge on this matter is extensive for soil plants but still considerably scarce regarding marsh plants roots adapted to high salinity media. Phragmites australis and Halimione portulacoides, two marsh plants commonly distributed in European estuarine salt marshes, were used to assess the response of roots of both species, in terms of ALMWOAs exudation, to Cu, Ni and Cd exposure (isolated and in mixture since in natural environment, they are exposed to mixture of metals). As previous studies were carried out in unrealistic and synthetic media, here a more natural medium was selected. Therefore, in vitro experiments were carried out, with specimens of both marsh plants, and in freshwater contaminated with two different Cu, Ni and Cd concentrations (individual metal and in mixture). Both marsh plants were capable of liberating ALMWOAs into the surrounding medium. Oxalic, citric and maleic acids were found in P. australis root exudate solutions and oxalic and maleic acids in H. portulacoides root exudate solutions. ALMWOA liberation by both plants was plant species and metal-dependent. For instance, Cu affected the exudation of oxalic acid by H. portulacoides and of oxalic and citric acids by P. australis roots. In contrast, Ni and Cd did not stimulate any specific response. Regarding the combination of all metals, H. portulacoides showed a similar response to that observed for Cu individually. However, in the P. australis case, at high metal concentration mixture, a synergetic effect led to the increase of oxalic acid levels in root exudate solution and to a decrease of citric acid liberation. A correlation between ALMWOAs exudation and metal accumulation could not be established. P. australis and H. portulacoides are considered suitable metal phytoremediators of estuarine impacted areas

  9. Computation of Raman Spectra from Density Matrix Linear Response Theory in Extended Lagrangian Born-Oppenheimer Molecular Dynamics

    Science.gov (United States)

    Niklasson, Anders; Coe, Joshua; Cawkwell, Marc

    2011-06-01

    Linear response calculations based on density matrix perturbation theory [A. M. N. Niklasson and M. Challacombe, Phys. Rev. Lett. 92, 193001 (2004)] have been developed within a self-consistent tight-binding method for extended Lagrangian Born-Oppenheimer molecular dynamics [A. M. N. Niklasson, Phys. Rev. Lett., 100, 123004 (2008)]. Besides the nuclear coordinates, extended auxiliary electronic degrees of freedom are added to the regular Born-Oppenheimer Lagrangian, both for the electronic ground state and response densities. This formalism enables highly efficient, on-the-fly, analytic computations of the polarizability autocorrelation functions and the Raman spectra during energy conserving Born-Oppenheimer molecular dynamics trajectories. We will illustrate these capabilities via time-resolved Raman spectra computed during explicit, reactive molecular dynamics simulations of the shock compression of methane, benzene, tert-butylacetylene. Comparisons will be made with experimental results where possible.

  10. Molecular phenology in plants: in natura systems biology for the comprehensive understanding of seasonal responses under natural environments.

    Science.gov (United States)

    Kudoh, Hiroshi

    2016-04-01

    Phenology refers to the study of seasonal schedules of organisms. Molecular phenology is defined here as the study of the seasonal patterns of organisms captured by molecular biology techniques. The history of molecular phenology is reviewed briefly in relation to advances in the quantification technology of gene expression. High-resolution molecular phenology (HMP) data have enabled us to study phenology with an approach of in natura systems biology. I review recent analyses of FLOWERING LOCUS C (FLC), a temperature-responsive repressor of flowering, along the six steps in the typical flow of in natura systems biology. The extensive studies of the regulation of FLC have made this example a successful case in which a comprehensive understanding of gene functions has been progressing. The FLC-mediated long-term memory of past temperatures creates time lags with other seasonal signals, such as photoperiod and short-term temperature. Major signals that control flowering time have a phase lag between them under natural conditions, and hypothetical phase lag calendars are proposed as mechanisms of season detection in plants. Transcriptomic HMP brings a novel strategy to the study of molecular phenology, because it provides a comprehensive representation of plant functions. I discuss future perspectives of molecular phenology from the standpoints of molecular biology, evolutionary biology and ecology.

