Exploiting the synthetic lethality between terminal respiratory oxidases to kill Mycobacterium tuberculosis and clear host infection

PubMed Central

Kalia, Nitin P.; Hasenoehrl, Erik J.; Ab Rahman, Nurlilah B.; Koh, Vanessa H.; Ang, Michelle L. T.; Sajorda, Dannah R.; Hards, Kiel; Grüber, Gerhard; Alonso, Sylvie; Cook, Gregory M.; Berney, Michael; Pethe, Kevin

2017-01-01

The recent discovery of small molecules targeting the cytochrome bc1:aa3 in Mycobacterium tuberculosis triggered interest in the terminal respiratory oxidases for antituberculosis drug development. The mycobacterial cytochrome bc1:aa3 consists of a menaquinone:cytochrome c reductase (bc1) and a cytochrome aa3-type oxidase. The clinical-stage drug candidate Q203 interferes with the function of the subunit b of the menaquinone:cytochrome c reductase. Despite the affinity of Q203 for the bc1:aa3 complex, the drug is only bacteriostatic and does not kill drug-tolerant persisters. This raises the possibility that the alternate terminal bd-type oxidase (cytochrome bd oxidase) is capable of maintaining a membrane potential and menaquinol oxidation in the presence of Q203. Here, we show that the electron flow through the cytochrome bd oxidase is sufficient to maintain respiration and ATP synthesis at a level high enough to protect M. tuberculosis from Q203-induced bacterial death. Upon genetic deletion of the cytochrome bd oxidase-encoding genes cydAB, Q203 inhibited mycobacterial respiration completely, became bactericidal, killed drug-tolerant mycobacterial persisters, and rapidly cleared M. tuberculosis infection in vivo. These results indicate a synthetic lethal interaction between the two terminal respiratory oxidases that can be exploited for anti-TB drug development. Our findings should be considered in the clinical development of drugs targeting the cytochrome bc1:aa3, as well as for the development of a drug combination targeting oxidative phosphorylation in M. tuberculosis. PMID:28652330

High atmospheric carbon dioxide-dependent alleviation of salt stress is linked to RESPIRATORY BURST OXIDASE 1 (RBOH1)-dependent H2O2 production in tomato (Solanum lycopersicum).

PubMed

Yi, Changyu; Yao, Kaiqian; Cai, Shuyu; Li, Huizi; Zhou, Jie; Xia, Xiaojian; Shi, Kai; Yu, Jingquan; Foyer, Christine Helen; Zhou, Yanhong

2015-12-01

Plants acclimate rapidly to stressful environmental conditions. Increasing atmospheric CO2 levels are predicted to influence tolerance to stresses such as soil salinity but the mechanisms are poorly understood. To resolve this issue, tomato (Solanum lycopersicum) plants were grown under ambient (380 μmol mol(-1)) or high (760 μmol mol(-1)) CO2 in the absence or presence of sodium chloride (100mM). The higher atmospheric CO2 level induced the expression of RESPIRATORY BURST OXIDASE 1 (SlRBOH1) and enhanced H2O2 accumulation in the vascular cells of roots, stems, leaf petioles, and the leaf apoplast. Plants grown with higher CO2 levels showed improved salt tolerance, together with decreased leaf transpiration rates and lower sodium concentrations in the xylem sap, vascular tissues, and leaves. Silencing SlRBOH1 abolished high CO2 -induced salt tolerance and increased leaf transpiration rates, as well as enhancing Na(+) accumulation in the plants. The higher atmospheric CO2 level increased the abundance of a subset of transcripts involved in Na(+) homeostasis in the controls but not in the SlRBOH1-silenced plants. It is concluded that high atmospheric CO2 concentrations increase salt stress tolerance in an apoplastic H2O2 dependent manner, by suppressing transpiration and hence Na(+) delivery from the roots to the shoots, leading to decreased leaf Na(+) accumulation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Chloride ion efflux regulates adherence, spreading, and respiratory burst of neutrophils stimulated by tumor necrosis factor-alpha (TNF) on biologic surfaces

PubMed Central

1996-01-01

Chloride ion efflux is an early event occurring after exposure of neutrophilic polymorphonuclear leukocytes (PMN) in suspension to several agonists, including cytokines such as tumor necrosis factor- alpha (TNF) and granulocyte/macrophage-colony stimulating factor (Shimizu, Y., R.H. Daniels, M.A. Elmore, M.J. Finnen, M.E. Hill, and J.M. Lackie. 1993. Biochem. Pharmacol. 9:1743-1751). We have studied TNF-induced Cl- movements in PMN residing on fibronectin (FN) (FN-PMN) and their relationships to adherence, spreading, and activation of the respiratory burst. Occupancy of the TNF-R55 and engagement of beta 2 integrins cosignaled for an early, marked, and prolonged Cl- efflux that was accompanied by a fall in intracellular chloride levels (Cl-i). A possible causal relationship between Cl- efflux, adherence, and respiratory burst was first suggested by kinetic studies, showing that TNF-induced Cl- efflux preceded both the adhesive and metabolic response, and was then confirmed by inhibition of all three responses by pretreating PMN with inhibitors of Cl- efflux, such as ethacrynic acid. Moreover, Cl- efflux induced by means other than TNF treatment, i.e., by using Cl(-)-free media, was followed by increased adherence, spreading, and metabolic activation, thus mimicking TNF effects. These studies provide the first evidence that a drastic decrease of Cl-i in FN-PMN may represent an essential step in the cascade of events leading to activation of proadhesive molecules, reorganization of the cytoskeleton network, and assembly of the O2(-)-forming NADPH oxidase. PMID:8896606

Minocycline affects human neutrophil respiratory burst and transendothelial migration.

PubMed

Parenti, Astrid; Indorato, Boris; Paccosi, Sara

2017-02-01

This study aimed at investigating the in vitro activity of minocycline and doxycycline on human polymorphonuclear (h-PMN) cell function. h-PMNs were isolated from whole venous blood of healthy subjects; PMN oxidative burst was measured by monitoring ROS-induced oxidation of luminol and transendothelial migration was studied by measuring PMN migration through a monolayer of human umbilical vein endothelial cells. Differences between multiple groups were determined by ANOVA followed by Tukey's multiple comparison test; Student's t test for unpaired data for two groups. Minocycline (1-300 µM) concentration dependently and significantly inhibited oxidative burst of h-PMNs stimulated with 100 nM fMLP. Ten micromolar concentrations, which are superimposable to C max following a standard oral dose of minocycline, promoted a 29.8 ± 4 % inhibition of respiratory burst (P < 0.001; n = 6). Doxycycline inhibited ROS production with a lesser extent and at higher concentrations. 10-100 µM minocycline impaired PMN transendothelial migration, with maximal effect at 100 µM (42.5 ± 7 %, inhibition, n = 5, P < 0.001). These results added new insight into anti-inflammatory effects of minocycline exerted on innate immune h-PMN cell function.

Characterization of three bioenergetically active respiratory terminal oxidases in the cyanobacterium Synechocystis sp. strain PCC 6803.

PubMed

Pils, D; Schmetterer, G

2001-09-25

Synechocystis sp. PCC 6803 contains three respiratory terminal oxidases (RTOs): cytochrome c oxidase (Cox), quinol oxidase (Cyd), and alternate RTO (ARTO). Mutants lacking combinations of the RTOs were used to characterize these key enzymes of respiration. Pentachlorophenol and 2-heptyl-4-hydroxy-quinoline-N-oxide inhibited Cyd completely, but had little effect on electron transport to the other RTOs. KCN inhibited all three RTOs but the in vivo K(I) for Cox and Cyd was quite different (7 vs. 27 microM), as was their affinity for oxygen (K(M) 1.0 vs. 0.35 microM). ARTO has a very low respiratory activity. However, when uptake of 3-O-methylglucose, an active H+ co-transport, was used to monitor energization of the cytoplasmic membrane, ARTO was similarly effective as the other RTOs. As removal of the gene for cytochrome c(553) had the same effects as removal of ARTO genes, we propose that the ARTO might be a second Cox. The possible functions, localization and regulation of the RTOs are discussed.

Mast cell granules modulate alveolar macrophage respiratory-burst activity and eicosanoid metabolism.

PubMed

Rock, M J; Despot, J; Lemanske, R F

1990-10-01

Alveolar macrophages (AMs) and mast cells reside in the airway, and both have been demonstrated to contribute independently to allergic inflammatory responses through the generation of respiratory-burst metabolites and the release of biologically active mediators, respectively. Since mast cell granules (MCGs) contain mediators that could potentially interact with the AM respiratory burst, we investigated the effects of isolated MCGs on this important inflammatory pathway of the AM. MCGs and AMs were obtained by peritoneal and tracheoalveolar lavage, respectively, of Sprague-Dawley rats. First, the overall respiratory-burst activity was measured by luminal-enhanced chemiluminescence (CL), and second, the individual oxygen species contributing to CL (superoxide anion [O2-], hydrogen peroxide [H2O2], and hypochlorous acid) were measured. MCGs alone enhanced AM CL responses to an equivalent degree compared to zymosan-stimulated AMs. However, AMs preincubated with MCGs followed by zymosan stimulation significantly and synergistically enhanced the CL responses. This enhanced CL was not due to an increased production of O2-, H2O2, or hypochlorous acid; in fact, there were decreased measured amounts of O2- and H2O2 from zymosan-stimulated AMs in the presence of MCGs, most likely caused by the content of granules of superoxide dismutase and peroxidase, respectively. The lipoxygenase inhibitor, nordihydroguaiaretic acid, completely abolished the enhanced CL of AM preincubated with MCGs and subsequently stimulated by zymosan, but O2- production was not affected by nordihydroguaiaretic acid. Taken together, these results suggest that derivatives of arachidonic acid metabolism, most likely those of the lipoxygenase pathway, are responsible for the enhanced AM CL response observed in the presence of MCGs. Thus, mast cell-macrophage interactions may be important within the airway in enhancing the generation of mediators that contribute to tissue inflammation and bronchospasm.

Phagocytosis and Respiratory Burst Activity in Lumpsucker (Cyclopterus lumpus L.) Leucocytes Analysed by Flow Cytometry

PubMed Central

Haugland, Gyri T.; Jakobsen, Ragnhild Aakre; Vestvik, Nils; Ulven, Kristian; Stokka, Lene; Wergeland, Heidrun I.

2012-01-01

In the present study, we have isolated leucocytes from peripheral blood, head kidney and spleen from lumpsucker (Cyclopterus lumpus L.), and performed functional studies like phagocytosis and respiratory burst, as well as morphological and cytochemical analyses. Different leucocytes were identified, such as lymphocytes, monocytes/macrophages and polymorphonuclear cells with bean shaped or bilobed nuclei. In addition, cells with similar morphology as described for dendritic cells in trout were abundant among the isolated leucocytes. Flow cytometry was successfully used for measuring phagocytosis and respiratory burst activity. The phagocytic capacity and ability were very high, and cells with different morphology in all three leucocyte preparations phagocytised beads rapidly. Due to lack of available cell markers, the identity of the phagocytic cells could not be determined. The potent non-specific phagocytosis was in accordance with a high number of cells positive for myeloperoxidase, an enzyme involved in oxygen-dependent killing mechanism present in phagocytic cells. Further, high respiratory burst activity was present in the leucocytes samples, verifying a potent oxygen- dependent degradation. At present, the specific antibody immune response could not be measured, as immunoglobulin or B-cells have not yet been isolated. Therefore, analyses of the specific immune response in this fish species await further clarification. The present study presents the first analyses of lumpsucker immunity and also the first within the order Scopaeniformes. PMID:23112870

Molecular cloning of rock bream (Oplegnathus fasciatus) tumor necrosis factor-alpha and its effect on the respiratory burst activity of phagocytes.

PubMed

Kim, Min Sun; Hwang, Yoon Jung; Yoon, Ki Joon; Zenke, Kosuke; Nam, Yoon Kwon; Kim, Sung Koo; Kim, Ki Hong

2009-11-01

Rock bream (Oplegnathus fasciatus) tumor necrosis factor-alpha (rbTNF-alpha) gene was cloned, recombinantly produced, and the effect of the recombinant rbTNF-alpha on the respiratory burst activity of rock bream phagocytes was analyzed. Structurally, genomic DNA of rbTNF-alpha was comprised with four exons and three introns, and deduced amino acid sequence of its cDNA possessed the TNF family signature, a transmembrane domain, a protease cleavage site, and two cysteine residues, which are the typical characteristics of TNF-alpha gene in mammals and fish. The chemiluminescent (CL) response of rock bream phagocytes was significantly enhanced by pre-incubation with recombinant rbTNF-alpha, when opsonized zymosan was used as a stimulant of the respiratory burst. However, CL enhancing effect of the recombinant rbTNF-alpha was very weak when the respiratory burst activity of phagocytes was triggered with phorbol-12-myristate-13-acetate (PMA) instead of zymosan. These results suggest that rock bream TNF-alpha might have an ability to prime the respiratory burst activity of phagocytes against receptor-mediated phagocytosis inducing stimulants, such as zymosan, but have little ability against stimulants not accompanying receptor-mediated phagocytosis.

The effects of emodin on cell viability, respiratory burst and gene expression of Nrf2-Keap1 signaling molecules in the peripheral blood leukocytes of blunt snout bream (Megalobrama amblycephala).

PubMed

Zhao, Zhenxin; Xie, Jun; Liu, Bo; Ge, Xianping; Song, Changyou; Ren, Mingchun; Zhou, Qunlan; Miao, Linghong; Zhang, Huimin; Shan, Fan; Yang, Zhenfei

2017-03-01

We determined the effects of emodin on the cell viability, respiratory burst activity, mRNA levels of antioxidative enzymes (Cu-Zn SOD, CAT and NOX2), and gene expressions of the Nrf2-Keap1 signaling molecules in the peripheral blood leukocytes of blunt snout bream. Triplicate groups of cultured cells were treated with different concentrations of emodin (0.04-25 μg/ml) for 24 h. Results showed that the emodin caused a dramatic loss in cell viability, and occurred in a dose-dependent manner. Emodin exposure (1-25 μg/ml) were significantly induced the ROS generation compared to the control. The respiratory burst and NADPH oxidase activities were significantly induced at a concentration of 0.20 μg/ml, and inhibited at 25 μg/ml. Besides, mRNA levels of antioxidant enzyme genes were dramatically regulated by emodin exposure for 24 h. During low concentrations of exposure, mRNA levels of Cu-Zn SOD in the cells treated with 0.04, 0.20 μg/ml, CAT, NOX2 and Nrf2 in the cells treated with 1 μg/ml were sharply increased, respectively. Whereas, high concentrations were dramatically down-regulated the gene expressions of CAT in the cells treated with 5, 25 μg/ml and NOX2 in the cells treated with 25 μg/ml. Furthermore, sharp increase in Keap1and Bach1 expression levels were observed a dose-dependent manner. In conclusion, this study demonstrated that emodin could induce antioxidant defenses which were involved in cytotoxic activities, respiratory burst and the transcriptional regulation levels of antioxidant enzymes and Nrf2-Keap1 signaling molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exocytosis of Neutrophil Granule Subsets and Activation of Prolyl Isomerase 1 are required for Respiratory Burst Priming

PubMed Central

McLeish, Kenneth R.; Uriarte, Silvia M.; Tandon, Shweta; Creed, Timothy M.; Le, Junyi; Ward, Richard A.

2013-01-01

This study tested the hypothesis that priming the neutrophil respiratory burst requires both granule exocytosis and activation of the prolyl isomerase, Pin1. Fusion proteins containing the TAT cell permeability sequence and either the SNARE domain of syntaxin-4 or the N-terminal SNARE domain of SNAP-23 were used to examine the role of granule subsets in TNF-mediated respiratory burst priming using human neutrophils. Concentration-inhibition curves for exocytosis of individual granule subsets and for priming of fMLF-stimulated superoxide release and phagocytosis-stimulated H2O2 production were generated. Maximal inhibition of priming ranged from 72% to 88%. Linear regression lines for inhibition of priming versus inhibition of exocytosis did not differ from the line of identity for secretory vesicles and gelatinase granules, while the slopes or the y-intercepts were different from the line of identity for specific and azurophilic granules. Inhibition of Pin1 reduced priming by 56%, while exocytosis of secretory vesicles and specific granules was not affected. These findings indicate that exocytosis of secretory vesicles and gelatinase granules and activation of Pin1 are independent events required for TNF-mediated priming of neutrophil respiratory burst. PMID:23363774

[Relationship between HPLC fingerprint chromatogram and inhibitory effect on respiratory burst of rat PMN of leaves of crataegus].

PubMed

Liu, Rong-hua; Yu, Bo-yang; Chen, Lan-ying; Liu, Ji-hua; Shao, Feng; Ma, Zhi-lin; Yang, Ming

2008-08-01

To study the relationship between HPLC fingerprint chromatogram and inhibitory effect on respiratory burst of rat PMN of leaves of crataegus L. HPLC fingerprint peaks of different species of hawthorn leaves were isolated and used for the effective experiment on the respiratory burst of rat PMN. The mathematic models of the relationship between the area and the effect of fingerprint peaks were established. According to the mathematic models, the HPLC fingerprint were change into bioactive fingerprint (include effective fingerprint and potency fingerprint) with the helps of mathematics, chemometrics, computer program simulation and etc. The chromatogram-effect relationship of leaves of crataegus. on respiratory burst of rat PMN was established. According to this relationship, the activities of fourteen samples of leaves of crataegus. were forecasted. It was positive correlation between the expected value and the practical value. And the correlation coefficients was 0.968 (P < 0.01). An all-around evaluative system, which includes not only chemical identification but also effective evaluation for traditional Chinese medicine was established. It will provide a new idea for study on fingerprint chromatogram of traditional Chinese medicine.

Comparative study of β-glucan induced respiratory burst measured by nitroblue tetrazolium assay and real-time luminol-enhanced chemiluminescence assay in common carp (Cyprinus carpio L.).

PubMed

Vera-Jimenez, N I; Pietretti, D; Wiegertjes, G F; Nielsen, M E

2013-05-01

The respiratory burst is an important feature of the immune system. The increase in cellular oxygen uptake that marks the initiation of the respiratory burst is followed by the production of reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide which plays a role in the clearance of pathogens and tissue regeneration processes. Therefore, the respiratory burst and associated ROS constitute important indicators of fish health status. This paper compares two methods for quantitation of ROS produced during the respiratory burst in common carp: the widely used, single-point measurement based on the intracellular reduction of nitroblue tetrazolium (NBT) and a real-time luminol-enhanced assay based on the detection of native chemiluminescence. Both assays allowed for detection of dose-dependent changes in magnitude of the respiratory burst response induced by β-glucans in head kidney cells of carp. However, whereas the NBT assay was shown to detect the production of only superoxide anions, the real-time luminol-enhanced assay could detect the production of both superoxide anions and hydrogen peroxide. Only the chemiluminescence assay could reliably record the production of ROS on a real-time scale at frequent and continual time intervals for time course experiments, providing more detailed information on the respiratory burst response. The real-time chemiluminescence assay was used to measure respiratory burst activity in macrophage and neutrophilic granulocyte-enriched head kidney cell fractions and total head kidney cell suspensions and proved to be a fast, reliable, automated multiwell microplate assay to quantitate fish health status modulated by β-glucans. Copyright © 2013 Elsevier Ltd. All rights reserved.

The mitochondrial alternative oxidase Aox1 is needed to cope with respiratory stress but dispensable for pathogenic development in Ustilago maydis

PubMed Central

Piñón-Zárate, Gabriela; Matus-Ortega, Genaro; Guerra, Guadalupe; Feldbrügge, Michael; Pardo, Juan Pablo

2017-01-01

The mitochondrial alternative oxidase is an important enzyme that allows respiratory activity and the functioning of the Krebs cycle upon disturbance of the respiration chain. It works as a security valve in transferring excessive electrons to oxygen, thereby preventing potential damage by the generation of harmful radicals. A clear biological function, besides the stress response, has so far convincingly only been shown for plants that use the alternative oxidase to generate heat to distribute volatiles. In fungi it was described that the alternative oxidase is needed for pathogenicity. Here, we investigate expression and function of the alternative oxidase at different stages of the life cycle of the corn pathogen Ustilago maydis (Aox1). Interestingly, expression of Aox1 is specifically induced during the stationary phase suggesting a role at high cell density when nutrients become limiting. Studying deletion strains as well as overexpressing strains revealed that Aox1 is dispensable for normal growth, for cell morphology, for response to temperature stress as well as for filamentous growth and plant pathogenicity. However, during conditions eliciting respiratory stress yeast-like growth as well as hyphal growth is strongly affected. We conclude that Aox1 is dispensable for the normal biology of the fungus but specifically needed to cope with respiratory stress. PMID:28273139

Lack of respiratory chain complex I impairs alternative oxidase engagement and modulates redox signaling during elicitor-induced cell death in tobacco.

PubMed

Vidal, Guillaume; Ribas-Carbo, Miquel; Garmier, Marie; Dubertret, Guy; Rasmusson, Allan G; Mathieu, Chantal; Foyer, Christine H; De Paepe, Rosine

2007-02-01

Alternative oxidase (AOX) functions in stress resistance by preventing accumulation of reactive oxygen species (ROS), but little is known about in vivo partitioning of electron flow between AOX and the cytochrome pathway. We investigated the relationships between AOX expression and in vivo activity in Nicotiana sylvestris and the complex I-deficient CMSII mutant in response to a cell death elicitor. While a specific AOX1 isoform in the active reduced state was constitutively overexpressed in CMSII, partitioning through the alternative pathway was similar to the wild type. Lack of correlation between AOX content and activity indicates severe metabolic constraints in nonstressed mutant leaves. The bacterial elicitor harpin N(Ea) induced similar timing and extent of cell death and a twofold respiratory burst in both genotypes with little change in AOX amounts. However, partitioning to AOX was increased twofold in the wild type but remained unchanged in CMSII. Oxidative phosphorylation modeling indicated a twofold ATP increase in both genotypes. By contrast, mitochondrial superoxide dismutase activity and reduced forms of ascorbate and glutathione were higher in CMSII than in the wild type. These results demonstrate genetically programmed flexibility of plant respiratory routes and antioxidants in response to elicitors and suggest that sustained ATP production, rather than AOX activity by itself or mitochondrial ROS, might be important for in planta cell death.

Evidence for a Key Role of Cytochrome bo3 Oxidase in Respiratory Energy Metabolism of Gluconobacter oxydans

PubMed Central

Richhardt, Janine; Luchterhand, Bettina; Büchs, Jochen

2013-01-01

The obligatory aerobic acetic acid bacterium Gluconobacter oxydans oxidizes a variety of substrates in the periplasm by membrane-bound dehydrogenases, which transfer the reducing equivalents to ubiquinone. Two quinol oxidases, cytochrome bo3 and cytochrome bd, then catalyze transfer of the electrons from ubiquinol to molecular oxygen. In this study, mutants lacking either of these terminal oxidases were characterized. Deletion of the cydAB genes for cytochrome bd had no obvious influence on growth, whereas the lack of the cyoBACD genes for cytochrome bo3 severely reduced the growth rate and the cell yield. Using a respiration activity monitoring system and adjusting different levels of oxygen availability, hints of a low-oxygen affinity of cytochrome bd oxidase were obtained, which were supported by measurements of oxygen consumption in a respirometer. The H+/O ratio of the ΔcyoBACD mutant with mannitol as the substrate was 0.56 ± 0.11 and more than 50% lower than that of the reference strain (1.26 ± 0.06) and the ΔcydAB mutant (1.31 ± 0.16), indicating that cytochrome bo3 oxidase is the main component for proton extrusion via the respiratory chain. Plasmid-based overexpression of cyoBACD led to increased growth rates and growth yields, both in the wild type and the ΔcyoBACD mutant, suggesting that cytochrome bo3 might be a rate-limiting factor of the respiratory chain. PMID:23852873

The cytochrome bd oxidase of Escherichia coli prevents respiratory inhibition by endogenous and exogenous hydrogen sulfide

PubMed Central

Korshunov, Sergey; Imlay, Karin R. C.; Imlay, James A.

2016-01-01

Summary When sulfur compounds are scarce or difficult to process, E. coli adapts by inducing the high-level expression of sulfur-compound importers. If cystine then becomes available, the cystine is rapidly overimported and reduced, leading to a burgeoning pool of intracellular cysteine. Most of the excess cysteine is exported, but some is adventitiously degraded, with the consequent release of sulfide. Sulfide is a potent ligand of copper and heme moieties, raising the prospect that it interferes with enzymes. We observed that when cystine was provided and sulfide levels rose, E. coli became strictly dependent upon cytochrome bd oxidase for continued respiration. Inspection revealed that low-micromolar levels of sulfide inhibited the proton-pumping cytochrome bo oxidase that is regarded as the primary respiratory oxidase. In the absence of the back-up cytochrome bd oxidase, growth failed. Exogenous sulfide elicited the same effect. The potency of sulfide was enhanced when oxygen concentrations were low. Natural oxic-anoxic interfaces are often sulfidic, including the intestinal environment where E. coli dwells. We propose that the sulfide resistance of the cytochrome bd oxidase is a key trait that permits respiration in such habitats. PMID:26991114

Purification and properties of two terminal oxidase complexes of Escherichia coli aerobic respiratory chain.

PubMed

Kita, K; Konishi, K; Anraku, Y

1986-01-01

Two terminal oxidase complexes, cytochrome b-562-o complex and cytochrome b-558-d complex, are isolated in highly purified forms which show ubiquinol oxidase activities. From the result of steady-state kinetics of cytochromes in the membrane and E'm values of purified cytochromes, we propose a branched arrangement of the late exponential phase of aerobic growth, as shown in Fig. 10. Cytochrome b-556 is reduced by several dehydrogenases and the gene for this cytochrome (cybA) is located in the sdh gene cluster. Recently, we found another low-potential b-type cytochrome, cytochrome b-561 (Em' = 20 mV), which is also reduced by dehydrogenases. The position of this new cytochrome in the aerobic respiratory chain is under investigation. Two terminal oxidase complexes branch at the site of ubiquinone-8, and the Km value for oxygen of the purified cytochrome b-558-d complex is about 8-fold lower than that of the purified cytochrome b-562-o complex when ubiquinol-1 is used as substrate. This result is consistent with the idea that the cytochrome b-558-d complex is synthesized as an alternative oxidase for more efficient utilization of oxygen at low oxygen concentration. Thus, E. coli cells can maintain efficient oxidative energy conservation over a wide range of oxygen pressures by simply changing the contents of the two terminal oxidases, each of which functions as a coupling site.

Does oral supplementation of a fermented papaya preparation correct respiratory burst function of innate immune cells in type 2 diabetes mellitus patients?

PubMed

Dickerson, Ryan; Banerjee, Jaideep; Rauckhorst, Adam; Pfeiffer, Douglas R; Gordillo, Gayle M; Khanna, Savita; Osei, Kwame; Roy, Sashwati

2015-02-01

Fermented papaya preparation (FPP) is a nutritional supplement reported to act as an antioxidant by scavenging reactive oxygen species (ROS) and removing "bad ROS," while inducing "respiratory burst" production of necessary "good ROS." We sought to investigate the safety of oral administration of FPP (9 g/day, 6 weeks) to T2D patients with regard to its effect on the hyperglycemia status of these patients. Peripheral blood was collected during a baseline visit, followed by subsequent collections both during and after supplementation. Induced "respiratory burst" ROS production was measured at each visit in addition to fasting blood glucose, lipid profile, glycated hemoglobin (HbA1c), and lipid/protein peroxidation. Oral FPP supplementation induced "respiratory burst" in peripheral blood mononuclear cells while not influencing other blood parameters studied. When human monocytic THP-1 cells were supplemented with sugar-based FPP, cellular ATP and NADPH concentrations were increased while matched glucose alone did not produce similar effects, suggesting a glucose-independent component of FPP to be responsible for increasing cellular energetics. THP-1 cells supplemented with FPP also exhibited higher mitochondrial membrane potential (Δψm) and oxygen consumption as compared with cells treated with glucose alone. Taken together, our observations lead to the hypothesis that FPP corrects inducible "respiratory burst" function in type 2 diabetes patients.

Effect of nicotine, cotinine and cigarette smoke extract on the neutrophil respiratory burst.

PubMed

Matthews, John B; Chen, Fa-Ming; Milward, Michael R; Wright, Helen J; Carter, Kevin; McDonagh, Anna; Chapple, Iain L C

2011-03-01

To determine the effect of nicotine, cotinine and cigarette smoke extract (CSE) on the neutrophil respiratory burst and their effect on activation of the nuclear factor-κB (NFκB) pathway in oral epithelium. Neutrophils from periodontally healthy individuals were treated with nicotine, cotinine and CSE before stimulation with Fusobacterium nucleatum, IgG-opsonized Staphylococcus aureus and Escherichia coli lipopolysaccharide. Total and extracellular reactive oxygen species (ROS) generation was determined by luminol/isoluminol chemiluminescence. Activation of NFκB in oral epithelial cells was determined by immunocytochemistry. Smoke extract alone caused increased neutrophil extracellular isoluminol-dependent chemiluminescence, not detectable with luminol. However, pre-treatment with smoke extract reduced both total and extracellular ROS generation in response to all stimuli. Nicotine and cotinine had no effect on the neutrophil respiratory burst. Smoke extract, nicotine and cotinine did not induce oral epithelial cell NFκB activation. These data demonstrate that smoke extract reduces the ability of neutrophils to generate ROS after stimulation with F. nucleatum and IgG-opsonized S. aureus but, at high concentrations, stimulates extracellular ROS generation. During periodontitis, cigarette smoking may differentially affect neutrophil function, generally preventing elimination of periodontal pathogens but, in heavy smokers, also stimulating ROS release and oxidative stress mediated tissue damage. © 2011 John Wiley & Sons A/S.

Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase.

PubMed

Vergis, Nikhil; Khamri, Wafa; Beale, Kylie; Sadiq, Fouzia; Aletrari, Mina O; Moore, Celia; Atkinson, Stephen R; Bernsmeier, Christine; Possamai, Lucia A; Petts, Gemma; Ryan, Jennifer M; Abeles, Robin D; James, Sarah; Foxton, Matthew; Hogan, Brian; Foster, Graham R; O'Brien, Alastair J; Ma, Yun; Shawcross, Debbie L; Wendon, Julia A; Antoniades, Charalambos G; Thursz, Mark R

2017-03-01

In order to explain the increased susceptibility to serious infection in alcoholic hepatitis, we evaluated monocyte phagocytosis, aberrations of associated signalling pathways and their reversibility, and whether phagocytic defects could predict subsequent infection. Monocytes were identified from blood samples of 42 patients with severe alcoholic hepatitis using monoclonal antibody to CD14. Phagocytosis and monocyte oxidative burst (MOB) were measured ex vivo using flow cytometry, luminometry and bacterial killing assays. Defects were related to the subsequent development of infection. Intracellular signalling pathways were investigated using western blotting and PCR. Interferon-γ (IFN-γ) was evaluated for its therapeutic potential in reversing phagocytic defects. Paired longitudinal samples were used to evaluate the effect of in vivo prednisolone therapy. MOB, production of superoxide and bacterial killing in response to Escherichia coli were markedly impaired in patients with alcoholic hepatitis. Pretreatment MOB predicted development of infection within two weeks with sensitivity and specificity that were superior to available clinical markers. Accordingly, defective MOB was associated with death at 28 and 90 days. Expression of the gp91 phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was reduced in patients with alcoholic hepatitis demonstrating defective MOB. Monocytes were refractory to IFN-γ stimulation and showed high levels of a negative regulator of cytokine signalling, suppressor of cytokine signalling-1. MOB was unaffected by 7 days in vivo prednisolone therapy. Monocyte oxidative burst and bacterial killing is impaired in alcoholic hepatitis while bacterial uptake by phagocytosis is preserved. Defective MOB is associated with reduced expression of NADPH oxidase in these patients and predicts the development of infection and death. Published by the BMJ Publishing Group Limited. For permission to use (where not already

Origin of the phagocytic respiratory burst and its role in gut epithelial phagocytosis in a basal chordate.

PubMed

Yang, Ping; Huang, Shengfeng; Yan, Xinyu; Huang, Guangrui; Dong, Xiangru; Zheng, Tingting; Yuan, Dongjuan; Wang, Ruihua; Li, Rui; Tan, Ying; Xu, Anlong

2014-05-01

The vertebrate phagocytic respiratory burst (PRB) is a highly specific and efficient mechanism for reactive oxygen species (ROS) production. This mechanism is mediated by NADPH oxidase 2 (NOX2) and used by vertebrate phagocytic leukocytes to destroy internalized microbes. Here we demonstrate the presence of the PRB in a basal chordate, the amphioxus Branchiostoma belcheri tsingtauense (bbt). We show that using the antioxidant NAC to scavenge the production of ROS significantly decreased the survival rates of infected amphioxus, indicating that ROS are indispensable for efficient antibacterial responses. Amphioxus NOX enzymes and cytosolic factors were found to colocalize in the epithelial cells of the gill, intestine, and hepatic cecum and could be upregulated after exposure to microbial pathogens. The ROS production in epithelial cell lysates could be reconstructed by supplementing recombinant cytosolic factors, including bbt-p47phox, bbt-p67phox, bbt-p47phox, and bbt-Rac; the restored ROS production could be inhibited by anti-bbt-NOX2 and anti-bbt-p67phox antibodies. We also reveal that the gut epithelial lining cells of the amphioxus are competent at bacterial phagocytosis, and there is evidence that the PRB machinery could participate in the initiation of this phagocytic process. In conclusion, we report the presence of the classical PRB machinery in nonvertebrates and provide the first evidence for the possible role of PRB in epithelial cell immunity and phagocytosis. Copyright © 2014 Elsevier Inc. All rights reserved.

The effects of oral consumption of selenium nanoparticles on chemotactic and respiratory burst activities of neutrophils in comparison with sodium selenite in sheep.

PubMed

Kojouri, Gholam Ali; Sadeghian, Sirous; Mohebbi, Abdonnaser; Mokhber Dezfouli, Mohammad Reza

2012-05-01

The present study was designed to compare the effects of nano-selenium and of sodium selenite on the chemotactic and respiratory burst activities of neutrophils in sheep. Fifteen sheep were randomly divided into three groups. Groups 1 and 2 received selenium nanoparticles (1 mg/kg) or sodium selenite (1 mg/kg) orally, respectively, for ten consecutive days, and the third group was considered as the control. To determine the chemotactic and respiratory burst activities of the neutrophils, the leading front assay and the NBT test were used on heparinized blood samples that were collected at different intervals (days 0, 10th, 20th, and 30th). The results obtained showed that the chemotactic activities in groups 1 and 2 increased significantly on the 10th, 20th, and 30th day, compared to day 0, and on the 20th day in comparison with the 10th day, while in group 2, there was a significant decrease on the 30th day compared to the 20th day. The chemotactic activities in group 1 were significantly higher than in group 2 on the 10th day and in the control group on the 10th, 20th, and 30th day, but the chemotactic activities in group 2 were significantly higher than those in the control group only on the 20th day. On the 30th day into the experiment, the respiratory bursts in groups 1 and 2 were significantly stronger in comparison with those at day 0. Overall, nano-selenium increased the chemotactic and respiratory burst activities more significantly than sodium selenite, which is suggestive of a stronger stimulatory effect of the Se nanoparticles on intracellular activities.

[Research on the mechanism and regulation of overtraining-related the function of neutrophils by the inhibitor of NADPH oxidase and glutamine supplementation].

PubMed

Dong, Jing-Mei; Chen, Pei-Jie

2013-07-01

To investigate the method and mechanism for exercise-related immunosuppression via the inhibitor of NADPH oxidase diphenyleneiodonium(DPI) and glutamine supplementation and on the function of neutrophils after overtraining. Fifty male Wistar rats were randomly divided into five groups: a negative control group (C), an overtraining group (E), an overtraining + DPI intervention group (D), an overtraining+ glutamine supplementation group(G) and combined glutamine + DPI intervention group(DG). After 36 - 40 h from the last training, eight rats were randomly selected from each group, and blood was sampled from the orbital vein. ELISAs were used to measure serum cytokine levels and lipid peroxidation in blood plasma. Flow cytometry was used to measure neutrophil respiratory burst and phagocytosis. The activity of NADPH oxidase was assessed by chemiluminescence and the gene expression of gp91(phox) and p47(phox) of the NADPH-oxidase subunit was checked by Western blot. Compared with group C, the plasma concentrations of NO increased in group G, and the NO, cytokine-induced neutrophil chemoattractant (CINC) concentrations in group DG increased significantly. The respiratory burst and phagocytosis function of neutrophils were decreased in group E, but in group DG were increased when compared with those of group E. After overtraining the expression of gp91(phox) and p47(phox) was up regulated in group E. There were no significant changes in other groups except group DG, in which the expression of gp91(phox) was down regulated. Compared with group E, the expression of gp91(phox) and p47(phox) was up regulated in group D, group G and group DG. The activation of NADPH oxidase is responsible for the production of superoxide anions, which may be related to the decrease in neutrophil function after over training and is the mechanism of exercise-related immunosuppression. The DPI treatment combined glutamine supplementation can reverse the decrease neutrophils function after

Cytochrome c oxidase rather than cytochrome c is a major determinant of mitochondrial respiratory capacity in skeletal muscle of aged rats: role of carnitine and lipoic acid.

PubMed

Tamilselvan, Jayavelu; Sivarajan, Kumarasamy; Anusuyadevi, Muthuswamy; Panneerselvam, Chinnakkannu

2007-09-01

The release of mitochondrial cytochrome c followed by activation of caspase cascade has been reported with aging in various tissues, whereas little is known about the caspase-independent pathway involved in mitochondrial dysfunction. To determine the functional impact of cytochrome c loss on mitochondrial respiratory capacity, we monitored NADH redox transitions and oxygen consumption in isolated skeletal muscle mitochondria of 4- and 24-month-old rats in the presence and absence of exogenous cytochrome c; and assessed the efficacy of cosupplementation of carnitine and lipoic acid on age-related alteration in mitochondrial respiration. The loss of mitochondrial cytochrome c with age was accompanied with alteration in respiratory transition, which in turn was not rescued by exogenous addition of cytochrome c to isolated mitochondria. The analysis of mitochondrial and nuclear-encoded cytochrome c oxidase subunits suggests that the decreased levels of cytochrome c oxidase may be attributed for the irresponsiveness to exogenously added cytochrome c on mitochondrial respiratory transitions, possibly through reduction of upstream electron carriers. Oral supplementation of carnitine and lipoic acid to aged rats help to maintaining the mitochondrial oxidative capacity by regulating the release of cytochrome c and improves cytochrome c oxidase transcript levels. Thus, carnitine and lipoic acid supplementation prevents the loss of cytochrome c and their associated decline in cytochrome c oxidase activity; thereby, effectively attenuating any putative decrease in cellular energy and redox status with age.

Effects of coarse chalk dust particles (2.5-10 μm) on respiratory burst and oxidative stress in alveolar macrophages.

PubMed

Zhang, Yuexia; Yang, Zhenhua; Feng, Yan; Li, Ruijin; Zhang, Quanxi; Geng, Hong; Dong, Chuan

2015-08-01

The main aim of the present study was to examine in vitro responses of rat alveolar macrophages (AMs) exposed to coarse chalk dust particles (particulate matter in the size range 2.5-10 μm, PM(coarse)) by respiratory burst and oxidative stress. Chalk PM(coarse)-induced respiratory burst in AMs was measured by using a luminol-dependent chemiluminescence (CL) method. Also, the cell viability; lactate dehydrogenase (LDH) release; levels of cellular superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and acid phosphatase (ACP); plasma membrane ATPase; and extracellular nitric oxide (NO) level were determined 4 h following the treatment with the different dosages of chalk PM(coarse). The results showed that chalk PM(coarse) initiated the respiratory burst of AMs as indicated by strong CL, which was inhibited by diphenyleneiodonium chloride and L-N-nitro-L-arginine methyl ester hydrochloride. It suggested that chalk PM(coarse) induced the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in AMs. This hypothesis was confirmed by the fact that chalk PM(coarse) resulted in a significant decrease of intracellular SOD, GSH, ACP, and ATPase levels and a notable increase of intracellular CAT, MDA content, and extracellular NO level, consequently leading to a decrease of the cell viability and a increase of LDH release. It was concluded that AMs exposed to chalk PM(coarse) can suffer from cytotoxicity which may be mediated by generation of excessive ROS/RNS. Graphical Abstract The possible mechanism of coarse chalk particles-induced adverse effects in AMs.

Glutamate release from activated microglia requires the oxidative burst and lipid peroxidation.

PubMed

Barger, Steven W; Goodwin, Mary E; Porter, Mandy M; Beggs, Marjorie L

2007-06-01

When activated by proinflammatory stimuli, microglia release substantial levels of glutamate, and mounting evidence suggests this contributes to neuronal damage during neuroinflammation. Prior studies indicated a role for the Xc exchange system, an amino acid transporter that antiports glutamate for cystine. Because cystine is used for synthesis of glutathione (GSH) synthesis, we hypothesized that glutamate release is an indirect consequence of GSH depletion by the respiratory burst, which produces superoxide from NADPH oxidase. Microglial glutamate release triggered by lipopolysaccharide was blocked by diphenylene iodonium chloride and apocynin, inhibitors of NADPH oxidase. This glutamate release was also blocked by vitamin E and elicited by lipid peroxidation products 4-hydroxynonenal and acrolein, suggesting that lipid peroxidation makes crucial demands on GSH. Although NADPH oxidase inhibitors also suppressed nitrite accumulation, vitamin E did not; moreover, glutamate release was largely unaffected by nitric oxide donors, inhibitors of nitric oxide synthase, or changes in gene expression. These findings indicate that a considerable degree of the neurodegenerative consequences of neuroinflammation may result from conversion of oxidative stress to excitotoxic stress. This phenomenon entails a biochemical chain of events initiated by a programmed oxidative stress and resultant mass-action amino acid transport. Indeed, some of the neuroprotective effects of antioxidants may be due to interference with these events rather than direct protection against neuronal oxidation.

Analysis of PAMP-Triggered ROS Burst in Plant Immunity.

PubMed

Sang, Yuying; Macho, Alberto P

2017-01-01

The plant perception of pathogen-associated molecular patterns triggers a plethora of cellular immune responses. One of these responses is a rapid and transient burst of reactive oxygen species (ROS) mediated by plasma membrane-localized NADPH oxidases. The ROS burst requires a functional receptor complex and the contribution of several additional regulatory components. In laboratory conditions, the ROS burst can be detected a few minutes after the treatment with an immunogenic microbial elicitor. For these reasons, the elicitor-triggered ROS burst has been often exploited as readout to probe the contribution of plant components to early immune responses. Here, we describe a detailed protocol for the measurement of elicitor-triggered ROS burst in a simple, fast, and easy manner.

Regulation of the NADPH Oxidase RBOHD During Plant Immunity.

PubMed

Kadota, Yasuhiro; Shirasu, Ken; Zipfel, Cyril

2015-08-01

Pathogen recognition induces the production of reactive oxygen species (ROS) by NADPH oxidases in both plants and animals. ROS have direct antimicrobial properties, but also serve as signaling molecules to activate further immune outputs. However, ROS production has to be tightly controlled to avoid detrimental effects on host cells, but yet must be produced in the right amount, at the right place and at the right time upon pathogen perception. Plant NADPH oxidases belong to the respiratory burst oxidase homolog (RBOH) family, which contains 10 members in the model plant Arabidopsis thaliana. The perception of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) leads to a rapid, specific and strong production of ROS, which is dependent on RBOHD. RBOHD is mainly controlled by Ca(2+) via direct binding to EF-hand motifs and phosphorylation by Ca(2+)-dependent protein kinases. Recent studies have, however, revealed a critical role for a Ca(2+)-independent regulation of RBOHD. The plasma membrane-associated cytoplasmic kinase BIK1 (BOTRYTIS-INDUCED KINASE1), which is a direct substrate of the PRR complex, directly interacts with and phosphorylates RBOHD upon PAMP perception. Impairment of these phosphorylation events completely abolishes the function of RBOHD in immunity. These results suggest that RBOHD activity is tightly controlled by multilayered regulations. In this review, we summarize recent advances in our understanding of the regulatory mechanisms controlling RBOHD activation. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Metabolic activation and nucleic acid binding of acetaminophen and related arylamine substrates by the respiratory burst of human granulocytes.

PubMed

Corbett, M D; Corbett, B R; Hannothiaux, M H; Quintana, S J

1989-01-01

Following stimulation with phorbol myristate acetate, human granulocytes were found to incorporate acetaminophen, p-phenetidine, p-aminophenol, and p-chloroaniline into cellular DNA and RNA. Phenacetin was not incorporated into nucleic acid or metabolized by such activated granulocytes. None of the substrates gave nucleic acid binding if the granulocyte cultures were not induced to undergo the respiratory burst. Additional studies on the binding of acetaminophen to DNA and RNA were made by use of both ring-14C-labeled and carbonyl-14C-labeled forms of this substrate. The finding that equivalent amounts of these two labeled acetaminophen substrates were bound to cellular DNA demonstrated that the intact acetaminophen molecule was incorporated into DNA. On the other hand, the finding that excess ring-14C-labeled acetaminophen was incorporated into cellular RNA implies partial hydrolysis of the acetaminophen substrate prior to RNA binding. Evidence was presented which strongly indicates that the nucleic acid binding of the substrates was covalent in nature. The inability of the respiratory burst to result in the binding of phenacetin to nucleic acid suggests that arylamides are not normally activated or metabolized by activated granulocytes. Acetaminophen is an exception to the recalcitrance of arylamides to such bioactivation processes because it also possesses the phenolic functional group, which, like the arylamine group, is oxidized by certain reactive oxygen species. Myeloperoxidase appears to be much more important in the binding of acetaminophen to DNA than it is in the DNA binding of arylamines in general. The role of the respiratory burst in causing the bioactivation of certain arylamines, which are not normally genotoxic via the more usual microsomal activation pathways, was extended to include certain amide substrates such as acetaminophen.

The Intimate and Controversial Relationship between Voltage Gated Proton Channels and the Phagocyte NADPH Oxidase

PubMed Central

DeCoursey, Thomas E.

2016-01-01

Summary One of the most fascinating and exciting periods in my scientific career entailed dissecting the symbiotic relationship between two membrane transporters, the NADPH oxidase complex and voltage gated proton channels (HV1). By the time I entered this field, there had already been substantial progress toward understanding NADPH oxidase, but HV1 were known only to a tiny handful of cognoscenti around the world. Having identified the first proton currents in mammalian cells in 1991, I needed to find a clear function for these molecules if the work was to become fundable. The then-recent discoveries of Henderson, Chappell, and colleagues in 1987–1988 that led them to hypothesize interactions of both molecules during the respiratory burst of phagocytes provided an excellent opportunity. In a nutshell, both transporters function by moving electrical charge across the membrane: NADPH oxidase moves electrons and HV1 moves protons. The consequences of electrogenic NADPH oxidase activity on both membrane potential and pH strongly self-limit this enzyme. Fortunately, both consequences specifically activate HV1, and HV1 activity counteracts both consequences, a kind of yin-yang relationship. Notwithstanding a decade starting in 1995 when many believed the opposite, these are two separate molecules that function independently despite their being functionally interdependent in phagocytes. The relationship between NADPH oxidase and HV1 has become a paradigm that somewhat surprisingly has now extended well beyond the phagocyte NADPH oxidase -- an industrial strength producer of reactive oxygen species (ROS) -- to myriad other cells that produce orders of magnitude less ROS for signaling purposes. These cells with their seven NADPH oxidase (NOX) isoforms provide a vast realm of mechanistic obscurity that will occupy future studies for years to come. PMID:27558336

The intimate and controversial relationship between voltage-gated proton channels and the phagocyte NADPH oxidase.

PubMed

DeCoursey, Thomas E

2016-09-01

One of the most fascinating and exciting periods in my scientific career entailed dissecting the symbiotic relationship between two membrane transporters, the Nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase complex and voltage-gated proton channels (HV 1). By the time I entered this field, there had already been substantial progress toward understanding NADPH oxidase, but HV 1 were known only to a tiny handful of cognoscenti around the world. Having identified the first proton currents in mammalian cells in 1991, I needed to find a clear function for these molecules if the work was to become fundable. The then-recent discoveries of Henderson, Chappell, and colleagues in 1987-1988 that led them to hypothesize interactions of both molecules during the respiratory burst of phagocytes provided an excellent opportunity. In a nutshell, both transporters function by moving electrical charge across the membrane: NADPH oxidase moves electrons and HV 1 moves protons. The consequences of electrogenic NADPH oxidase activity on both membrane potential and pH strongly self-limit this enzyme. Fortunately, both consequences specifically activate HV 1, and HV 1 activity counteracts both consequences, a kind of yin-yang relationship. Notwithstanding a decade starting in 1995 when many believed the opposite, these are two separate molecules that function independently despite their being functionally interdependent in phagocytes. The relationship between NADPH oxidase and HV 1 has become a paradigm that somewhat surprisingly has now extended well beyond the phagocyte NADPH oxidase - an industrial strength producer of reactive oxygen species (ROS) - to myriad other cells that produce orders of magnitude less ROS for signaling purposes. These cells with their seven NADPH oxidase (NOX) isoforms provide a vast realm of mechanistic obscurity that will occupy future studies for years to come. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bursting Types and Bifurcation Analysis in the Pre-Bötzinger Complex Respiratory Rhythm Neuron

NASA Astrophysics Data System (ADS)

Wang, Jing; Lu, Bo; Liu, Shenquan; Jiang, Xiaofang

Many types of neurons and excitable cells could intrinsically generate bursting activity, even in an isolated case, which plays a vital role in neuronal signaling and synaptic plasticity. In this paper, we have mainly investigated bursting types and corresponding bifurcations in the pre-Bötzinger complex respiratory rhythm neuron by using fast-slow dynamical analysis. The numerical simulation results have showed that for some appropriate parameters, the neuron model could exhibit four distinct types of fast-slow bursters. We also explored the bifurcation mechanisms related to these four types of bursters through the analysis of phase plane. Moreover, the first Lyapunov coefficient of the Hopf bifurcation, which can decide whether it is supercritical or subcritical, was calculated with the aid of MAPLE software. In addition, we analyzed the codimension-two bifurcation for equilibria of the whole system and gave a detailed theoretical derivation of the Bogdanov-Takens bifurcation. Finally, we obtained expressions for a fold bifurcation curve, a nondegenerate Hopf bifurcation curve, and a saddle homoclinic bifurcation curve near the Bogdanov-Takens bifurcation point.

Respiratory terminal oxidases alleviate photo-oxidative damage in photosystem I during repetitive short-pulse illumination in Synechocystis sp. PCC 6803.

PubMed

Shimakawa, Ginga; Miyake, Chikahiro

2018-03-08

Oxygenic phototrophs are vulnerable to damage by reactive oxygen species (ROS) that are produced in photosystem I (PSI) by excess photon energy over the demand of photosynthetic CO 2 assimilation. In plant leaves, repetitive short-pulse (rSP) illumination produces ROS to inactivate PSI. The production of ROS is alleviated by oxidation of the reaction center chlorophyll in PSI, P700, during the illumination with the short-pulse light, which is supported by flavodiiron protein (FLV). In this study, we found that in the cyanobacterium Synechocystis sp. PCC 6803 P700 was oxidized and PSI was not inactivated during rSP illumination even in the absence of FLV. Conversely, the mutant deficient in respiratory terminal oxidases was impaired in P700 oxidation during the illumination with the short-pulse light to suffer from photo-oxidative damage in PSI. Interestingly, the other cyanobacterium Synechococcus sp. PCC 7002 could not oxidize P700 without FLV during rSP illumination. These data indicate that respiratory terminal oxidases are critical to protect PSI from ROS damage during rSP illumination in Synechocystis sp. PCC 6803 but not Synechococcus sp. PCC 7002.

Characterization of an ntrX mutant of Neisseria gonorrhoeae reveals a response regulator that controls expression of respiratory enzymes in oxidase-positive proteobacteria.

PubMed

Atack, John M; Srikhanta, Yogitha N; Djoko, Karrera Y; Welch, Jessica P; Hasri, Norain H M; Steichen, Christopher T; Vanden Hoven, Rachel N; Grimmond, Sean M; Othman, Dk Seti Maimonah Pg; Kappler, Ulrike; Apicella, Michael A; Jennings, Michael P; Edwards, Jennifer L; McEwan, Alastair G

2013-06-01

NtrYX is a sensor-histidine kinase/response regulator two-component system that has had limited characterization in a small number of Alphaproteobacteria. Phylogenetic analysis of the response regulator NtrX showed that this two-component system is extensively distributed across the bacterial domain, and it is present in a variety of Betaproteobacteria, including the human pathogen Neisseria gonorrhoeae. Microarray analysis revealed that the expression of several components of the respiratory chain was reduced in an N. gonorrhoeae ntrX mutant compared to that in the isogenic wild-type (WT) strain 1291. These included the cytochrome c oxidase subunit (ccoP), nitrite reductase (aniA), and nitric oxide reductase (norB). Enzyme activity assays showed decreased cytochrome oxidase and nitrite reductase activities in the ntrX mutant, consistent with microarray data. N. gonorrhoeae ntrX mutants had reduced capacity to survive inside primary cervical cells compared to the wild type, and although they retained the ability to form a biofilm, they exhibited reduced survival within the biofilm compared to wild-type cells, as indicated by LIVE/DEAD staining. Analyses of an ntrX mutant in a representative alphaproteobacterium, Rhodobacter capsulatus, showed that cytochrome oxidase activity was also reduced compared to that in the wild-type strain SB1003. Taken together, these data provide evidence that the NtrYX two-component system may be a key regulator in the expression of respiratory enzymes and, in particular, cytochrome c oxidase, across a wide range of proteobacteria, including a variety of bacterial pathogens.

Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease

PubMed Central

Bustamante, Jacinta; Arias, Andres A; Vogt, Guillaume; Picard, Capucine; Galicia, Lizbeth Blancas; Prando, Carolina; Grant, Audrey V; Marchal, Christophe C; Hubeau, Marjorie; Chapgier, Ariane; de Beaucoudrey, Ludovic; Puel, Anne; Feinberg, Jacqueline; Valinetz, Ethan; Jannière, Lucile; Besse, Céline; Boland, Anne; Brisseau, Jean-Marie; Blanche, Stéphane; Lortholary, Olivier; Fieschi, Claire; Emile, Jean-François; Boisson-Dupuis, Stéphanie; Al-Muhsen, Saleh; Woda, Bruce; Newburger, Peter E; Condino-Neto, Antonio; Dinauer, Mary C; Abel, Laurent; Casanova, Jean-Laurent

2011-01-01

Germline mutations in CYBB, the human gene encoding the gp91phox subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD). We report here two kindreds in which otherwise healthy male adults developed X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD) syndromes. These patients had previously unknown mutations in CYBB that resulted in an impaired respiratory burst in monocyte-derived macrophages but not in monocytes or granulocytes. The macrophage-specific functional consequences of the germline mutation resulted from cell-specific impairment in the assembly of the NADPH oxidase. This ‘experiment of nature’ indicates that CYBB is associated with MSMD and demonstrates that the respiratory burst in human macrophages is a crucial mechanism for protective immunity to tuberculous mycobacteria. PMID:21278736

Lipopolysaccharides elicit an oxidative burst as a component of the innate immune system in the seagrass Thalassia testudinum.

PubMed

Loucks, Kyle; Waddell, David; Ross, Cliff

2013-09-01

This study represents the first report characterizing the biological effects of a lipopolysaccharide (LPS) immune modulator on a marine vascular plant. LPS was shown to serve as a strong elicitor of the early defense response in the subtropical seagrass Thalassia testudinum Banks ex König and was capable of inducing an oxidative burst identified at the single cell level. The formation of reactive oxygen species (ROS), detected by a redox-sensitive fluorescent probe and luminol-based chemiluminescence, included a diphenyleneiodonium sensitive response, suggesting the involvement of an NADPH oxidase. A 900 bp cDNA fragment coding for this enzyme was sequenced and found to encode a NAD binding pocket domain with extensive homology to the Arabidopsis thaliana rbohF (respiratory burst oxidase homolog) gene. The triggered release of ROS occurred at 20 min post-elicitation and was dose-dependent, requiring a minimal threshold of 50 μg/mL LPS. Pharmacological dissection of the early events preceding ROS emission indicated that the signal transduction chain of events involved extracellular alkalinization, G-proteins, phospholipase A2, as well as K(+), Ca(2+), and anion channels. Despite exclusively thriving in a marine environment, seagrasses contain ROS-generating machinery and signal transduction components that appear to be evolutionarily conserved with the well-characterized defense response systems found in terrestrial plants. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Post-160-km race illness rates and decreases in granulocyte respiratory burst and salivary IgA output are not countered by quercetin ingestion.

PubMed

Henson, D; Nieman, D; Davis, J M; Dumke, C; Gross, S; Murphy, A; Carmichael, M; Jenkins, D P; Quindry, J; McAnulty, S; McAnulty, L; Utter, A; Mayer, E

2008-10-01

This study measured the influence of the flavonoid quercetin on immune changes and incidence rates of upper respiratory tract infections in ultramarathoners competing in the 160-km Western States Endurance Run. Sixty-three runners were randomized to quercetin and placebo groups, and under double-blinded methods ingested 1000 mg/day quercetin for 3 wks before, during, and 2 wks after the race. Thirty-nine of the 63 subjects (n = 18 for quercetin, n = 21 for placebo) finished the race and provided blood and saliva samples the morning before the race and 15 - 30 min postrace. Upper respiratory tract infections were assessed during the week before and the 2-wk period after the race using an illness symptom checklist. Race times did not differ significantly between quercetin and placebo groups. Significant pre- to postrace decreases were measured for natural killer cells (43 %), granulocyte respiratory burst activity (55 %), and salivary IgA output (48 %), and increases for neutrophil (288 %) and monocyte (211 %) cell counts, with no significant group differences. Postrace illness rates did not differ between groups. In conclusion, quercetin supplementation for 3 wks before and 2 wks after the Western States Endurance Run had no effect on illness rates, perturbations in leukocyte subset counts, or decreases in granulocyte respiratory burst activity and salivary IgA.

Exogenously induced expression of ethylene biosynthesis, ethylene perception, phospholipase D, and Rboh-oxidase genes in broccoli seedlings

PubMed Central

Jakubowicz, Małgorzata; Gałgańska, Hanna; Nowak, Witold; Sadowski, Jan

2010-01-01

In higher plants, copper ions, hydrogen peroxide, and cycloheximide have been recognized as very effective inducers of the transcriptional activity of genes encoding the enzymes of the ethylene biosynthesis pathway. In this report, the transcriptional patterns of genes encoding the 1-aminocyclopropane-1-carboxylate synthases (ACSs), 1-aminocyclopropane-1-carboxylate oxidases (ACOs), ETR1, ETR2, and ERS1 ethylene receptors, phospholipase D (PLD)-α1, -α2, -γ1, and -δ, and respiratory burst oxidase homologue (Rboh)-NADPH oxidase-D and -F in response to these inducers in Brassica oleracea etiolated seedlings are shown. ACS1, ACO1, ETR2, PLD-γ1, and RbohD represent genes whose expression was considerably affected by all of the inducers used. The investigations were performed on the seedlings with (i) ethylene insensitivity and (ii) a reduced level of the PLD-derived phosphatidic acid (PA). The general conclusion is that the expression of ACS1, -3, -4, -5, -7, and -11, ACO1, ETR1, ERS1, and ETR2, PLD-γ 1, and RbohD and F genes is undoubtedly under the reciprocal cross-talk of the ethylene and PAPLD signalling routes; both signals affect it in concerted or opposite ways depending on the gene or the type of stimuli. The results of these studies on broccoli seedlings are in agreement with the hypothesis that PA may directly affect the ethylene signal transduction pathway via an inhibitory effect on CTR1 (constitutive triple response 1) activity. PMID:20581125

The Effects of Plantago major on the Activation of the Neutrophil Respiratory Burst

PubMed Central

Reina, Elaine; Al-Shibani, Nouf; Allam, Eman; Gregson, Karen S.; Kowolik, Michael; Windsor, L. Jack

2013-01-01

Plantago major is a common plant that grows worldwide in temperate zones and is found in fields, lawns, and on the roadsides. Its leaves and seeds have been used in almost all parts of the world for centuries as a wound healer, analgesic, antioxidant, and antibiotic, as well as an immune system modulator, antiviral, antifungal, and anti-inflammatory agent. Baicalein and aucubin are the two most biologically active components of P. major, and both have been shown to have antioxidant, anti-inflammatory, and anticancer properties. Neutrophils have a pivotal role in wound healing and inflammation. Their principal mechanism of host defense is the killing of pathogens via the production of reactive oxygen species (ROS). The aim of the present study was to determine the in vitro effects of P. major extract, baicalein, and aucubin on human neutrophil respiratory burst activity. The cytotoxicity of the agents was assessed by lactate dehydrogenase (LDH) assays. A standard luminol-dependent chemiluminescence (CL) assay was utilized to monitor the respiratory burst of the neutrophils after exposure to P. major extract and its two active ingredients, baicalein and aucubin. Three replicates per group were included in each of the three runs of the experiments and analysis of variance (ANOVA) was used for statistical analysis. P. major and baicalein were not toxic to the cells at any of the concentrations examined. Aucubin was toxic to the cells only at the highest concentration tested (P = 0.0081). However, genistein was toxic to the cells at all of the concentrations examined except for the lowest concentration of 16.9 μg/ml (P = 0.985). P. major (−0.10 ± 0.11), aucubin (0.06 ± 0.16), baicalein (−0.10 ± 0.11), and genistein (−0.18 ± 0.07) all significantly (P < 0.0001) inhibited ROS production from the neutrophils. P. major extract inhibited neutrophil ROS production, as did aucubin and baicalein. Therefore, these components should be investigated further with

The Effects of Plantago major on the Activation of the Neutrophil Respiratory Burst.

PubMed

Reina, Elaine; Al-Shibani, Nouf; Allam, Eman; Gregson, Karen S; Kowolik, Michael; Windsor, L Jack

2013-10-01

Plantago major is a common plant that grows worldwide in temperate zones and is found in fields, lawns, and on the roadsides. Its leaves and seeds have been used in almost all parts of the world for centuries as a wound healer, analgesic, antioxidant, and antibiotic, as well as an immune system modulator, antiviral, antifungal, and anti-inflammatory agent. Baicalein and aucubin are the two most biologically active components of P. major, and both have been shown to have antioxidant, anti-inflammatory, and anticancer properties. Neutrophils have a pivotal role in wound healing and inflammation. Their principal mechanism of host defense is the killing of pathogens via the production of reactive oxygen species (ROS). The aim of the present study was to determine the in vitro effects of P. major extract, baicalein, and aucubin on human neutrophil respiratory burst activity. The cytotoxicity of the agents was assessed by lactate dehydrogenase (LDH) assays. A standard luminol-dependent chemiluminescence (CL) assay was utilized to monitor the respiratory burst of the neutrophils after exposure to P. major extract and its two active ingredients, baicalein and aucubin. Three replicates per group were included in each of the three runs of the experiments and analysis of variance (ANOVA) was used for statistical analysis. P. major and baicalein were not toxic to the cells at any of the concentrations examined. Aucubin was toxic to the cells only at the highest concentration tested (P = 0.0081). However, genistein was toxic to the cells at all of the concentrations examined except for the lowest concentration of 16.9 μg/ml (P = 0.985). P. major (-0.10 ± 0.11), aucubin (0.06 ± 0.16), baicalein (-0.10 ± 0.11), and genistein (-0.18 ± 0.07) all significantly (P < 0.0001) inhibited ROS production from the neutrophils. P. major extract inhibited neutrophil ROS production, as did aucubin and baicalein. Therefore, these components should be investigated further with relation to

A gene encoding the plant-like alternative oxidase is present in Phytomonas but absent in Leishmania spp.

PubMed

Van Hellemond, J J; Simons, B; Millenaar, F F; Tielens, A G

1998-01-01

The constituents of the respiratory chain are believed to differ among the trypanosomatids; bloodstream stages of African trypanosomes and Phytomonas promastigotes oxidize ubiquinol by a ubiquinol:oxygen oxidoreductase, also known as alternative oxidase, whereas Leishmania spp. oxidize ubiquinol via a classic cytochrome-containing respiratory chain. The molecular basis for this elementary difference in ubiquinol oxidation by the mitochondrial electron-transport chain in distinct trypanosomatids was investigated. The presence of a gene encoding the plant-like alternative oxidase could be demonstrated in Phytomonas and Trypanosoma brucei, trypanosomatids that are known to contain alternative oxidase activity. Our results further demonstrated that Leishmania spp. lack a gene encoding the plant-like alternative oxidase, and therefore, all stages of Leishmania spp. will lack the alternative oxidase protein. The observed fundamental differences between the respiratory chains of distinct members of the trypanosomatid family are thus caused by the presence or absence of a gene encoding the plant-like alternative oxidase.

Identification of NADPH oxidase family members associated with cold stress in strawberry.

PubMed

Zhang, Yunting; Li, Yali; He, Yuwei; Hu, Wenjie; Zhang, Yong; Wang, Xiaorong; Tang, Haoru

2018-04-01

NADPH oxidase is encoded by a small gene family (Respiratory burst oxidase homologs, Rbohs ) and plays an important role in regulating various biological processes. However, little information about this gene family is currently available for strawberry. In this study, a total of seven Rboh genes were identified from strawberry through genomewide analysis. Gene structure analysis showed the number of exons ranged from 10 to 23, implying that this variation occurred in FvRboh genes by the insertion and distribution of introns; the order and approximate size of exons were relatively conserved. FvRbohC was predicted to localize to the thylakoid membrane of the chloroplast, while other members were computed to localize to the plasma membrane, indicating different functions. Amino acid sequence alignment, conserved domain, and motif analysis showed that all identified FvRbohs had typical features of plant Rbohs. Phylogenetic analysis of Rbohs from strawberry, grape, Arabidopsis, and rice suggested that the FvRbohs could be divided into five subgroups and showed a closer relationship with those from grape and Arabidopsis than those from rice. The expression patterns of FvRboh genes in root, stem, leaf, flower, and fruit revealed robust tissue specificity. The expression levels of FvRbohA and FvRbohD were quickly induced by cold stress, followed by an increase in NADPH oxidase activity, leading to O2- accumulation and triggering the antioxidant reaction by the transient increases in SOD activity. This suggested these two genes may be involved in cold stress and defense responses in strawberry.

Localization of essential rhombomeres for respiratory rhythm generation in bullfrog tadpoles using a binary search algorithm: Rhombomere 7 is essential for the gill rhythm and suppresses lung bursts before metamorphosis.

PubMed

Duchcherer, Maryana; Baghdadwala, Mufaddal I; Paramonov, Jenny; Wilson, Richard J A

2013-12-01

Frog metamorphosis includes transition from water breathing to air breathing but the extent to which such a momentous change in behavior requires fundamental changes in the organization of the brainstem respiratory circuit is unknown. Here, we combine a vertically mounted isolated brainstem preparation, "the Sheep Dip," with a search algorithm used in computer science, to identify essential rhombomeres for generation of ventilatory motor bursts in metamorphosing bullfrog tadpoles. Our data suggest that rhombomere 7, which in mammals hosts the PreBötC (PreBötzinger Complex; the likely inspiratory oscillator), is essential for gill and buccal bursts. Whereas rhombomere 5, in close proximity to a brainstem region associated with the mammalian expiratory oscillator, is essential for lung bursts at both stages. Therefore, we conclude there is no rhombomeric translocation of respiratory oscillators in bullfrogs as previously suggested. In premetamorphic tadpoles, functional ablation of rhombomere 7 caused ectopic expression of precocious lung bursts, suggesting the gill oscillator suppresses an otherwise functional lung oscillator in early development. Copyright © 2013 Wiley Periodicals, Inc.

Isolated sulfite oxidase deficiency.

PubMed

Rupar, C A; Gillett, J; Gordon, B A; Ramsay, D A; Johnson, J L; Garrett, R M; Rajagopalan, K V; Jung, J H; Bacheyie, G S; Sellers, A R

1996-12-01

Isolated sulfite oxidase (SO) deficiency is an autosomal recessively inherited inborn error of sulfur metabolism. In this report of a ninth patient the clinical history, laboratory results, neuropathological findings and a mutation in the sulfite oxidase gene are described. The data from this patient and previously published patients with isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are summarized to characterize this rare disorder. The patient presented neonatally with intractable seizures and did not progress developmentally beyond the neonatal stage. Dislocated lenses were apparent at 2 months. There was increased urine excretion of sulfite and S-sulfocysteine and a decreased concentration of plasma cystine. A lactic acidemia was present for 6 months. Liver sulfite oxidase activity was not detectable but xanthine dehydrogenase activity was normal. The boy died of respiratory failure at 32 months. Neuropathological findings of cortical necrosis and extensive cavitating leukoencephalopathy were reminiscent of those seen in severe perinatal asphyxia suggesting an etiology of energy deficiency. A point mutation that resulted in a truncated protein missing the molybdenum-binding site has been identified.

Distinguishing the Roles of Thylakoid Respiratory Terminal Oxidases in the Cyanobacterium Synechocystis sp. PCC 6803.

PubMed

Ermakova, Maria; Huokko, Tuomas; Richaud, Pierre; Bersanini, Luca; Howe, Christopher J; Lea-Smith, David J; Peltier, Gilles; Allahverdiyeva, Yagut

2016-06-01

Various oxygen-utilizing electron sinks, including the soluble flavodiiron proteins (Flv1/3), and the membrane-localized respiratory terminal oxidases (RTOs), cytochrome c oxidase (Cox) and cytochrome bd quinol oxidase (Cyd), are present in the photosynthetic electron transfer chain of Synechocystis sp. PCC 6803. However, the role of individual RTOs and their relative importance compared with other electron sinks are poorly understood, particularly under light. Via membrane inlet mass spectrometry gas exchange, chlorophyll a fluorescence, P700 analysis, and inhibitor treatment of the wild type and various mutants deficient in RTOs, Flv1/3, and photosystem I, we investigated the contribution of these complexes to the alleviation of excess electrons in the photosynthetic chain. To our knowledge, for the first time, we demonstrated the activity of Cyd in oxygen uptake under light, although it was detected only upon inhibition of electron transfer at the cytochrome b6f site and in ∆flv1/3 under fluctuating light conditions, where linear electron transfer was drastically inhibited due to impaired photosystem I activity. Cox is mostly responsible for dark respiration and competes with P700 for electrons under high light. Only the ∆cox/cyd double mutant, but not single mutants, demonstrated a highly reduced plastoquinone pool in darkness and impaired gross oxygen evolution under light, indicating that thylakoid-based RTOs are able to compensate partially for each other. Thus, both electron sinks contribute to the alleviation of excess electrons under illumination: RTOs continue to function under light, operating on slower time ranges and on a limited scale, whereas Flv1/3 responds rapidly as a light-induced component and has greater capacity. © 2016 American Society of Plant Biologists. All Rights Reserved.

Cellular glutathione levels in HL-60 cells during respiratory burst are not correlated with ultra-weak photon emission.

PubMed

Burgos, Rosilene Cristina Rossetto; Zhang, Wei; van Wijk, Eduard P A; Hankemeier, Thomas; Ramautar, Rawi; van der Greef, Jan

2017-10-01

Recently, ultra-weak photon emission (UPE) was developed as a novel tool for measuring oxidative metabolic processes, as its generation is related to reactive oxygen species (ROS). Both an imbalance in ROS or the uncontrolled production of ROS can lead to oxidative stress, which is commonly associated with many diseases. In addition to playing several biological functions, the thiol amino acid glutathione has an important antioxidant function in the body's defense against ROS. Specifically, glutathione is an important endogenous antioxidant that helps maintain oxidant levels. At the cellular level, glutathione is present in its reduced form (GSH) at relatively high concentrations (in the millimolar range) and in its oxidized form (GSSG) at low concentrations (in the micromolar range). Thus, the GSH/GSSG ratio is often used as an indicator of cellular redox state. Here, we used the HL-60 cell line as a model system in order to determine whether UPE is correlated with intracellular GSH and GSSG levels. HL-60 cells were differentiated into neutrophil-like cells and then stimulated to undergo respiratory burst. We then recorded UPE in real time for 9000 seconds and used capillary electrophoresis coupled to mass spectrometry to measure GSH and GSSG levels in cell extracts. We found that although respiratory burst significantly decreased the GSH/GSSG ratio, this change was not significantly correlated with the UPE profile. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute Respiratory Distress Syndrome Neutrophils Have a Distinct Phenotype and Are Resistant to Phosphoinositide 3-Kinase Inhibition

PubMed Central

Juss, Jatinder K.; House, David; Amour, Augustin; Begg, Malcolm; Herre, Jurgen; Storisteanu, Daniel M. L.; Hoenderdos, Kim; Bradley, Glyn; Lennon, Mark; Summers, Charlotte; Hessel, Edith M.; Condliffe, Alison

2016-01-01

Rationale: Acute respiratory distress syndrome is refractory to pharmacological intervention. Inappropriate activation of alveolar neutrophils is believed to underpin this disease’s complex pathophysiology, yet these cells have been little studied. Objectives: To examine the functional and transcriptional profiles of patient blood and alveolar neutrophils compared with healthy volunteer cells, and to define their sensitivity to phosphoinositide 3-kinase inhibition. Methods: Twenty-three ventilated patients underwent bronchoalveolar lavage. Alveolar and blood neutrophil apoptosis, phagocytosis, and adhesion molecules were quantified by flow cytometry, and oxidase responses were quantified by chemiluminescence. Cytokine and transcriptional profiling were used in multiplex and GeneChip arrays. Measurements and Main Results: Patient blood and alveolar neutrophils were distinct from healthy circulating cells, with increased CD11b and reduced CD62L expression, delayed constitutive apoptosis, and primed oxidase responses. Incubating control cells with disease bronchoalveolar lavage recapitulated the aberrant functional phenotype, and this could be reversed by phosphoinositide 3-kinase inhibitors. In contrast, the prosurvival phenotype of patient cells was resistant to phosphoinositide 3-kinase inhibition. RNA transcriptomic analysis revealed modified immune, cytoskeletal, and cell death pathways in patient cells, aligning closely to sepsis and burns datasets but not to phosphoinositide 3-kinase signatures. Conclusions: Acute respiratory distress syndrome blood and alveolar neutrophils display a distinct primed prosurvival profile and transcriptional signature. The enhanced respiratory burst was phosphoinositide 3-kinase–dependent but delayed apoptosis and the altered transcriptional profile were not. These unexpected findings cast doubt over the utility of phosphoinositide 3-kinase inhibition in acute respiratory distress syndrome and highlight the importance of

Characterization of oxidative phosphorylation in the colorless chlorophyte Polytomella sp. Its mitochondrial respiratory chain lacks a plant-like alternative oxidase.

PubMed

Reyes-Prieto, Adrián; El-Hafidi, Mohammed; Moreno-Sánchez, Rafael; González-Halphen, Diego

2002-07-01

The presence of an alternative oxidase (AOX) in Polytomella sp., a colorless relative of Chlamydomonas reinhardtii, was explored. Oxygen uptake in Polytomella sp. mitochondria was inhibited by KCN (94%) or antimycin (96%), and the remaining cyanide-resistant respiration was not blocked by the AOX inhibitors salicylhydroxamic acid (SHAM) or n-propylgallate. No stimulation of an AOX activity was found upon addition of either pyruvate, alpha-ketoglutarate, or AMP, or by treatment with DTT. An antibody raised against C. reinhardtii AOX did not recognized any polypeptide band of Polytomella sp. mitochondria in Western blots. Also, PCR experiments and Southern blot analysis failed to identify an Aox gene in this colorless alga. Finally, KCN exposure of cell cultures failed to stimulate an AOX activity. Nevertheless, KCN exposure of Polytomella sp. cells induced diminished mitochondrial respiration (20%) and apparent changes in cytochrome c oxidase affinity towards cyanide. KCN-adapted cells exhibited a significant increase of a-type cytochromes, suggesting accumulation of inactive forms of cytochrome c oxidase. Another effect of KCN exposure was the reduction of the protein/fatty acid ratio of mitochondrial membranes, which may affect the observed respiratory activity. We conclude that Polytomella lacks a plant-like AOX, and that its corresponding gene was probably lost during the divergence of this colorless genus from its close photosynthetic relatives.

An NADPH Oxidase RBOH Functions in Rice Roots during Lysigenous Aerenchyma Formation under Oxygen-Deficient Conditions

PubMed Central

Yoshioka, Miki; Fukazawa, Aya; Nishizawa, Naoko K.