  11. Lung extracellular matrix and redox regulation.

    Science.gov (United States)

    Watson, Walter H; Ritzenthaler, Jeffrey D; Roman, Jesse

    2016-08-01

    Pulmonary fibrosis affects millions worldwide and, even though there has been a significant investment in understanding the processes involved in wound healing and maladaptive repair, a complete understanding of the mechanisms responsible for lung fibrogenesis eludes us, and interventions capable of reversing or halting disease progression are not available. Pulmonary fibrosis is characterized by the excessive expression and uncontrolled deposition of extracellular matrix (ECM) proteins resulting in erosion of the tissue structure. Initially considered an 'end-stage' process elicited after injury, these events are now considered pathogenic and are believed to contribute to the course of the disease. By interacting with integrins capable of signal transduction and by influencing tissue mechanics, ECM proteins modulate processes ranging from cell adhesion and migration to differentiation and growth factor expression. In doing so, ECM proteins help orchestrate complex developmental processes and maintain tissue homeostasis. However, poorly controlled deposition of ECM proteins promotes inflammation, fibroproliferation, and aberrant differentiation of cells, and has been implicated in the pathogenesis of pulmonary fibrosis, atherosclerosis and cancer. Considering their vital functions, ECM proteins are the target of investigation, and oxidation-reduction (redox) reactions have emerged as important regulators of the ECM. Oxidative stress invariably accompanies lung disease and promotes ECM expression directly or through the overproduction of pro-fibrotic growth factors, while affecting integrin binding and activation. In vitro and in vivo investigations point to redox reactions as targets for intervention in pulmonary fibrosis and related disorders, but studies in humans have been disappointing probably due to the narrow impact of the interventions tested, and our poor understanding of the factors that regulate these complex reactions. This review is not meant to

  12. Lung extracellular matrix and redox regulation

    Directory of Open Access Journals (Sweden)

    Walter H. Watson

    2016-08-01

    Full Text Available Pulmonary fibrosis affects millions worldwide and, even though there has been a significant investment in understanding the processes involved in wound healing and maladaptive repair, a complete understanding of the mechanisms responsible for lung fibrogenesis eludes us, and interventions capable of reversing or halting disease progression are not available. Pulmonary fibrosis is characterized by the excessive expression and uncontrolled deposition of extracellular matrix (ECM proteins resulting in erosion of the tissue structure. Initially considered an ‘end-stage’ process elicited after injury, these events are now considered pathogenic and are believed to contribute to the course of the disease. By interacting with integrins capable of signal transduction and by influencing tissue mechanics, ECM proteins modulate processes ranging from cell adhesion and migration to differentiation and growth factor expression. In doing so, ECM proteins help orchestrate complex developmental processes and maintain tissue homeostasis. However, poorly controlled deposition of ECM proteins promotes inflammation, fibroproliferation, and aberrant differentiation of cells, and has been implicated in the pathogenesis of pulmonary fibrosis, atherosclerosis and cancer. Considering their vital functions, ECM proteins are the target of investigation, and oxidation–reduction (redox reactions have emerged as important regulators of the ECM. Oxidative stress invariably accompanies lung disease and promotes ECM expression directly or through the overproduction of pro-fibrotic growth factors, while affecting integrin binding and activation. In vitro and in vivo investigations point to redox reactions as targets for intervention in pulmonary fibrosis and related disorders, but studies in humans have been disappointing probably due to the narrow impact of the interventions tested, and our poor understanding of the factors that regulate these complex reactions. This

  13. Molecular keys unlock the mysteries of variable survival responses of blue crabs to hypoxia.

    Science.gov (United States)