2017-01-01

Reactive oxygen species (ROS) produced by the NADPH oxidase, respiratory burst oxidase homolog (RBOH), trigger signal transduction in diverse biological processes in plants. However, the functions of RBOH homologs in rice (Oryza sativa) and other gramineous plants are poorly understood. Ethylene induces the formation of lysigenous aerenchyma, which consists of internal gas spaces created by programmed cell death of cortical cells, in roots of gramineous plants under oxygen-deficient conditions. Here, we report that, in rice, one RBOH isoform (RBOHH) has a role in ethylene-induced aerenchyma formation in roots. Induction of RBOHH expression under oxygen-deficient conditions was greater in cortical cells than in cells of other root tissues. In addition, genes encoding group I calcium-dependent protein kinases (CDPK5 and CDPK13) were strongly expressed in root cortical cells. Coexpression of RBOHH with CDPK5 or CDPK13 induced ROS production in Nicotiana benthamiana leaves. Inhibitors of RBOH activity or cytosolic calcium influx suppressed ethylene-induced aerenchyma formation. Moreover, knockout of RBOHH by CRISPR/Cas9 reduced ROS accumulation and inducible aerenchyma formation in rice roots. These results suggest that RBOHH-mediated ROS production, which is stimulated by CDPK5 and/or CDPK13, is essential for ethylene-induced aerenchyma formation in rice roots under oxygen-deficient conditions. PMID:28351990

The temporal relationship between non-respiratory burst activity of expiratory laryngeal motoneurons and phrenic apnoea during stimulation of the superior laryngeal nerve in rat

PubMed Central

Sun, Qi-Jian; Bautista, Tara G; Berkowitz, Robert G; Zhao, Wen-Jing; Pilowsky, Paul M

2011-01-01

Abstract A striking effect of stimulating the superior laryngeal nerve (SLN) is its ability to inhibit central inspiratory activity (cause ‘phrenic apnoea’), but the mechanism underlying this inhibition remains unclear. Here we demonstrate, by stimulating the SLN at varying frequencies, that the evoked non-respiratory burst activity recorded from expiratory laryngeal motoneurons (ELMs) has an intimate temporal relationship with phrenic apnoea. During 1–5 Hz SLN stimulation, occasional absences of phrenic nerve discharge (PND) occurred such that every absent PND was preceded by an ELM burst activity. During 10–20 Hz SLN stimulation, more bursts were evoked together with more absent PNDs, leading eventually to phrenic apnoea. Interestingly, subsequent microinjections of isoguvacine (10 mm, 20–40 nl) into ipsilateral Bötzinger complex (BötC) and contralateral nucleus tractus solitarii (NTS) significantly attenuated the apnoeic response but not the ELM burst activity. Our results suggest a bifurcating projection from NTS to both the caudal nucleus ambiguus and BötC, which mediates the closely related ELM burst and apnoeic response, respectively. We believe that such an intimate timing between laryngeal behaviour and breathing is crucial for the effective elaboration of the different airway protective behaviours elicited following SLN stimulation, including the laryngeal adductor reflex, swallowing and cough. PMID:21320890

The oxidative burst reaction in mammalian cells depends on gravity

PubMed Central

2013-01-01

Gravity has been a constant force throughout the Earth’s evolutionary history. Thus, one of the fundamental biological questions is if and how complex cellular and molecular functions of life on Earth require gravity. In this study, we investigated the influence of gravity on the oxidative burst reaction in macrophages, one of the key elements in innate immune response and cellular signaling. An important step is the production of superoxide by the NADPH oxidase, which is rapidly converted to H2O2 by spontaneous and enzymatic dismutation. The phagozytosis-mediated oxidative burst under altered gravity conditions was studied in NR8383 rat alveolar macrophages by means of a luminol assay. Ground-based experiments in “functional weightlessness” were performed using a 2 D clinostat combined with a photomultiplier (PMT clinostat). The same technical set-up was used during the 13th DLR and 51st ESA parabolic flight campaign. Furthermore, hypergravity conditions were provided by using the Multi-Sample Incubation Centrifuge (MuSIC) and the Short Arm Human Centrifuge (SAHC). The results demonstrate that release of reactive oxygen species (ROS) during the oxidative burst reaction depends greatly on gravity conditions. ROS release is 1.) reduced in microgravity, 2.) enhanced in hypergravity and 3.) responds rapidly and reversible to altered gravity within seconds. We substantiated the effect of altered gravity on oxidative burst reaction in two independent experimental systems, parabolic flights and 2D clinostat / centrifuge experiments. Furthermore, the results obtained in simulated microgravity (2D clinorotation experiments) were proven by experiments in real microgravity as in both cases a pronounced reduction in ROS was observed. Our experiments indicate that gravity-sensitive steps are located both in the initial activation pathways and in the final oxidative burst reaction itself, which could be explained by the role of cytoskeletal dynamics in the assembly and

The oxidative burst reaction in mammalian cells depends on gravity.

PubMed

Adrian, Astrid; Schoppmann, Kathrin; Sromicki, Juri; Brungs, Sonja; von der Wiesche, Melanie; Hock, Bertold; Kolanus, Waldemar; Hemmersbach, Ruth; Ullrich, Oliver

2013-12-20

Gravity has been a constant force throughout the Earth's evolutionary history. Thus, one of the fundamental biological questions is if and how complex cellular and molecular functions of life on Earth require gravity. In this study, we investigated the influence of gravity on the oxidative burst reaction in macrophages, one of the key elements in innate immune response and cellular signaling. An important step is the production of superoxide by the NADPH oxidase, which is rapidly converted to H2O2 by spontaneous and enzymatic dismutation. The phagozytosis-mediated oxidative burst under altered gravity conditions was studied in NR8383 rat alveolar macrophages by means of a luminol assay. Ground-based experiments in "functional weightlessness" were performed using a 2 D clinostat combined with a photomultiplier (PMT clinostat). The same technical set-up was used during the 13th DLR and 51st ESA parabolic flight campaign. Furthermore, hypergravity conditions were provided by using the Multi-Sample Incubation Centrifuge (MuSIC) and the Short Arm Human Centrifuge (SAHC). The results demonstrate that release of reactive oxygen species (ROS) during the oxidative burst reaction depends greatly on gravity conditions. ROS release is 1.) reduced in microgravity, 2.) enhanced in hypergravity and 3.) responds rapidly and reversible to altered gravity within seconds. We substantiated the effect of altered gravity on oxidative burst reaction in two independent experimental systems, parabolic flights and 2D clinostat / centrifuge experiments. Furthermore, the results obtained in simulated microgravity (2D clinorotation experiments) were proven by experiments in real microgravity as in both cases a pronounced reduction in ROS was observed. Our experiments indicate that gravity-sensitive steps are located both in the initial activation pathways and in the final oxidative burst reaction itself, which could be explained by the role of cytoskeletal dynamics in the assembly and function

Activation of multiple pH-regulatory pathways in granulocytes by a phosphotyrosine phosphatase antagonist.

PubMed Central

Bianchini, L; Nanda, A; Wasan, S; Grinstein, S

1994-01-01

Activated phagocytes undergo a massive burst of metabolic acid generation, yet must be able to maintain their cytosolic pH (pHi) within physiological limits. Peroxides of vanadate (V(4+)-OOH), potent inhibitors of phosphotyrosine phosphatases, have recently been shown to produce activation of the respiratory burst in HL60 granulocytes. We therefore investigated the effects of V(4+)-OOH on pHi homoeostasis in HL60 granulocytes, using a pH-sensitive fluorescent dye. V(4+)-OOH stimulation induced a biphasic pH change: a transient cytosolic acidification followed by a significant alkalinization. The initial acidification was prevented by inhibition of the NADPH oxidase and was absent in undifferentiated cells lacking oxidase activity. Analysis of the alkalinization phase demonstrated the involvement of the Na+/H+ antiporter, and also provided evidence for activation of two alternative H(+)-extrusion pathways: a bafilomycin-sensitive component, likely reflecting vacuolar-type H(+)-ATPase activity, and a Zn(2+)-sensitive H(+)-conductive pathway. Our results indicate that V(4+)-OOH stimulation not only activated the NADPH oxidase but concomitantly stimulated H(+)-extrusion pathways, enabling the cells to compensate for the massive production of intracellular H+ associated with the respiratory burst. PMID:8043000

The hemibiotrophic cacao pathogen Moniliophthora perniciosa depends on a mitochondrial alternative oxidase for biotrophic development

USDA-ARS?s Scientific Manuscript database

The mitochondrial alternative oxidase (AOX) is a non-energy conserving ubiquinol oxidase found in most fungal genomes studied to date. With the development of fungicides containing cytochrome-dependent respiratory chain (CRC) inhibitors, a strong interest in studying AOX functions in phytopathogenic...

Alternative oxidase: a respiratory electron transport chain pathway essential for maintaining photosynthetic performance during drought stress.

PubMed

Vanlerberghe, Greg C; Martyn, Greg D; Dahal, Keshav

2016-07-01

Photosynthesis and respiration are the hubs of energy metabolism in plants. Drought strongly perturbs photosynthesis as a result of both diffusive limitations resulting from stomatal closure, and in some cases biochemical limitations that are associated with a reduced abundance of key photosynthetic components. The effects of drought on respiration, particularly respiration in the light (RL ), are less understood. The plant mitochondrial electron transport chain includes a non-energy conserving terminal oxidase called alternative oxidase (AOX). Several studies have shown that drought increases AOX transcript, protein and maximum capacity. Here we review recent studies comparing wild-type (WT) tobacco to transgenic lines with altered AOX protein amount. Specifically during drought, RL was compromised in AOX knockdown plants and enhanced in AOX overexpression plants, compared with WT. Significantly, these differences in RL were accompanied by dramatic differences in photosynthetic performance. Knockdown of AOX increased the susceptibility of photosynthesis to drought-induced biochemical limitations, while overexpression of AOX delayed the development of such biochemical limitations, compared with WT. Overall, the results indicate that AOX is essential to maintaining RL during drought, and that this non-energy conserving respiration maintains photosynthesis during drought by promoting energy balance in the chloroplast. This review also outlines several areas for future research, including the possibility that enhancement of non-energy conserving respiratory electron sinks may be a useful biotechnological approach to increase plant performance during stress. © 2016 Scandinavian Plant Physiology Society.

Diazotrophic specific cytochrome c oxidase required to overcome light stress in the cyanobacterium Nostoc muscorum.

PubMed

Bhargava, Santosh; Chouhan, Shweta

2016-01-01

Diazotrophic, filamentous and heterocystous cyanobacterium Nostoc muscorum perform photosynthesis in vegetative whereas nitrogen fixation occurs in heterocyst only. However, despite their metabolic plasticity, respiration takes place both in vegetative cells and heterocysts. The role of the respiratory electron transport system and terminal oxidases under light stress is not evident so far. As compared to the diazotrophically grown cultures, the non-diazotrophically grown cultures of the N. muscorum show a slight decrease in their growth, chlorophyll a contents and photosynthetic O2 evolution under light stress. Whereas respiratory O2 uptake under identical stress condition increases several fold. Likewise, nitrogen fixing enzyme i.e. nitrogenase over-expresses itself under light stress condition. The terminal enzyme of respiratory electron transport chain i.e. cytochrome c oxidase shows more activity under light stress, whilst light stress has no impact on Ca(++)-dependent ATPase activity. This leads to the conclusion that under light stress, cytochrome c oxidase plays a vital role in mitigating given light stress.

Bursting Transition Dynamics Within the Pre-Bötzinger Complex

NASA Astrophysics Data System (ADS)

Duan, Lixia; Chen, Xi; Tang, Xuhui; Su, Jianzhong

The pre-Bötzinger complex of the mammalian brain stem plays a crucial role in the respiratory rhythms generation. Neurons within the pre-Bötzinger complex have been found experimentally to yield different firing activities. In this paper, we study the spiking and bursting activities related to the respiratory rhythms in the pre-Bötzinger complex based on a mathematical model proposed by Butera. Using the one-dimensional first recurrence map induced by dynamics, we investigate the different bursting patterns and their transition of the pre-Bötzinger complex neurons based on the Butera model, after we derived a one-dimensional map from the dynamical characters of the differential equations, and we obtained conditions for the transition of different bursting patterns. These analytical results were verified through numerical simulations. We conclude that the one-dimensional map contains similar rhythmic patterns as the Butera model and can be used as a simpler modeling tool to study fast-slow models like pre-Bötzinger complex neural circuit.

Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P.

PubMed

Shvarev, Y N; Lagercrantz, H

2006-10-01

Developmental changes in the respiratory activity and its modulation by substance P (SP) were studied in the neonatal rat brainstem-spinal cord preparation from the day of birth to day 3 (P0-P3). The respiratory network activity in the ventrolateral medulla was represented by two types of bursts: basic regular bursts with typical decrementing shape and biphasic bursts appearing after augmented biphasic discharges in inspiratory neurons. With advancing postnatal age the respiratory output was considerably modified; the basic rhythm became faster by 20%, whereas the biphasic burst rate, which was originally 15 times slower, declined further by 180% and the C4 burst duration significantly decreased by 20% due to reduced decay time without preceding changes in the central inspiratory drive. SP had an age-dependent excitatory effect on respiratory activity. In the basic rhythm, SP could induce transient rhythm cessations on P0-P2 but not on P3. For the biphasic burst frequency, the sensitivity to SP significantly decreased from P0 to P3, whereas the range of SP-induced changes increased. In both types of bursts, SP prolonged C4 burst duration due to increasing decay time. This effect was three times greater on P3 and did not depend on the central inspiratory drive. Our results suggest that the potency of SP to regulate the respiratory activity elevates during the early postnatal period. The developmental changes in the respiratory activity appear to represent the transient stage in the maturation of rhythm and pattern generation mechanisms facilitating adaptive behavior of a quickly growing organism.

Priming of the neutrophil NADPH oxidase activation: role of p47phox phosphorylation and NOX2 mobilization to the plasma membrane.

PubMed

El-Benna, Jamel; Dang, Pham My-Chan; Gougerot-Pocidalo, Marie-Anne

2008-07-01

Neutrophils play an essential role in host defense against microbial pathogens and in the inflammatory reaction. Upon activation, neutrophils produce superoxide anion (O*2), which generates other reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), hydroxyl radical (OH*) and hypochlorous acid (HOCl), together with microbicidal peptides and proteases. The enzyme responsible for O2* production is called the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two trans-membrane proteins (p22phox and gp91phox/NOX2, which form the cytochrome b558), three cytosolic proteins (p47phox, p67phox, p40phox) and a GTPase (Rac1 or Rac2), which assemble at membrane sites upon cell activation. NADPH oxidase activation in phagocytes can be induced by a large number of soluble and particulate factors. Three major events accompany NAPDH oxidase activation: (1) protein phosphorylation, (2) GTPase activation, and (3) translocation of cytosolic components to the plasma membrane to form the active enzyme. Actually, the neutrophil NADPH oxidase exists in different states: resting, primed, activated, or inactivated. The resting state is found in circulating blood neutrophils. The primed state can be induced by neutrophil adhesion, pro-inflammatory cytokines, lipopolysaccharide, and other agents and has been characterized as a "ready to go" state, which results in a faster and higher response upon exposure to a second stimulus. The active state is found at the inflammatory or infection site. Activation is induced by the pathogen itself or by pathogen-derived formylated peptides and other agents. Finally, inactivation of NADPH oxidase is induced by anti-inflammatory agents to limit inflammation. Priming is a "double-edged sword" process as it contributes to a rapid and efficient elimination of the pathogens but can also induce the generation of large quantities of toxic ROS by hyperactivation of

Are pacemaker properties required for respiratory rhythm generation in adult turtle brain stems in vitro?

PubMed

Johnson, Stephen M; Wiegel, Liana M; Majewski, David J

2007-08-01

The role of pacemaker properties in vertebrate respiratory rhythm generation is not well understood. To address this question from a comparative perspective, brain stems from adult turtles were isolated in vitro, and respiratory motor bursts were recorded on hypoglossal (XII) nerve rootlets. The goal was to test whether burst frequency could be altered by conditions known to alter respiratory pacemaker neuron activity in mammals (e.g., increased bath KCl or blockade of specific inward currents). While bathed in artificial cerebrospinal fluid (aCSF), respiratory burst frequency was not correlated with changes in bath KCl (0.5-10.0 mM). Riluzole (50 microM; persistent Na(+) channel blocker) increased burst frequency by 31 +/- 5% (P < 0.05) and decreased burst amplitude by 42 +/- 4% (P < 0.05). In contrast, flufenamic acid (FFA, 20-500 microM; Ca(2+)-activated cation channel blocker) reduced and abolished burst frequency in a dose- and time-dependent manner (P < 0.05). During synaptic inhibition blockade with bicuculline (50 microM; GABA(A) channel blocker) and strychnine (50 muM; glycine receptor blocker), rhythmic motor activity persisted, and burst frequency was directly correlated with extracellular KCl (0.5-10.0 mM; P = 0.005). During synaptic inhibition blockade, riluzole (50 microM) did not alter burst frequency, whereas FFA (100 microM) abolished burst frequency (P < 0.05). These data are most consistent with the hypothesis that turtle respiratory rhythm generation requires Ca(2+)-activated cation channels but not pacemaker neurons, which thereby favors the group-pacemaker model. During synaptic inhibition blockade, however, the rhythm generator appears to be transformed into a pacemaker-driven network that requires Ca(2+)-activated cation channels.

Inhibition of the alveolar macrophage oxidative burst by a diffusible component from the surface of the spores of the fungus Aspergillus fumigatus.

PubMed Central

Slight, J.; Nicholson, W. J.; Mitchell, C. G.; Pouilly, N.; Beswick, P. H.; Seaton, A.; Donaldson, K.

1996-01-01

acted to inhibit the assembly of the macrophage NADPH-oxidase complex. Fractions of < 10 kD also inhibited the spreading of alveolar macrophages, confirming that the toxin had an additional effect on macrophages that leads to loss of adherence or impairment of cytoskeletal function. In reversed phase HPLC fractions the inhibitory activity eluted with an associated carbohydrate, although the exact chemical nature of the toxin remains to be elucidated. CONCLUSIONS: This spore toxin may, through its ability to diffuse rapidly into lung lining fluid, diminish the macrophage respiratory burst and play a part in allowing A fumigatus to persist in the lung and manifest its well known pathogenic effects. Future research will be focused on further molecular characterisation of the toxin and elaboration of the effect of the toxin on intracellular signalling pathways involved in the activation of alveolar macrophages. PMID:8733491

Alternative Oxidase: A Mitochondrial Respiratory Pathway to Maintain Metabolic and Signaling Homeostasis during Abiotic and Biotic Stress in Plants

PubMed Central

Vanlerberghe, Greg C.

2013-01-01

Alternative oxidase (AOX) is a non-energy conserving terminal oxidase in the plant mitochondrial electron transport chain. While respiratory carbon oxidation pathways, electron transport, and ATP turnover are tightly coupled processes, AOX provides a means to relax this coupling, thus providing a degree of metabolic homeostasis to carbon and energy metabolism. Beside their role in primary metabolism, plant mitochondria also act as “signaling organelles”, able to influence processes such as nuclear gene expression. AOX activity can control the level of potential mitochondrial signaling molecules such as superoxide, nitric oxide and important redox couples. In this way, AOX also provides a degree of signaling homeostasis to the organelle. Evidence suggests that AOX function in metabolic and signaling homeostasis is particularly important during stress. These include abiotic stresses such as low temperature, drought, and nutrient deficiency, as well as biotic stresses such as bacterial infection. This review provides an introduction to the genetic and biochemical control of AOX respiration, as well as providing generalized examples of how AOX activity can provide metabolic and signaling homeostasis. This review also examines abiotic and biotic stresses in which AOX respiration has been critically evaluated, and considers the overall role of AOX in growth and stress tolerance. PMID:23531539

The Respiratory System and Diazotrophic Activity of Acetobacter diazotrophicus PAL5

PubMed Central

Flores-Encarnación, M.; Contreras-Zentella, M.; Soto-Urzua, L.; Aguilar, G. R.; Baca, B. E.; Escamilla, J. E.

1999-01-01

The characteristics of the respiratory system of Acetobacter diazotrophicus PAL5 were investigated. Increasing aeration (from 0.5 to 4.0 liters of air min−1 liter of medium−1) had a strong positive effect on growth and on the diazotrophic activity of cultures. Cells obtained from well-aerated and diazotrophically active cultures possessed a highly active, membrane-bound electron transport system with dehydrogenases for NADH, glucose, and acetaldehyde as the main electron donors. Ethanol, succinate, and gluconate were also oxidized but to only a minor extent. Terminal cytochrome c oxidase-type activity was poor as measured by reduced N,N,N,N′-tetramethyl-p-phenylenediamine, but quinol oxidase-type activity, as measured by 2,3,5,6-tetrachloro-1,4-benzenediol, was high. Spectral and high-pressure liquid chromatography analysis of membranes revealed the presence of cytochrome ba as a putative oxidase in cells obtained from diazotrophically active cultures. Cells were also rich in c-type cytochromes; four bands of high molecular mass (i.e., 67, 56, 52, and 45 kDa) were revealed by a peroxidase activity stain in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. KCN inhibition curves of respiratory oxidase activities were biphasic, with a highly resistant component. Treatment of membranes with 0.2% Triton X-100 solubilized c-type cytochromes and resulted in a preparation that was significantly more sensitive to cyanide. Repression of diazotrophic activity in well-aerated cultures by 40 mM (NH4)2SO4 caused a significant decrease of the respiratory activities. It is noteworthy that the levels of glucose dehydrogenase and putative oxidase ba decreased 6.8- and 10-fold, respectively. In these cells, a bd-type cytochrome seems to be the major terminal oxidase. Thus, it would seem that glucose dehydrogenase and cytochrome ba are key components of the respiratory system of A. diazotrophicus during aerobic diazotrophy. PMID:10559164

Effects of banding or burdizzo castration of bulls on neutrophil phagocytosis and respiratory burst, CD62-L expression, and serum interleukin-8 concentration.

PubMed

Pang, W Y; Earley, B; Sweeney, T; Pirani, S; Gath, V; Crowe, M A

2009-10-01

The objective was to investigate measures of neutrophil function in response to banding or burdizzo castration of bulls. Thirty-two Holstein-Friesian bulls (14 mo old, 505 +/- 7.8 kg of BW) were assigned to 1 of 4 treatment groups: 1) sham-handled control (CON); 2) banding castration alone (BAND); 3) burdizzo castration alone (BURD); or 4) cortisol infusion (CORT) as a further control group. For each group on d -14, 8 animals (2 animals/treatment) were tied up in tie stalls (day of treatment = d 0). At -2, 2, 6, 12, 24, 48, 72, and 144 h relative to treatment time, blood samples were collected for analyses of neutrophil phagocytosis and respiratory burst, neutrophil CD62-L expression, and serum IL-8 concentration. Leukocyte counts, phagocytosis activity, and CD62-L expression were similar (P > 0.05) among the 4 treatment groups. The BURD castrates had greater burst activity compared with BAND castrates (P = 0.048) and CON (P = 0.01) at 72 h posttreatment. The BURD castrates had a greater percentage of granulocyte positive leukocytes (Gr%; P < 0.01) at 2 h posttreatment compared with CON and CORT bulls. The BURD castrates had greater (P < 0.05) Gr% compared with BAND, CON, and CORT animals at 24, 48, and 72 h posttreatment. The BURD and BAND castrates had greater Gr% (P < 0.05) compared with CORT bulls at 144 h posttreatment. In general, BAND, BURD, and CORT did not affect serum IL-8 concentration. Banding castration, BURD, and CORT did not induce leukocytosis, whereas BURD induced a modest neutrophilia. Neutrophil functioning in terms of phagocytosis and respiratory burst and serum IL-8 concentration were not compromised by BAND, BURD, and CORT. These findings indicate nonsurgical castration is unlikely to induce a severe acute systemic inflammatory response in terms of neutrophil function.

Timescales and Mechanisms of Sigh-Like Bursting and Spiking in Models of Rhythmic Respiratory Neurons.

PubMed

Wang, Yangyang; Rubin, Jonathan E

2017-12-01

Neural networks generate a variety of rhythmic activity patterns, often involving different timescales. One example arises in the respiratory network in the pre-Bötzinger complex of the mammalian brainstem, which can generate the eupneic rhythm associated with normal respiration as well as recurrent low-frequency, large-amplitude bursts associated with sighing. Two competing hypotheses have been proposed to explain sigh generation: the recruitment of a neuronal population distinct from the eupneic rhythm-generating subpopulation or the reconfiguration of activity within a single population. Here, we consider two recent computational models, one of which represents each of the hypotheses. We use methods of dynamical systems theory, such as fast-slow decomposition, averaging, and bifurcation analysis, to understand the multiple-timescale mechanisms underlying sigh generation in each model. In the course of our analysis, we discover that a third timescale is required to generate sighs in both models. Furthermore, we identify the similarities of the underlying mechanisms in the two models and the aspects in which they differ.

Physiology and pathophysiology of respiratory arrest by cyanide poisoning

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

Klimmek, R.

1993-05-13

Respiratory arrest, preceded by hyperventilation, is the primary cause of death in acute cyanide poisoning. Hyperventilation followed by apnea is also observed without intoxication. Hyperventilation and apnea in untoxicated subjects and animals are analyzed for the underlying physiological and biochemical changes and compared with those found during cyanide poisoning. The study reveals that the respiratory autoregulation appears to be the same under both conditions. Respiratory arrest is controlled by cerebral PCO2 and can occur without hypoxia or inhibition of cytochrome oxidase. It is postulated that respiratory arrest is a 'desperate act' thrust on the respiratory neurons by a critical exhaustionmore » of their energy store (ATP) due to the rapid firing in the period of hyperventilation. The point of no return may be reached when anoxia and/or partial inhibition of cytochrome oxidase prevent the neurons from replenishing the ATP store. The formation of Fe3+ cyanide complexes. exemplified by the metHb producer DMAP, appears to give the best results with regard to the restoration of spontaneous respiration. The study of respiratory autoregulation may also be helpful in developing and understanding other therapeutic approaches.« less

Regulation of superoxide anion production by NADPH oxidase in monocytes/macrophages: contributions to atherosclerosis.

PubMed

Cathcart, Martha K

2004-01-01

Monocyte extravasation into the vessel wall has been shown to be a critical step in the development of atherosclerosis. Upon activation, monocytes produce a burst of superoxide anion due to activation of the NADPH oxidase enzyme complex. Monocyte-derived superoxide anion contributes to oxidant stress in inflammatory sites, is required for monocyte-mediated LDL oxidation, and alters basic cell functions such as adhesion and proliferation. We hypothesize that monocyte-derived superoxide anion production contributes to atherosclerotic lesion formation. In this brief review, we summarize our current understanding of the signal transduction pathways regulating NADPH oxidase activation and related superoxide anion production in activated human monocytes. Novel pathways are identified that may serve as future targets for therapeutic intervention in this pathogenic process. The contributions of superoxide anion and NADPH oxidase to atherogenesis are discussed. Future experiments are needed to clarify the exact role of NADPH oxidase-derived superoxide anion in atherogenesis, particularly that derived from monocytes.

Sympathetic network drive during water deprivation does not increase respiratory or cardiac rhythmic sympathetic nerve activity.

PubMed

Holbein, Walter W; Toney, Glenn M

2013-06-15

Effects of water deprivation on rhythmic bursting of sympathetic nerve activity (SNA) were investigated in anesthetized, bilaterally vagotomized, euhydrated (control) and 48-h water-deprived (WD) rats (n = 8/group). Control and WD rats had similar baseline values of mean arterial pressure, heart rate, end-tidal CO2, and central respiratory drive. Although integrated splanchnic SNA (sSNA) was greater in WD rats than controls (P < 0.01), analysis of respiratory rhythmic bursting of sSNA revealed that inspiratory rhythmic burst amplitude was actually smaller (P < 0.005) in WD rats (+68 ± 6%) than controls (+208 ± 20%), and amplitudes of the early expiratory (postinspiratory) trough and late expiratory burst of sSNA were not different between groups. Further analysis revealed that water deprivation had no effect on either the amplitude or periodicity of the cardiac rhythmic oscillation of sSNA. Collectively, these data indicate that the increase of sSNA produced by water deprivation is not attributable to either increased respiratory or cardiac rhythmic burst discharge. Thus the sympathetic network response to acute water deprivation appears to differ from that of chronic sympathoexcitation in neurogenic forms of arterial hypertension, where increased respiratory rhythmic bursting of SNA and baroreflex adaptations have been reported.

Influence of Rhodococcus equi on the respiratory burst of resident alveolar macrophages from horses

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

Brumbaugh, G.W.

1986-01-01

Rhodococcus equi is the etiologic agent of a devastating pneumonia of sporadic incidence in foals. The purpose of this study was to evaluate the influence of R. equi on the superoxide anion production, measured spectrophotometrically as the reduction of cytochrome C, and hexose monophosphate shunt activity, measured by /sup 14/CO/sub 2/ liberation from /sup 14/C-1-D-glucose, of alveolar macrophages from horses. Alveolar macrophages were harvested from 6 anesthetized, healthy, light-breed, adult horses by bronchoalveolar lavage. Following a randomized complete block design, the suspension of cells was divided into aliquots of 10/sup 6/ viable alveolar macrophages which were exposed to 1, 10more » or 100 g. of opsonized R. equi or opsonized zymosan A at 37 C for 2 hours. In this study the respiratory burst of equine alveolar macrophages was only evidenced by the hexose monophosphate shunt activity and superoxide anion was not coincidentally produced. Rhodococcus equi did not adversely affect that response. The insignificant superoxide anion production by the alveolar macrophages suggests that this may not be a significant oxygen metabolite in those cells.« less

Specific Inhibition of the Cyanide-insensitive Respiratory Pathway in Plant Mitochondria by Hydroxamic Acids

PubMed Central

Schonbaum, Gregory R.; Bonner, Walter D.; Storey, Bayard T.; Bahr, James T.

1971-01-01

Hydroxamic acids, R-CONHOH, are inhibitors specific to the respiratory pathway through the alternate, cyanide-insensitive terminal oxidase of plant mitochondria. The nature of the R group in these compounds affects the concentration at which the hydroxamic acids are effective, but it appears that all hydroxamic acids inhibit if high enough concentrations are used. The benzhydroxamic acids are effective at relatively low concentrations; of these, the most effective are m-chlorobenzhydroxamic acid and m-iodobenzhydroxamic acid. The concentrations required for half-maximal inhibition of the alternate oxidase pathway in mung bean (Phaseolus aureus) mitochondria are 0.03 mm for m-chlorobenzhydroxamic acid and 0.02 mm for m-iodobenzhydroxamic acid. With skunk cabbage (Symplocarpus foetidus) mitochondria, the required concentrations are 0.16 for m-chlorobenzhydroxamic acid and 0.05 for m-iodobenzhydroxamic acid. At concentrations which inhibit completely the alternate oxidase pathway, these two compounds have no discernible effect on either the respiratory pathway through cytochrome oxidase, or on the energy coupling reactions of these mitochondria. These inhibitors make it possible to isolate the two respiratory pathways and study their mode of action separately. These inhibitors also enhance an electron paramagnetic resonance signal near g = 2 in anaerobic, submitochondrial particles from skunk cabbage, which appears to be specific to the alternate oxidase and thus provides a means for its assay. PMID:5543780

A biohybrid hydrogel for the urate-responsive release of urate oxidase.

PubMed

Geraths, Christian; Daoud-El Baba, Marie; Charpin-El Hamri, Ghislaine; Weber, Wilfried

2013-10-10

Functional biomaterials that detect and correct pathological parameters hold high promises for biomedical application. In this study we describe a biohybrid hydrogel that detects elevated concentrations of uric acid and responds by dissolution and the release of uric acid-degrading urate oxidase. This material was synthesized by incorporating PEG-stabilized urate oxidase into a polyacrylamide hydrogel that was crosslinked by the uric acid-sensitive interaction between the uric acid transcription factor HucR and its operator hucO. We characterize the uric acid responsiveness of the material and demonstrate that it can effectively be applied to counteract flares of uric acid in a mouse model. This approach might be a first step towards a biomedical device autonomously managing uric acid burst associated to gouty arthritis and the tumor lysis syndrome. © 2013.

SHIP-1 Increases Early Oxidative Burst and Regulates Phagosome Maturation in Macrophages1

PubMed Central

Kamen, Lynn A.; Levinsohn, Jonathan; Cadwallader, Amy; Tridandapani, Susheela; Swanson, Joel A.

2010-01-01

Although the inositol phosphatase SHIP-1 is generally thought to inhibit signaling for Fc receptor-mediated phagocytosis, the product of its activity, phosphatidylinositol 3,4 bisphosphate (PI(3,4)P2) has been implicated in activation of the NADPH oxidase. This suggests that SHIP-1 positively regulates generation of reactive oxygen species after phagocytosis. To examine how SHIP-1 activity contributes to Fc receptor-mediated phagocytosis, we measured and compared phospholipid dynamics, membrane trafficking and the oxidative burst in macrophages from SHIP-1-deficient and wild-type mice. SHIP-1-deficient macrophages showed significantly elevated ratios of PI(3,4,5) P3 to PI(3,4)P2 on phagosomal membranes. Imaging reactive oxygen intermediate activities in phagosomes revealed decreased early NADPH oxidase activity in SHIP-1-deficient macrophages. SHIP-1-deficiency also altered later stages of phagosome maturation, as indicated by the persistent elevation of PI(3)P and the early localization of Rab5a to phagosomes. These direct measurements of individual organelles indicate that phagosomal SHIP-1 enhances the early oxidative burst through localized alteration of the membrane 3′ phosphoinositide composition. PMID:18490750

Biochemical analysis of respiratory metabolism in the heterofermentative Lactobacillus spicheri and Lactobacillus reuteri.

PubMed

Ianniello, R G; Zheng, J; Zotta, T; Ricciardi, A; Gänzle, M G

2015-09-01

This study evaluated the aerobic and respiratory metabolism in Lactobacillus reuteri and Lactobacillus spicheri, two heterofermentative species used in sourdough fermentation. In silico genome analysis, production of metabolites and gene expression of pyruvate oxidase, pyruvate dehydrogenase and cytochrome oxidase were assessed in anaerobic and aerobic cultures of Lact. reuteri and Lact. spicheri. Respiring homofermentative Lactobacillus casei N87 and Lact. rhamnosus N132 were used for comparison. Aerobiosis and respiration increased the biomass production of heterofermentative strains compared to anaerobic cultivation. Respiration led to acetoin production by Lact. rhamnosus and Lact. casei, but not in heterofermentative strains, in which lactate and acetate were the major end-products. Lactobacillus spicheri LP38 showed the highest oxygen uptake. Pyruvate oxidase, respiratory cytochromes, NADH oxidase and NADH peroxidase were present in the genome of Lact. spicheri LP38. Both Lact. spicheri LP38 and Lact. rhamnosus N132 overexpressed pox in aerobic cultures, while cydA was up-regulated only when haeme was supplied; pdh was repressed during aerobic growth. Aerobic and respiratory growth provided physiological and metabolic advantages also in heterofermentative lactobacilli. The exploitation of oxygen-tolerant phenotypes of Lact. spicheri may be useful for the development of improved starter cultures. © 2015 The Society for Applied Microbiology.

In vivo low-level light therapy increases cytochrome oxidase in skeletal muscle.

PubMed

Hayworth, Christopher R; Rojas, Julio C; Padilla, Eimeira; Holmes, Genevieve M; Sheridan, Eva C; Gonzalez-Lima, F

2010-01-01

Low-level light therapy (LLLT) increases survival of cultured cells, improves behavioral recovery from neurodegeneration and speeds wound healing. These beneficial effects are thought to be mediated by upregulation of mitochondrial proteins, especially the respiratory enzyme cytochrome oxidase. However, the effects of in vivo LLLT on cytochrome oxidase in intact skeletal muscle have not been previously investigated. We used a sensitive method for enzyme histochemistry of cytochrome oxidase to examine the rat temporalis muscle 24 h after in vivo LLLT. The findings showed for the first time that in vivo LLLT induced a dose- and fiber type-dependent increase in cytochrome oxidase in muscle fibers. LLLT was particularly effective at enhancing the aerobic capacity of intermediate and red fibers. The findings suggest that LLLT may enhance the oxidative energy metabolic capacity of different types of muscle fibers, and that LLLT may be used to enhance the aerobic potential of skeletal muscle.

Dual Stimulus-Dependent Effect of Oenothera paradoxa Extract on the Respiratory Burst in Human Leukocytes: Suppressing for Escherichia coli and Phorbol Myristate Acetate and Stimulating for Formyl-Methionyl-Leucyl-Phenylalanine

PubMed Central

Burzynska-Pedziwiatr, Izabela; Bukowiecka-Matusiak, Malgorzata; Wojcik, Marzena; Machala, Waldemar; Bienkiewicz, Malgorzata; Spolnik, Grzegorz; Danikiewicz, Witold; Wozniak, Lucyna Alicja

2014-01-01

Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA), and formyl-methionyl-leucyl-phenylalanine (fMLP). Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05) and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05). Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-β-(D)-glucose (PGG), the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC) coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans. PMID:25298860

Dual stimulus-dependent effect of Oenothera paradoxa extract on the respiratory burst in human leukocytes: suppressing for Escherichia coli and phorbol myristate acetate and stimulating for formyl-methionyl-leucyl-phenylalanine.

PubMed

Burzynska-Pedziwiatr, Izabela; Bukowiecka-Matusiak, Malgorzata; Wojcik, Marzena; Machala, Waldemar; Bienkiewicz, Malgorzata; Spolnik, Grzegorz; Danikiewicz, Witold; Wozniak, Lucyna Alicja

2014-01-01

Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA), and formyl-methionyl-leucyl-phenylalanine (fMLP). Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05) and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05). Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-β-(D)-glucose (PGG), the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC) coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans.

Neutrophil oxidative burst activation and the pattern of respiratory physiologic abnormalities in the fulminant post-traumatic adult respiratory distress syndrome.

PubMed

Rivkind, A I; Siegel, J H; Littleton, M; De Gaetano, A; Mamantov, T; Laghi, F; Stoklosa, J C

1991-01-01

The role of neutrophil oxidative burst activation (OBA) in the development of fulminant post-trauma adult respiratory distress syndrome (ARDS) was studied in 30 patients. Neutrophil (PMN) chemiluminescence (LE) was used as the index of OBA. Serially, for 8 days post-trauma, patient neutrophils (Pc) were studied in their own serum (Ps) normal serum (Ns), or Gey's solution (G). Ps was checked against normal neutrophils (Nc) for inhibition. LE was initiated by the addition of preopsonized zymosan to 1 x 10(6) PMN, the LE response monitored by luminometer, and the peak of the integral of LE recorded. Seven developed ARDS within the first 4 days; 12 patients developed sepsis (TS) but no ARDS, and 11 patients had uncomplicated trauma (TR). All ARDS showed increased LE (P less than 0.0001), at 48-96 hr. Patients without ARDS showed no significant increase in LE, although their mean injury severity (ISS) was the same. The ARDS LE response was mediated by activation of Pc [74%] with only a small but significant additional effect (6%) by ARDS serum (Ps): LE = 0.672 (Pc) + 0.24 [ARDS(Ps)] + 1343; N = 146, r2 0.733, P less than 0.0001. However, sera (Ps or Ns) was required, as incubation in G inhibited LE; [cells + s] greater than [cells + G], P less than 0.0001. LE is a biologic marker of ARDS, and the delay between injury and the LE indicated that initiation of ARDS may have therapeutic importance. Neutrophil activation in ARDS requires sera, but the ARDS effect appears mainly due to cells with only a small ARDS-specific serum-mediated role. The physiologic response to ARDS was evaluated by serial 8-hr studies of blood gases and pH; the respiratory index (RI) to pulmonary shunt (QS/QT) relationship, compliance (COMPL), and net fluid balance (DFLUID) PMN and platelet (PLAT) counts were also measured. Compared with TR and TS, the ARDS patients at 48-96 hr, showed increased RI, QS/QT, and DFluid requiring increased FiO2 and PEEP as COMPL and PLAT fell and LE rose. These changes

KatG and KatE Confer Acinetobacter Resistance to Hydrogen Peroxide but Sensitize Bacteria to Killing by Phagocytic Respiratory Burst

PubMed Central

Sun, Daqing; Crowell, Sara A.; Harding, Christian M.; De Silva, P. Malaka; Harrison, Alistair; Fernando, Dinesh M.; Mason, Kevin M.; Santana, Estevan; Loewen, Peter C.; Kumar, Ayush; Liu, Yusen

2016-01-01

Aims Catalase catalyzes the degradation of H2O2. Acinetobacter species have four predicted catalase genes, katA, katE, katG, and katX. The aims of the present study seek to determine which catalase(s) plays a predominant role in determining the resistance to H2O2, and to assess the role of catalase in Acinetobacter virulence. Main Methods Mutants of A. baumannii and A. nosocomialis with deficiencies in katA, katE, katG, and katX were tested for sensitivity to H2O2, either by halo assays or by liquid culture assays. Respiratory burst of neutrophils, in response to A. nosocomialis, was assessed by chemiluminescence to examine the effects of catalase on the production of reactive oxygen species (ROS)1 in neutrophils. Bacterial virulence was assessed using a Galleria mellonella larva infection model. Key findings The capacities of A. baumannii and A. nosocomialis to degrade H2O2 are largely dependent on katE. The resistance of both A. baumannii and A. nosocomialis to H2O2 is primarily determined by the katG gene, although katE also plays a minor role in H2O2 resistance. Bacteria lacking both the katG and katE genes exhibit the highest sensitivity to H2O2. While A. nosocomialis bacteria with katE and/or katG were able to decrease ROS production by neutrophils, these cells also induced a more robust respiratory burst in neutrophils than did cells deficient in both katE and katG. We also found that A. nosocomialis deficient in both katE and katG was more virulent than the wildtype A. nosocomialis strain. Significance Our findings suggest that inhibition of Acinetobacter catalase may help to overcome the resistance of Acinetobacter species to microbicidal H2O2 and facilitate bacterial disinfection. PMID:26860891

Cyanide-insensitive quinol oxidase (CIO) from Gluconobacter oxydans is a unique terminal oxidase subfamily of cytochrome bd.

PubMed

Miura, Hiroshi; Mogi, Tatsushi; Ano, Yoshitaka; Migita, Catharina T; Matsutani, Minenosuke; Yakushi, Toshiharu; Kita, Kiyoshi; Matsushita, Kazunobu

2013-06-01

Cyanide-insensitive terminal quinol oxidase (CIO) is a subfamily of cytochrome bd present in bacterial respiratory chain. We purified CIO from the Gluconobacter oxydans membranes and characterized its properties. The air-oxidized CIO showed some or weak peaks of reduced haemes b and of oxygenated and ferric haeme d, differing from cytochrome bd. CO- and NO-binding difference spectra suggested that haeme d serves as the ligand-binding site of CIO. Notably, the purified CIO showed an extraordinary high ubiquinol-1 oxidase activity with the pH optimum of pH 5-6. The apparent Vmax value of CIO was 17-fold higher than that of G. oxydans cytochrome bo3. In addition, compared with Escherichia coli cytochrome bd, the quinol oxidase activity of CIO was much more resistant to cyanide, but sensitive to azide. The Km value for O2 of CIO was 7- to 10-fold larger than that of G. oxydans cytochrome bo3 or E. coli cytochrome bd. Our results suggest that CIO has unique features attributable to the structure and properties of the O2-binding site, and thus forms a new sub-group distinct from cytochrome bd. Furthermore, CIO of acetic acid bacteria may play some specific role for rapid oxidation of substrates under acidic growth conditions.

Dual Roles of Reactive Oxygen Species and NADPH Oxidase RBOHD in an Arabidopsis-Alternaria Pathosystem1[W

PubMed Central

Pogány, Miklós; von Rad, Uta; Grün, Sebastian; Dongó, Anita; Pintye, Alexandra; Simoneau, Philippe; Bahnweg, Günther; Kiss, Levente; Barna, Balázs; Durner, Jörg

2009-01-01

Arabidopsis (Arabidopsis thaliana) NADPH oxidases have been reported to suppress the spread of pathogen- and salicylic acid-induced cell death. Here, we present dual roles of RBOHD (for respiratory burst oxidase homolog D) in an Arabidopsis-Alternaria pathosystem, suggesting either initiation or prevention of cell death dependent on the distance from pathogen attack. Our data demonstrate that a rbohD knockout mutant exhibits increased spread of cell death at the macroscopic level upon inoculation with the fungus Alternaria brassicicola. However, the cellular patterns of reactive oxygen species accumulation and cell death are fundamentally different in the AtrbohD mutant compared with the wild type. Functional RBOHD causes marked extracellular hydrogen peroxide accumulation as well as cell death in distinct, single cells of A. brassicicola-infected wild-type plants. This single cell response is missing in the AtrbohD mutant, where infection triggers spreading-type necrosis preceded by less distinct chloroplastic hydrogen peroxide accumulation in large clusters of cells. While the salicylic acid analog benzothiadiazole induces the action of RBOHD and the development of cell death in infected tissues, the ethylene inhibitor aminoethoxyvinylglycine inhibits cell death, indicating that both salicylic acid and ethylene positively regulate RBOHD and cell death. Moreover, A. brassicicola-infected AtrbohD plants hyperaccumulate ethylene and free salicylic acid compared with the wild type, suggesting negative feedback regulation of salicylic acid and ethylene by RBOHD. We propose that functional RBOHD triggers death in cells that are damaged by fungal infection but simultaneously inhibits death in neighboring cells through the suppression of free salicylic acid and ethylene levels. PMID:19726575

Respiratory processes in non-photosynthetic plastids

PubMed Central

Renato, Marta; Boronat, Albert; Azcón-Bieto, Joaquín

2015-01-01

Chlororespiration is a respiratory process located in chloroplast thylakoids which consists in an electron transport chain from NAD(P)H to oxygen. This respiratory chain involves the NAD(P)H dehydrogenase complex, the plastoquinone pool and the plastid terminal oxidase (PTOX), and it probably acts as a safety valve to prevent the over-reduction of the photosynthetic machinery in stress conditions. The existence of a similar respiratory activity in non-photosynthetic plastids has been less studied. Recently, it has been reported that tomato fruit chromoplasts present an oxygen consumption activity linked to ATP synthesis. Etioplasts and amyloplasts contain several electron carriers and some subunits of the ATP synthase, so they could harbor a similar respiratory process. This review provides an update on the study about respiratory processes in chromoplasts, identifying the major gaps that need to be addressed in future research. It also reviews the proteomic data of etioplasts and amyloplasts, which suggest the presence of a respiratory electron transport chain in these plastids. PMID:26236317

Post-natal hypoxic activity of the central respiratory command is improved in transgenic mice overexpressing Epo in the brain.

PubMed

Caravagna, Céline; Kinkead, Richard; Soliz, Jorge

2014-08-15

Previous studies indicated that erythropoietin modulates central respiratory command in mice. Specifically, a one-hour incubation of the brainstems with erythropoietin attenuates hypoxia-induced central respiratory depression. Here, using transgenic mice constitutively overexpressing erythropoietin specifically in the brain (Tg21), we investigated the effect of chronic erythropoietin stimulation on central respiratory command activity during post-natal development. In vitro brainstem-spinal cord preparations from mice at 0 (P0) or 3 days of age (P3) were used to record the fictive inspiratory activity from the C4 ventral root. Our results show that erythropoietin already stimulates the hypoxic burst frequency at P0, and at P3, erythropoietin effectively stimulates the hypoxic burst frequency and amplitude. Because the maturation of the central respiratory command in mice is characterized by a decrease in the burst frequency with age, our results also suggest that erythropoietin accelerates the maturation of the newborn respiratory network and its response to hypoxia. Copyright © 2014 Elsevier B.V. All rights reserved.

Cloning and Analysis of the Alternative Oxidase Gene of Neurospora Crassa

PubMed Central

Li, Q.; Ritzel, R. G.; McLean, LLT.; McIntosh, L.; Ko, T.; Bertrand, H.; Nargang, F. E.

1996-01-01

Mitochondria of Neurospora crassa contain a cyanide-resistant alternative respiratory pathway in addition to the cytochrome pathway. The alternative oxidase is present only when electron flow through the cytochrome chain is restricted. Both genomic and cDNA copies for the alternative oxidase gene have been isolated and analyzed. The sequence of the predicted protein is homologous to that of other species. The mRNA for the alternative oxidase is scarce in wild-type cultures grown under normal conditions, but it is abundant in cultures grown in the presence of chloramphenicol, an inhibitor of mitochondrial protein synthesis, or in mutants deficient in mitochondrial cytochromes. Thus, induction of alternative oxidase appears to be at the transcriptional level. Restriction fragment length polymorphism mapping of the isolated gene demonstrated that it is located in a position corresponding to the aod-1 locus. Sequence analysis of mutant aod-1 alleles reveals mutations affecting the coding sequence of the alternative oxidase. The level of aod-1 mRNA in an aod-2 mutant strain that had been grown in the presence of chloramphenicol was reduced several fold relative to wild-type, supporting the hypothesis that the product of aod-2 is required for optimal expression of aod-1. PMID:8770590

A Biochemical Approach to Study the Role of the Terminal Oxidases in Aerobic Respiration in Shewanella oneidensis MR-1

PubMed Central

Le Laz, Sébastien; Kpebe, Arlette; Bauzan, Marielle; Lignon, Sabrina; Rousset, Marc; Brugna, Myriam

2014-01-01

The genome of the facultative anaerobic γ-proteobacterium Shewanella oneidensis MR-1 encodes for three terminal oxidases: a bd-type quinol oxidase and two heme-copper oxidases, a A-type cytochrome c oxidase and a cbb 3-type oxidase. In this study, we used a biochemical approach and directly measured oxidase activities coupled to mass-spectrometry analysis to investigate the physiological role of the three terminal oxidases under aerobic and microaerobic conditions. Our data revealed that the cbb 3-type oxidase is the major terminal oxidase under aerobic conditions while both cbb 3-type and bd-type oxidases are involved in respiration at low-O2 tensions. On the contrary, the low O2-affinity A-type cytochrome c oxidase was not detected in our experimental conditions even under aerobic conditions and would therefore not be required for aerobic respiration in S. oneidensis MR-1. In addition, the deduced amino acid sequence suggests that the A-type cytochrome c oxidase is a ccaa 3-type oxidase since an uncommon extra-C terminal domain contains two c-type heme binding motifs. The particularity of the aerobic respiratory pathway and the physiological implication of the presence of a ccaa 3-type oxidase in S. oneidensis MR-1 are discussed. PMID:24466040

Spectrophotometric determination of H2O2-generating oxidases using oxyhemoglobin as oxygen donor and indicator.

PubMed

Bârzu, O; Dânşoreanu, M

1980-01-01

1. Spectrophotometric determination of oxygen uptake using oxyhemoglobin as oxygen donor and indicator was used for assay of H2O2-generating oxidases like monoamine oxidase and glucose oxidase. 2. In order to decompose H2O2 formed during the oxygen uptake, catalase and methanol (or ethanol) was added to the respiratory system. At pH values higher than 7.5 the oxydation of deoxygenated hemoglobin to methemoglobin was less than 3%. 2. Oxidases with low Km for oxygen can be assayed using the spectrophotometric method if suitable correction factors are introduced into the calculation of oxygen uptake. The correction factor represents the ratio of the rate of formation (or disappearance) of one of the reactants and the rate of oxyhemoglobin deoxygenation, measured under identical experimental conditions.

Inactivity-induced respiratory plasticity: Protecting the drive to breathe in disorders that reduce respiratory neural activity☆

PubMed Central

Strey, K.A.; Baertsch, N.A.; Baker-Herman, T.L.

2013-01-01

Multiple forms of plasticity are activated following reduced respiratory neural activity. For example, in ventilated rats, a central neural apnea elicits a rebound increase in phrenic and hypoglossal burst amplitude upon resumption of respiratory neural activity, forms of plasticity called inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF), respectively. Here, we provide a conceptual framework for plasticity following reduced respiratory neural activity to guide future investigations. We review mechanisms giving rise to iPMF and iHMF, present new data suggesting that inactivity-induced plasticity is observed in inspiratory intercostals (iIMF) and point out gaps in our knowledge. We then survey conditions relevant to human health characterized by reduced respiratory neural activity and discuss evidence that inactivity-induced plasticity is elicited during these conditions. Understanding the physiological impact and circumstances in which inactivity-induced respiratory plasticity is elicited may yield novel insights into the treatment of disorders characterized by reductions in respiratory neural activity. PMID:23816599

ArxA, a new clade of arsenite oxidase within the DMSO reductase family of molybdenum oxidoreductases

USGS Publications Warehouse

Zargar, Kamrun; Conrad, Alison; Bernick, David L.; Lowe, Todd M.; Stolc, Viktor; Hoeft, Shelley; Oremland, Ronald S.; Stolz, John; Saltikov, Chad W.

2012-01-01

Arsenotrophy, growth coupled to autotrophic arsenite oxidation or arsenate respiratory reduction, occurs only in the prokaryotic domain of life. The enzymes responsible for arsenotrophy belong to distinct clades within the DMSO reductase family of molybdenum-containing oxidoreductases: specifically arsenate respiratory reductase, ArrA, and arsenite oxidase, AioA (formerly referred to as AroA and AoxB). A new arsenite oxidase clade, ArxA, represented by the haloalkaliphilic bacterium Alkalilimnicola ehrlichii strain MLHE-1 was also identified in the photosynthetic purple sulfur bacterium Ectothiorhodospira sp. strain PHS-1. A draft genome sequence of PHS-1 was completed and an arx operon similar to MLHE-1 was identified. Gene expression studies showed that arxA was strongly induced with arsenite. Microbial ecology investigation led to the identification of additional arxA-like sequences in Mono Lake and Hot Creek sediments, both arsenic-rich environments in California. Phylogenetic analyses placed these sequences as distinct members of the ArxA clade of arsenite oxidases. ArxA-like sequences were also identified in metagenome sequences of several alkaline microbial mat environments of Yellowstone National Park hot springs. These results suggest that ArxA-type arsenite oxidases appear to be widely distributed in the environment presenting an opportunity for further investigations of the contribution of Arx-dependent arsenotrophy to the arsenic biogeochemical cycle.

Respiratory chain supercomplexes associate with the cysteine desulfurase complex of the iron–sulfur cluster assembly machinery

PubMed Central

Böttinger, Lena; Mårtensson, Christoph U.; Song, Jiyao; Zufall, Nicole; Wiedemann, Nils; Becker, Thomas

2018-01-01

Mitochondria are the powerhouses of eukaryotic cells. The activity of the respiratory chain complexes generates a proton gradient across the inner membrane, which is used by the F1FO-ATP synthase to produce ATP for cellular metabolism. In baker’s yeast, Saccharomyces cerevisiae, the cytochrome bc1 complex (complex III) and cytochrome c oxidase (complex IV) associate in respiratory chain supercomplexes. Iron–sulfur clusters (ISC) form reactive centers of respiratory chain complexes. The assembly of ISC occurs in the mitochondrial matrix and is essential for cell viability. The cysteine desulfurase Nfs1 provides sulfur for ISC assembly and forms with partner proteins the ISC-biogenesis desulfurase complex (ISD complex). Here, we report an unexpected interaction of the active ISD complex with the cytochrome bc1 complex and cytochrome c oxidase. The individual deletion of complex III or complex IV blocks the association of the ISD complex with respiratory chain components. We conclude that the ISD complex binds selectively to respiratory chain supercomplexes. We propose that this molecular link contributes to coordination of iron–sulfur cluster formation with respiratory activity. PMID:29386296

Lysyl Oxidase Is Essential for Normal Development and Function of the Respiratory System and for the Integrity of Elastic and Collagen Fibers in Various Tissues

PubMed Central

Mäki, Joni M.; Sormunen, Raija; Lippo, Sari; Kaarteenaho-Wiik, Riitta; Soininen, Raija; Myllyharju, Johanna

2005-01-01

Lysyl oxidases, a family comprising LOX and four LOX-like enzymes, catalyze crosslinking of elastin and collagens. Mouse Lox was recently shown to be crucial for development of the cardiovascular system because null mice died perinatally of aortic aneurysms and cardiovascular dysfunction. We show here that Lox is also essential for development of the respiratory system and the integrity of elastic and collagen fibers in the lungs and skin. The lungs of E18.5 Lox−/− embryos showed impaired development of the distal and proximal airways. Elastic fibers in E18.5 Lox−/− lungs were markedly less intensely stained and more disperse than in the wild type, especially in the mesenchyme surrounding the distal airways, bronchioles, bronchi, and trachea, and were fragmented in pulmonary arterial walls. The organization of individual collagen fibers into tight bundles was likewise abnormal. Similar elastic and collagen fiber abnormalities were seen in the skin. Lysyl oxidase activity in cultured Lox−/− skin fibroblasts and aortic smooth muscle cells was reduced by ∼80%, indicating that Lox is the main isoenzyme in these cells. LOX abnormalities may thus be critical for the pathogenesis of several common diseases, including pulmonary, skin, and cardiovascular disorders. PMID:16192629

Respiratory arsenate reductase as a bidirectional enzyme

USGS Publications Warehouse

Richey, C.; Chovanec, P.; Hoeft, S.E.; Oremland, R.S.; Basu, P.; Stolz, J.F.

2009-01-01

The haloalkaliphilic bacterium Alkalilimnicola ehrlichii is capable of anaerobic chemolithoautotrophic growth by coupling the oxidation of arsenite (As(III)) to the reduction of nitrate and carbon dioxide. Analysis of its complete genome indicates that it lacks a conventional arsenite oxidase (Aox), but instead possesses two operons that each encode a putative respiratory arsenate reductase (Arr). Here we show that one homolog is expressed under chemolithoautotrophic conditions and exhibits both arsenite oxidase and arsenate reductase activity. We also demonstrate that Arr from two arsenate respiring bacteria, Alkaliphilus oremlandii and Shewanella sp. strain ANA-3, is also biochemically reversible. Thus Arr can function as a reductase or oxidase. Its physiological role in a specific organism, however, may depend on the electron potentials of the molybdenum center and [Fe–S] clusters, additional subunits, or constitution of the electron transfer chain. This versatility further underscores the ubiquity and antiquity of microbial arsenic metabolism.

The coxBAC Operon Encodes a Cytochrome c Oxidase Required for Heterotrophic Growth in the Cyanobacterium Anabaena variabilis Strain ATCC 29413

PubMed Central

Schmetterer, Georg; Valladares, Ana; Pils, Dietmar; Steinbach, Susanne; Pacher, Margit; Muro-Pastor, Alicia M.; Flores, Enrique; Herrero, Antonia

2001-01-01

Three genes, coxB, coxA, and coxC, found in a clone from a gene library of the cyanobacterium Anabaena variabilis strain ATCC 29413, were identified by hybridization with an oligonucleotide specific for aa3-type cytochrome c oxidases. Deletion of these genes from the genome of A. variabilis strain ATCC 29413 FD yielded strain CSW1, which displayed no chemoheterotrophic growth and an impaired cytochrome c oxidase activity. Photoautotrophic growth of CSW1, however, was unchanged, even with dinitrogen as the nitrogen source. A higher cytochrome c oxidase activity was detected in membrane preparations from dinitrogen-grown CSW1 than from nitrate-grown CSW1, but comparable activities of respiratory oxygen uptake were found in the wild type and in CSW1. Our data indicate that the identified cox gene cluster is essential for fructose-dependent growth in the dark, but not for growth on dinitrogen, and that other terminal respiratory oxidases are expressed in this cyanobacterium. Transcription analysis showed that coxBAC constitutes an operon which is expressed from two transcriptional start points. The use of one of them was stimulated by fructose. PMID:11591688

A decade of crystallization drops: Crystallization of the cbb3 cytochrome c oxidase from Pseudomonas stutzeri

PubMed Central

Buschmann, Sabine; Richers, Sebastian; Ermler, Ulrich; Michel, Hartmut

2014-01-01

The cbb3 cytochrome c oxidases are distant members of the superfamily of heme copper oxidases. These terminal oxidases couple O2 reduction with proton transport across the plasma membrane and, as a part of the respiratory chain, contribute to the generation of an electrochemical proton gradient. Compared with other structurally characterized members of the heme copper oxidases, the recently determined cbb3 oxidase structure at 3.2 Å resolution revealed significant differences in the electron supply system, the proton conducting pathways and the coupling of O2 reduction to proton translocation. In this paper, we present a detailed report on the key steps for structure determination. Improvement of the protein quality was achieved by optimization of the number of lipids attached to the protein as well as the separation of two cbb3 oxidase isoenzymes. The exchange of n-dodecyl-β-d-maltoside for a precisely defined mixture of two α-maltosides and decanoylsucrose as well as the choice of the crystallization method had a most profound impact on crystal quality. This report highlights problems frequently encountered in membrane protein crystallization and offers meaningful approaches to improve crystal quality. PMID:24488923

A decade of crystallization drops: crystallization of the cbb3 cytochrome c oxidase from Pseudomonas stutzeri.

PubMed

Buschmann, Sabine; Richers, Sebastian; Ermler, Ulrich; Michel, Hartmut

2014-04-01

The cbb3 cytochrome c oxidases are distant members of the superfamily of heme copper oxidases. These terminal oxidases couple O2 reduction with proton transport across the plasma membrane and, as a part of the respiratory chain, contribute to the generation of an electrochemical proton gradient. Compared with other structurally characterized members of the heme copper oxidases, the recently determined cbb3 oxidase structure at 3.2 Å resolution revealed significant differences in the electron supply system, the proton conducting pathways and the coupling of O2 reduction to proton translocation. In this paper, we present a detailed report on the key steps for structure determination. Improvement of the protein quality was achieved by optimization of the number of lipids attached to the protein as well as the separation of two cbb3 oxidase isoenzymes. The exchange of n-dodecyl-β-D-maltoside for a precisely defined mixture of two α-maltosides and decanoylsucrose as well as the choice of the crystallization method had a most profound impact on crystal quality. This report highlights problems frequently encountered in membrane protein crystallization and offers meaningful approaches to improve crystal quality. © 2014 The Protein Society.

Abnormal kinetic behavior of cytochrome oxidase in a case of Leigh disease.

PubMed Central

Glerum, M; Robinson, B H; Spratt, C; Wilson, J; Patrick, D

1987-01-01

Cultured skin fibroblasts from a child with fatal lacticacidemia displayed an abnormally high lactate:pyruvate ratio of 77:1, compared with control values of 22:1-27:1. When protease-treated isolated mitochondria were used, activity of the respiratory-chain enzymes was found to be approximately 60% of normal, and adenosine triphosphate synthesis was found to be normal with all substrates tested. In mitochondria prepared by means of digitonin treatment, adenosine triphosphate synthesis was depressed with all substrates tested, suggesting a defect in the operation of the cytochrome oxidase complex. In disrupted whole cells from the patient, cytochrome oxidase activity was 56% of the activity in the control cell line with the lowest activity. In the presence of a twofold excess of oxidized cytochrome c, patient cells showed 31% of the activity in controls. Cytochrome oxidase activity in both sonicated whole-cell preparations and in sonicated mitochondria displayed abnormal kinetics with regard to the substrate-reduced cytochrome c, which was particularly evident in the presence of excess oxidized cytochrome c. We believe that kinetically abnormal cytochrome oxidase complex is responsible for the biochemical and clinical abnormalities present in this patient. PMID:2821802

Structural insights into electron transfer in caa3-type cytochrome oxidase

PubMed Central

Lyons, Joseph A.; Aragão, David; Slattery, Orla; Pisliakov, Andrei V.; Soulimane, Tewfik; Caffrey, Martin

2012-01-01

Summary Paragraph Cytochrome c oxidase is a member of the heme copper oxidase superfamily (HCO)1. HCOs function as the terminal enzymes in the respiratory chain of mitochondria and aerobic prokaryotes, coupling molecular oxygen reduction to transmembrane proton pumping. Integral to the enzyme’s function is the transfer of electrons from cytochrome c to the oxidase via a transient association of the two proteins. Electron entry and exit are proposed to occur from the same site on cytochrome c2–4. Here we report the crystal structure of the caa3-type cytochrome oxidase from Thermus thermophilus, which has a covalently tethered cytochrome c domain. Crystals were grown in a bicontinuous mesophase using a synthetic short-chain monoacylglycerol as the hosting lipid. From the electron density map, at 2.36 Å resolution, a novel integral membrane subunit and a native glycoglycerophospholipid embedded in the complex were identified. Contrary to previous electron transfer mechanisms observed for soluble cytochrome c, the structure reveals the architecture of the electron transfer complex for the fused cupredoxin/cytochrome c domain which implicates different sites on cytochrome c for electron entry and exit. Support for an alternative to the classical proton gate characteristic of this HCO class is presented. PMID:22763450

NADPH Oxidase-Dependent Signaling in Endothelial Cells: Role in Physiology and Pathophysiology

PubMed Central

Ushio-Fukai, Masuko; Malik, Asrar B.

2009-01-01

Abstract Reactive oxygen species (ROS) including superoxide (O2·−) and hydrogen peroxide (H2O2) are produced endogenously in response to cytokines, growth factors; G-protein coupled receptors, and shear stress in endothelial cells (ECs). ROS function as signaling molecules to mediate various biological responses such as gene expression, cell proliferation, migration, angiogenesis, apoptosis, and senescence in ECs. Signal transduction activated by ROS, “oxidant signaling,” has received intense investigation. Excess amount of ROS contribute to various pathophysiologies, including endothelial dysfunction, atherosclerosis, hypertension, diabetes, and acute respiratory distress syndrome (ARDS). The major source of ROS in EC is a NADPH oxidase. The prototype phagaocytic NADPH oxidase is composed of membrane-bound gp91phox and p22hox, as well as cytosolic subunits such as p47phox, p67phox and small GTPase Rac. In ECs, in addition to all the components of phagocytic NADPH oxidases, homologues of gp91phox (Nox2) including Nox1, Nox4, and Nox5 are expressed. The aim of this review is to provide an overview of the emerging area of ROS derived from NADPH oxidase and oxidant signaling in ECs linked to physiological and pathophysiological functions. Understanding these mechanisms may provide insight into the NADPH oxidase and oxidant signaling components as potential therapeutic targets. Antioxid. Redox Signal. 11, 791–810. PMID:18783313

Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat

PubMed Central

Jones, Sarah E.

2016-01-01

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. PMID:26888109

Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat.

PubMed

Jones, Sarah E; Dutschmann, Mathias

2016-05-01

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. Copyright © 2016 the American Physiological Society.

Cellular defense of the avian respiratory system: effects of Pasteurella multocida on respiratory burst activity of avian respiratory tract phagocytes.

PubMed

Ochs, D L; Toth, T E; Pyle, R H; Siegel, P B

1988-12-01

The respiratory tract of healthy chickens contain few free-residing phagocytic cells. Intratracheal inoculation with Pasteurella multocida stimulated a significant (P less than 0.05) migration of cells to the lungs and air sacs of White Rock chickens within 2 hours after inoculation. We found the maximal number of avian respiratory tract phagocytes (22.9 +/- 14.0 x 10(6] at 8 hours after inoculation. Flow cytometric analysis of these cells revealed 2 populations on the basis of cell-size and cellular granularity. One of these was similar in size and granularity to those of blood heterophils. Only this population was capable of generating oxidative metabolites in response to phorbol myristate acetate. The ability of the heterophils to produce hydrogen peroxide, measured as the oxidation of intracellularly loaded 2',7'-dichlorofluorescein, decreased with time after inoculation. These results suggest that the migration of heterophils, which are capable of high levels of oxidative metabolism, to the lungs and air sacs may be an important defense mechanism of poultry against bacterial infections of the respiratory tract.

How long does a burst burst?

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

Zhang, Bin-Bin; Connaughton, Valerie; Briggs, Michael S.

2014-05-20

Several gamma-ray bursts (GRBs) last much longer (∼hours) in γ-rays than typical long GRBs (∼minutes), and it has recently been proposed that these 'ultra-long GRBs' may form a distinct population, probably with a different (e.g., blue supergiant) progenitor than typical GRBs. However, Swift observations suggest that many GRBs have extended central engine activities manifested as flares and internal plateaus in X-rays. We perform a comprehensive study on a large sample of Swift GRBs with X-Ray Telescope observations to investigate GRB central engine activity duration and to determine whether ultra-long GRBs are unusual events. We define burst duration t {sub burst}more » based on both γ-ray and X-ray light curves rather than using γ-ray observations alone. We find that t {sub burst} can be reliably measured in 343 GRBs. Within this 'good' sample, 21.9% GRBs have t {sub burst} ≳ 10{sup 3} s and 11.5% GRBs have t {sub burst} ≳ 10{sup 4} s. There is an apparent bimodal distribution of t {sub burst} in this sample. However, when we consider an 'undetermined' sample (304 GRBs) with t {sub burst} possibly falling in the gap between GRB duration T {sub 90} and the first X-ray observational time, as well as a selection effect against t {sub burst} falling into the first Swift orbital 'dead zone' due to observation constraints, the intrinsic underlying t {sub burst} distribution is consistent with being a single component distribution. We found that the existing evidence for a separate ultra-long GRB population is inconclusive, and further multi-wavelength observations are needed to draw a firmer conclusion. We also discuss the theoretical implications of our results. In particular, the central engine activity duration of GRBs is generally much longer than the γ-ray T {sub 90} duration and it does not even correlate with T {sub 90}. It would be premature to make a direct connection between T {sub 90} and the size of the progenitor star.« less

The effect of artichoke (Cynara scolymus L.) extract on respiratory chain system activity in rat liver mitochondria.

PubMed

Juzyszyn, Z; Czerny, B; Myśliwiec, Z; Pawlik, A; Droździk, M

2010-06-01

The effect of artichoke extract on mitochondrial respiratory chain (MRC) activity in isolated rat liver mitochondria (including reaction kinetics) was studied. The effect of the extract on the activity of isolated cytochrome oxidase was also studied. Extract in the range of 0.68-2.72 microg/ml demonstrated potent and concentration-dependent inhibitory activity. Concentrations > or =5.4 microg/ml entirely inhibited MRC activity. The succinate oxidase system (MRC complexes II-IV) was the most potently inhibited, its activity at an extract concentration of 1.36 microg/ml being reduced by 63.3% compared with the control (p < 0.05). The results suggest a complex inhibitory mechanism of the extract. Inhibition of the succinate oxidase system was competitive (K(i) = 0.23 microg/ml), whereas isolated cytochrome oxidase was inhibited noncompetitively (K(i) = 126 microg/ml). The results of this study suggest that the salubrious effects of artichoke extracts may rely in part on the effects of their active compounds on the activity of the mitochondrial respiratory chain system.

Respiratory arsenate reductase as a bidirectional enzyme

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

Richey, Christine; Chovanec, Peter; Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282

2009-05-01

The haloalkaliphilic bacterium Alkalilimnicola ehrlichii is capable of anaerobic chemolithoautotrophic growth by coupling the oxidation of arsenite (As(III)) to the reduction of nitrate and carbon dioxide. Analysis of its complete genome indicates that it lacks a conventional arsenite oxidase (Aox), but instead possesses two operons that each encode a putative respiratory arsenate reductase (Arr). Here we show that one homolog is expressed under chemolithoautotrophic conditions and exhibits both arsenite oxidase and arsenate reductase activity. We also demonstrate that Arr from two arsenate respiring bacteria, Alkaliphilus oremlandii and Shewanella sp. strain ANA-3, is also biochemically reversible. Thus Arr can function asmore » a reductase or oxidase. Its physiological role in a specific organism, however, may depend on the electron potentials of the molybdenum center and [Fe-S] clusters, additional subunits, or constitution of the electron transfer chain. This versatility further underscores the ubiquity and antiquity of microbial arsenic metabolism.« less

WRKY Transcription Factors Phosphorylated by MAPK Regulate a Plant Immune NADPH Oxidase in Nicotiana benthamiana[OPEN

PubMed Central

Adachi, Hiroaki; Nakano, Takaaki; Miyagawa, Noriko; Ishihama, Nobuaki; Yoshioka, Miki; Katou, Yuri; Yaeno, Takashi

2015-01-01

Pathogen attack sequentially confers pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) after sensing of pathogen patterns and effectors by plant immune receptors, respectively. Reactive oxygen species (ROS) play pivotal roles in PTI and ETI as signaling molecules. Nicotiana benthamiana RBOHB, an NADPH oxidase, is responsible for both the transient PTI ROS burst and the robust ETI ROS burst. Here, we show that RBOHB transactivation mediated by MAPK contributes to R3a/AVR3a-triggered ETI (AVR3a-ETI) ROS burst. RBOHB is markedly induced during the ETI and INF1-triggered PTI (INF1-PTI), but not flg22-tiggered PTI (flg22-PTI). We found that the RBOHB promoter contains a functional W-box in the R3a/AVR3a and INF1 signal-responsive cis-element. Ectopic expression of four phospho-mimicking mutants of WRKY transcription factors, which are MAPK substrates, induced RBOHB, and yeast one-hybrid analysis indicated that these mutants bind to the cis-element. Chromatin immunoprecipitation assays indicated direct binding of the WRKY to the cis-element in plants. Silencing of multiple WRKY genes compromised the upregulation of RBOHB, resulting in impairment of AVR3a-ETI and INF1-PTI ROS bursts, but not the flg22-PTI ROS burst. These results suggest that the MAPK-WRKY pathway is required for AVR3a-ETI and INF1-PTI ROS bursts by activation of RBOHB. PMID:26373453

Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1

PubMed Central

Yang, Long; Xie, Peng; Wu, Jianjiang; Yu, Jin; Yu, Tian; Wang, Haiying; Wang, Jiang; Xia, Zhengyuan; Zheng, Hong

2016-01-01

Background: Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats. Methods: The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, postconditioning was performed using sevoflurane alone or in combination with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). The changes in hemodynamic parameters, HIF-1α protein expression levels, mitochondrial respiratory function and enzyme activity, mitochondrial reactive oxygen species (ROS) production rates, and mitochondrial ultrastructure were measured or observed. Results: Compared to the ischemia-reperfusion (I/R) group, HIF-1α expression in the SPostC group was significantly up-regulated. Additionally, cardiac function indicators, mitochondrial state 3 respiratory rate, respiratory control ratio (RCR), cytochrome C oxidase (CcO), NADH oxidase (NADHO), and succinate oxidase (SUCO) activities, mitochondrial ROS production rate, and mitochondrial ultrastructure were significantly better than those in the I/R group. However, these advantages were completely reversed by the HIF-1α specific inhibitor 2ME2 (P<0.05). Conclusion: The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1α expression. PMID:27830025

Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1.

PubMed

Yang, Long; Xie, Peng; Wu, Jianjiang; Yu, Jin; Yu, Tian; Wang, Haiying; Wang, Jiang; Xia, Zhengyuan; Zheng, Hong

2016-01-01

Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats. The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, postconditioning was performed using sevoflurane alone or in combination with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). The changes in hemodynamic parameters, HIF-1α protein expression levels, mitochondrial respiratory function and enzyme activity, mitochondrial reactive oxygen species (ROS) production rates, and mitochondrial ultrastructure were measured or observed. Compared to the ischemia-reperfusion (I/R) group, HIF-1α expression in the SPostC group was significantly up-regulated. Additionally, cardiac function indicators, mitochondrial state 3 respiratory rate, respiratory control ratio (RCR), cytochrome C oxidase (C c O), NADH oxidase (NADHO), and succinate oxidase (SUCO) activities, mitochondrial ROS production rate, and mitochondrial ultrastructure were significantly better than those in the I/R group. However, these advantages were completely reversed by the HIF-1α specific inhibitor 2ME2 ( P <0.05). The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1α expression.

Pathophysiological Approaches of Acute Respiratory Distress syndrome: Novel Bases for Study of Lung Injury

PubMed Central

Castillo, R.L; Carrasco Loza, R; Romero-Dapueto, C

2015-01-01

Experimental approaches have been implemented to research the lung damage related-mechanism. These models show in animals pathophysiological events for acute respiratory distress syndrome (ARDS), such as neutrophil activation, reactive oxygen species burst, pulmonary vascular hypertension, exudative edema, and other events associated with organ dysfunction. Moreover, these approaches have not reproduced the clinical features of lung damage. Lung inflammation is a relevant event in the develop of ARDS as component of the host immune response to various stimuli, such as cytokines, antigens and endotoxins. In patients surviving at the local inflammatory states, transition from injury to resolution is an active mechanism regulated by the immuno-inflammatory signaling pathways. Indeed, inflammatory process is regulated by the dynamics of cell populations that migrate to the lung, such as neutrophils and on the other hand, the role of the modulation of transcription factors and reactive oxygen species (ROS) sources, such as nuclear factor kappaB and NADPH oxidase. These experimental animal models reproduce key components of the injury and resolution phases of human ALI/ARDS and provide a methodology to explore mechanisms and potential new therapies. PMID:26312099

Blockade of brain stem gap junctions increases phrenic burst frequency and reduces phrenic burst synchronization in adult rat.

PubMed

Solomon, Irene C; Chon, Ki H; Rodriguez, Melissa N

2003-01-01

Recent investigations have examined the influence of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in vitro using transverse medullary slice and en bloc brain stem-spinal cord preparations obtained from neonatal (1-5 days postnatal) mice. Gap junction proteins, however, have been identified in both neurons and glia in brain stem regions implicated in respiratory control in both neonatal and adult rodents. Here, we used an in vitro arterially perfused rat preparation to examine the role of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents. We recorded rhythmic inspiratory motor activity from one or both phrenic nerves before and during pharmacological blockade (i.e., uncoupling) of brain stem gap junctions using carbenoxolone (100 microM), 18alpha-glycyrrhetinic acid (25-100 microM), 18beta-glycyrrhetinic acid (25-100 microM), octanol (200-300 microM), or heptanol (200 microM). During perfusion with a gap junction uncoupling agent, we observed an increase in the frequency of phrenic bursts (~95% above baseline frequency; P < 0.001) and a decrease in peak amplitude of integrated phrenic nerve discharge (P < 0.001). The increase in frequency of phrenic bursts resulted from a decrease in both T(I) (P < 0.01) and T(E) (P < 0.01). In addition, the pattern of phrenic nerve discharge shifted from an augmenting discharge pattern to a "bell-shaped" or square-wave discharge pattern in most experiments. Spectral analyses using a fast Fourier transform (FFT) algorithm revealed a reduction in the peak power of both the 40- to 50-Hz peak (corresponding to the MFO) and 90- to 110-Hz peak (corresponding to the HFO) although spurious higher frequency activity (> or =130 Hz) was observed, suggesting an overall loss or reduction in inspiratory-phase synchronization. Although additional experiments are required to

Phenylethylamine-induced generation of reactive oxygen species and ascorbate free radicals in tobacco suspension culture: mechanism for oxidative burst mediating Ca2+ influx.