    Bell, Geoffrey W; Eggleston, David B; Noga, Edward J

    2010-05-01

    Hypoxia is a major stressor in coastal ecosystems, yet generalizing its impacts on fish and shellfish populations across hypoxic events is difficult due to variability among individuals in their history of exposure to hypoxia and related abiotic variables, and subsequent behavioral and survival responses. Although aquatic animals have diverse physiological responses to cope with hypoxia, we know little about how inter-individual variation in physiological state affects survival and behavioral decisions under hypoxic conditions. Laboratory experiments coupled with molecular techniques determined how extrinsic factors (e.g., water body and temperature) and respiratory physiology (hemocyanin concentration and structure) affected survival and behavior of adult blue crabs (Callinectes sapidus) exposed to different levels of hypoxia over a 30-h time period. Nearly 100% of crabs survived the 1.3 mg dissolved oxygen (DO) l(-1) treatment (18.4% air saturation), suggesting that adult blue crabs are tolerant of severe hypoxia. Probability of survival decreased with increasing hypoxic exposure time, lower DO, and increasing temperature. Individual-level differences in survival correlated with water body and crab size. Crabs collected from the oligo/mesohaline and hypoxic Neuse River Estuary (NRE), North Carolina, USA survived hypoxic exposures longer than crabs from the euhaline and normoxic Bogue and Back Sounds, North Carolina. Furthermore, small NRE crabs survived longer than large NRE crabs. Hemocyanin (Hcy) concentration did not explain these individual-level differences, however, hypoxia-tolerant crabs had Hcy structures indicative of a high-O(2)-affinity form of Hcy, suggesting Hcy "quality" (i.e., structure) may be more important for hypoxia survival than Hcy "quantity" (i.e., concentration). The geographic differences in survival we observed also highlight the importance of carefully selecting experimental animals when planning to extrapolate results to the population

  14. The Physiological and Molecular Responses of Arabidopsis thaliana to the Stress of Oxalic Acid

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-ting; LIN Jie; SHAO Xue-feng; OU Xiao-ming; WANG Zong-hua; LU Guo-dong

    2009-01-01

    Many fungal phytopathogens can secrete oxalic acid (OA), which is the crucial pathogenic determinant and plays important roles in pathogenicity and virulence of pathogen during infection process. However, how plants respond to OA stress still needs further characterization. In this study, we observed the physiological and molecular responses of Arabidopsis thaliana to OA stress. The leaves of 6-wk-old A. thaliana were sprayed with OA and distilled water respectively, and 0, 2, 4, 8, 12, and 24 h later, the leaves were collected and the contents of MDA, H2O2, and GSH, and the activities of CAT, SOD, and POD were determined and the expressions of PR1 and PDF1.2 were also studied. Under the stress of 30 mmol L-1 OA, SOD activity was first enhanced to reduce the accumulation of O2-. But immediately, POD, CAT, and GSH all decreased extremely resulting in the accumulation of H2O2, and the MDA content increased 24 h later. GSH activity was enhanced significantly at 24 h after OA used. However, H2O2 wasn't eliminated at the same time, suggesting that the activity inhibitions of POD and CAT might be the reasons that caused Arabidopsis cells' impairment under OA stress. RT-PCR results indicated that PDF1.2, a marker gene of the JA/ET signaling was significantly induced; PR1, an indicator gene in SA signaling, was slighlty induced from 8 to 12 h after OA stress. In conclusion, Arabidopsis may recruit metabolism of reactive oxygen, both JA/ET and SA signaling pathways to respond to OA stress. These results will facilitate our further understanding the mechanisms of plant response to OA and OA-dependent fungal infection.

  15. Physiological, biochemical and molecular responses in four Prunus rootstocks submitted to drought stress.

    Science.gov (United States)

    Jiménez, Sergio; Dridi, Jihène; Gutiérrez, Diego; Moret, David; Irigoyen, Juan J; Moreno, María A; Gogorcena, Yolanda

    2013-10-01

    An understanding of the mechanisms that determine plant response to reduced water availability is essential to improve water-use efficiency (WUE) of stone fruit crops. The physiological, biochemical and molecular drought responses of four Prunus rootstocks (GF 677, Cadaman, ROOTPAC 20 and ROOTPAC(®) R) budded with 'Catherina' peach cultivar were studied. Trees were grown in 15-l containers and subjected to a progressive water stress for 26 days, monitoring soil moisture content by time domain reflectometry. Photosynthetic and gas exchange parameters were determined. Root and leaf soluble sugars and proline content were also measured. At the end of the experiment, stressed plants showed lower net photosynthesis rate, stomatal conductance and transpiration rate, and higher intrinsic leaf WUE (AN/gs). Soluble sugars and proline concentration changes were observed, in both root and leaf tissues, especially in an advanced state of stress. The accumulation of proline in roots and leaves with drought stress was related to the decrease in osmotic potential and increase in WUE, whereas the accumulation of sorbitol in leaves, raffinose in roots and proline in both tissues was related only to the increase in the WUE. Owing to the putative role of raffinose and proline as antioxidants and their low concentration, they could be ameliorating deleterious effects of drought-induced oxidative stress by protecting membranes and enzymes rather than acting as active osmolytes. Higher expression of P5SC gene in roots was also consistent with proline accumulation in the tolerant genotype GF 677. These results indicate that accumulation of sorbitol, raffinose and proline in different tissues and/or the increase in P5SC expression could be used as markers of drought tolerance in peach cultivars grafted on Prunus rootstocks.

  16. Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy.

    Science.gov (United States)

    Pastorek, Michal; Simko, Veronika; Takacova, Martina; Barathova, Monika; Bartosova, Maria; Hunakova, Luba; Sedlakova, Olga; Hudecova, Sona; Krizanova, Olga; Dequiedt, Franck; Pastorekova, Silvia; Sedlak, Jan

    2015-07-01

    One of the recently emerging anticancer strategies is the use of natural dietary compounds, such as sulforaphane, a cancer-chemopreventive isothiocyanate found in broccoli. Based on the growing evidence, sulforaphane acts through molecular mechanisms that interfere with multiple oncogenic pathways in diverse tumor cell types. Herein, we investigated the anticancer effects of bioavailable concentrations of sulforaphane in ovarian carcinoma cell line A2780 and its two derivatives, adriamycin-resistant A2780/ADR and cisplatin-resistant A2780/CP cell lines. Since tumor microenvironment is characterized by reduced oxygenation that induces aggressive tumor phenotype (such as increased invasiveness and resistance to chemotherapy), we evaluated the effects of sulforaphane in ovarian cancer cells exposed to hypoxia (2% O2). Using the cell-based reporter assay, we identified several oncogenic pathways modulated by sulforaphane in hypoxia by activating anticancer responses (p53, ARE, IRF-1, Pax-6 and XRE) and suppressing responses supporting tumor progression (AP-1 and HIF-1). We further showed that sulforaphane decreases the level of HIF-1α protein without affecting its transcription and stability. It can also diminish transcription and protein level of the HIF-1 target, CA IX, which protects tumor cells from hypoxia-induced pH imbalance and facilitates their migration/invasion. Accordingly, sulforaphane treatment leads to diminished pH regulation and reduced migration of ovarian carcinoma cells. These effects occur in all three ovarian cell lines suggesting that sulforaphane can overcome the chemoresistance of cancer cells. This offers a path potentially exploitable in sensitizing resistant cancer cells to therapy, and opens a window for the combined treatments of sulforaphane either with conventional chemotherapy, natural compounds, or with other small molecules.

  17. Humoral response to low molecular weight antigens of Mycobacterium tuberculosis by tuberculosis patients and contacts

    Directory of Open Access Journals (Sweden)

    Beck S.T.

    2005-01-01

    Full Text Available Much effort has been devoted to the identification of immunologically important antigens of Mycobacterium tuberculosis and to the combination of target antigens to which antibodies from serum of tuberculous patients could react specifically. We searched for IgG antibodies specific for antigens of 45 to 6 kDa obtained after sonication of the well-characterized wild M. tuberculosis strain in order to detect differences in the antibody response to low molecular weight antigens from M. tuberculosis between patients with pulmonary tuberculosis and contacts. Specific IgG antibodies for these antigens were detected by Western blot analysis of 153 serum samples collected from 51 patients with confirmed pulmonary tuberculosis. Three samples were collected from each patient: before therapy, and after 2 and 6 months of treatment. We also analyzed 25 samples obtained from contacts, as well as 30 samples from healthy individuals with known tuberculin status, 50 samples from patients with other lung diseases and 200 samples from healthy blood donors. The positive predictive value for associated IgG reactivity against the 6-kDa and 16-kDa antigens, 6 and 38 kDa, and 16 and 38 kDa was 100% since simultaneous reactivity for these antigens was absent in healthy individuals and individuals with other lung diseases. This association was observed in 67% of the patients, but in only 8% of the contacts. The humoral response against antigens of 16 and 6 kDa seems to be important for the detection of latent tuberculosis since the associated reactivity to these antigens is mainly present in individuals with active disease.