PubMed

Kawano, T; Pinontoan, R; Uozumi, N; Morimitsu, Y; Miyake, C; Asada, K; Muto, S

2000-11-01

In the previous paper [Kawano et al. (2000a) Plant Cell Physiol. 41: 1251], we demonstrated that addition of phenylethylamine (PEA) and benzylamine can induce an immediate and transient burst of active oxygen species (AOS) in tobacco suspension culture. Detected AOS include H2O2, superoxide anion and hydroxyl radicals. Use of several inhibitors suggested the presence of monoamine oxidase-like H2O2-generating activity in the cellular soluble fraction. It was also suggested that peroxidase(s) or copper amine oxidase(s) are involved in the extracellular superoxide production as a consequence of H2O2 production. Since more than 85% of the PEA-dependent AOS generating activity was localized in the extracellular space (extracellular fluid + cell wall), extracellularly secreted enzymes, probably peroxidases, may largely contribute to the oxidative burst induced by PEA. The PEA-induced AOS generation was also observed in the horseradish peroxidase (HRP) reaction mixture, supporting the hypothesis that peroxidases catalyze the oxidation of PEA leading to AOS generation. In addition to AOS production, we observed that PEA induced an increase in monodehydroascorbate radicals (MDA) in the cell suspension culture and in HRP reaction mixture using electron spin resonance spectroscopy and the newly invented MDA reductase-coupled method. Here we report that MDA production is an indicator of peroxidase-mediated generation of PEA radical species in tobacco suspension culture.

NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder.

PubMed

Petrovic, Romana; Puskas, Laslo; Jevtic Dozudic, Gordana; Stojkovic, Tihomir; Velimirovic, Milica; Nikolic, Tatjana; Zivkovic, Milica; Djorovic, Djordje J; Nenadovic, Milutin; Petronijevic, Natasa

2018-05-26

Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

Splitting of the O–O bond at the heme-copper catalytic site of respiratory oxidases

PubMed Central

Poiana, Federica; von Ballmoos, Christoph; Gonska, Nathalie; Blomberg, Margareta R. A.; Ädelroth, Pia; Brzezinski, Peter

2017-01-01

Heme-copper oxidases catalyze the four-electron reduction of O2 to H2O at a catalytic site that is composed of a heme group, a copper ion (CuB), and a tyrosine residue. Results from earlier experimental studies have shown that the O–O bond is cleaved simultaneously with electron transfer from a low-spin heme (heme a/b), forming a ferryl state (PR; Fe4+=O2−, CuB2+–OH−). We show that with the Thermus thermophilus ba3 oxidase, at low temperature (10°C, pH 7), electron transfer from the low-spin heme b to the catalytic site is faster by a factor of ~10 (τ ≅ 11 μs) than the formation of the PR ferryl (τ ≅110 μs), which indicates that O2 is reduced before the splitting of the O–O bond. Application of density functional theory indicates that the electron acceptor at the catalytic site is a high-energy peroxy state [Fe3+–O−–O−(H+)], which is formed before the PR ferryl. The rates of heme b oxidation and PR ferryl formation were more similar at pH 10, indicating that the formation of the high-energy peroxy state involves proton transfer within the catalytic site, consistent with theory. The combined experimental and theoretical data suggest a general mechanism for O2 reduction by heme-copper oxidases. PMID:28630929

Mechanisms of CO2/H+ chemoreception by respiratory rhythm generator neurons in the medulla from newborn rats in vitro.

PubMed

Kawai, Akira; Onimaru, Hiroshi; Homma, Ikuo

2006-04-15

We investigated mechanisms of CO(2)/H(+) chemoreception in the respiratory centre of the medulla by measuring membrane potentials of pre-inspiratory neurons, which are putative respiratory rhythm generators, in the brainstem-spinal cord preparation of the neonatal rat. Neuronal response was tested by changing superfusate CO(2) concentration from 2% to 8% at constant HCO(3)(-) concentration (26 mm) or by changing pH from 7.8 to 7.2 by reducing HCO(3)(-) concentration at constant CO(2) (5%). Both respiratory and metabolic acidosis lead to depolarization of neurons with increased excitatory synaptic input and increased burst rate. Respiratory acidosis potentiated the amplitude of the neuronal drive potential. In the presence of tetrodotoxin (TTX), membrane depolarization persisted during respiratory and metabolic acidosis. However, the depolarization was smaller than that before application of TTX, which suggests that some neurons are intrinsically, and others synaptically, chemosensitive to CO(2)/H(+). Application of Ba(2+) blocked membrane depolarization by respiratory acidosis, whereas significant depolarization in response to metabolic acidosis still remained after application of Cd(2+) and Ba(2+). We concluded that the intrinsic responses to CO(2)/H(+)changes were mediated by potassium channels during respiratory acidosis, and that some other mechanisms operate during metabolic acidosis. In low-Ca(2+), high-Mg(2+) solution, an increased CO(2) concentration induced a membrane depolarization with a simultaneous increase of the burst rate. Pre-inspiratory neurons could adapt their baseline membrane potential to external CO(2)/H(+) changes by integration of these mechanisms to modulate their burst rates. Thus, pre-inspiratory neurons might play an important role in modulation of respiratory rhythm by central chemoreception in the brainstem-spinal cord preparation.

The NADPH oxidase Cpnox1 is required for full pathogenicity of the ergot fungus Claviceps purpurea.

PubMed

Giesbert, Sabine; Schürg, Timo; Scheele, Sandra; Tudzynski, Paul

2008-05-01

The role of reactive oxygen species (ROS) in interactions between phytopathogenic fungi and their hosts is well established. An oxidative burst mainly caused by superoxide formation by membrane-associated NADPH oxidases is an essential element of plant defence reactions. Apart from primary effects, ROS play a major role as a second messenger in host response. Recently, NADPH oxidase (nox)-encoding genes have been identified in filamentous fungi. Functional analyses have shown that these fungal enzymes are involved in sexual differentiation, and there is growing evidence that they also affect developmental programmes involved in fungus-plant interactions. Here we show that in the biotrophic plant pathogen Claviceps purpurea deletion of the cpnox1 gene, probably encoding an NADPH oxidase, has impact on germination of conidia and pathogenicity: Deltacpnox1 mutants can penetrate the host epidermis, but they are impaired in colonization of the plant ovarian tissue. In the few cases where macroscopic signs of infection (honeydew) appear, they are extremely delayed and fully developed sclerotia have never been observed. C. purpurea Nox1 is important for the interaction with its host, probably by directly affecting pathogenic differentiation of the fungus.

NADPH oxidase-mediated generation of reactive oxygen species is critically required for survival of undifferentiated human promyelocytic leukemia cell line HL-60.

PubMed

Dong, Jing-Mei; Zhao, Sheng-Guo; Huang, Guo-Yin; Liu, Qing

2004-06-01

Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) mediated generation of reactive oxygen species (ROS) was originally identified as the powerful host defense machinery against microorganism in phagocytes. But recent reports indicated that some non-phagocytic cells also have the NADPH oxidase activity, and the ROS produced by it may act as cell signal molecule. But as far as today, whether the NADPH oxidase also plays similar role in phagocyte has not been paid much attention. Utilizing the undifferentiated HL-60 promyelocytic leukemia cells as a model, the aim of the present study was to determine whether NADPH oxidase plays a role on ROS generation in undifferentiated HL-60, and the ROS mediated by it was essential for cell's survival. For the first time, we verified that the release of ROS in undifferentiated HL-60 was significantly increased by the stimulation with Calcium ionophore or opsonized zymosan, which are known to trigger respiration burst in phagocytes by NADPH oxidase pathway. Diphenylene iodonium (DPI) or apocynin (APO), two inhibitors of NADPH oxidase, significantly suppressed the increasing of ROS caused by opsonized zymosan. Cell survival assay and fluorescence double dyeing with acridine orange and ethidium bromide showed that DPI and APO, as well as superoxide dismutase (SOD) and catalase (CAT) concentration-dependently decreased the viability of undifferentiated HL-60 cells, whereas exogenous H2O2 can rescue the cells from death obviously. Our results suggested that the ROS, generated by NADPH oxidase play an essential role in the survival of undifferentiated HL-60 cells.

Biphasic effects of substance P on respiratory activity and respiration-related neurones in ventrolateral medulla in the neonatal rat brainstem in vitro.

PubMed

Shvarev, Y N; Lagercrantz, H; Yamamoto, Y

2002-01-01

The effects of substance P (SP) on respiratory activity in the brainstem-spinal cord preparation from neonatal rats (0-4 days old) were investigated. The respiratory activity was recorded from C4 ventral roots and intracellularly from three types of respiration-related neurones, i.e. pre-inspiratory (or biphasic E), three subtypes of inspiratory; expiratory and tonic neurones in the ventrolateral medulla (VLM). After the onset of SP bath application (10 nM-1 microM) a dose-dependent decline of burst rate (by 48%) occurred, followed by a weaker dose-dependent increase (by 17.5%) in burst rate. The biphasic effect of SP on inspiratory burst rate was associated with sustained membrane depolarization (in a range of 0.5-13 mV) of respiration-related and tonic neurones. There were no significant changes in membrane resistance in any type of neurones when SP was applied alone or when synaptic transmission was blocked with tetrodotoxin (TTX). The initial depolarization was associated with an increase in inspiratory drive potential (by 25%) as well as in bursting time (by 65%) and membrane excitability in inspiratory and pre-inspiratory neurones, which corresponded to the decrease in burst rate (C4 activity). The spiking frequency of expiratory and tonic neurones was also increased (by 36 and 48%). This activation was followed by restoration of the synaptic drive potential and bursting time in inspiratory and to a less extent in pre-inspiratory neurones, which corresponded to the increase in burst rate. The discharge frequency of expiratory and tonic neurones also decreased to control values. This phase followed the peak membrane depolarization. At the peak depolarization, SP reduced the amplitude of the action potential by 4-8% in all types of neurones. Our results suggest that SP exerts a general excitatory effect on respiration-related neurones and synaptic coupling within the respiratory network in the VLM. The transient changes in neuronal activity in the VLM may

Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma.

PubMed

Gaurav, Rohit; Bewtra, Againdra K; Agrawal, Devendra K

2015-08-01

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β- and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very low expression of NOX1, NOX3, and NOX5 and no NOX4 mRNA. The level of NOX2 mRNA transcripts increased with disease severity in the eosinophils of subjects with asthma compared with healthy nonatopic volunteers. Change in granularity and size in eosinophils, but no change in intracellular ROS, was observed with phorbol myristate acetate (PMA). PMA, TGF-β, and eotaxin used the CLC3-dependent pathway to increase superoxide radicals. TGF-β and eotaxin induced CLC3-dependent chemotaxis of eosinophils. These findings support the requirement of CLC3 in the activation and migration of human blood eosinophils and may provide a potential novel therapeutic target to regulate eosinophil hyperactivity in allergic airway inflammation in asthma.

Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma

PubMed Central

Gaurav, Rohit; Bewtra, Againdra K.

2015-01-01

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β– and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very low expression of NOX1, NOX3, and NOX5 and no NOX4 mRNA. The level of NOX2 mRNA transcripts increased with disease severity in the eosinophils of subjects with asthma compared with healthy nonatopic volunteers. Change in granularity and size in eosinophils, but no change in intracellular ROS, was observed with phorbol myristate acetate (PMA). PMA, TGF-β, and eotaxin used the CLC3-dependent pathway to increase superoxide radicals. TGF-β and eotaxin induced CLC3-dependent chemotaxis of eosinophils. These findings support the requirement of CLC3 in the activation and migration of human blood eosinophils and may provide a potential novel therapeutic target to regulate eosinophil hyperactivity in allergic airway inflammation in asthma. PMID:25514499

Salicylic Acid Regulation of Respiration in Higher Plants: Alternative Oxidase Expression.

PubMed Central

Rhoads, DM; McIntosh, L

1992-01-01

Alternative respiratory pathway capacity increases during the development of the thermogenic appendix of a voodoo lily inflorescence. The levels of the alternative oxidase proteins increased dramatically between D-4 (4 days prior to the day of anthesis) and D-3 and continued to increase until the day of anthesis (D-day). The level of salicylic acid (SA) in the appendix is very low early on D-1, but increases to a high level in the evening of D-1. Thermogenesis occurs after a few hours of light on D-day. Therefore, the initial accumulation of the alternative oxidase proteins precedes the increase in SA by 3 days, indicating that other regulators may be involved. A 1.6-kb transcript encoding the alternative oxidase precursor protein accumulated to a high level in the appendix tissue by D-1. Application of SA to immature appendix tissue caused an increase in alternative pathway capacity and a dramatic accumulation of the alternative oxidase proteins and the 1.6-kb transcript. Time course experiments showed that the increase in capacity, protein levels, and transcript level corresponded precisely. The response to SA was blocked by cycloheximide or actinomycin D, indicating that de novo transcription and translation are required. However, nuclear, in vitro transcription assays indicated that the accumulation of the 1.6-kb transcript did not result from a simple increase in the rate of transcription of aox1. PMID:12297672

Burst-by-burst laser frequency monitor

NASA Technical Reports Server (NTRS)

Esproles, Carlos (Inventor)

1994-01-01

The invention is a system for real-time frequency monitoring and display of an RF burst where the burst frequency is analyzed and displayed on a burst-by-burst basis in order to allow for frequency control. Although the invention was made for monitoring the laser frequency of a LIDAR system, it has other applications where realtime monitoring is required. The novelty of the invention resides in the use of a counter that is reset at the beginning of each unit time of monitoring and then gated for a unit of time. The invention also has an LED bar graph for displaying the measure of frequency at the end of each unit time in either a bar length mode or a moving dot mode. In the latter mode, the operator makes necessary adjustments to maintain the dot at the center of the bar graph.

Allotopic expression of a mitochondrial alternative oxidase confers cyanide resistance to human cell respiration

PubMed Central

Hakkaart, Gerrit A J; Dassa, Emmanuel P; Jacobs, Howard T; Rustin, Pierre

2006-01-01

Human mitochondrial respiration is distinct from that of most plants, microorganisms and even some metazoans in that it reduces molecular oxygen only through the highly cyanide-sensitive enzyme cytochrome c oxidase. Here we show that expression of the cyanide-insensitive alternative oxidase (AOX), recently identified in the ascidian Ciona intestinalis, is well tolerated by cultured human cells and confers spectacular cyanide resistance to mitochondrial substrate oxidation. The expressed AOX seems to be confined to mitochondria. AOX involvement in electron flow is triggered by a highly reduced redox status of the respiratory chain (RC) and enhanced by pyruvate; otherwise, the enzyme remains essentially inactive. AOX expression promises to be a valuable tool to limit the deleterious consequences of RC deficiency in human cells and whole animals. PMID:16322757

Magnetar Bursts

NASA Technical Reports Server (NTRS)

Kouveliotou, Chryssa

2014-01-01

The Fermi/Gamma-ray Burst Monitor (GBM) was launched in June 2008. During the last five years the instrument has observed several hundreds of bursts from 8 confirmed magnetars and 19 events from unconfirmed sources. I will discuss the results of the GBM magnetar burst catalog, expand on the different properties of their diverse source population, and compare these results with the bursting activity of past sources. I will then conclude with thoughts of how these properties fit the magnetar theoretical models.

A neuronal mechanism of propofol-induced central respiratory depression in newborn rats.

PubMed

Kashiwagi, Masanori; Okada, Yasumasa; Kuwana, Shun-Ichi; Sakuraba, Shigeki; Ochiai, Ryoichi; Takeda, Junzo

2004-07-01

The neural mechanisms of propofol-induced central respiratory depression remain poorly understood. In the present study, we studied these mechanisms and the involvement of gamma-aminobutyric acid (GABA)A receptors in propofol-induced central respiratory depression. The brainstem and the cervical spinal cord of 1- to 4-day-old rats were isolated, and preparations were maintained in vitro with oxygenated artificial cerebrospinal fluid. Rhythmic inspiratory burst activity was recorded from the C4 spinal ventral root. The activity of respiratory neurons in the ventrolateral medulla was recorded using a perforated patch-clamp technique. We found that bath-applied propofol decreased C4 inspiratory burst rate, which could be reversed by the administration of a GABAA antagonist, bicuculline. Propofol caused resting membrane potentials to hyperpolarize and suppressed the firing of action potentials in preinspiratory and expiratory neurons. In contrast, propofol had little effect on resting membrane potentials and action potential firing in inspiratory neurons. Our findings suggest that the depressive effects of propofol are, at least in part, mediated by the agonistic action of propofol on GABAA receptors. It is likely that the GABAA receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression in the newborn rat.

Mechanisms of CO2/H+ chemoreception by respiratory rhythm generator neurons in the medulla from newborn rats in vitro

PubMed Central

Kawai, Akira; Onimaru, Hiroshi; Homma, Ikuo

2006-01-01

We investigated mechanisms of CO2/H+ chemoreception in the respiratory centre of the medulla by measuring membrane potentials of pre-inspiratory neurons, which are putative respiratory rhythm generators, in the brainstem–spinal cord preparation of the neonatal rat. Neuronal response was tested by changing superfusate CO2 concentration from 2% to 8% at constant HCO3− concentration (26 mm) or by changing pH from 7.8 to 7.2 by reducing HCO3− concentration at constant CO2 (5%). Both respiratory and metabolic acidosis lead to depolarization of neurons with increased excitatory synaptic input and increased burst rate. Respiratory acidosis potentiated the amplitude of the neuronal drive potential. In the presence of tetrodotoxin (TTX), membrane depolarization persisted during respiratory and metabolic acidosis. However, the depolarization was smaller than that before application of TTX, which suggests that some neurons are intrinsically, and others synaptically, chemosensitive to CO2/H+. Application of Ba2+ blocked membrane depolarization by respiratory acidosis, whereas significant depolarization in response to metabolic acidosis still remained after application of Cd2+ and Ba2+. We concluded that the intrinsic responses to CO2/H+changes were mediated by potassium channels during respiratory acidosis, and that some other mechanisms operate during metabolic acidosis. In low-Ca2+, high-Mg2+ solution, an increased CO2 concentration induced a membrane depolarization with a simultaneous increase of the burst rate. Pre-inspiratory neurons could adapt their baseline membrane potential to external CO2/H+ changes by integration of these mechanisms to modulate their burst rates. Thus, pre-inspiratory neurons might play an important role in modulation of respiratory rhythm by central chemoreception in the brainstem–spinal cord preparation. PMID:16469786

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants

PubMed Central

Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants. PMID:29033963

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants.

PubMed

Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants.

Comparison of brain mitochondrial cytochrome c oxidase activity with cyanide LD(50) yields insight into the efficacy of prophylactics.

PubMed

Marziaz, Mandy L; Frazier, Kathryn; Guidry, Paul B; Ruiz, Robyn A; Petrikovics, Ilona; Haines, Donovan C

2013-01-01

Cyanide inhibits cytochrome c oxidase, the terminal oxidase of the mitochondrial respiratory pathway, therefore inhibiting the cell oxygen utilization and resulting in the condition of histotoxic anoxia. The enzyme rhodanese detoxifies cyanide by utilizing sulfur donors to convert cyanide to thiocyanate, and new and improved sulfur donors are actively sought as researchers seek to improve cyanide prophylactics. We have determined brain cytochrome c oxidase activity as a marker for cyanide exposure for mice pre-treated with various cyanide poisoning prophylactics, including sulfur donors thiosulfate (TS) and thiotaurine (TT3). Brain mitochondria were isolated by differential centrifugation, the outer mitochondrial membrane was disrupted by a maltoside detergent, and the decrease in absorbance at 550 nm as horse heart ferrocytochrome c (generated by the dithiothreitol reduction of ferricytochrome c) was oxidized was monitored. Overall, the TS control prophylactic treatment provided significant protection of the cytochrome c oxidase activity. The TT3-treated mice showed reduced cytochrome c oxidase activity even in the absence of cyanide. In both treatment series, addition of exogenous Rh did not significantly enhance the prevention of cytochrome c oxidase inhibition, but the addition of sodium nitrite did. These findings can lead to a better understanding of the protection mechanism by various cyanide antidotal systems. Copyright © 2011 John Wiley & Sons, Ltd.

Cytochrome c oxidase loses catalytic activity and structural integrity during the aging process in Drosophila melanogaster

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

Ren, Jian-Ching; Rebrin, Igor; Klichko, Vladimir

2010-10-08

Research highlights: {yields} Cytochrome c oxidase loses catalytic activity during the aging process. {yields} Abundance of seven nuclear-encoded subunits of cytochrome c oxidase decreased with age in Drosophila. {yields} Cytochrome c oxidase is specific intra-mitochondrial site of age-related deterioration. -- Abstract: The hypothesis, that structural deterioration of cytochrome c oxidase (CcO) is a causal factor in the age-related decline in mitochondrial respiratory activity and an increase in H{sub 2}O{sub 2} generation, was tested in Drosophila melanogaster. CcO activity and the levels of seven different nuclear DNA-encoded CcO subunits were determined at three different stages of adult life, namely, young-, middle-,more » and old-age. CcO activity declined progressively with age by 33%. Western blot analysis, using antibodies specific to Drosophila CcO subunits IV, Va, Vb, VIb, VIc, VIIc, and VIII, indicated that the abundance these polypeptides decreased, ranging from 11% to 40%, during aging. These and previous results suggest that CcO is a specific intra-mitochondrial site of age-related deterioration, which may have a broad impact on mitochondrial physiology.« less

Involvement of alternative oxidase in the regulation of sensitivity of Sclerotinia sclerotiorum to the fungicides azoxystrobin and procymidone.

PubMed

Xu, Ting; Wang, Ya-Ting; Liang, Wu-Sheng; Yao, Fei; Li, Yong-Hong; Li, Dian-Rong; Wang, Hao; Wang, Zheng-Yi

2013-06-01

Sclerotinia sclerotiorum is a filamentous fungal pathogen that can infect many economically important crops and vegetables. Alternative oxidase is the terminal oxidase of the alternative respiratory pathway in fungal mitochondria. The function of alternative oxidase was investigated in the regulation of sensitivity of S. sclerotiorum to two commercial fungicides, azoxystrobin and procymidone which have different fungitoxic mechanisms. Two isolates of S. sclerotiorum were sensitive to both fungicides. Application of salicylhydroxamic acid, a specific inhibitor of alternative oxidase, significantly increased the values of effective concentration causing 50% mycelial growth inhibition (EC50) of azoxystrobin to both S. sclerotiorum isolates, whereas notably decreased the EC50 values of procymidone. In mycelial respiration assay azoxystrobin displayed immediate inhibitory effect on cytochrome pathway capacity, but had no immediate effect on alternative pathway capacity. In contrast, procymidone showed no immediate impact on capacities of both cytochrome and alternative pathways in the mycelia. However, alternative oxidase encoding gene (aox) transcript and protein levels, alternative respiration pathway capacity of the mycelia were obviously increased by pre-treatment for 24 h with both azoxystrobin and procymidone. These results indicate that alternative oxidase was involved in the regulation of sensitivity of S. sclerotiorum to the fungicides azoxystrobin and procymidone, and that both fungicides could affect aox gene expression and the alternative respiration pathway capacity development in mycelia of this fungal pathogen.

Error signals as powerful stimuli for the operant conditioning-like process of the fictive respiratory output in a brainstem-spinal cord preparation from rats.

PubMed

Formenti, Alessandro; Zocchi, Luciano

2014-10-01

Respiratory neuromuscular activity needs to adapt to physiologic and pathologic conditions. We studied the conditioning effects of sensory fiber (putative Ia and II type from neuromuscular spindles) stimulation on the fictive respiratory output to the diaphragm, recorded from C4 phrenic ventral root, of in-vitro brainstem-spinal cord preparations from rats. The respiratory burst frequency in these preparations decreased gradually (from 0.26±0.02 to 0.09±0.003 bursts(-1)±SEM) as the age of the donor rats increased from zero to 4 days. The frequency greatly increased when the pH of the bath was lowered, and was significantly reduced by amiloride. C4 low threshold, sensory fiber stimulation, mimicking a stretched muscle, induced a short-term facilitation of the phrenic output increasing burst amplitude and frequency. When the same stimulus was applied contingently on the motor bursts, in an operant conditioning paradigm (a 500ms pulse train with a delay of 700ms from the beginning of the burst) a strong and persistent (>1h) increase in burst frequency was observed (from 0.10±0.007 to 0.20±0.018 bursts(-1)). Conversely, with random stimulation burst frequency increased only slightly and declined again within minutes to control levels after stopping stimulation. A forward model is assumed to interpret the data, and the notion of error signal, i.e. the sensory fiber activation indicating an unexpected stretched muscle, is re-considered in terms of the reward/punishment value. The signal, gaining hedonic value, is reviewed as a powerful unconditioned stimulus suitable in establishing a long-term operant conditioning-like process. Copyright © 2014 Elsevier B.V. All rights reserved.

A Nontriggered Burst Supplement to the BATSE Gamma-Ray Burst Catalogs

NASA Technical Reports Server (NTRS)

Kommers, Jefferson M.; Lewin, Walter H. G.; Kouveliotou, Chryssa; vanParadijs, Jan; Pendleton, Geoffrey N.; Meegan, Charles A.; Fishman, Gerald J.

2001-01-01

The Burst and Transient Source Experiment (BATSE) on the Compton Gamma Ray Observatory detects gamma-ray bursts (GRBs) with a real-time burst detection (or "trigger") system running onboard the spacecraft. Under some circumstances, however, a GRB may not activate the on-board burst trigger. For example, the burst may be too faint to exceed the on-board detection threshold, or it may occur while the on-board burst trigger is disabled for technical reasons. This paper describes a catalog of 873 "nontriggered" GRBs that were detected in a search of the archival continuous data from BATSE recorded between 1991 December 9.0 and 1997 December 17.0. For each burst, the catalog gives an estimated source direction, duration, peak flux, and fluence. Similar data are presented for 50 additional bursts of unknown origin that were detected in the 25-50 keV range; these events may represent the low-energy "tail" of the GRB spectral distribution. This catalog increases the number of GRBs detected with BATSE by 48% during the time period covered by the search.

A Non-Triggered Burst Supplement to the BATSE Gamma-Ray Burst Catalogs

NASA Technical Reports Server (NTRS)

Kommers, J.; Lewin, W. H.; Kouveliotou, C.; vanParadijs, J.; Pendleton, G. N.; Meegan, C. A.; Fishman, G. J.

1998-01-01

The Burst and Transient Source Experiment (BATSE) on the Compton Gamma Ray Observatory detects gamma-ray bursts (GRBs) with a real-time burst detection (or "trigger") system running onboard the spacecraft. Under some circumstances, however, a GRB may not activate the onboard burst trigger. For example, the burst may be too faint to exceed the onboard detection threshold, or it may occur while the onboard burst trigger is disabled for technical reasons. This paper is a catalog of such "non-triggered" GRBs that were detected in a search of the archival continuous data from BATSE. It lists 873 non-triggered bursts that were recorded between 1991 December 9.0 and 1997 December 17.0. For each burst, the catalog gives an estimated source direction, duration, peak flux, and fluence. Similar data are presented for 50 additional bursts of unknown origin that were detected in the 25-50 keV range; these events may represent the low-energy "tail" of the GRB spectral distribution. This catalog increases the number of GRBs detected with BATSE by 48% during the time period covered by the search.

Quantum key based burst confidentiality in optical burst switched networks.

PubMed

Balamurugan, A M; Sivasubramanian, A

2014-01-01

The optical burst switching (OBS) is an emergent result to the technology concern that could achieve a feasible network in future. They are endowed with the ability to meet the bandwidth requirement of those applications that require intensive bandwidth. There are more domains opening up in the OBS that evidently shows their advantages and their capability to face the future network traffic. However, the concept of OBS is still far from perfection facing issues in case of security threat. The transfer of optical switching paradigm to optical burst switching faces serious downfall in the fields of burst aggregation, routing, authentication, dispute resolution, and quality of service (QoS). This paper deals with employing RC4 (stream cipher) to encrypt and decrypt bursts thereby ensuring the confidentiality of the burst. Although the use of AES algorithm has already been proposed for the same issue, by contrasting the two algorithms under the parameters of burst encryption and decryption time, end-to-end delay, it was found that RC4 provided better results. This paper looks to provide a better solution for the confidentiality of the burst in OBS networks.

Quantum Key Based Burst Confidentiality in Optical Burst Switched Networks

PubMed Central

Balamurugan, A. M.; Sivasubramanian, A.

2014-01-01

The optical burst switching (OBS) is an emergent result to the technology concern that could achieve a feasible network in future. They are endowed with the ability to meet the bandwidth requirement of those applications that require intensive bandwidth. There are more domains opening up in the OBS that evidently shows their advantages and their capability to face the future network traffic. However, the concept of OBS is still far from perfection facing issues in case of security threat. The transfer of optical switching paradigm to optical burst switching faces serious downfall in the fields of burst aggregation, routing, authentication, dispute resolution, and quality of service (QoS). This paper deals with employing RC4 (stream cipher) to encrypt and decrypt bursts thereby ensuring the confidentiality of the burst. Although the use of AES algorithm has already been proposed for the same issue, by contrasting the two algorithms under the parameters of burst encryption and decryption time, end-to-end delay, it was found that RC4 provided better results. This paper looks to provide a better solution for the confidentiality of the burst in OBS networks. PMID:24578663

[Involvement of hydrogen peroxide in the regulation of coexpression of alternative oxidase and rotenone-insensitive NADH dehydrogenase in tomato leaves and calluses].

PubMed

Eprintsev, A T; Mal'tseva, E V; Shatskikh, A S; Popov, V N

2011-01-01

The involvement of active oxygen forms in the regulation of the expression of mitochondrial respiratory chain components, which are not related to energy storing, has been in vitro and in vivo studied in Lycopersicum esculentum L. The highest level of transcription of genes encoding alternative oxidase and NADH dehydrogenase has been observed in green tomato leaves. It has been shown that even low H2O2 concentrations activate both aoxlalpha and ndb1 genes, encoding alternative oxidase and external mitochondrial rotenone-insensitive NADH dehydrogenase, respectively. According to our results, in the case of an oxidative stress, alternative oxidase and NADH dehydrogenase are coexpressed in tomato plant tissues, and active oxygen forms serve as the secondary messengers of their coexpression.

Expression and crystallization of the plant alternative oxidase.

PubMed

May, Benjamin; Elliott, Catherine; Iwata, Momi; Young, Luke; Shearman, Julia; Albury, Mary S; Moore, Anthony L

2015-01-01

The alternative oxidase (AOX) is an integral monotopic membrane protein located on the inner surface of the inner mitochondrial membrane. Branching from the traditional respiratory chain at the quinone pool, AOX is responsible for cyanide-resistant respiration in plants and fungi, heat generation in thermogenic plants, and survival of parasites, such as Trypanosoma brucei, in the human host. A recently solved AOX structure provides insight into its active site, thereby facilitating rational phytopathogenic and antiparasitic drug design. Here, we describe expression of recombinant AOX using two different expression systems. Purification protocols for the production of highly pure and stable AOX protein in sufficient quantities to facilitate further kinetic, biophysical, and structural analyses are also described.

Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

NASA Astrophysics Data System (ADS)

Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

2013-10-01

Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

Heterodimerization controls localization of Duox-DuoxA NADPH oxidases in airway cells.

PubMed

Luxen, Sylvia; Noack, Deborah; Frausto, Monika; Davanture, Suzel; Torbett, Bruce E; Knaus, Ulla G

2009-04-15

Duox NADPH oxidases generate hydrogen peroxide at the air-liquid interface of the respiratory tract and at apical membranes of thyroid follicular cells. Inactivating mutations of Duox2 have been linked to congenital hypothyroidism, and epigenetic silencing of Duox is frequently observed in lung cancer. To study Duox regulation by maturation factors in detail, its association with these factors, differential use of subunits and localization was analyzed in a lung cancer cell line and undifferentiated or polarized lung epithelial cells. We show here that Duox proteins form functional heterodimers with their respective DuoxA subunits, in close analogy to the phagocyte NADPH oxidase. Characterization of novel DuoxA1 isoforms and mispaired Duox-DuoxA complexes revealed that heterodimerization is a prerequisite for reactive oxygen species production. Functional Duox1 and Duox2 localize to the leading edge of migrating cells, augmenting motility and wound healing. DuoxA subunits are responsible for targeting functional oxidases to distinct cellular compartments in lung epithelial cells, including Duox2 expression in ciliated cells in an ex vivo differentiated lung epithelium. As these locations probably define signaling specificity of Duox1 versus Duox2, these findings will facilitate monitoring Duox isoform expression in lung disease, a first step for early screening procedures and rational drug development.

Differences in activity of cytochrome C oxidase in brain between sleep and wakefulness.

PubMed

Nikonova, Elena V; Vijayasarathy, Camasamudram; Zhang, Lin; Cater, Jacqueline R; Galante, Raymond J; Ward, Stephen E; Avadhani, Narayan G; Pack, Allan I

2005-01-01

Increased mRNA level of subunit 1 cytochrome c oxidase (COXI) during wakefulness and after short-term sleep deprivation has been described in brain. We hypothesized that this might contribute to increased activity of cytochrome oxidase (COX) enzyme during wakefulness, as part of the mechanisms to provide sufficient amounts of adenosine triphosphate to meet increased neuronal energy demands. COX activity was measured in isolated mitochondria from different brain regions in groups of rats with 3 hours of spontaneous sleep, 3 hours of spontaneous wake, and 3 hours of sleep deprivation. The group with 3 hours of spontaneous wake was added to delineate the circadian component of changes in the enzyme activity. Northern blot analysis was performed to examine the mRNA levels of 2 subunits of the enzyme COXI and COXIV, encoded by mitochondrial and nuclear DNA, respectively. Laboratory of Biochemistry, Department of Animal Biology, and Center for Sleep and Respiratory Neurobiology, University of Pennsylvania. 2-month-old male Fischer rats (N = 21) implanted for polygraphic recording. For COX activity, there was a main effect by analysis of variance of experimental group (P < .0001) with significant increases in COX activity in wake and sleep-deprived groups as compared to the sleep group. A main effect of brain region was also significant (P < .001). There was no difference between brain regions in the degree of increase in enzyme activity in wakefulness. Both COXI and COXIV mRNA were increased with wakefulness as compared to sleep. There is an increase in COX activity after both 3 hours of spontaneous wake and 3 hours of sleep deprivation as compared with 3 hours of spontaneous sleep in diverse brain regions, which could be, in part, explained by the increased levels of bigenomic transcripts of the enzyme. This likely contributes to increased adenosine triphosphate production during wakefulness. ADP, adenosine diphosphate; ATP, adenosine triphosphate; COXI, cytochrome c

Independent prognostic importance of respiratory instability and sympathetic nerve activity in patients with chronic heart failure.

PubMed

Asanoi, Hidetsugu; Harada, Daisuke; Oda, Yoshitaka; Ueno, Hiroshi; Takagawa, Junya; Ishise, Hisanari; Goso, Yukiko; Joho, Shuji; Inoue, Hiroshi

2017-11-01

Respiratory instability in chronic heart failure (CHF) is characterized by irregularly rapid respiration or non-periodic breathing rather than by Cheyne-Stokes respiration. We developed a new quantitative measure of respiratory instability (RSI) and examined its independent prognostic impact upon CHF. In 87 patients with stable CHF, respiratory flow and muscle sympathetic nerve activity (MSNA) were simultaneously recorded. RSI was calculated from the frequency distribution of respiratory spectral components and very low frequency components. During a mean follow-up of 85±38 months, 24 patients died. Sixteen patients who died of cardiac causes had a lower RSI (16±6 vs. 30±21, p<0.01), a lower specific activity scale (4.3±1.4 Mets vs. 5.7±1.4 Mets, p<0.005), a higher MSNA burst area (16±5% vs. 11±4%, p<0.001), and a higher brain natriuretic peptide (BNP) level (514±559pg/ml vs. 234±311pg/ml, p<0.05) than 71 patients who did not die of cardiac causes. Multivariate analysis revealed that RSI (p=0.015), followed by MSNA burst area (p=0.033), was an independent predictor of subsequent all-cause deaths and that RSI (p=0.026), MSNA burst area (p=0.001), and BNP (p=0.048) were independent predictors of cardiac deaths. Patients at very high risk of fatal outcome could be identified by an RSI<20. The daytime respiratory instability quantified by a new measure of RSI has prognostic importance independent of sympathetic nerve activation in patients with clinically stable CHF. An RSI of <20 identifies patients at very high risk for subsequent all-cause and cardiovascular death. Copyright © 2017. Published by Elsevier Ltd.

Respiratory Pathways Reconstructed by Multi-Omics Analysis in Melioribacter roseus, Residing in a Deep Thermal Aquifer of the West-Siberian Megabasin

PubMed Central

Gavrilov, Sergey; Podosokorskaya, Olga; Alexeev, Dmitry; Merkel, Alexander; Khomyakova, Maria; Muntyan, Maria; Altukhov, Ilya; Butenko, Ivan; Bonch-Osmolovskaya, Elizaveta; Govorun, Vadim; Kublanov, Ilya

2017-01-01

Melioribacter roseus, a representative of recently proposed Ignavibacteriae phylum, is a metabolically versatile thermophilic bacterium, inhabiting subsurface biosphere of the West-Siberian megabasin and capable of growing on various substrates and electron acceptors. Genomic analysis followed by inhibitor studies and membrane potential measurements of aerobically grown M. roseus cells revealed the activity of aerobic respiratory electron transfer chain comprised of respiratory complexes I and IV, and an alternative complex III. Phylogeny reconstruction revealed that oxygen reductases belonged to atypical cc(o/b)o3-type and canonical cbb3–type cytochrome oxidases. Also, two molybdoenzymes of M. roseus were affiliated either with Ttr or Psr/Phs clades, but not with typical respiratory arsenate reductases of the Arr clade. Expression profiling, both at transcripts and protein level, allowed us to assign the role of the terminal respiratory oxidase under atmospheric oxygen concentration for the cc(o/b)o3 cytochrome oxidase, previously proposed to serve for oxygen detoxification only. Transcriptomic analysis revealed the involvement of both molybdoenzymes of M. roseus in As(V) respiration, yet differences in the genomic context of their gene clusters allow to hypothesize about their distinct roles in arsenate metabolism with the ‘Psr/Phs’-type molybdoenzyme being the most probable candidate respiratory arsenate reductase. Basing on multi-omics data, the pathways for aerobic and arsenate respiration were proposed. Our results start to bridge the vigorously increasing gap between homology-based predictions and experimentally verified metabolic processes, what is especially important for understudied microorganisms of novel lineages from deep subsurface environments of Eurasia, which remained separated from the rest of the biosphere for several geological periods. PMID:28713355

Substance P modulation of TRPC3/7 channels improves respiratory rhythm regularity and ICAN-dependent pacemaker activity

PubMed Central

Ben-Mabrouk, Faiza; Tryba, Andrew Kieran

2011-01-01

Neuromodulators, such as Substance P (SubP) play an important role in modulating many rhythmic activities driven by central pattern generators (e.g., locomotion, respiration). However, the mechanism by which SubP enhances breathing regularity has not been determined. Here, we used mouse brainstem slices containing the pre-Bötzinger Complex (Pre-BötC) to demonstrate, for the first time, that SubP activates transient receptor protein canonical (TRPC) channels to enhance respiratory rhythm regularity. Moreover, SubP enhancement of network regularity is accomplished via selective enhancement of ICAN-dependent intrinsic bursting properties. In contrast to INaP-dependant pacemakers, ICAN-dependant pacemaker bursting activity is TRPC dependent. Western Blots reveal TRPC3 and TRPC7 channels are expressed in rhythmically active ventral respiratory group (VRG) island preparations. Taken together, these data suggest that SubP-mediated activation of TRPC3/7 channels underlies rhythmic ICAN-dependent pacemaker activity and enhances the regularity of respiratory rhythm activity. PMID:20345918

Substance P modulation of TRPC3/7 channels improves respiratory rhythm regularity and ICAN-dependent pacemaker activity.