  18. Biochemical, physiological and molecular responses of Ricinus communis seeds and seedlings to different temperatures: a multi-omics approach

    NARCIS (Netherlands)

    Ribeiro de Jesus, P.R.

    2015-01-01

    Biochemical, physiological and molecular responses of Ricinus communis seeds and seedlings to different temperatures: a multi-omics approach by Paulo Roberto Ribeiro de Jesus The main objective of this thesis was to provide a detailed analysis of physiological, bioc

  19. Biochemical, physiological and molecular responses of Ricinus communis seeds and seedlings to different temperatures: a multi-omics approach

    NARCIS (Netherlands)

    Ribeiro de Jesus, P.R.

    2015-01-01

    Biochemical, physiological and molecular responses of Ricinus communis seeds and seedlings to different temperatures: a multi-omics approach by Paulo Roberto Ribeiro de Jesus The main objective of this thesis was to provide a detailed analysis of physiological,

  20. Redox Biology Course Evaluation Form | Center for Cancer Research

    Science.gov (United States)

    To improve the Redox Biology (RB) course in future years, we would appreciate your feedback by completing this course evaluation. Please score the course elements as poor, fair, average, good or excellent. Please type any comments that you have in response to the questions at the bottom of the form. Remember to include your name as you wish it to appear on the certificate. Thank you for your feedback.

  1. Molecular Typing of Staphylococcus Aureus Isolate Responsible for Staphylococcal Poisoning Incident in Homemade Food

    Science.gov (United States)

    Bellio, Alberto; Bianchi, Daniela Manila; Gallina, Silvia; Adriano, Daniela; Zuccon, Fabio; Chiesa, Francesco; Acutis, Pier Luigi; Casalinuovo, Francesco; Decastelli, Lucia

    2016-01-01

    In October 2012, two persons fell ill with symptoms consistent with staphylococcal food poisoning after eating home-canned tuna fish and tomatoes. Laboratory investigation detected the enterotoxins in the home-canned tuna and molecular analysis of the isolated Staphylococcus aureus confirmed it carried toxin genes. Qualitative enzyme-linked immunosorbent assay and enzime linked fluorescent assay methods and quantitative assay identified the enterotoxins in the food leftovers, specifically staphylococcal enterotoxins type A (SEA) and D (SED), respectively 0.49 and 2.04 ng/g. The laboratory results are discussed considering the relation to the fish in oil, survival and heat resistance of S. aureus, and presumptive microbial contamination due to improper handling during home-canning procedures. This is the first reported cluster of foodborne illnesses due to staphylococcal enterotoxins in tuna in Italy. In this study, we reported cases described and analysed for their spa-type. Showing a high heterogeneity of isolates, spa-type t13252 is correlated in a node of the minimum spanning tree and it has never been reported as responsible for foodborne outbreak. This case underlines the importance of risk communication and dissemination of home-canning guidelines to reduce the incidence of foodborne outbreaks caused by homemade conserves.

  2. Heat shock protein 90 in plants: molecular mechanisms and roles in stress responses.

    Science.gov (United States)

    Xu, Zhao-Shi; Li, Zhi-Yong; Chen, Yang; Chen, Ming; Li, Lian-Cheng; Ma, You-Zhi

    2012-11-23

    The heat shock protein 90 (Hsp90) family mediates stress signal transduction, and plays important roles in the control of normal growth of human cells and in promoting development of tumor cells. Hsp90s have become a currently important subject in cellular immunity, signal transduction, and anti-cancer research. Studies on the physiological functions of Hsp90s began much later in plants than in animals and fungi. Significant progress has been made in understanding complex mechanisms of HSP90s in plants, including ATPase-coupled conformational changes and interactions with cochaperone proteins. A wide range of signaling proteins interact with HSP90s. Recent studies revealed that plant Hsp90s are important in plant development, environmental stress response, and disease and pest resistance. In this study, the plant HSP90 family was classified into three clusters on the basis of phylogenetic relationships, gene structure, and biological functions. We discuss the molecular functions of Hsp90s, and systematically review recent progress of Hsp90 research in plants.

  3. Molecular Typing of Staphylococcus Aureus Isolate Responsible for Staphylococcal Poisoning Incident in Homemade Food.

    Science.gov (United States)

    Macori, Guerrino; Bellio, Alberto; Bianchi, Daniela Manila; Gallina, Silvia; Adriano, Daniela; Zuccon, Fabio; Chiesa, Francesco; Acutis, Pier Luigi; Casalinuovo, Francesco; Decastelli, Lucia

    2016-04-19

    In October 2012, two persons fell ill with symptoms consistent with staphylococcal food poisoning after eating home-canned tuna fish and tomatoes. Laboratory investigation detected the enterotoxins in the home-canned tuna and molecular analysis of the isolated Staphylococcus aureus confirmed it carried toxin genes. Qualitative enzyme-linked immunosorbent assay and enzime linked fluorescent assay methods and quantitative assay identified the enterotoxins in the food leftovers, specifically staphylococcal enterotoxins type A (SEA) and D (SED), respectively 0.49 and 2.04 ng/g. The laboratory results are discussed considering the relation to the fish in oil, survival and heat resistance of S. aureus, and presumptive microbial contamination due to improper handling during home-canning procedures. This is the first reported cluster of foodborne illnesses due to staphylococcal enterotoxins in tuna in Italy. In this study, we reported cases described and analysed for their spa-type. Showing a high heterogeneity of isolates, spa-type t13252 is correlated in a node of the minimum spanning tree and it has never been reported as responsible for foodborne outbreak. This case underlines the importance of risk communication and dissemination of home-canning guidelines to reduce the incidence of foodborne outbreaks caused by homemade conserves.

  4. Molecular typing of Staphylococcus aureus isolate responsible for staphylococcal poisoning incident in homemade food

    Directory of Open Access Journals (Sweden)

    Guerrino Macori

    2016-06-01

    Full Text Available In October 2012, two persons fell ill with symptoms consistent with staphylococcal food poisoning after eating home-canned tuna fish and tomatoes. Laboratory investigation detected the enterotoxins in the home-canned tuna and molecular analysis of the isolated Staphylococcus aureus confirmed it carried toxin genes. Qualitative enzyme-linked immunosorbent assay and enzime linked fluorescent assay methods and quantitative assay identified the enterotoxins in the food leftovers, specifically staphylococcal enterotoxins type A (SEA and D (SED, respectively 0.49 and 2.04 ng/g. The laboratory results are discussed considering the relation to the fish in oil, survival and heat resistance of S. aureus, and presumptive microbial contamination due to improper handling during home-canning procedures. This is the first reported cluster of foodborne illnesses due to staphylococcal enterotoxins in tuna in Italy. In this study, we reported cases described and analysed for their spa-type. Showing a high heterogeneity of isolates, spa-type t13252 is correlated in a node of the minimum spanning tree and it has never been reported as responsible for foodborne outbreak. This case underlines the importance of risk communication and dissemination of home-canning guidelines to reduce the incidence of foodborne outbreaks caused by homemade conserves.

  5. Clinical, Molecular and Genetic Changes in Response to a Left Ventricular Assist Device

    Science.gov (United States)

    Hall, Jennifer L.; Fermin, David R.; Birks, Emma J.; Barton, Paul J.R.; Slaughter, Mark; Eckman, Peter; Baba, Hideo A.; Wohlschlaeger, Jeremias Jeremias; Miller, Leslie W.