PubMed

Ben-Mabrouk, Faiza; Tryba, Andrew K

2010-04-01

Neuromodulators, such as substance P (SubP), play an important role in modulating many rhythmic activities driven by central pattern generators (e.g. locomotion, respiration). However, the mechanism by which SubP enhances breathing regularity has not been determined. Here, we used mouse brainstem slices containing the pre-Bötzinger complex to demonstrate, for the first time, that SubP activates transient receptor protein canonical (TRPC) channels to enhance respiratory rhythm regularity. Moreover, SubP enhancement of network regularity is accomplished via selective enhancement of ICAN (inward non-specific cation current)-dependent intrinsic bursting properties. In contrast to INaP (persistent sodium current)-dependent pacemakers, ICAN-dependent pacemaker bursting activity is TRPC-dependent. Western Blots reveal TRPC3 and TRPC7 channels are expressed in rhythmically active ventral respiratory group island preparations. Taken together, these data suggest that SubP-mediated activation of TRPC3/7 channels underlies rhythmic ICAN-dependent pacemaker activity and enhances the regularity of respiratory rhythm activity.

NAD(P)H Oxidase Activity in the Small Intestine Is Predominantly Found in Enterocytes, Not Professional Phagocytes.

PubMed

Lindquist, Randall L; Bayat-Sarmadi, Jannike; Leben, Ruth; Niesner, Raluca; Hauser, Anja E

2018-05-04

The balance between various cellular subsets of the innate and adaptive immune system and microbiota in the gastrointestinal tract is carefully regulated to maintain tolerance to the normal flora and dietary antigens, while protecting against pathogens. The intestinal epithelial cells and the network of dendritic cells and macrophages in the lamina propria are crucial lines of defense that regulate this balance. The complex relationship between the myeloid compartment (dendritic cells and macrophages) and lymphocyte compartment (T cells and innate lymphoid cells), as well as the impact of the epithelial cell layer have been studied in depth in recent years, revealing that the regulatory and effector functions of both innate and adaptive immune compartments exhibit more plasticity than had been previously appreciated. However, little is known about the metabolic activity of these cellular compartments, which is the basic function underlying all other additional tasks the cells perform. Here we perform intravital NAD(P)H fluorescence lifetime imaging in the small intestine of fluorescent reporter mice to monitor the NAD(P)H-dependent metabolism of epithelial and myeloid cells. The majority of myeloid cells which comprise the surveilling network in the lamina propria have a low metabolic activity and remain resting even upon stimulation. Only a few myeloid cells, typically localized at the tip of the villi, are metabolically active and are able to activate NADPH oxidases upon stimulation, leading to an oxidative burst. In contrast, the epithelial cells are metabolically highly active and, although not considered professional phagocytes, are also able to activate NADPH oxidases, leading to massive production of reactive oxygen species. Whereas the oxidative burst in myeloid cells is mainly catalyzed by the NOX2 isotype, in epithelial cells other isotypes of the NADPH oxidases family are involved, especially NOX4. They are constitutively expressed by the epithelial

Regulation of nitrite resistance of the cytochrome cbb3 oxidase by cytochrome c ScyA in Shewanella oneidensis

PubMed Central

Yin, Jianhua; Jin, Miao; Zhang, Haiyan; Ju, Lili; Zhang, Lili; Gao, Haichun

2015-01-01

Cytochrome c proteins, as enzymes to exchange electrons with substrates or as pure electron carriers to shuttle electrons, play vital roles in bacterial respiration and photosynthesis. In Shewanella oneidensis, a research model for the respiratory diversity, at least 42 c-type cytochromes are predicted to be encoded in the genome and are regarded to be the foundation of its highly branched electron transport pathways. However, only a small number of c-type cytochromes have been extensively studied. In this study, we identify soluble cytochrome c ScyA as an important factor influencing the nitrite resistance of a strain devoid of the bd oxidase by utilizing a newly developed transposon mutagenesis vector, which enables overexpression of the gene(s) downstream of the insertion site. We show that when in overabundance ScyA facilitates growth against nitrite inhibition by enhancing nitrite resistance of the cbb3 oxidase. Based on the data presented in this study, we suggest two possible mechanisms underlying the observed effect of ScyA: (1) ScyA increases electron flow to the cbb3 oxidase; (2) ScyA promotes nitrite resistance of the cbb3 oxidase, possibly by direct interaction. PMID:25417822

NADPH oxidase 2 (NOX2) enzyme activation in patients with chronic inflammatory demyelinating polyneuropathy.

PubMed

Marrali, G; Salamone, P; Casale, F; Fuda, G; Cugnasco, P; Caorsi, C; Amoroso, A; Calvo, A; Lopiano, L; Cocito, D; Chiò, A

2016-05-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immunomediated condition affecting the peripheral nervous system where probably macrophages are the primary effector cells for demyelination. Reactive oxygen species (ROS), catalyzed by the NOX family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzymes, can induce peroxidation and are potentially injurious to myelin. Our aim was to assess the activity of NOX2, an isoform of NOX, in a series of CIDP patients and to analyze the effect of intravenous immunoglobulin (IVIg) on NOX2. Thirty CIDP patients treated with IVIg and 30 control subjects were enrolled. To evaluate NOX2 activity, neutrophil and monocyte oxidative burst was measured directly in fresh whole blood using the Phagoburst™ assay, a fluorescence-activated cell sorting method. The mean fluorescence intensity, emitted in response to different stimuli, leads to the production of ROS and corresponds to the percentage of oxidizing cells and their enzymatic activity. Mean fluorescence intensity values for granulocyte and monocyte burst in patients (mean 633.3, SD 191; mean 111.8, SD 28.5) were different from those measured in healthy controls (granulocytes, mean 436.6, SD 137.0, P = 0.0003; monocytes, mean 78.2, SD 17.3, P = 0.000001). Moreover, IVIg administration increased both granulocyte (P = 0.005) and monocyte (P = 0.0009) burst. Our findings demonstrate that oxidative burst is significantly increased in CIDP patients and that treatment with IVIg enhances oxidative values, thus representing a possible IVIg therapeutic effect linked to a regulatory effect of ROS. Based on this, the development of treatments targeting the specific activation of NOX may be beneficial in autoimmune disorders. © 2016 EAN.

Alternative mitochondrial respiratory chains from two crustaceans: Artemia franciscana nauplii and the white shrimp, Litopenaeus vannamei.

PubMed

Rodriguez-Armenta, Chrystian; Uribe-Carvajal, Salvador; Rosas-Lemus, Monica; Chiquete-Felix, Natalia; Huerta-Ocampo, Jose Angel; Muhlia-Almazan, Adriana

2018-04-01

Mitochondrial ATP is synthesized by coupling between the electron transport chain and complex V. In contrast, physiological uncoupling of these processes allows mitochondria to consume oxygen at high rates without ATP synthesis. Such uncoupling mechanisms prevent reactive oxygen species overproduction. One of these mechanisms are the alternative redox enzymes from the mitochondrial respiratory chain, which may help cells to maintain homeostasis under stress independently of ATP synthesis. To date, no reports have been published on alternative redox enzymes in crustaceans mitochondria. Specific inhibitors were used to identify alternative redox enzymes in mitochondria isolated from Artemia franciscana nauplii, and the white shrimp, Litopenaeus vannamei. We report the presence of two alternative redox enzymes in the respiratory chain of A. franciscana nauplii, whose isolated mitochondria used glycerol-3-phosphate as a substrate, suggesting the existence of a glycerol-3-phosphate dehydrogenase. In addition, cyanide and octyl-gallate were necessary to fully inhibit this species' mitochondrial oxygen consumption, suggesting an alternative oxidase is present. The in-gel activity analysis confirmed that additional mitochondrial redox proteins exist in A. franciscana. A mitochondrial glycerol-3-phosphate dehydrogenase oxidase was identified by protein sequencing as part of a branched respiratory chain, and an alternative oxidase was also identified in this species by western blot. These results indicate different adaptive mechanisms from artemia to face environmental challenges related to the changing levels of oxygen concentration in seawater through their life cycles. No alternative redox enzymes were found in shrimp mitochondria, further efforts will determine the existence of an uncoupling mechanism such as uncoupling proteins.

Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCγ2 signaling axis in mice

PubMed Central

Graham, Daniel B.; Robertson, Charles M.; Bautista, Jhoanne; Mascarenhas, Francesca; Diacovo, M. Julia; Montgrain, Vivianne; Lam, Siu Kit; Cremasco, Viviana; Dunne, W. Michael; Faccio, Roberta; Coopersmith, Craig M.; Swat, Wojciech

2007-01-01

Oxidative burst, a critical antimicrobial mechanism of neutrophils, involves the rapid generation and release of reactive oxygen intermediates (ROIs) by the NADPH oxidase complex. Genetic mutations in an NADPH oxidase subunit, gp91 (also referred to as NOX2), are associated with chronic granulomatous disease (CGD), which is characterized by recurrent and life-threatening microbial infections. To combat such infections, ROIs are produced by neutrophils after stimulation by integrin-dependent adhesion to the ECM in conjunction with stimulation from inflammatory mediators, or microbial components containing pathogen-associated molecular patterns. In this report, we provide genetic evidence that both the Vav family of Rho GTPase guanine nucleotide exchange factors (GEFs) and phospholipase C–γ2 (PLC-γ2) are critical mediators of adhesion-dependent ROI production by neutrophils in mice. We also demonstrated that Vav was critically required for neutrophil-dependent host defense against systemic infection by Staphylococcus aureus and Pseudomonas aeruginosa, 2 common pathogens associated with fatal cases of hospital-acquired pneumonia. We identified a molecular pathway in which Vav GEFs linked integrin-mediated signaling with PLC-γ2 activation, release of intracellular Ca2+ cations, and generation of diacylglycerol to control assembly of the NADPH oxidase complex and ROI production by neutrophils. Taken together, our data indicate that integrin-dependent signals generated during neutrophil adhesion contribute to the activation of NADPH oxidase by a variety of distinct effector pathways, all of which require Vav. PMID:17932569

A ROS-Assisted Calcium Wave Dependent on the AtRBOHD NADPH Oxidase and TPC1 Cation Channel Propagates the Systemic Response to Salt Stress.

PubMed

Evans, Matthew J; Choi, Won-Gyu; Gilroy, Simon; Morris, Richard J

2016-07-01

Plants exhibit rapid, systemic signaling systems that allow them to coordinate physiological and developmental responses throughout the plant body, even to highly localized and quickly changing environmental stresses. The propagation of these signals is thought to include processes ranging from electrical and hydraulic networks to waves of reactive oxygen species (ROS) and cytoplasmic Ca(2+) traveling throughout the plant. For the Ca(2+) wave system, the involvement of the vacuolar ion channel TWO PORE CHANNEL1 (TPC1) has been reported. However, the precise role of this channel and the mechanism of cell-to-cell propagation of the wave have remained largely undefined. Here, we use the fire-diffuse-fire model to analyze the behavior of a Ca(2+) wave originating from Ca(2+) release involving the TPC1 channel in Arabidopsis (Arabidopsis thaliana). We conclude that a Ca(2+) diffusion-dominated calcium-induced calcium-release mechanism is insufficient to explain the observed wave transmission speeds. The addition of a ROS-triggered element, however, is able to quantitatively reproduce the observed transmission characteristics. The treatment of roots with the ROS scavenger ascorbate and the NADPH oxidase inhibitor diphenyliodonium and analysis of Ca(2+) wave propagation in the Arabidopsis respiratory burst oxidase homolog D (AtrbohD) knockout background all led to reductions in Ca(2+) wave transmission speeds consistent with this model. Furthermore, imaging of extracellular ROS production revealed a systemic spread of ROS release that is dependent on both AtRBOHD and TPC1 These results suggest that, in the root, plant systemic signaling is supported by a ROS-assisted calcium-induced calcium-release mechanism intimately involving ROS production by AtRBOHD and Ca(2+) release dependent on the vacuolar channel TPC1. © 2016 American Society of Plant Biologists. All Rights Reserved.

QKD-Based Secured Burst Integrity Design for Optical Burst Switched Networks

NASA Astrophysics Data System (ADS)

Balamurugan, A. M.; Sivasubramanian, A.; Parvathavarthini, B.

2016-03-01

The field of optical transmission has undergone numerous advancements and is still being researched mainly due to the fact that optical data transmission can be done at enormous speeds. It is quite evident that people prefer optical communication when it comes to large amount of data involving its transmission. The concept of switching in networks has matured enormously with several researches, architecture to implement and methods starting with Optical circuit switching to Optical Burst Switching. Optical burst switching is regarded as viable solution for switching bursts over networks but has several security vulnerabilities. However, this work exploited the security issues associated with Optical Burst Switching with respect to integrity of burst. This proposed Quantum Key based Secure Hash Algorithm (QKBSHA-512) with enhanced compression function design provides better avalanche effect over the conventional integrity algorithms.

A repeating fast radio burst

NASA Astrophysics Data System (ADS)

Spitler, L. G.; Scholz, P.; Hessels, J. W. T.; Bogdanov, S.; Brazier, A.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J.; Ferdman, R. D.; Freire, P. C. C.; Kaspi, V. M.; Lazarus, P.; Lynch, R.; Madsen, E. C.; McLaughlin, M. A.; Patel, C.; Ransom, S. M.; Seymour, A.; Stairs, I. H.; Stappers, B. W.; van Leeuwen, J.; Zhu, W. W.

2016-03-01

Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

A repeating fast radio burst.

PubMed

Spitler, L G; Scholz, P; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

2016-03-10

Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

Proton channel HVCN1 is required for effector functions of mouse eosinophils

PubMed Central

2013-01-01

Background Proton currents are required for optimal respiratory burst in phagocytes. Recently, HVCN1 was identified as the molecule required for the voltage-gated proton channel activity associated with the respiratory burst in neutrophils. Although there are similarities between eosinophils and neutrophils regarding their mechanism for respiratory burst, the role of proton channels in eosinophil functions has not been fully understood. Results In the present study, we first identified the expression of the proton channel HVCN1 in mouse eosinophils. Furthermore, using HVCN1-deficient eosinophils, we demonstrated important cell-specific effector functions for HVCN1. Similar to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils produced significantly less reactive oxygen species (ROS) upon phorbol myristate acetate (PMA) stimulation compared with WT eosinophils. In contrast to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils did not show impaired calcium mobilization or migration ability compared with wild-type (WT) cells. Uniquely, HVCN1-deficient eosinophils underwent significantly increased cell death induced by PMA stimulation compared with WT eosinophils. The increased cell death was dependent on NADPH oxidase activation, and correlated with the failure of HVCN1-deficient cells to maintain membrane polarization and intracellular pH in the physiological range upon activation. Conclusions Eosinophils require proton channel HVCN1 for optimal ROS generation and prevention of activation-induced cell death. PMID:23705768

Investigation of primordial black hole bursts using interplanetary network gamma-ray bursts

DOE PAGES

Ukwatta, Tilan Niranjan; Hurley, Kevin; MacGibbon, Jane H.; ...

2016-07-25

The detection of a gamma-ray burst (GRB) in the solar neighborhood would have very important implications for GRB phenomenology. The leading theories for cosmological GRBs would not be able to explain such events. The final bursts of evaporating primordial black holes (PBHs), however, would be a natural explanation for local GRBs. We present a novel technique that can constrain the distance to GRBs using detections from widely separated, non-imaging spacecraft. This method can determine the actual distance to the burst if it is local. We applied this method to constrain distances to a sample of 36 short-duration GRBs detected bymore » the Interplanetary Network (IPN) that show observational properties that are expected from PBH evaporations. These bursts have minimum possible distances in the 10 13–10 18 cm (7–10 5 au) range, which are consistent with the expected PBH energetics and with a possible origin in the solar neighborhood, although none of the bursts can be unambiguously demonstrated to be local. Furthermore, assuming that these bursts are real PBH events, we estimate lower limits on the PBH burst evaporation rate in the solar neighborhood.« less

Decrease in free-radical production with age in rat peritoneal macrophages.

PubMed Central

Alvarez, E; Conde, M; Machado, A; Sobrino, F; Santa Maria, C

1995-01-01

The respiratory-burst reaction has been studied in rat peritoneal macrophages of different ages (3, 12 and 24 months) using phorbol 12-myristate 13-acetate (PMA) to stimulate NADPH oxidase. Production of O2-. and H2O2 decreased with age (about 50 and 75% respectively); however, no difference in NADPH oxidase activity was found. NO. production was also reduced with age (40%). Furthermore, a progressive and significant decrease in the pentose phosphate flux was detected as a function of age in control and PMA-stimulated macrophages. The NADPH/NADP+ ratio decreased with age in control and PMA-stimulated macrophages. Glucose uptake was lower in middle-aged (12 months) and old (24 months) animals but no differences were found between these groups. PMID:8526870

Structure–function characterization reveals new catalytic diversity in the galactose oxidase and glyoxal oxidase family

PubMed Central

Yin, DeLu (Tyler); Urresti, Saioa; Lafond, Mickael; Johnston, Esther M.; Derikvand, Fatemeh; Ciano, Luisa; Berrin, Jean-Guy; Henrissat, Bernard; Walton, Paul H.; Davies, Gideon J.; Brumer, Harry

2015-01-01

Alcohol oxidases, including carbohydrate oxidases, have a long history of research that has generated fundamental biological understanding and biotechnological applications. Despite a long history of study, the galactose 6-oxidase/glyoxal oxidase family of mononuclear copper-radical oxidases, Auxiliary Activity Family 5 (AA5), is currently represented by only very few characterized members. Here we report the recombinant production and detailed structure–function analyses of two homologues from the phytopathogenic fungi Colletotrichum graminicola and C. gloeosporioides, CgrAlcOx and CglAlcOx, respectively, to explore the wider biocatalytic potential in AA5. EPR spectroscopy and crystallographic analysis confirm a common active-site structure vis-à-vis the archetypal galactose 6-oxidase from Fusarium graminearum. Strikingly, however, CgrAlcOx and CglAlcOx are essentially incapable of oxidizing galactose and galactosides, but instead efficiently catalyse the oxidation of diverse aliphatic alcohols. The results highlight the significant potential of prospecting the evolutionary diversity of AA5 to reveal novel enzyme specificities, thereby informing both biology and applications. PMID:26680532

Gamma Ray Bursts - Observations

NASA Technical Reports Server (NTRS)

Gehrels, N.; Cannizzo, J. K.

2010-01-01

We are in an exciting period of discovery for gamma-ray bursts. The Swift observatory is detecting 100 bursts per year, providing arcsecond localizations and sensitive observations of the prompt and afterglow emission. The Fermi observatory is observing 250 bursts per year with its medium-energy GRB instrument and about 10 bursts per year with its high-energy LAT instrument. In addition, rapid-response telescopes on the ground are providing new capabilities to study optical emission during the prompt phase and spectral signatures of the host galaxies. The combined data set is enabling great advances in our understanding of GRBs including afterglow physics, short burst origin, and high energy emission.

Heterogeneity in Short Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Norris, Jay P.; Gehrels Neil; Scargle, Jeffrey D.

2011-01-01

We analyze the Swift/BAT sample of short gamma-ray bursts, using an objective Bayesian Block procedure to extract temporal descriptors of the bursts' initial pulse complexes (IPCs). The sample comprises 12 and 41 bursts with and without extended emission (EE) components, respectively. IPCs of non-EE bursts are dominated by single pulse structures, while EE bursts tend to have two or more pulse structures. The medians of characteristic timescales - durations, pulse structure widths, and peak intervals - for EE bursts are factors of approx 2-3 longer than for non-EE bursts. A trend previously reported by Hakkila and colleagues unifying long and short bursts - the anti-correlation of pulse intensity and width - continues in the two short burst groups, with non-EE bursts extending to more intense, narrower pulses. In addition we find that preceding and succeeding pulse intensities are anti-correlated with pulse interval. We also examine the short burst X-ray afterglows as observed by the Swift/XRT. The median flux of the initial XRT detections for EE bursts (approx 6 X 10(exp -10) erg / sq cm/ s) is approx > 20 x brighter than for non-EE bursts, and the median X-ray afterglow duration for EE bursts (approx 60,000 s) is approx 30 x longer than for non-EE bursts. The tendency for EE bursts toward longer prompt-emission timescales and higher initial X-ray afterglow fluxes implies larger energy injections powering the afterglows. The longer-lasting X-ray afterglows of EE bursts may suggest that a significant fraction explode into more dense environments than non-EE bursts, or that the sometimes-dominant EE component efficiently p()wers the afterglow. Combined, these results favor different progenitors for EE and non-EE short bursts.

Role of glutamate and substance P in the amphibian respiratory network during development

PubMed Central

Chen, Anna K.; Hedrick, Michael S.

2008-01-01

This study tested the hypothesis that glutamatergic ionotropic (AMPA/kainate) receptors and neurokinin receptors (NKR) are important in the regulation of respiratory motor output during development in the bullfrog. The roles of these receptors were studied with in vitro brainstem preparations from pre-metamorphic tadpoles and post-metamorphic frogs. Brainstems were superfused with an artificial cerebrospinal fluid at 20–22°C containing CNQX, a selective non-NMDA antagonist, or with substance P (SP), an agonist of NKR. Blockade of glutamate receptors with CNQX in both groups caused a reduction of lung burst frequency that was reversibly abolished at 5 μM (P<0.01). CNQX, but not SP, application produced a significant increase (P<0.05) in gill and buccal frequency in tadpoles and frogs, respectively. SP caused a significant increase (P<0.05) in lung burst frequency at 5 μM in both groups. These results suggest that glutamatergic activation of AMPA/kainate receptors is necessary for generation of lung burst activity and that SP is an excitatory neurotransmitter for lung burst frequency generation. Both glutamate and SP provide excitatory input for lung burst generation throughout the aquatic to terrestrial developmental transition in bullfrogs. PMID:18450524

Role of glutamate and substance P in the amphibian respiratory network during development.

PubMed

Chen, Anna K; Hedrick, Michael S

2008-06-30

This study tested the hypothesis that glutamatergic ionotropic (AMPA/kainate) receptors and neurokinin receptors (NKR) are important in the regulation of respiratory motor output during development in the bullfrog. The roles of these receptors were studied with in vitro brainstem preparations from pre-metamorphic tadpoles and post-metamorphic frogs. Brainstems were superfused with an artificial cerebrospinal fluid at 20-22 degrees C containing CNQX, a selective non-NMDA antagonist, or with substance P (SP), an agonist of NKR. Blockade of glutamate receptors with CNQX in both groups caused a reduction of lung burst frequency that was reversibly abolished at 5 microM (P<0.01). CNQX, but not SP, application produced a significant increase (P<0.05) in gill and buccal frequency in tadpoles and frogs, respectively. SP caused a significant increase (P<0.05) in lung burst frequency at 5 microM in both groups. These results suggest that glutamatergic activation of AMPA/kainate receptors is necessary for generation of lung burst activity and that SP is an excitatory neurotransmitter for lung burst frequency generation. Both glutamate and SP provide excitatory input for lung burst generation throughout the aquatic to terrestrial developmental transition in bullfrogs.

Cardiorespiratory Coupling: Common Rhythms in Cardiac, Sympathetic, and Respiratory Activities

PubMed Central

Dick, Thomas E.; Hsieh, Yee-Hsee; Dhingra, Rishi R.; Baekey, David M.; Galán, Roberto F.; Wehrwein, Erica; Morris, Kendall F.

2014-01-01

Cardiorespiratory coupling is an encompassing term describing more than the well-recognized influences of respiration on heart rate and blood pressure. Our data indicate that cardiorespiratory coupling reflects a reciprocal interaction between autonomic and respiratory control systems, and the cardiovascular system modulates the ventilatory pattern as well. For example, cardioventilatory coupling refers to the influence of heart beats and arterial pulse pressure on respiration and is the tendency for the next inspiration to start at a preferred latency after the last heart beat in expiration. Multiple complementary, well-described mechanisms mediate respiration’s influence on cardiovascular function, whereas mechanisms mediating the cardiovascular system’s influence on respiration may only be through the baroreceptors but are just being identified. Our review will describe a differential effect of conditioning rats with either chronic intermittent or sustained hypoxia on sympathetic nerve activity but also on ventilatory pattern variability. Both intermittent and sustained hypoxia increase sympathetic nerve activity after 2 weeks but affect sympatho-respiratory coupling differentially. Intermittent hypoxia enhances sympatho-respiratory coupling, which is associated with low variability in the ventilatory pattern. In contrast, after constant hypobaric hypoxia, 1-to-1 coupling between bursts of sympathetic and phrenic nerve activity is replaced by 2-to-3 coupling. This change in coupling pattern is associated with increased variability of the ventilatory pattern. After baro-denervating hypobaric hypoxic-conditioned rats, splanchnic sympathetic nerve activity becomes tonic (distinct bursts are absent) with decreases during phrenic nerve bursts and ventilatory pattern becomes regular. Thus, conditioning rats to either intermittent or sustained hypoxia accentuates the reciprocal nature of cardiorespiratory coupling. Finally, identifying a compelling physiologic

NADPH oxidase inhibitors: a patent review.

PubMed

Kim, Jung-Ae; Neupane, Ganesh Prasad; Lee, Eung Seok; Jeong, Byeong-Seon; Park, Byung Chul; Thapa, Pritam

2011-08-01

NADPH oxidases, a family of multi-subunit enzyme complexes, catalyze the production of reactive oxygen species (ROS), which may contribute to the pathogenesis of a variety of diseases. In addition to the first NADPH oxidase found in phagocytes, four non-phagocytic NADPH oxidase isoforms have been identified, which all differ in their catalytic subunit (Nox1-5) and tissue distribution. This paper provides a comprehensive review of the patent literature on NADPH oxidase inhibitors, small molecule Nox inhibitors, peptides and siRNAs. Since each member of the NADPH oxidase family has great potential as a therapeutic target, several different compounds have been registered as NADPH oxidase inhibitors in the patent literature. As yet, none have gone through clinical trials, and some have not completed preclinical trials, including safety and specificity evaluation. Recently, small molecule pyrazolopyridine and triazolopyrimidine derivatives have been submitted as potent NADPH oxidase inhibitors and reported as first-in-class inhibitors for idiopathic pulmonary fibrosis and acute stroke, respectively. Further clinical efficacy and safety data are warranted to prove their actual clinical utility.

Diet supplementation of Pediococcus pentosaceus in cobia (Rachycentron canadum) enhances growth rate, respiratory burst and resistance against photobacteriosis.

PubMed

Xing, Chen-Fu; Hu, Hung-Hsi; Huang, Jian-Bin; Fang, Han-Chun; Kai, Yu-Hsuan; Wu, Yu-Chi; Chi, Shau-Chi

2013-10-01

Cobia (Rachycentron canadum) is an economically important fish species for aquaculture in tropical and sub-tropical areas. Cobia aquaculture industry has severely damaged due to photobacteriosis caused by Photobacterium damselae subsp. piscicida (Pdp), especially in Taiwan. Antibiotics and vaccines have been applied to control Pdp infection, but the efficacy has been inconsistent. One species of lactic acid bacteria, Pediococcus pentosaceus strain 4012 (LAB 4012), was isolated from the intestine of adult cobia, and its culture supernatant can effectively inhibit Pdp growth in vitro. The acidic pH derived from metabolic acids in LAB culture supernatant was demonstrated to be an important factor for the suppression. After a 2-week feeding of LAB 4012, the growth rate of the fed cobia was 12% higher than that of the non-fed group, and the relative percentage of survival (RPS) of the fed cobia was found to be 74.4 in Pdp immersion challenge. In addition, the respiratory burst (RB) of peripheral blood leukocytes (PBL) in the LAB 4012-fed group was significantly higher than that of the non-fed group. Although feeding LAB 4012 did not improve specific antibody response in cobia after immunization with Pdp vaccine, it still significantly raised the survival rate by 22% over that of the non-fed group after Pdp immersion challenge. Judging by the quick induction of high protection against Pdp infection and promotion of growth in larvae, LAB 4012 was considered to be a viable probiotic for cobia aquaculture. Copyright © 2013 Elsevier Ltd. All rights reserved.

Generation of proton-motive force by an archaeal terminal quinol oxidase from Sulfolobus acidocaldarius.

PubMed

Gleissner, M; Elferink, M G; Driessen, A J; Konings, W N; Anemüller, S; Schäfer, G

1994-09-15

The terminal quinol oxidase of the cytochrome aa3 type was isolated from the extreme thermoacidophilic archaeon Sulfolobus acidocaldarius. In micellar solution, the enzyme oxidized various quinols and exerted the highest activity with the physiological substrate caldariella quinol. The enzyme was functionally reconstituted into monolayer liposomes composed of archaeal tetraether lipids also derived from S. acidocaldarius. With the electron donor system ascorbate and N,N,N',N'-tetramethyl-p-phenylenediamine, the reconstituted enzyme was more active in the archaeal lipids as compared to lipids derived from Escherichia coli at temperatures above 50 degrees C. Due to the low proton permeability of the tetraether lipids, it was possible to generate a steady-state transmembrane electrical potential (delta psi, interior negative), and transmembrane pH gradient (delta pH, interior alkaline) at temperatures up to 70 degrees C. The successful functional reconstitution of the cytochrome aa3-type quinol oxidase from Sulfolobus identifies it as the key energy converter in the respiratory system of this hyperthermophilic archaeon.

Prolonged dark period modulates the oxidative burst and enzymatic antioxidant systems in the leaves of salicylic acid-treated tomato.

PubMed

Poór, Péter; Takács, Zoltán; Bela, Krisztina; Czékus, Zalán; Szalai, Gabriella; Tari, Irma

2017-06-01

Salicylic acid (SA) is an important plant growth regulator playing a role in the hypersensitive reaction (HR) and the induction of systemic acquired resistance. Since the SA-mediated signalling pathways and the formation of reactive oxygen species (ROS) are light-dependent, the time- and concentration-specific induction of oxidative stress was investigated in leaves of tomato plants kept under light and dark conditions after treatments with 0.1mM and 1mM SA. The application of exogenous SA induced early superoxide- and H 2 O 2 production in the leaves, which was different in the absence or presence of light and showed time- and concentration-dependent changes. 1mM SA, which induced HR-like cell death resulted in two peaks in the H 2 O 2 production in the light but the first, priming peak was not detected in the dark. Unlike 0.1mM SA, 1mM SA application induced NADPH oxidase activity leading to increased superoxide production in the first hours of SA treatments in the light. Moreover, SA treatments inhibited catalase (CAT) activity and caused a transient decline in ascorbate peroxidase (APX), the two main enzymes responsible for H 2 O 2 degradation, which led to a fast H 2 O 2 burst in the light. Their activity as well as the expression of some isoenzymes of SOD and APX increased only from the 12th h in the illuminated samples. The activity of NADPH oxidase and expression SlRBOH1 gene encoding a NADPH oxidase subunit was much lower in the dark. In spite of low CAT and APX activity after SA treatments in the dark, the activation of guaiacol-dependent peroxidase (POD) could partially substitute H 2 O 2 scavenging activity of these enzymes in the dark, which reduced the ROS burst and development of lesion formation in the leaves. Copyright © 2017 Elsevier GmbH. All rights reserved.

Heterogeneity in Short Gamma-Ray Bursts

NASA Astrophysics Data System (ADS)

Norris, Jay P.; Gehrels, Neil; Scargle, Jeffrey D.

2011-07-01

We analyze the Swift/BAT sample of short gamma-ray bursts, using an objective Bayesian Block procedure to extract temporal descriptors of the bursts' initial pulse complexes (IPCs). The sample is comprised of 12 and 41 bursts with and without extended emission (EE) components, respectively. IPCs of non-EE bursts are dominated by single pulse structures, while EE bursts tend to have two or more pulse structures. The medians of characteristic timescales—durations, pulse structure widths, and peak intervals—for EE bursts are factors of ~2-3 longer than for non-EE bursts. A trend previously reported by Hakkila and colleagues unifying long and short bursts—the anti-correlation of pulse intensity and width—continues in the two short burst groups, with non-EE bursts extending to more intense, narrower pulses. In addition, we find that preceding and succeeding pulse intensities are anti-correlated with pulse interval. We also examine the short burst X-ray afterglows as observed by the Swift/X-Ray Telescope (XRT). The median flux of the initial XRT detections for EE bursts (~6×10-10 erg cm-2 s-1) is gsim20× brighter than for non-EE bursts, and the median X-ray afterglow duration for EE bursts (~60,000 s) is ~30× longer than for non-EE bursts. The tendency for EE bursts toward longer prompt-emission timescales and higher initial X-ray afterglow fluxes implies larger energy injections powering the afterglows. The longer-lasting X-ray afterglows of EE bursts may suggest that a significant fraction explode into denser environments than non-EE bursts, or that the sometimes-dominant EE component efficiently powers the afterglow. Combined, these results favor different progenitors for EE and non-EE short bursts.

The Effects of Lidocaine on Central Respiratory Neuron Activity and Nociceptive-Related Responses in the Brainstem-Spinal Cord Preparation of the Newborn Rat.

PubMed

Shakuo, Tomoharu; Lin, Shih-Tien; Onimaru, Hiroshi

2016-05-01

Lidocaine is widely used in the clinical setting as a local anesthetic and antiarrhythmic drug. Although it has been suggested that lidocaine exerts inhibitory effects on the central and peripheral neurons, there are no reports on its effects on central respiratory activity in vertebrates. In this study, we examined the effects of lidocaine on respiratory rhythm generation and nociceptive response in brainstem-spinal cord preparations from the newborn rats. Preparations were isolated from Wistar rats (postnatal day 0-3) and superfused with artificial cerebrospinal fluid equilibrated with 95% O2 and 5% CO2, pH 7.4, at 25°C to 26°C. We examined the effects of lidocaine on the fourth cervical ventral root (C4)-inspiratory activity and on the preinspiratory and inspiratory neurons in the rostral medulla. We also examined the effects on the C4/C5 reflex responses induced by ipsilateral C7/C8 dorsal root stimulation, which are thought to be related to the nociceptive response. The application of low doses of lidocaine (10-20 μM) resulted in a slight increase of the C4 burst rate, whereas high doses of lidocaine (100-400 μM) decreased the burst rate in a dose-dependent manner, eventually resulting in the complete cessation of respiratory rhythm. High doses of lidocaine decreased the burst duration and negative slope conductance of preinspiratory neurons, suggesting that lidocaine blocked persistent Na+ current. After the burst generation of the respiratory neurons ceased, depolarizing current stimulation continued to induce action potentials; however, the induction of the spike train was depressed because of strong adaptation. A low dose of lidocaine (20 μM) depressed C4/C5 spinal reflex responses. Our findings indicate that lidocaine depressed nociception-related responses at lower concentrations than those that induced respiratory depression. Our report provides the basic neuronal mechanisms to support the clinical use of lidocaine, which shows antinociceptive

A search for optical bursts from the repeating fast radio burst FRB 121102

NASA Astrophysics Data System (ADS)

Hardy, L. K.; Dhillon, V. S.; Spitler, L. G.; Littlefair, S. P.; Ashley, R. P.; De Cia, A.; Green, M. J.; Jaroenjittichai, P.; Keane, E. F.; Kerry, P.; Kramer, M.; Malesani, D.; Marsh, T. R.; Parsons, S. G.; Possenti, A.; Rattanasoon, S.; Sahman, D. I.

2017-12-01

We present a search for optical bursts from the repeating fast radio burst FRB 121102 using simultaneous observations with the high-speed optical camera ULTRASPEC on the 2.4-m Thai National Telescope and radio observations with the 100-m Effelsberg Radio Telescope. A total of 13 radio bursts were detected, but we found no evidence for corresponding optical bursts in our 70.7-ms frames. The 5σ upper limit to the optical flux density during our observations is 0.33 mJy at 767 nm. This gives an upper limit for the optical burst fluence of 0.046 Jy ms, which constrains the broad-band spectral index of the burst emission to α ≤ -0.2. Two of the radio pulses are separated by just 34 ms, which may represent an upper limit on a possible underlying periodicity (a rotation period typical of pulsars), or these pulses may have come from a single emission window that is a small fraction of a possible period.

On vortex bursting

NASA Technical Reports Server (NTRS)

Werle, H.

1984-01-01

Vortex bursting is studied by means of visualization. The physical behavior of the phenomenon is emphasized, and its similarity with boundary layer separation or wake bursting becomes apparent. The essential influence of an increasing pressure gradient on the initiation, the position and the type of bursting is clearly confirmed. The evolution of the phenomena as a function of several parameters is analyzed in the case of delta wings, alone or installed on aircraft models, and compared with the results of similar wind tunnel or flight tests.

Gamma-ray burst models.

PubMed

King, Andrew

2007-05-15

I consider various possibilities for making gamma-ray bursts, particularly from close binaries. In addition to the much-studied neutron star+neutron star and black hole+neutron star cases usually considered good candidates for short-duration bursts, there are also other possibilities. In particular, neutron star+massive white dwarf has several desirable features. These systems are likely to produce long-duration gamma-ray bursts (GRBs), in some cases definitely without an accompanying supernova, as observed recently. This class of burst would have a strong correlation with star formation and occur close to the host galaxy. However, rare members of the class need not be near star-forming regions and could have any type of host galaxy. Thus, a long-duration burst far from any star-forming region would also be a signature of this class. Estimates based on the existence of a known progenitor suggest that this type of GRB may be quite common, in agreement with the fact that the absence of a supernova can only be established in nearby bursts.

Effects of heat stress on respiratory burst, oxidative damage and SERPINH1 (HSP47) mRNA expression in rainbow trout Oncorhynchus mykiss.