    2012-01-01

    The use of left ventricular assist devices (LVADs) in treating patients with end stage heart failure has increased significantly in recent years, both as a bridge to transplant and as destination therapy in those who are ineligible for cardiac transplantation. This increase is based largely on the results of several recently completed clinical trials with the new second generation continuous flow devices that showed significant improvement in survival, functional capacity, and quality of life. Additional information on the use of the first generation and second generation LVADs has come from a recently released report spanning the years 2006–2009, from The Interagency Registry for Mechanical Circulatory Support (INTERMACS), a National Heart Lung and Blood Institute sponsored collaboration between the United States Food and Drug Administration (FDA), the Center for Medicare and Medicaid (CMS) and the scientific community (1). This paper provides a review of the latest clinical trials and data from the INTERMACS registry with tight integration of the landmark molecular, cellular and genomic research that accompanies the reverse remodeling of the human heart in response to the LVAD and functional recovery that has been reported in a subset of these patients. PMID:21292124

  6. Temperature control of molecular circuit switch responsible for virulent phenotype expression in uropathogenic Escherichia coli

    Science.gov (United States)

    Samoilov, Michael

    2010-03-01

    The behavior and fate of biological organisms are to a large extent dictated by their environment, which can be often viewed as a collection of features and constraints governed by physics laws. Since biological systems comprise networks of molecular interactions, one such key physical property is temperature, whose variations directly affect the rates of biochemical reactions involved. For instance, temperature is known to control many gene regulatory circuits responsible for pathogenicity in bacteria. One such example is type 1 fimbriae (T1F) -- the foremost virulence factor in uropathogenic E. coli (UPEC), which accounts for 80-90% of all community-acquired urinary tract infections (UTIs). The expression of T1F is randomly `phase variable', i.e. individual cells switch between virulent/fimbriate and avirulent/afimbriate phenotypes, with rates regulated by temperature. Our computational investigation of this process, which is based on FimB/FimE recombinase-mediated inversion of fimS DNA element, offers new insights into its discrete-stochastic kinetics. In particular, it elucidates the logic of T1F control optimization to the host temperature and contributes further understanding toward the development of novel therapeutic approaches to UPEC-caused UTIs.

  7. Fast response dry-type artificial molecular muscles with [c2]daisy chains

    Science.gov (United States)

    Iwaso, Kazuhisa; Takashima, Yoshinori; Harada, Akira

    2016-06-01

    Hierarchically organized myosin and actin filaments found in biological systems exhibit contraction and expansion behaviours that produce work and force by consuming chemical energy. Inspired by these naturally occurring examples, we have developed photoresponsive wet- and dry-type molecular actuators built from rotaxane-based compounds known as [c2]daisy chains (specifically, [c2]AzoCD2 hydrogel and [c2]AzoCD2 xerogel). These actuators were prepared via polycondensation between four-armed poly(ethylene glycol) and a [c2]daisy chain based on α-cyclodextrin as the host component and azobenzene as a photoresponsive guest component. The light-induced actuation arises from the sliding motion of the [c2]daisy chain unit. Ultraviolet irradiation caused the gels to bend towards the light source. The response of the [c2]AzoCD2 xerogel, even under dry conditions, is very fast (7° every second), which is 10,800 times faster than the [c2]AzoCD2 hydrogel (7° every 3 h). In addition, the [c2]AzoCD2 xerogel was used as a crane arm to lift an object using ultraviolet irradiation to produce mechanical work.

  8. Molecular Response to Toxic Diatom-Derived Aldehydes in the Sea Urchin Paracentrotus lividus

    Directory of Open Access Journals (Sweden)

    Stefano Varrella

    2014-04-01

    Full Text Available Diatoms are dominant photosynthetic organisms in the world’s oceans and represent a major food source for zooplankton and benthic filter-feeders. However, their beneficial role in sustaining marine food webs has been challenged after the discovery that they produce secondary metabolites, such as polyunsaturated aldehydes (PUAs, which negatively affect the reproductive success of many invertebrates. Here, we report the effects of two common diatom PUAs, heptadienal and octadienal, which have never been tested before at the molecular level, using the sea urchin, Paracentrotus lividus, as a model organism. We show that both PUAs are able to induce teratogenesis (i.e., malformations, as already reported for decadienal, the better-studied PUA of this group. Moreover, post-recovery experiments show that embryos can recover after treatment with all three PUAs, indicating that negative effects depend both on PUA concentrations and the exposure time of the embryos to these metabolites. We also identify the time range during which PUAs exert the greatest effect on sea urchin embryogenesis. Finally, we report the expression levels of thirty one genes (having a key role in a broad range of functional responses, such as stress, development, differentiation, skeletogenesis and detoxification processes in order to identify the common targets affected by PUAs and their correlation with morphological abnormalities. This study opens new perspectives for understanding how marine organisms afford protection from environmental toxicants through an integrated network of genes.

  9. Molecular Response to Toxic Diatom-Derived Aldehydes in the Sea Urchin Paracentrotus lividus

    Science.gov (United States)

    Varrella, Stefano; Romano, Giovanna; Ianora, Adrianna; Bentley, Matt G.; Ruocco, Nadia; Costantini, Maria

    2014-01-01

    Diatoms are dominant photosynthetic organisms in the world’s oceans and represent a major food source for zooplankton and benthic filter-feeders. However, their beneficial role in sustaining marine food webs has been challenged after the discovery that they produce secondary metabolites, such as polyunsaturated aldehydes (PUAs), which negatively affect the reproductive success of many invertebrates. Here, we report the effects of two common diatom PUAs, heptadienal and octadienal, which have never been tested before at the molecular level, using the sea urchin, Paracentrotus lividus, as a model organism. We show that both PUAs are able to induce teratogenesis (i.e., malformations), as already reported for decadienal, the better-studied PUA of this group. Moreover, post-recovery experiments show that embryos can recover after treatment with all three PUAs, indicating that negative effects depend both on PUA concentrations and the exposure time of the embryos to these metabolites. We also identify the time range during which PUAs exert the greatest effect on sea urchin embryogenesis. Finally, we report the expression levels of thirty one genes (having a key role in a broad range of functional responses, such as stress, development, differentiation, skeletogenesis and detoxification processes) in order to identify the common targets affected by PUAs and their correlation with morphological abnormalities. This study opens new perspectives for understanding how marine organisms afford protection from environmental toxicants through an integrated network of genes. PMID:24714125

  10. Heat Shock Protein 90 in Plants: Molecular Mechanisms and Roles in Stress Responses

    Directory of Open Access Journals (Sweden)

    You-Zhi Ma

    2012-11-01

    Full Text Available The heat shock protein 90 (Hsp90 family mediates stress signal transduction, and plays important roles in the control of normal growth of human cells and in promoting development of tumor cells. Hsp90s have become a currently important subject in cellular immunity, signal transduction, and anti-cancer research. Studies on the physiological functions of Hsp90s began much later in plants than in animals and fungi. Significant progress has been made in understanding complex mechanisms of HSP90s in plants, including ATPase-coupled conformational changes and interactions with cochaperone proteins. A wide range of signaling proteins interact with HSP90s. Recent studies revealed that plant Hsp90s are important in plant development, environmental stress response, and disease and pest resistance. In this study, the plant HSP90 family was classified into three clusters on the basis of phylogenetic relationships, gene structure, and biological functions. We discuss the molecular functions of Hsp90s, and systematically review recent progress of Hsp90 research in plants.

  11. Anisotropic compressive response of Stone-Thrower-Wales defects in graphene: A molecular dynamics study

    Science.gov (United States)

    Rajasekaran, G.; Parashar, Avinash

    2016-09-01

    The mechanical properties of graphene sheet can be tailored with the help of topological defects. In this research article, the effects of Stone-Thrower-Wales (STW) defects on the mechanical properties of graphene sheet was investigated with the help of molecular dynamics based simulations. Authors has made an attempt to analyse the stress field developed in and around the vicinity of defect due to bond reorientation and further systematic evaluation has been carried out to study the effect of these stress fields against the applied axial compressive load. The results obtained with the pristine graphene were made to compare with the available open literature and the results were reported to be in good agreement with theoretical and experimental data. It was predicted that graphene with STW defect cannot able to bear compressive strength in zigzag direction, whereas on the other hand it was predicted that graphene sheet containing STW defect can bear higher compressive load in armchair direction, which shows an anisotropic response of STW defects in graphene. From the obtained results it can be observed that orientation of STW defects and the loading direction plays an important role to alter the strength of graphene under axial compression.

  12. Redox pioneer: professor Barry Halliwell.

    Science.gov (United States)

    Pervaiz, Shazib

    2011-05-01

    Professor Barry Halliwell is recognized as a Redox Pioneer because he has published eight articles on redox biology that have been each cited more than 1000 times, and 158 articles