PubMed

Wang, Yanni; Liu, Zhe; Li, Zhen; Shi, Haina; Kang, Yujun; Wang, Jianfu; Huang, Jinqiang; Jiang, Li

2016-04-01

For rainbow trout Oncorhynchus mykiss, high temperature is a major abiotic stress that limits its growth and productivity. In this study, spleen macrophage respiratory burst (RB), serum superoxide dismutase (SOD), serum malondialdehyde (MDA) and mRNA expression of the SERPINH1 (HSP47) gene in different tissues (liver, spleen, head kidney and heart) were measured in unstressed (18 °C) and heat-stressed (25 °C) fish. Spleen macrophage RB activity, serum SOD activity and MDA content all increased significantly (P < 0.05) during heat shock, and peaked at 8, 12 and 4 h, respectively. SERPINH1 mRNA expression responded in a time- and tissue-specific manner to heat stress, which was mainly reflected in the significant up-regulation in all tissues (P < 0.05) and greater expression in the liver than the other tissues (P < 0.05). During the heat-shock recovery period, the MDA content returned to the unstressed level. These results indicate that heat shock causes cell injury, induces oxidative damage and promotes SERPINH1 mRNA expression, which plays an important protective function during heat stress in O. mykiss. In practice, close attention should be given to temperature changes in O. mykiss production to reduce the effects of high temperature.

Targeting NADPH oxidases in vascular pharmacology

PubMed Central

Schramm, Agata; Matusik, Paweł; Osmenda, Grzegorz; Guzik, Tomasz J

2012-01-01

Oxidative stress is a molecular dysregulation in reactive oxygen species (ROS) metabolism, which plays a key role in the pathogenesis of atherosclerosis, vascular inflammation and endothelial dysfunction. It is characterized by a loss of nitric oxide (NO) bioavailability. Large clinical trials such as HOPE and HPS have not shown a clinical benefit of antioxidant vitamin C or vitamin E treatment, putting into question the role of oxidative stress in cardiovascular disease. A change in the understanding of the molecular nature of oxidative stress has been driven by the results of these trials. Oxidative stress is no longer perceived as a simple imbalance between the production and scavenging of ROS, but as a dysfunction of enzymes involved in ROS production. NADPH oxidases are at the center of these events, underlying the dysfunction of other oxidases including eNOS uncoupling, xanthine oxidase and mitochondrial dysfunction. Thus NADPH oxidases are important therapeutic targets. Indeed, HMG-CoA reductase inhibitors (statins) as well as drugs interfering with the renin-angiotensin-aldosterone system inhibit NADPH oxidase activation and expression. Angiotensin-converting enzyme (ACE) inhibitors, AT1 receptor antagonists (sartans) and aliskiren, as well as spironolactone or eplerenone, have been discussed. Molecular aspects of NADPH oxidase regulation must be considered, while thinking about novel pharmacological targeting of this family of enzymes consisting of several homologs Nox1, Nox2, Nox3, Nox4 and Nox5 in humans. In order to properly design trials of antioxidant therapies, we must develop reliable techniques for the assessment of local and systemic oxidative stress. Classical antioxidants could be combined with novel oxidase inhibitors. In this review, we discuss NADPH oxidase inhibitors such as VAS2870, VAS3947, GK-136901, S17834 or plumbagin. Therefore, our efforts must focus on generating small molecular weight inhibitors of NADPH oxidases, allowing the

Solar microwave bursts - A review

NASA Technical Reports Server (NTRS)

Kundu, M. R.; Vlahos, L.

1982-01-01

Observational and theoretical results on the physics of microwave bursts that occur in the solar atmosphere are reviewed. Special attention is given to the advances made in burst physics over the last few years with the great improvement in spatial and time resolution, especially with instruments like the NRAO three-element interferometer, the Westerbork Synthesis Radio Telescope, and more recently the Very Large Array. Observations made on the preflare build-up of an active region at centimeter wavelengths are reviewed. Three distinct phases in the evolution of cm bursts, namely the impulsive phase, the post-burst phase, and the gradual rise and fall, are discussed. Attention is also given to the flux density spectra of centimeter bursts. Descriptions are given of observations of fine structures with temporal resolution of 10-100 ms in the intensity profiles of cm-wavelength bursts. High spatial resolution observations are analyzed, with special reference to the one- and two-dimensional maps of cm burst sources.

Do gamma-ray burst sources repeat?

NASA Technical Reports Server (NTRS)

Meegan, C. A.; Hartmann, D. H.; Brainerd, J. J.; Briggs, M.; Paciesas, W. S.; Pendleton, G.; Kouveliotou, C.; Fishman, G.; Blumenthal, G.; Brock, M.

1994-01-01

The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al. 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic ad the two-point angular correlation function. We find the data to be consistent with the hypothesis that burst sources do not repeat; however, a repeater fraction of up to about 20% of the bursts cannot be excluded.

Solar Radio Bursts and Space Weather

NASA Technical Reports Server (NTRS)

Gopalswamy, Natchimuthuk,

2012-01-01

Radio bursts from the Sun are produced by electron accelerated to relativistic energies by physical processes on the Sun such as solar flares and coronal mass ejections (CMEs). The radio bursts are thus good indicators of solar eruptions. Three types of nonthermal radio bursts are generally associated with CMEs. Type III bursts due to accelerated electrons propagating along open magnetic field lines. The electrons are thought to be accelerated at the reconnection region beneath the erupting CME, although there is another view that the electrons may be accelerated at the CME-driven shock. Type II bursts are due to electrons accelerated at the shock front. Type II bursts are also excellent indicators of solar energetic particle (SEP) events because the same shock is supposed accelerate electrons and ions. There is a hierarchical relationship between the wavelength range of type /I bursts and the CME kinetic energy. Finally, Type IV bursts are due to electrons trapped in moving or stationary structures. The low frequency stationary type IV bursts are observed occasionally in association with very fast CMEs. These bursts originate from flare loops behind the erupting CME and hence indicate tall loops. This paper presents a summary of radio bursts and their relation to CMEs and how they can be useful for space weather predictions.

Glucose Modulates Respiratory Complex I Activity in Response to Acute Mitochondrial Dysfunction

PubMed Central

Cannino, Giuseppe; El-Khoury, Riyad; Pirinen, Marja; Hutz, Bettina; Rustin, Pierre; Jacobs, Howard T.; Dufour, Eric

2012-01-01

Proper coordination between glycolysis and respiration is essential, yet the regulatory mechanisms involved in sensing respiratory chain defects and modifying mitochondrial functions accordingly are unclear. To investigate the nature of this regulation, we introduced respiratory bypass enzymes into cultured human (HEK293T) cells and studied mitochondrial responses to respiratory chain inhibition. In the absence of respiratory chain inhibitors, the expression of alternative respiratory enzymes did not detectably alter cell physiology or mitochondrial function. However, in permeabilized cells NDI1 (alternative NADH dehydrogenase) bypassed complex I inhibition, whereas alternative oxidase (AOX) bypassed complex III or IV inhibition. In contrast, in intact cells the effects of the AOX bypass were suppressed by growth on glucose, whereas those produced by NDI1 were unaffected. Moreover, NDI1 abolished the glucose suppression of AOX-driven respiration, implicating complex I as the target of this regulation. Rapid Complex I down-regulation was partly released upon prolonged respiratory inhibition, suggesting that it provides an “emergency shutdown” system to regulate metabolism in response to dysfunctions of the oxidative phosphorylation. This system was independent of HIF1, mitochondrial superoxide, or ATP synthase regulation. Our findings reveal a novel pathway for adaptation to mitochondrial dysfunction and could provide new opportunities for combatting diseases. PMID:23007390

Do gamma-ray burst sources repeat?

NASA Technical Reports Server (NTRS)

Meegan, Charles A.; Hartmann, Dieter H.; Brainerd, J. J.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey; Kouveliotou, Chryssa; Fishman, Gerald; Blumenthal, George; Brock, Martin

1995-01-01

The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports (Quashnock and Lamb, 1993; Wang and Lingenfelter, 1993) of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al., 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic and the two-point angular correlation function. We find the data to be consistent with the hypothesis that burst sources do not repeat; however, a repeater fraction of up to about 20% of the observed bursts cannot be excluded.

Pathophysiology and Treatments of Oxidative Injury in Ischemic Stroke: Focus on the Phagocytic NADPH Oxidase 2

PubMed Central

Carbone, Federico; Teixeira, Priscila Camillo; Braunersreuther, Vincent; Mach, François; Vuilleumier, Nicolas

2015-01-01

Abstract Significance: Phagocytes play a key role in promoting the oxidative stress after ischemic stroke occurrence. The phagocytic NADPH oxidase (NOX) 2 is a membrane-bound enzyme complex involved in the antimicrobial respiratory burst and free radical production in these cells. Recent Advances: Different oxidants have been shown to induce opposite effects on neuronal homeostasis after a stroke. However, several experimental models support the detrimental effects of NOX activity (especially the phagocytic isoform) on brain recovery after stroke. Therapeutic strategies selectively targeting the neurotoxic ROS and increasing neuroprotective oxidants have recently produced promising results. Critical Issues: NOX2 might promote carotid plaque rupture and stroke occurrence. In addition, NOX2-derived reactive oxygen species (ROS) released by resident and recruited phagocytes enhance cerebral ischemic injury, activating the inflammatory apoptotic pathways. The aim of this review is to update evidence on phagocyte-related oxidative stress, focusing on the role of NOX2 as a potential therapeutic target to reduce ROS-related cerebral injury after stroke. Future Directions: Radical scavenger compounds (such as Ebselen and Edaravone) are under clinical investigation as a therapeutic approach against stroke. On the other hand, NOX inhibition might represent a promising strategy to prevent the stroke-related injury. Although selective NOX inhibitors are not yet available, nonselective compounds (such as apocynin and fasudil) provided encouraging results in preclinical studies. Whereas additional studies are needed to better evaluate this therapeutic potential in human beings, the development of specific NOX inhibitors (such as monoclonal antibodies, small-molecule inhibitors, or aptamers) might further improve brain recovery after stroke. Antioxid. Redox Signal. 23, 460–489. PMID:24635113

Chemoheterotrophic Growth of the Cyanobacterium Anabaena sp. Strain PCC 7120 Dependent on a Functional Cytochrome c Oxidase

PubMed Central

Stebegg, Ronald; Wurzinger, Bernhard; Mikulic, Markus

2012-01-01

Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium commonly used as a model organism for studying cyanobacterial cell differentiation and nitrogen fixation. For many decades, this cyanobacterium was considered an obligate photo-lithoautotroph. We now discovered that this strain is also capable of mixotrophic, photo-organoheterotrophic, and chemo-organoheterotrophic growth if high concentrations of fructose (at least 50 mM and up to 200 mM) are supplied. Glucose, a substrate used by some facultatively organoheterotrophic cyanobacteria, is not effective in Anabaena sp. PCC 7120. The gtr gene from Synechocystis sp. PCC 6803 encoding a glucose carrier was introduced into Anabaena sp. PCC 7120. Surprisingly, the new strain containing the gtr gene did not grow on glucose but was very sensitive to glucose, with a 5 mM concentration being lethal, whereas the wild-type strain tolerated 200 mM glucose. The Anabaena sp. PCC 7120 strain containing gtr can grow mixotrophically and photo-organoheterotrophically, but not chemo-organoheterotrophically with fructose. Anabaena sp. PCC 7120 contains five respiratory chains ending in five different respiratory terminal oxidases. One of these enzymes is a mitochondrial-type cytochrome c oxidase. As in almost all cyanobacteria, this enzyme is encoded by three adjacent genes called coxBAC1. When this locus was disrupted, the cells lost the capability for chemo-organoheterotrophic growth. PMID:22730128

Optothermally actuated capillary burst valve

NASA Astrophysics Data System (ADS)

Eriksen, Johan; Bilenberg, Brian; Kristensen, Anders; Marie, Rodolphe

2017-04-01

We demonstrate the optothermal actuation of individual capillary burst valves in an all-polymer microfluidic device. The capillary burst valves are realised in a planar design by introducing a fluidic constriction in a microfluidic channel of constant depth. We show that a capillary burst valve can be burst by raising the temperature due to the temperature dependence of the fluid surface tension. We address individual valves by using a local heating platform based on a thin film of near infrared absorber dye embedded in the lid used to seal the microfluidic device [L. H. Thamdrup et al., Nano Lett. 10, 826-832 (2010)]. An individual valve is burst by focusing the laser in its vicinity. We demonstrate the capture of single polystyrene 7 μm beads in the constriction triggered by the bursting of the valve.

Cosmological gamma-ray bursts

NASA Technical Reports Server (NTRS)

Paczynski, Bohdan

1991-01-01

The distribution in angle and flux of gamma-ray bursts indicates that the majority of gamma-ray bursters are at cosmological distances, i.e., at z of about 1. The rate is then about 10 exp -8/yr in a galaxy like the Milky Way, i.e., orders of magnitude lower than the estimated rate for collisions between neutron stars in close binary systems. The energy per burst is about 10 exp 51 ergs, assuming isotropic emission. The events appear to be less energetic and more frequent if their emission is strongly beamed. Some tests for the distance scale are discussed: a correlation between the burst's strength and its spectrum; the absorption by the Galactic gas below about 2 keV; the X-ray tails caused by forward scattering by the Galactic dust; about 1 month recurrence of some bursts caused by gravitational lensing by foreground galaxies; and a search for gamma-ray bursts in M31. The bursts appear to be a manifestation of something exotic, but conventional compact objects can provide an explanation. The best possibility is offered by a decay of a bindary composed of a spinning-stellar-mass black-hole primary and a neutron or a strange-quark star secondary. In the final phase the secondary is tidally disrupted, forms an accretion disk, and up to 10 exp 54 ergs are released. A very small fraction of this energy powers the gamma-ray burst.

Presynaptic modulation of tonic and respiratory inputs to cardiovagal motoneurons by substance P.

PubMed

Hou, Lili; Tang, Hongtai; Chen, Yonghua; Wang, Lin; Zhou, Xujiao; Rong, Weifang; Wang, Jijiang

2009-08-11

Substance P (SP) has been implicated in vagal control of heart rate and cardiac functions, but the mechanisms of SP actions on cardiac vagal activity remain obscure. The present study has investigated the effects of SP on the synaptic inputs of preganglionic cardiovagal motoneurons (CVNs) in brainstem slices of neonatal rat. Whole-cell voltage-clamp recordings were performed on retrogradely labeled CVNs in the nucleus ambiguus. The results show that in thin slices (400 microm thickness) without respiratory-like rhythm, globally applied SP (1 microM) significantly enhanced both the GABAergic and the glycinergic inputs, but had no effect on the glutamatergic inputs, of CVNs. Since inspiratory-related augmentation of the inhibitory inputs of CVNs in individual respiratory cycles is known to play an important role in the genesis of respiratory sinus arrhythmia, the effects of SP on the inhibitory inputs of CVNs were further examined in thick slices (500-800 microm thickness) with respiratory-like rhythm, and SP (1 microM) was focally applied to the CVNs under patch-clamp recording. Focally applied SP caused frequency increases of the GABAergic and the glycinergic inputs both during inspiratory bursts and during inspiratory intervals. However, the inspiratory-related augmentation of the GABAergic and the glycinergic inputs of CVNs, measured by the frequency increases during inspiratory bursts in percentage of the frequency during inspiratory intervals, was significantly decreased by SP. These results suggest that SP inhibits CVNs via enhancement of their inhibitory synaptic inputs, and SP diminishes the respiratory-related fluctuation of cardiac vagal activity in individual respiratory cycles. These results also indicate that SP may play a role in altering the vagal control of the heart in some cardiovascular diseases such as myocardial ischemia and hypertension, since these diseases are characterized by weakened cardiac vagal tone and heart rate variability, and have

NADPH Oxidases in Vascular Pathology

PubMed Central

Konior, Anna; Schramm, Agata; Czesnikiewicz-Guzik, Marta

2014-01-01

Abstract Significance: Reactive oxygen species (ROS) play a critical role in vascular disease. While there are many possible sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases play a central role. They are a source of “kindling radicals,” which affect other enzymes, such as nitric oxide synthase endothelial nitric oxide synthase or xanthine oxidase. This is important, as risk factors for atherosclerosis (hypertension, diabetes, hypercholesterolemia, and smoking) regulate the expression and activity of NADPH oxidases in the vessel wall. Recent Advances: There are seven isoforms in mammals: Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2. Nox1, Nox2, Nox4, and Nox5 are expressed in endothelium, vascular smooth muscle cells, fibroblasts, or perivascular adipocytes. Other homologues have not been found or are expressed at very low levels; their roles have not been established. Nox1/Nox2 promote the development of endothelial dysfunction, hypertension, and inflammation. Nox4 may have a role in protecting the vasculature during stress; however, when its activity is increased, it may be detrimental. Calcium-dependent Nox5 has been implicated in oxidative damage in human atherosclerosis. Critical Issues: NADPH oxidase-derived ROS play a role in vascular pathology as well as in the maintenance of normal physiological vascular function. We also discuss recently elucidated mechanisms such as the role of NADPH oxidases in vascular protection, vascular inflammation, pulmonary hypertension, tumor angiogenesis, and central nervous system regulation of vascular function and hypertension. Future Directions: Understanding the role of individual oxidases and interactions between homologues in vascular disease is critical for efficient pharmacological regulation of vascular NADPH oxidases in both the laboratory and clinical practice. Antioxid. Redox Signal. 20, 2794–2814. PMID:24180474

Complex transitions between spike, burst or chaos synchronization states in coupled neurons with coexisting bursting patterns

NASA Astrophysics Data System (ADS)

Gu, Hua-Guang; Chen, Sheng-Gen; Li, Yu-Ye

2015-05-01

We investigated the synchronization dynamics of a coupled neuronal system composed of two identical Chay model neurons. The Chay model showed coexisting period-1 and period-2 bursting patterns as a parameter and initial values are varied. We simulated multiple periodic and chaotic bursting patterns with non-(NS), burst phase (BS), spike phase (SS), complete (CS), and lag synchronization states. When the coexisting behavior is near period-2 bursting, the transitions of synchronization states of the coupled system follows very complex transitions that begins with transitions between BS and SS, moves to transitions between CS and SS, and to CS. Most initial values lead to the CS state of period-2 bursting while only a few lead to the CS state of period-1 bursting. When the coexisting behavior is near period-1 bursting, the transitions begin with NS, move to transitions between SS and BS, to transitions between SS and CS, and then to CS. Most initial values lead to the CS state of period-1 bursting but a few lead to the CS state of period-2 bursting. The BS was identified as chaos synchronization. The patterns for NS and transitions between BS and SS are insensitive to initial values. The patterns for transitions between CS and SS and the CS state are sensitive to them. The number of spikes per burst of non-CS bursting increases with increasing coupling strength. These results not only reveal the initial value- and parameter-dependent synchronization transitions of coupled systems with coexisting behaviors, but also facilitate interpretation of various bursting patterns and synchronization transitions generated in the nervous system with weak coupling strength. Project supported by the National Natural Science Foundation of China (Grant Nos. 11372224 and 11402039) and the Fundamental Research Funds for Central Universities designated to Tongji University (Grant No. 1330219127).

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist

PubMed Central

Mifflin, Steve W.

2017-01-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N-methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO2/pH chemosensitivity. PMID:28202437

Observations of short gamma-ray bursts.

PubMed

Fox, Derek B; Roming, Peter W A

2007-05-15

We review recent observations of short-hard gamma-ray bursts and their afterglows. The launch and successful ongoing operations of the Swift satellite, along with several localizations from the High-Energy Transient Explorer mission, have provoked a revolution in short-burst studies: first, by quickly providing high-quality positions to observers; and second, via rapid and sustained observations from the Swift satellite itself. We make a complete accounting of Swift-era short-burst localizations and proposed host galaxies, and discuss the implications of these observations for the distances, energetics and environments of short bursts, and the nature of their progenitors. We then review the physical modelling of short-burst afterglows: while the simplest afterglow models are inadequate to explain the observations, there have been several notable successes. Finally, we address the case of an unusual burst that threatens to upset the simple picture in which long bursts are due to the deaths of massive stars, and short bursts to compact-object merger events.

Two NADPH oxidase isoforms are required for sexual reproduction and ascospore germination in the filamentous fungus Podospora anserina.

PubMed

Malagnac, Fabienne; Lalucque, Hervé; Lepère, Gersende; Silar, Philippe

2004-11-01

NADPH oxidases are enzymes that produce reactive oxygen species (ROS) using electrons derived from intracellular NADPH. In plants and mammals, ROS have been proposed to be second messengers that signal defence responses or cell proliferation. By inactivating PaNox1 and PaNox2, two genes encoding NADPH oxidases, we demonstrate the crucial role of these enzymes in the control of two key steps of the filamentous fungus Podospora anserina life cycle. PaNox1 mutants are impaired in the differentiation of fruiting bodies from their progenitor cells, and the deletion of the PaNox2 gene specifically blocks ascospore germination. Furthermore, we show that PaNox1 likely acts upstream of PaASK1, a MAPKKK previously implicated in stationary phase differentiation and cell degeneration. Using nitro blue tetrazolium (NBT) and diaminobenzidine (DAB) assays, we detect a regulated secretion of both superoxide and peroxide during P. anserina vegetative growth. In addition, two oxidative bursts are shown to occur during fruiting body development and ascospore germination. Analysis of mutants establishes that PaNox1, PaNox2, and PaASK1, as well as a still unknown additional source of ROS, modulate these secretions. Altogether, our data point toward a role for NADPH oxidases in signalling fungal developmental transitions with respect to nutrient availability. These enzymes are conserved in other multicellular eukaryotes, suggesting that early eukaryotes were endowed with a redox network used for signalling purposes.

X-ray bursts: Observation versus theory

NASA Technical Reports Server (NTRS)

Lewin, W. H. G.

1981-01-01

Results of various observations of common type I X-ray bursts are discussed with respect to the theory of thermonuclear flashes in the surface layers of accreting neutron stars. Topics covered include burst profiles; irregular burst intervals; rise and decay times and the role of hydrogen; the accuracy of source distances; accuracy in radii determination; radius increase early in the burst; the super Eddington limit; temperatures at burst maximum; and the role of the magnetic field.

Search for optical bursts from the gamma ray burst source GBS 0526-66

NASA Astrophysics Data System (ADS)

Seetha, S.; Sreenivasaiah, K. V.; Marar, T. M. K.; Kasturirangan, K.; Rao, U. R.; Bhattacharyya, J. C.

1985-08-01

Attempts were made to detect optical bursts from the gamma-ray burst source GBS 0526-66 during Dec. 31, 1984 to Jan. 2, 1985 and Feb. 23 to Feb. 24, 1985, using the one meter reflector of the Kavalur Observatory. Jan. 1, 1985 coincided with the zero phase of the predicted 164 day period of burst activity from the source (Rothschild and Lingenfelter, 1984). A new optical burst photon counting system with adjustable trigger threshold was used in parallel with a high speed photometer for the observations. The best time resolution was 1 ms and maximum count rate capability was 255,000 counts s(-1). Details of the instrumentation and observational results are presented.

Immunolocalization of an alternative respiratory chain in Antonospora (Paranosema) locustae spores: mitosomes retain their role in microsporidial energy metabolism.

PubMed

Dolgikh, Viacheslav V; Senderskiy, Igor V; Pavlova, Olga A; Naumov, Anton M; Beznoussenko, Galina V

2011-04-01

Microsporidia are a group of fungus-related intracellular parasites with severely reduced metabolic machinery. They lack canonical mitochondria, a Krebs cycle, and a respiratory chain but possess genes encoding glycolysis enzymes, a glycerol phosphate shuttle, and ATP/ADP carriers to import host ATP. The recent finding of alternative oxidase genes in two clades suggests that microsporidial mitosomes may retain an alternative respiratory pathway. We expressed the fragments of mitochondrial chaperone Hsp70 (mitHsp70), mitochondrial glycerol-3-phosphate dehydrogenase (mitG3PDH), and alternative oxidase (AOX) from the microsporidium Antonospora (Paranosema) locustae in Escherichia coli. Immunoblotting with antibodies against recombinant polypeptides demonstrated specific accumulation of both metabolic enzymes in A. locustae spores. At the same time comparable amounts of mitochondrial Hsp70 were found in spores and in stages of intracellular development as well. Immunoelectron microscopy of ultrathin cryosections of spores confirmed mitosomal localization of the studied proteins. Small amounts of enzymes of an alternative respiratory chain in merogonial and early sporogonial stages, alongside their accumulation in mature spores, suggest conspicuous changes in components and functions of mitosomes during the life cycle of microsporidia and the important role of these organelles in parasite energy metabolism, at least at the final stages of sporogenesis.

Secured Hash Based Burst Header Authentication Design for Optical Burst Switched Networks

NASA Astrophysics Data System (ADS)

Balamurugan, A. M.; Sivasubramanian, A.; Parvathavarthini, B.

2017-12-01

The optical burst switching (OBS) is a promising technology that could meet the fast growing network demand. They are featured with the ability to meet the bandwidth requirement of applications that demand intensive bandwidth. OBS proves to be a satisfactory technology to tackle the huge bandwidth constraints, but suffers from security vulnerabilities. The objective of this proposed work is to design a faster and efficient burst header authentication algorithm for core nodes. There are two important key features in this work, viz., header encryption and authentication. Since the burst header is an important in optical burst switched network, it has to be encrypted; otherwise it is be prone to attack. The proposed MD5&RC4-4S based burst header authentication algorithm runs 20.75 ns faster than the conventional algorithms. The modification suggested in the proposed RC4-4S algorithm gives a better security and solves the correlation problems between the publicly known outputs during key generation phase. The modified MD5 recommended in this work provides 7.81 % better avalanche effect than the conventional algorithm. The device utilization result also shows the suitability of the proposed algorithm for header authentication in real time applications.

Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNF-α in cerebral vascular endothelial cells

PubMed Central

Basuroy, Shyamali; Bhattacharya, Sujoy; Leffler, Charles W.; Parfenova, Helena

2009-01-01

Inflammatory brain disease may damage cerebral vascular endothelium leading to cerebral blood flow dysregulation. The proinflammatory cytokine TNF-α causes oxidative stress and apoptosis in cerebral microvascular endothelial cells (CMVEC) from newborn pigs. We investigated contribution of major cellular sources of reactive oxygen species to endothelial inflammatory response. Nitric oxide synthase and xanthine oxidase inhibitors (Nω-nitro-l-arginine and allopurinol) had no effect, while mitochondrial electron transport inhibitors (CCCP, 2-thenoyltrifluoroacetone, and rotenone) attenuated TNF-α-induced superoxide (O2•−) and apoptosis. NADPH oxidase inhibitors (diphenylene iodonium and apocynin) greatly reduced TNF-α-evoked O2•− generation and apoptosis. TNF-α rapidly increased NADPH oxidase activity in CMVEC. Nox4, the cell-specific catalytic subunit of NADPH oxidase, is highly expressed in CMVEC, contributes to basal O2•− production, and accounts for a burst of oxidative stress in response to TNF-α. Nox4 small interfering RNA, but not Nox2, knockdown prevented oxidative stress and apoptosis caused by TNF-α in CMVEC. Nox4 is colocalized with HO-2, the constitutive isoform of heme oxygenase (HO), which is critical for endothelial protection against TNF-α toxicity. The products of HO activity, bilirubin and carbon monoxide (CO, as a CO-releasing molecule, CORM-A1), inhibited Nox4-generated O2•− and apoptosis caused by TNF-α stimulation. We conclude that Nox4 is the primary source of inflammation- and TNF-α-induced oxidative stress leading to apoptosis in brain endothelial cells. The ability of CO and bilirubin to combat TNF-α-induced oxidative stress by inhibiting Nox4 activity and/or by O2•− scavenging, taken together with close intracellular compartmentalization of HO-2 and Nox4 in cerebral vascular endothelium, may contribute to HO-2 cytoprotection against inflammatory cerebrovascular disease. PMID:19118162

Phylogenetic trends in respiratory rhythmogenesis: insights from ectothermic vertebrates.

PubMed

Kinkead, Richard

2009-08-31

Understanding the neural substrate driving breathing has puzzled physiologists for more than a century. The discovery of the pre-Bötzinger complex (preBötC) in newborn rodents as a structure with a unique physiological function in respiratory rhythm generation was an important progress in respiratory neurobiology that stimulated much research. Owing to the extensive literature describing the location, organisation, and function of the preBötC mainly in newborn rodents, this structure has become the point of reference in studies addressing respiratory rhythm generation in other mammals and various classes of vertebrates. This paper reviews recent progress made in non-mammalian vertebrates in our understanding of the location and function of the neural networks driving respiratory activity. As in newborn rodents, data from lampreys, air breathing fish, and amphibians show that the production of eupnea is the result of interactions between multiple (at least two) rhythmogenic networks. These networks are located in anatomically distinct areas and show different functional properties in terms of their ability to produce (or not) bursting activity in the absence of synaptic inputs (e.g. pacemaker neurons) and their sensitivity to specific neuromodulators such as substance P, somatostatin, and opioids. Current data indicate that respiratory rhythmogenesis is a phylogenetically ancient function that was highly conserved throughout evolution and that a comparative approach remains important to derive broader biological principles and a more comprehensive view.

Solar Drift-Pair Bursts

NASA Astrophysics Data System (ADS)

Stanislavsky, A.; Volvach, Ya.; Konovalenko, A.; Koval, A.

2017-08-01

In this paper a new sight on the study of solar bursts historically called drift pairs (DPs) is presented. Having a simple morphology on dynamic spectra of radio records (two short components separated in time, and often they are very similar) and discovered at the dawn of radio astronomy, their features remain unexplained totally up to now. Generally, the DPs are observed during the solar storms of type III bursts, but not every storm of type III bursts is linked with DPs. Detected by ground-based instruments at decameter and meter wavelengths, the DP bursts are limited in frequency bandwidth. They can drift from high frequencies to low ones and vice versa. Their frequency drift rate may be both lower and higher than typical rates of type III bursts at the same frequency range. The development of low-frequency radio telescopes and data processing provide additional possibilities in the research. In this context the fresh analysis of DPs, made from recent observations in the summer campaign of 2015, are just considered. Their study was implemented by updated tools of the UTR-2 radio telescope at 9-33 MHz. During 10-12 July of 2015, DPs forming the longest patterns on dynamic spectra are about 7% of the total number of recorded DPs. Their marvelous resemblance in frequency drift rates with the solar S-bursts is discussed.

SPERMINE OXIDASE: AN AMINE OXIDASE WITH SPECIFICITY FOR SPERMINE AND SPERMIDINE

PubMed Central

Hirsch, James G.

1953-01-01

Sheep serum and bovine serum contain an enzyme which brings about a rapid oxidative deamination of certain biological amines. This enzyme differs from previously described amine oxidases in several regards and especially in its substrate specificity. Studies thus far indicate that only spermine and the closely related compound spermidine serve as substrates for the enzyme in sheep serum. For this reason, the enzyme has been named spermine oxidase. Spermine oxidase is active in a variety of fluids of various ionic strength and buffer composition. The reaction takes place between pH 6.0 and pH 8.0 with an optimal rate in the vicinity of neutrality. Under certain conditions, the rate of oxygen consumption during the initial phase of the reaction is independent of the concentration of substrate. The diminution in rate observed during the latter phase of the enzymatic attack appears to be due to an alteration in the kinetics at low concentrations of substrate, or to competitive inhibition by a product of the reaction. Carbonyl reagents almost completely block the action of spermine oxidase, while certain amines and the cyanide ion bring about partial inhibition. Thiol reagents and sequestering compounds do not alter the course of the oxidative process. In the presence of low concentrations of mercuric chloride, the sheep serum-spermine system consumes approximately twice as much oxygen as controls containing no mercuric ion. The mechanism by which the mercuric ion stimulates additional oxygen uptake is obscure. PMID:13052805

30 CFR 57.3461 - Rock bursts.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Rock bursts. 57.3461 Section 57.3461 Mineral...-Underground Only § 57.3461 Rock bursts. (a) Operators of mines which have experienced a rock burst shall— (1) Within twenty four hours report to the nearest MSHA office each rock burst which: (i) Causes persons to...

30 CFR 57.3461 - Rock bursts.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Rock bursts. 57.3461 Section 57.3461 Mineral...-Underground Only § 57.3461 Rock bursts. (a) Operators of mines which have experienced a rock burst shall— (1) Within twenty four hours report to the nearest MSHA office each rock burst which: (i) Causes persons to...

30 CFR 57.3461 - Rock bursts.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Rock bursts. 57.3461 Section 57.3461 Mineral...-Underground Only § 57.3461 Rock bursts. (a) Operators of mines which have experienced a rock burst shall— (1) Within twenty four hours report to the nearest MSHA office each rock burst which: (i) Causes persons to...

30 CFR 57.3461 - Rock bursts.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Rock bursts. 57.3461 Section 57.3461 Mineral...-Underground Only § 57.3461 Rock bursts. (a) Operators of mines which have experienced a rock burst shall— (1) Within twenty four hours report to the nearest MSHA office each rock burst which: (i) Causes persons to...

30 CFR 57.3461 - Rock bursts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Rock bursts. 57.3461 Section 57.3461 Mineral...-Underground Only § 57.3461 Rock bursts. (a) Operators of mines which have experienced a rock burst shall— (1) Within twenty four hours report to the nearest MSHA office each rock burst which: (i) Causes persons to...

Adipogenesis-related increase of semicarbazide-sensitive amine oxidase and monoamine oxidase in human adipocytes.

PubMed

Bour, Sandy; Daviaud, Danièle; Gres, Sandra; Lefort, Corinne; Prévot, Danielle; Zorzano, Antonio; Wabitsch, Martin; Saulnier-Blache, Jean-Sébastien; Valet, Philippe; Carpéné, Christian

2007-08-01

A strong induction of semicarbazide-sensitive amine oxidase (SSAO) has previously been reported during murine preadipocyte lineage differentiation but it remains unknown whether this emergence also occurs during adipogenesis in man. Our aim was to compare SSAO and monoamine oxidase (MAO) expression during in vitro differentiation of human preadipocytes and in adipose and stroma-vascular fractions of human fat depots. A human preadipocyte cell strain from a patient with Simpson-Golabi-Behmel syndrome was first used to follow amine oxidase expression during in vitro differentiation. Then, human preadipocytes isolated from subcutaneous adipose tissues were cultured under conditions promoting ex vivo adipose differentiation and tested for MAO and SSAO expression. Lastly, human adipose tissue was separated into mature adipocyte and stroma-vascular fractions for analyses of MAO and SSAO at mRNA, protein and activity levels. Both SSAO and MAO were increased from undifferentiated preadipocytes to lipid-laden cells in all the models: 3T3-F442A and 3T3-L1 murine lineages, human SGBS cell strain or human preadipocytes in primary culture. In human subcutaneous adipose tissue, the adipocyte-enriched fraction exhibited seven-fold higher amine oxidase activity and contained three- to seven-fold higher levels of mRNAs encoded by MAO-A, MAO-B, AOC3 and AOC2 genes than the stroma-vascular fraction. MAO-A and AOC3 genes accounted for the majority of their respective MAO and SSAO activities in human adipose tissue. Most of the SSAO and MAO found in adipose tissue originated from mature adipocytes. Although the mechanism and role of adipogenesis-related increase in amine oxidase expression remain to be established, the resulting elevated levels of amine oxidase activities found in human adipocytes may be of potential interest for therapeutic intervention in obesity.

The Mystery of Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Fishman, Gerald J.

2004-01-01

Gamma-ray bursts remain one of the greatest mysteries in astrophysics. Observations of gamma-ray bursts made by the BATSE experiment on the Compton Gamma-Ray Observatory will be described. Most workers in the field now believe that they originate from cosmological distances. This view has been reinforced by observations this year of several optical afterglow counterparts to gamma-ray bursts. A summary of these recent discoveries will be presented, along with their implications for models of the burst emission mechanism and the energy source of the bursts.

Stimulus induced bursts in severe postanoxic encephalopathy.

PubMed

Tjepkema-Cloostermans, Marleen C; Wijers, Elisabeth T; van Putten, Michel J A M

2016-11-01

To report on a distinct effect of auditory and sensory stimuli on the EEG in comatose patients with severe postanoxic encephalopathy. In two comatose patients admitted to the Intensive Care Unit (ICU) with severe postanoxic encephalopathy and burst-suppression EEG, we studied the effect of external stimuli (sound and touch) on the occurrence of bursts. In patient A bursts could be induced by either auditory or sensory stimuli. In patient B bursts could only be induced by touching different facial regions (forehead, nose and chin). When stimuli were presented with relatively long intervals, bursts persistently followed the stimuli, while stimuli with short intervals (<1s) did not induce bursts. In both patients bursts were not accompanied by myoclonia. Both patients deceased. Bursts in patients with a severe postanoxic encephalopathy can be induced by external stimuli, resulting in stimulus-dependent burst-suppression. Stimulus induced bursts should not be interpreted as prognostic favourable EEG reactivity. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Various applications of immobilized glucose oxidase and polyphenol oxidase in a conducting polymer matrix.

PubMed

Cil, M; Böyükbayram, A E; Kiralp, S; Toppare, L; Yağci, Y

2007-06-01

In this study, glucose oxidase and polyphenol oxidase were immobilized in conducting polymer matrices; polypyrrole and poly(N-(4-(3-thienyl methylene)-oxycarbonyl phenyl) maleimide-co-pyrrole) via electrochemical method. Fourier transform infrared and scanning electron microscope were employed to characterize the copolymer of (N-(4-(3-thienyl methylene)-oxycarbonyl phenyl) maleimide) with pyrrole. Kinetic parameters, maximum reaction rate and Michealis-Menten constant, were determined. Effects of temperature and pH were examined for immobilized enzymes. Also, storage and operational stabilities of enzyme electrodes were investigated. Glucose and polyphenol oxidase enzyme electrodes were used for determination of the glucose amount in orange juices and human serum and phenolic amount in red wines, respectively.

Lung respiratory rhythm and pattern generation in the bullfrog: role of neurokinin-1 and mu-opioid receptors.

PubMed

Davies, B L; Brundage, C M; Harris, M B; Taylor, B E

2009-07-01

Location of the lung respiratory rhythm generator (RRG) in the bullfrog brainstem was investigated by examining neurokinin-1 and mu-opioid receptor (NK1R, muOR) colocalization by immunohistochemistry and characterizing the role of these receptors in lung rhythm and episodic pattern generation. NK1R and muOR occurred in brainstems from all developmental stages. In juvenile bullfrogs a distinct area of colocalization was coincident with high-intensity fluorescent labeling of muOR; high-intensity labeling of muOR was not distinctly and consistently localized in tadpole brainstems. NK1R labeling intensity did not change with development. Similarity in colocalization is consistent with similarity in responses to substance P (SP, NK1R agonist) and DAMGO (muOR agonist) when bath applied to bullfrog brainstems of different developmental stages. In early stage tadpoles and juvenile bullfrogs, SP increased and DAMGO decreased lung burst frequency. In juvenile bullfrogs, SP increased lung burst frequency, episode frequency, but decreased number of lung bursts per episode and lung burst duration. In contrast, DAMGO decreased lung burst frequency and burst cycle frequency, episode frequency, and number of lung bursts per episode but increased all other lung burst parameters. Based on these results, we hypothesize that NK1R and muOR colocalization together with a metamorphosis-related increase in muOR intensity marks the location of the lung RRG but not necessarily the lung episodic pattern generator.

UWB dual burst transmit driver

DOEpatents

Dallum, Gregory E [Livermore, CA; Pratt, Garth C [Discovery Bay, CA; Haugen, Peter C [Livermore, CA; Zumstein, James M [Livermore, CA; Vigars, Mark L [Livermore, CA; Romero, Carlos E [Livermore, CA

2012-04-17

A dual burst transmitter for ultra-wideband (UWB) communication systems generates a pair of precisely spaced RF bursts from a single trigger event. An input trigger pulse produces two oscillator trigger pulses, an initial pulse and a delayed pulse, in a dual trigger generator. The two oscillator trigger pulses drive a gated RF burst (power output) oscillator. A bias driver circuit gates the RF output oscillator on and off and sets the RF burst packet width. The bias driver also level shifts the drive signal to the level that is required for the RF output device.

The Respiratory Arsenite Oxidase: Structure and the Role of Residues Surrounding the Rieske Cluster

PubMed Central

Warelow, Thomas P.; Oke, Muse; Schoepp-Cothenet, Barbara; Dahl, Jan U.; Bruselat, Nicole; Sivalingam, Ganesh N.; Leimkühler, Silke; Thalassinos, Konstantinos; Kappler, Ulrike; Naismith, James H.; Santini, Joanne M.

2013-01-01

The arsenite oxidase (Aio) from the facultative autotrophic Alphaproteobacterium Rhizobium sp. NT-26 is a bioenergetic enzyme involved in the oxidation of arsenite to arsenate. The enzyme from the distantly related heterotroph, Alcaligenes faecalis, which is thought to oxidise arsenite for detoxification, consists of a large α subunit (AioA) with bis-molybdopterin guanine dinucleotide at its active site and a 3Fe-4S cluster, and a small β subunit (AioB) which contains a Rieske 2Fe-2S cluster. The successful heterologous expression of the NT-26 Aio in Escherichia coli has resulted in the solution of its crystal structure. The NT-26 Aio, a heterotetramer, shares high overall similarity to the heterodimeric arsenite oxidase from A. faecalis but there are striking differences in the structure surrounding the Rieske 2Fe-2S cluster which we demonstrate explains the difference in the observed redox potentials (+225 mV vs. +130/160 mV, respectively). A combination of site-directed mutagenesis and electron paramagnetic resonance was used to explore the differences observed in the structure and redox properties of the Rieske cluster. In the NT-26 AioB the substitution of a serine (S126 in NT-26) for a threonine as in the A. faecalis AioB explains a −20 mV decrease in redox potential. The disulphide bridge in the A. faecalis AioB which is conserved in other betaproteobacterial AioB subunits and the Rieske subunit of the cytochrome bc 1 complex is absent in the NT-26 AioB subunit. The introduction of a disulphide bridge had no effect on Aio activity or protein stability but resulted in a decrease in the redox potential of the cluster. These results are in conflict with previous data on the betaproteobacterial AioB subunit and the Rieske of the bc 1 complex where removal of the disulphide bridge had no effect on the redox potential of the former but a decrease in cluster stability was observed in the latter. PMID:24023621

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist.

PubMed

Lalley, Peter M; Mifflin, Steve W

2017-05-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N -methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO 2 /pH chemosensitivity. Copyright © 2017 the American Physiological Society.

Methylxanthines do not affect rhythmogenic preBötC inspiratory network activity but impair bursting of preBötC-driven motoneurons.

PubMed

Panaitescu, B; Kuribayashi, J; Ruangkittisakul, A; Leung, V; Iizuka, M; Ballanyi, K

2013-01-01

Clinical stimulation of preterm infant breathing with methylxanthines like caffeine and theophylline can evoke seizures. It is unknown whether underlying neuronal hyperexcitability involves the rhythmogenic inspiratory active pre-Bötzinger complex (preBötC) in the brainstem or preBötC-driven motor networks. Inspiratory-related preBötC interneuronal plus spinal (cervical/phrenic) or cranial hypoglossal (XII) motoneuronal bursting was studied in newborn rat en bloc brainstem-spinal cords and brainstem slices, respectively. Non-respiratory bursting perturbed inspiratory cervical nerve activity in en bloc models at >0.25mM theophylline or caffeine. Rhythm in the exposed preBötC of transected en bloc preparations was less perturbed by 10mM theophylline than cervical root bursting which was more affected than phrenic nerve activity. In the preBötC of slices, even 10mM methylxanthine did not evoke seizure-like bursting whereas >1mM masked XII rhythm via large amplitude 1-10Hz oscillations. Blocking A-type γ-aminobutyric (GABAA) receptors evoked seizure-like cervical activity whereas in slices neither XII nor preBötC rhythm was disrupted. Methylxanthines (2.5-10mM), but not blockade of adenosine receptors, phosphodiesterase-4 or the sarcoplasmatic/endoplasmatic reticulum ATPase countered inspiratory depression by muscimol-evoked GABAA receptor activation that was associated with a hyperpolarization and input resistance decrease silencing preBötC neurons in slices. The latter blockers did neither affect preBötC or cranial/spinal motor network bursting nor evoke seizure-like activity or mask corresponding methylxanthine-evoked discharges. Our findings show that methylxanthine-evoked hyperexcitability originates from motor networks, leaving preBötC activity largely unaffected, and suggest that GABAA receptors contribute to methylxanthine-evoked seizure-like perturbation of spinal motoneurons whereas non-respiratory XII motoneuron oscillations are of different

Organotypic slice cultures containing the preBötzinger complex generate respiratory-like rhythms

PubMed Central

Phillips, Wiktor S.; Herly, Mikkel; Del Negro, Christopher A.

2015-01-01

Study of acute brain stem slice preparations in vitro has advanced our understanding of the cellular and synaptic mechanisms of respiratory rhythm generation, but their inherent limitations preclude long-term manipulation and recording experiments. In the current study, we have developed an organotypic slice culture preparation containing the preBötzinger complex (preBötC), the core inspiratory rhythm generator of the ventrolateral brain stem. We measured bilateral synchronous network oscillations, using calcium-sensitive fluorescent dyes, in both ventrolateral (presumably the preBötC) and dorsomedial regions of slice cultures at 7–43 days in vitro. These calcium oscillations appear to be driven by periodic bursts of inspiratory neuronal activity, because whole cell recordings from ventrolateral neurons in culture revealed inspiratory-like drive potentials, and no oscillatory activity was detected from glial fibrillary associated protein-expressing astrocytes in cultures. Acute slices showed a burst frequency of 10.9 ± 4.2 bursts/min, which was not different from that of brain stem slice cultures (13.7 ± 10.6 bursts/min). However, slice cocultures that include two cerebellar explants placed along the dorsolateral border of the brainstem displayed up to 193% faster burst frequency (22.4 ± 8.3 bursts/min) and higher signal amplitude (340%) compared with acute slices. We conclude that preBötC-containing slice cultures retain inspiratory-like rhythmic function and therefore may facilitate lines of experimentation that involve extended incubation (e.g., genetic transfection or chronic drug exposure) while simultaneously being amenable to imaging and electrophysiology at cellular, synaptic, and network levels. PMID:26655824

Neurotransmitters and neuromodulators controlling the hypoxic respiratory response in anaesthetized cats.

PubMed

Richter, D W; Schmidt-Garcon, P; Pierrefiche, O; Bischoff, A M; Lalley, P M

1999-01-15

1. The contributions of neurotransmitters and neuromodulators to the responses of the respiratory network to acute hypoxia were analysed in anaesthetized cats. 2. Samples of extracellular fluid were collected at 1-1.5 min time intervals by microdialysis in the medullary region of ventral respiratory group neurones and analysed for their content of glutamate, gamma-aminobutyric acid (GABA), serotonin and adenosine by high performance liquid chromatography. Phrenic nerve activity was correlated with these measurements. 3. Levels of glutamate and GABA increased transiently during early periods of hypoxia, coinciding with augmented phrenic nerve activity and then fell below control during central apnoea. Serotonin and adenosine increased slowly and steadily with onset of hypoxic depression of phrenic nerve activity. 4. The possibility that serotonin contributes to hypoxic respiratory depression was tested by microinjecting the 5-HT-1A receptor agonist 8-OH-DPAT into the medullary region that is important for rhythmogenesis. Hypoxic activation of respiratory neurones and phrenic nerve activity were suppressed. Microinjections of NAN-190, a 5-HT-1A receptor blocker, enhanced hypoxic augmentation resulting in apneustic prolongation of inspiratory bursts. 5. The results reveal a temporal sequence in the release of neurotransmitters and neuromodulators and suggest a specific role for each of them in the sequential development of hypoxic respiratory disturbances.

Identification, expression, and taxonomic distribution of alternative oxidases in non-angiosperm plants.

PubMed

Neimanis, Karina; Staples, James F; Hüner, Norman P A; McDonald, Allison E

2013-09-10

Alternative oxidase (AOX) is a terminal ubiquinol oxidase present in the respiratory chain of all angiosperms investigated to date, but AOX distribution in other members of the Viridiplantae is less clear. We assessed the taxonomic distribution of AOX using bioinformatics. Multiple sequence alignments compared AOX proteins and examined amino acid residues involved in AOX catalytic function and post-translational regulation. Novel AOX sequences were found in both Chlorophytes and Streptophytes and we conclude that AOX is widespread in the Viridiplantae. AOX multigene families are common in non-angiosperm plants and the appearance of AOX1 and AOX2 subtypes pre-dates the divergence of the Coniferophyta and Magnoliophyta. Residues involved in AOX catalytic function are highly conserved between Chlorophytes and Streptophytes, while AOX post-translational regulation likely differs in these two lineages. We demonstrate experimentally that an AOX gene is present in the moss Physcomitrella patens and that the gene is transcribed. Our findings suggest that AOX will likely exert an influence on plant respiration and carbon metabolism in non-angiosperms such as green algae, bryophytes, liverworts, lycopods, ferns, gnetophytes, and gymnosperms and that further research in these systems is required. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of Thermonuclear X-Ray Bursts on Non-burst Emissions in the Soft State of 4U 1728–34

NASA Astrophysics Data System (ADS)

Bhattacharyya, Sudip; Yadav, J. S.; Sridhar, Navin; Verdhan Chauhan, Jai; Agrawal, P. C.; Antia, H. M.; Pahari, Mayukh; Misra, Ranjeev; Katoch, Tilak; Manchanda, R. K.; Paul, Biswajit

2018-06-01

It has recently been shown that the persistent emission of a neutron star low-mass X-ray binary (LMXB) evolves during a thermonuclear (type-I) X-ray burst. The reason of this evolution, however, is not fully known. This uncertainty can introduce significant systematics in the neutron star radius measurement using burst spectra, particularly if an unknown but significant fraction of the burst emission, which is reprocessed, contributes to the changes in the persistent emission during the burst. Here, by analyzing individual burst data of AstroSat/LAXPC from the neutron star LMXB 4U 1728–34 in the soft state, we show that the burst emission is not significantly reprocessed by a corona covering the neutron star. Rather, our analysis suggests that the burst emission enhances the accretion disk emission, possibly by increasing the accretion rate via disk. This enhanced disk emission, which is Comptonized by a corona covering the disk, can explain an increased persistent emission observed during the burst. This finding provides an understanding of persistent emission components and their interaction with the thermonuclear burst emission. Furthermore, as burst photons are not significantly reprocessed, non-burst and burst emissions can be reliably separated, which is required to reduce systematic uncertainties in the stellar radius measurement.

The Mystery of Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Fishman, Gerald J.

1998-01-01

Gamma-ray bursts remain on of the greatest mysteries in astrophysics in spite of recent observational advances and intense theoretical work. Although some of the basic properties of bursts were known 25 years ago, new and more detailed observations have been made by the BATSE (Burst and Transient Source Experiment) experiment on the Compton Gamma Ray Observatory in the past five years. Recent observations of bursts and some proposed models will be discussed.

Release of cystic fibrosis airway inflammatory markers from Pseudomonas aeruginosa-stimulated human neutrophils involves NADPH oxidase-dependent extracellular DNA trap formation.

PubMed

Yoo, Dae-goon; Winn, Matthew; Pang, Lan; Moskowitz, Samuel M; Malech, Harry L; Leto, Thomas L; Rada, Balázs

2014-05-15

Cystic fibrosis (CF) airways are characterized by bacterial infections, excess mucus production, and robust neutrophil recruitment. The main CF airway pathogen is Pseudomonas aeruginosa. Neutrophils are not capable of clearing the infection. Neutrophil primary granule components, myeloperoxidase (MPO) and human neutrophil elastase (HNE), are inflammatory markers in CF airways, and their increased levels are associated with poor lung function. Identifying the mechanism of MPO and HNE release from neutrophils is of high clinical relevance for CF. In this article, we show that human neutrophils release large amounts of neutrophil extracellular traps (NETs) in the presence of P. aeruginosa. Bacteria are entangled in NETs and colocalize with extracellular DNA. MPO, HNE, and citrullinated histone H4 are all associated with DNA in Pseudomonas-triggered NETs. Both laboratory standard strains and CF isolates of P. aeruginosa induce DNA, MPO, and HNE release from human neutrophils. The increase in peroxidase activity of neutrophil supernatants after Pseudomonas exposure indicates that enzymatically active MPO is released. P. aeruginosa induces a robust respiratory burst in neutrophils that is required for extracellular DNA release. Inhibition of the cytoskeleton prevents Pseudomonas-initiated superoxide production and DNA release. NADPH oxidase inhibition suppresses Pseudomonas-induced release of active MPO and HNE. Blocking MEK/ERK signaling results in only minimal inhibition of DNA release induced by Pseudomonas. Our data describe in vitro details of DNA, MPO, and HNE release from neutrophils activated by P. aeruginosa. We propose that Pseudomonas-induced NET formation is an important mechanism contributing to inflammatory conditions characteristic of CF airways.

BATSE Observations of Gamma-Ray Burst Tails

NASA Technical Reports Server (NTRS)

Connaughton, Valerie; Six, N. Frank (Technical Monitor)

2001-01-01

With the discovery of low-energy radiation appearing to come from the site of gamma-ray bursts in the hours to weeks after the initial burst of gamma rays, it would appear that astronomers have seen a cosmological imprint made by the burster on its surroundings. I discuss in this paper the phenomenon of post-burst emission in BATSE (Burst and Transient Source Experiment) gamma-ray bursts at energies traditionally associated with prompt emission. By summing the background-subtracted signals from hundreds of bursts, I find that tails out to hundreds of seconds after the trigger may be a common feature of long events (duration greater than 2s), and perhaps of the shorter bursts at a lower and shorter-lived level. The tail component appears independent of both the duration (within the long GRB sample) and brightness of the prompt burst emission, and may be softer. Some individual bursts have visible tails at gamma-ray energies and the spectrum in at least a few cases is different from that of the prompt emission. Afterglow at lower energies was detected for one of these bursts, GRB-991216, raising the possibility of afterglow observations over large energy ranges using the next generation of GRB detectors in conjunction with sensitive space or ground-based telescopes.

Fast Radio Bursts

NASA Astrophysics Data System (ADS)

Kaspi, Victoria M.

2017-01-01

Fast Radio Bursts (FRBs) are a recently discovered phenomenon consisting of short (few ms) bursts of radio waves that have dispersion measures that strongly suggest an extragalactic and possibly cosmological origin. Current best estimates for the rate of FRBs is several thousand per sky per day at radio frequencies near 1.4 GHz. Even with so high a rate, to date, fewer than 20 FRBs have been reported, with one source showing repeated bursts. In this talk I will describe known FRB properties including what is known about the lone repeating source, as well as models for the origin of these mysterious events. I will also describe the CHIME radio telescope, currently under construction in Canada. Thanks to its great sensitivity and unprecedented field-of-view, CHIME promises major progress on FRBs.

Gamma-Ray Bursts in the Swift Era

NASA Technical Reports Server (NTRS)

Gehrels, Neil; Ramirez-Ruiz, E.; Fox, D. B.

2010-01-01

With its rapid-response capability and multiwavelength complement of instruments, the Swift satellite has transformed our physical understanding of gamma-ray bursts. Providing high-quality observations of hundreds of bursts, and facilitating a wide range of follow-up observations within seconds of each event, Swift has revealed an unforeseen richness in observed burst properties, shed light on the nature of short-duration bursts, and helped realize the promise of gamma-ray bursts as probes of the processes and environments of star formation out to the earliest cosmic epochs. These advances have opened new perspectives on the nature and properties of burst central engines, interactions with the burst environment from microparsec to gigaparsec scales, and the possibilities for non-photonic signatures. Our understanding of these extreme cosmic sources has thus advanced substantially; yet more than forty years after their discovery, gamma-ray bursts continue to present major challenges on both observational and theoretical fronts.

Excess close burst pairs in FRB 121102

NASA Astrophysics Data System (ADS)

Katz, J. I.

2018-05-01

The repeating FRB 121102 emitted a pair of apparently discrete bursts separated by 37 ms and another pair, 131 d later, separated by 34 ms, during observations that detected bursts at a mean rate of ˜2 × 10-4 s-1. While FRB 121102 is known to produce multipeaked bursts, here I assume that these `burst pairs' are truly separate bursts and not multicomponent single bursts, and consider the implications of that assumption. Their statistics are then non-Poissonian. Assuming that the emission comes from a narrow range of rotational phase, then the measured burst intervals constrain any possible periodic modulation underlying the highly episodic emission. If more such short intervals are measured a period may be determined or periodicity may be excluded. The excess of burst intervals much shorter than their mean recurrence time may be explained if FRB emit steady but narrow beams that execute a random walk in direction, perhaps indicating origin in a black hole's accretion disc.

Rhodobacter capsulatus contains a novel cb-type cytochrome c oxidase without a CuA center.

PubMed

Gray, K A; Grooms, M; Myllykallio, H; Moomaw, C; Slaughter, C; Daldal, F

1994-03-15

The facultative phototrophic bacterium Rhodobacter capsulatus is capable of growth in a wide range of environmental conditions using a highly branched electron-transfer chain. During respiratory growth of this organism reducing equivalents are conveyed to oxygen via two terminal oxidases, previously called "cyt b410" (cytochrome c oxidase) and "cyt b260" (quinol oxidase). The cytochrome c oxidase was purified to homogeneity from a semiaerobically grown R. capsulatus strain. The purified enzyme consumes oxygen at a rate of 600 s-1, oxidizes reduced equine cyt c and R. capsulatus cyt c2, and has high sensitivity to cyanide. The complex is composed of three major polypeptides of apparent molecular masses 45, 32, and 28 kDa on SDS-PAGE. The 32- and 28-kDa proteins also stain with tetramethylbenzidine, indicating that they are c-type cytochromes. Partial amino acid sequences obtained from each of the subunits reveal significant homology to the fixN, fixO, and fixP gene products of Bradyrhizobium japonicum and Rhizobium meliloti. The reduced enzyme has an optical absorption spectrum with distinct features near 550 and 560 nm and an asymmetric Soret band centered at 418 nm, indicating the presence of both c- and b-type cytochromes. Two electrochemically distinct cyt c are apparent, with redox midpoint potentials (Em7) of 265 and 320 mV, while the low-spin cyt b has an Em7 value of 385 mV. The enzyme binds carbon monoxide, and the CO difference spectrum indicates that CO binds to a high-spin cyt b. Pyridine hemochrome and HPLC analyses suggest that the complex contains 1 mol of heme C to 1 mol of protoheme and that neither heme O nor heme A is present.(ABSTRACT TRUNCATED AT 250 WORDS)

The rotational phase dependence of magnetar bursts

NASA Astrophysics Data System (ADS)

Elenbaas, C.; Watts, A. L.; Huppenkothen, D.

2018-05-01

The trigger for the short bursts observed in γ-rays from many magnetar sources remains unknown. One particular open question in this context is the localization of burst emission to a singular active region or a larger area across the neutron star. While several observational studies have attempted to investigate this question by looking at the phase dependence of burst properties, results have been mixed. At the same time, it is not obvious a priori that bursts from a localized active region would actually give rise to a detectable phase dependence, taking into account issues such as geometry, relativistic effects, and intrinsic burst properties such brightness and duration. In this paper, we build a simple theoretical model to investigate the circumstances under which the latter effects could affect detectability of dependence of burst emission on rotational phase. We find that even for strongly phase-dependent emission, inferred burst properties may not show a rotational phase dependence, depending on the geometry of the system and the observer. Furthermore, the observed properties of bursts with durations short as 10-20 per cent of the spin period can vary strongly depending on the rotational phase at which the burst was emitted. We also show that detectability of a rotational phase dependence depends strongly on the minimum number of bursts observed, and find that existing burst samples may simply be too small to rule out a phase dependence.

FRB121102 Bursts Show Detailed Spectrotemporal Structure

NASA Astrophysics Data System (ADS)

Hessels, Jason; Seymour, Andrew; Spitler, Laura; Michilli, Daniele; Lynch, Ryan S.; Gajjar, Vishal; Gourdji, Kelly

2018-01-01

FRB121102 is a sporadic emitter of millisecond-duration radio bursts, and is associated with a compact, persistent radio source in the primary star-forming region of a dwarf galaxy at ~ 1 Gpc. Key to understanding FRB121102's physical nature is using the observed burst properties to elucidate the underlying emission mechanism and its local environment. Here we present a sample of high signal-to-noise bursts that reveal hitherto unseen spectrotemporal features. We find that the bursts are often composed of sub-bursts with finite bandwidths, and characteristic frequencies that drift downwards during the burst. While this behavior could be an intrinsic feature of the burst emission mechanism, we also discuss an interpretation in terms of plasma lensing in the source environment, similar to the pulse echoes sometimes seen from the Crab pulsar.

Gamma-Ray Bursts: An Overview

NASA Technical Reports Server (NTRS)

Fishman, Gerald J.

1995-01-01

A history and overview of the observed properties of gamma-ray bursts are presented. The phenomenon of gamma-ray bursts is without precedent in astronomy, having no observed property that would be a direct indicator of their distance and no counterpart object in another wavelength region. Their brief, random appearance only in the gamma-ray region has made their study difficult. The observed time profiles, spectral properties, and durations of gamma-ray bursts cover a wide range. All proposed models for their origin must be considered speculative. It is humbling to think that even after 25 years since their discovery, the distance scale of gamma-ray bursts is still very much debatable.

Importance of the alternative oxidase (AOX) pathway in regulating cellular redox and ROS homeostasis to optimize photosynthesis during restriction of the cytochrome oxidase pathway in Arabidopsis thaliana

PubMed Central

Vishwakarma, Abhaypratap; Tetali, Sarada Devi; Selinski, Jennifer; Scheibe, Renate; Padmasree, Kollipara

2015-01-01

Background and Aims The importance of the alternative oxidase (AOX) pathway, particularly AOX1A, in optimizing photosynthesis during de-etiolation, under elevated CO2, low temperature, high light or combined light and drought stress is well documented. In the present study, the role of AOX1A in optimizing photosynthesis was investigated when electron transport through the cytochrome c oxidase (COX) pathway was restricted at complex III. Methods Leaf discs of wild-type (WT) and aox1a knock-out mutants of Arabidopsis thaliana were treated with antimycin A (AA) under growth-light conditions. To identify the impact of AOX1A deficiency in optimizing photosynthesis, respiratory O2 uptake and photosynthesis-related parameters were measured along with changes in redox couples, reactive oxygen species (ROS), lipid peroxidation and expression levels of genes related to respiration, the malate valve and the antioxidative system. Key Results In the absence of AA, aox1a knock-out mutants did not show any difference in physiological, biochemical or molecular parameters compared with WT. However, after AA treatment, aox1a plants showed a significant reduction in both respiratory O2 uptake and NaHCO3-dependent O2 evolution. Chlorophyll fluorescence and P700 studies revealed that in contrast to WT, aox1a knock-out plants were incapable of maintaining electron flow in the chloroplastic electron transport chain, and thereby inefficient heat dissipation (low non-photochemical quenching) was observed. Furthermore, aox1a mutants exhibited significant disturbances in cellular redox couples of NAD(P)H and ascorbate (Asc) and consequently accumulation of ROS and malondialdehyde (MDA) content. By contrast, WT plants showed a significant increase in transcript levels of CSD1, CAT1, sAPX, COX15 and AOX1A in contrast to aox1a mutants. Conclusions These results suggest that AOX1A plays a significant role in sustaining the chloroplastic redox state and energization to optimize photosynthesis by

The GLAST Burst Monitor

NASA Technical Reports Server (NTRS)

Meegan, Charles A.

2004-01-01

The Gamma Ray Large Area Space Telescope (GLAST) observatory, scheduled for launch in 2007, comprises the Large Area Telescope (LAT) and the GLAST Burst Monitor (GBM). spectral changes that are known to occur within GRBs. between the NASA Marshall Space Flight Center, the University of Alabama in Huntsville, and the Max Planck Institute for Extraterrestrial Physics. It consists of an array of NaI and BGO scintillation detectors operating in the 10 kev to 25 MeV range. The field of view includes the entire unocculted sky when the observatory is pointing close to the zenith. The GBM will enhance LAT observations of GRBs by extending the spectral coverage into the range of current GRB databases, and will provide a trigger for reorienting the spacecraft to observe delayed emission from bursts outside the LAT field of view. GBM is expected to trigger on about 200 bursts per year, and will provide on-board locations of strong bursts accurate to better than 10 degrees.

Critical Bursts in Filtration

NASA Astrophysics Data System (ADS)

Bianchi, Filippo; Thielmann, Marcel; de Arcangelis, Lucilla; Herrmann, Hans Jürgen

2018-01-01

Particle detachment bursts during the flow of suspensions through porous media are a phenomenon that can severely affect the efficiency of deep bed filters. Despite the relevance in several industrial fields, little is known about the statistical properties and the temporal organization of these events. We present experiments of suspensions of deionized water carrying quartz particles pushed with a peristaltic pump through a filter of glass beads measuring simultaneously the pressure drop, flux, and suspension solid fraction. We find that the burst size distribution scales consistently with a power law, suggesting that we are in the presence of a novel experimental realization of a self-organized critical system. Temporal correlations are present in the time series, like in other phenomena such as earthquakes or neuronal activity bursts, and also an analog to Omori's law can be shown. The understanding of burst statistics could provide novel insights in different fields, e.g., in the filter and petroleum industries.

Differential affinity of BsSCO for Cu(II) and Cu(I) suggests a redox role in copper transfer to the Cu(A) center of cytochrome c oxidase.

PubMed

Hill, Bruce C; Andrews, Diann

2012-06-01

SCO (synthesis of cytochrome c oxidase) proteins are involved in the assembly of the respiratory chain enzyme cytochrome c oxidase acting to assist in the assembly of the Cu(A) center contained within subunit II of the oxidase complex. The Cu(A) center receives electrons from the reductive substrate ferrocytochrome c, and passes them on to the cytochrome a center. Cytochrome a feeds electrons to the oxygen reaction site composed of cytochrome a(3) and Cu(B). Cu(A) consists of two copper ions positioned within bonding distance and ligated by two histidine side chains, one methionine, a backbone carbonyl and two bridging cysteine residues. The complex structure and redox capacity of Cu(A) present a potential assembly challenge. SCO proteins are members of the thioredoxin family which led to the early suggestion of a disulfide exchange function for SCO in Cu(A) assembly, whereas the copper binding capacity of the Bacillus subtilis version of SCO (i.e., BsSCO) suggests a direct role for SCO proteins in copper transfer. We have characterized redox and copper exchange properties of apo- and metalated-BsSCO. The release of copper (II) from its complex with BsSCO is best achieved by reducing it to Cu(I). We propose a mechanism involving both disulfide and copper exchange between BsSCO and the apo-Cu(A) site. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. Copyright © 2011 Elsevier B.V. All rights reserved.

Structure of the Zymomonas mobilis respiratory chain: oxygen affinity of electron transport and the role of cytochrome c peroxidase.

PubMed

Balodite, Elina; Strazdina, Inese; Galinina, Nina; McLean, Samantha; Rutkis, Reinis; Poole, Robert K; Kalnenieks, Uldis

2014-09-01

The genome of the ethanol-producing bacterium Zymomonas mobilis encodes a bd-type terminal oxidase, cytochrome bc1 complex and several c-type cytochromes, yet lacks sequences homologous to any of the known bacterial cytochrome c oxidase genes. Recently, it was suggested that a putative respiratory cytochrome c peroxidase, receiving electrons from the cytochrome bc1 complex via cytochrome c552, might function as a peroxidase and/or an alternative oxidase. The present study was designed to test this hypothesis, by construction of a cytochrome c peroxidase mutant (Zm6-perC), and comparison of its properties with those of a mutant defective in the cytochrome b subunit of the bc1 complex (Zm6-cytB). Disruption of the cytochrome c peroxidase gene (ZZ60192) caused a decrease of the membrane NADH peroxidase activity, impaired the resistance of growing culture to exogenous hydrogen peroxide and hampered aerobic growth. However, this mutation did not affect the activity or oxygen affinity of the respiratory chain, or the kinetics of cytochrome d reduction. Furthermore, the peroxide resistance and membrane NADH peroxidase activity of strain Zm6-cytB had not decreased, but both the oxygen affinity of electron transport and the kinetics of cytochrome d reduction were affected. It is therefore concluded that the cytochrome c peroxidase does not terminate the cytochrome bc1 branch of Z. mobilis, and that it is functioning as a quinol peroxidase. © 2014 The Authors.

Cytochrome oxidase assembly does not require catalytically active cytochrome C.

PubMed

Barrientos, Antoni; Pierre, Danielle; Lee, Johnson; Tzagoloff, Alexander

2003-03-14

Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the transfer of electrons from reduced cytochrome c to molecular oxygen. COX assembly requires the coming together of nuclear- and mitochondrial-encoded subunits and the assistance of a large number of nuclear gene products acting at different stages of maturation of the enzyme. In Saccharomyces cerevisiae, expression of cytochrome c, encoded by CYC1 and CYC7, is required not only for electron transfer but also for COX assembly through a still unknown mechanism. We have attempted to distinguish between a functional and structural requirement of cytochrome c in COX assembly. A cyc1/cyc7 double null mutant strain was transformed with the cyc1-166 mutant gene (Schweingruber, M. E., Stewart, J. W., and Sherman, F. (1979) J. Biol. Chem. 254, 4132-4143) that expresses stable but catalytically inactive iso-1-cytochrome c. The COX content of the cyc1/cyc7 double mutant strain harboring non-functional iso-1-cytochrome c has been characterized spectrally, functionally, and immunochemically. The results of these studies demonstrate that cytochrome c plays a structural rather than functional role in assembly of cytochrome c oxidase. In addition to its requirement for COX assembly, cytochrome c also affects turnover of the enzyme. Mutants containing wild type apocytochrome c in mitochondria lack COX, suggesting that only the folded and mature protein is able to promote COX assembly.

X-Ray Bursts from NGC 6652

NASA Astrophysics Data System (ADS)

Morgan, Edward

The possibly transient X-ray Source in the globular cluster NGC 6652 has been seen by BeppoSax and the ASM on RXTE to undergo X-ray bursts, possibly Type I. Very little is known about this X-ray source, and confirmation of its bursts type-I nature would identify it as a neutron star binary. Type I bursts in 6 other sources have been shown to exhibit intervals of millisecond ocsillation that most likely indicate the neutron star spin period. Radius-expansion bursts can reveal information about the mass and size of the neutron star. We propose to use the ASM to trigger an observation of this source to maximize the probability of catching a burst in the PCA.

Transitions to Synchrony in Coupled Bursting Neurons

NASA Astrophysics Data System (ADS)

Dhamala, Mukeshwar; Jirsa, Viktor K.; Ding, Mingzhou

2004-01-01

Certain cells in the brain, for example, thalamic neurons during sleep, show spike-burst activity. We study such spike-burst neural activity and the transitions to a synchronized state using a model of coupled bursting neurons. In an electrically coupled network, we show that the increase of coupling strength increases incoherence first and then induces two different transitions to synchronized states, one associated with bursts and the other with spikes. These sequential transitions to synchronized states are determined by the zero crossings of the maximum transverse Lyapunov exponents. These results suggest that synchronization of spike-burst activity is a multi-time-scale phenomenon and burst synchrony is a precursor to spike synchrony.

BATSE Observations of Gamma-Ray Burst Tails

NASA Technical Reports Server (NTRS)

Connaughton, Valerie

2002-01-01

With the observation of low-energy radiation coming from the site of gamma-ray bursts in the hours to weeks after the initial gamma ray burst, it appears that astronomers have discovered a cosmological imprint made by the burster on its surroundings. This paper discusses the phenomenon of postburst emission in Burst and Transient Source Experiment (BATSE) gamma-ray bursts at energies usually associated with prompt emission. After summing up the background-subtracted signals from hundreds of bursts, it is found that tails out to hundreds of seconds after the trigger could be a common feature of events of a duration greater than 2 seconds, and perhaps of the shorter bursts at a lower and shorter-lived level. The tail component may be softer and seems independent of the duration (within the long-GRB sample) and brightness of the prompt burst emission. Some individual bursts have visible tails at gamma-ray energies, and the spectrum in a few cases differs from that of the prompt emission. For one of these bursts, GRB 991216, afterglow at lower energies was detected, which raised the possibility of seeing afterglow observations over large energy ranges using the next generation of GRB detectors in addition to sensitive space- or ground-based telescopes.

Characterizing Oscillatory Bursts in Single-Trial EEG Data

NASA Technical Reports Server (NTRS)

Knuth, K. H.; Shah, A. S.; Lakatos, P.; Schroeder, C. E.

2004-01-01

Oscillatory bursts in numerous bands ranging from low (theta) to high frequencies (e.g., gamma) undoubtedly play an important role in cortical dynamics. Largely because of the inadequacy of existing analytic techniques. however, oscillatory bursts and their role in cortical processing remains poorly understood. To study oscillatory bursts effectively one must be able to isolate them and characterize them in the single trial. We describe a series of straightforward analysis techniques that produce useful indices of burst characteristics. First, stimulus-evoked responses are estimated using Differentially Variable Component Analysis (dVCA), and are subtracted from the single-trial. The single-trial characteristics of the evoked responses are stored to identify possible correlations with burst activity. Time-frequency (T-F), or wavelet, analyses are then applied to the single trial residuals. While T-F plots have been used in recent studies to identify and isolate bursts, we go further by fitting each burst in the T-F plot with a two-dimensional Gaussian. This provides a set of burst characteristics, such as, center time. burst duration, center frequency. frequency dispersion. and amplitude, all of which contribute to the accurate characterization of the individual burst. The burst phase can also be estimated. Burst characteristics can be quantified with several standard techniques (e.g.. histogramming and clustering), as well as Bayesian techniques (e.g., blocking) to allow a more parametric description analysis of the characteristics of oscillatory bursts, and the relationships of specific parameters to cortical excitability and stimulus integration.

The Second SWIFT Burst Alert Telescope (BAT) Gamma-Ray Burst Catalog

NASA Technical Reports Server (NTRS)

Sakamoto, T.; Barthelmy, S. D.; Baumgartner, W. H.; Cummings, J. R.; Fenimore, E. E.; Gehrels, N.; Krimm, H. A.; Markwardt, C. B.; Palmer, D. M.; Parsons, A. M.;

ADP study of gamma-ray bursts

NASA Technical Reports Server (NTRS)

Lamb, Don Q.; Wang, John C. L.; Heuter, Geoffry J.; Graziani, Carlo; Loredo, Tom; Freeman, Peter

1991-01-01

This grant supported study of cyclotron scattering lines in the spectra of gamma-ray bursts through analysis of Ginga and HEAO-1 archival data, and modeling of the results in terms of radiation transfer calculations of cyclotron scattering in a strong magnetic field. A Monte Carlo radiation transfer code with which we are able to calculate the expected properties of cyclotron scattering lines in the spectra of gamma-ray bursts was developed. The extensive software necessary in order to carry out fits of these model spectra to gamma-ray burst spectral data, including folding of the model spectra through the detector response functions was also developed. Fits to Ginga satellite data on burst GB880205 were completed and fits to Ginga satellite data on burst GB870303 are being carried out. These fits have allowed us to test our software, as well as to garner new scientific results. This work has demonstrated that cyclotron resonant scattering successfully accounts for the locations, strengths, and widths of the observed line features in GB870303 and GB880205. The success of the model provides compelling evidence that these gamma-ray bursts come from strongly magnetic neutron stars and are galactic in origin, resolving longstanding controversies about the nature and distance of the burst sources. These results were reported in two papers which are in press in the proceedings of the Taos Workshop on Gamma-Ray Bursts, and in a paper submitted for publication.

Type III Radio Burst Duration and SEP Events

NASA Technical Reports Server (NTRS)

Gopalswamy, N.; Makela, P.; Xie, H.

2010-01-01

Long-duration (>15 min), low-frequency (<14 MHz) type III radio bursts have been reported to be indicative of solar energetic particle events. We measured the durations of type III bursts associated with large SEP events of solar cycle 23. The Type III durations are distributed symmetrically at 1 MHz yielding a mean value of approximately 33 min (median = 32 min) for the large SEP events. When the SEP events with ground level enhancement (GLE,) are considered, the distribution is essentially unchanged (mean = 32 min, median = 30 min). To test the importance of type III bursts in indicating SEP events, we considered a set of six type III bursts from the same active region (AR 10588) whose durations fit the "long duration" criterion. We analyzed the coronal mass ejections (CMEs), flares, and type II radio bursts associated with the type III bursts. The CMEs were of similar speeds and the flares are also of similar size and duration. All but one of the type III bursts was not associated with a type II burst in the metric or longer wavelength domains. The burst without type II burst also lacked a solar energetic particle (SEP) event at energies >25 MeV. The 1-MHz duration of the type III burst (28 rein) is near the median value of type III durations found for gradual SEP events and ground level enhancement (GLE) events. Yet, there was no sign of SEP events. On the other hand, two other type III bursts from the same active region had similar duration but accompanied by WAVES type 11 bursts; these bursts were also accompanied by SEP events detected by SOHO/ERNE. This study suggests that the type III burst duration may not be a good indicator of an SEP event, consistent with the statistical study of Cliver and Ling (2009, ApJ ).

UWB multi-burst transmit driver for averaging receivers

DOEpatents

Dallum, Gregory E

2012-11-20

A multi-burst transmitter for ultra-wideband (UWB) communication systems generates a sequence of precisely spaced RF bursts from a single trigger event. There are two oscillators in the transmitter circuit, a gated burst rate oscillator and a gated RF burst or RF power output oscillator. The burst rate oscillator produces a relatively low frequency, i.e., MHz, square wave output for a selected transmit cycle, and drives the RF burst oscillator, which produces RF bursts of much higher frequency, i.e., GHz, during the transmit cycle. The frequency of the burst rate oscillator sets the spacing of the RF burst packets. The first oscillator output passes through a bias driver to the second oscillator. The bias driver conditions, e.g., level shifts, the signal from the first oscillator for input into the second oscillator, and also controls the length of each RF burst. A trigger pulse actuates a timing circuit, formed of a flip-flop and associated reset time delay circuit, that controls the operation of the first oscillator, i.e., how long it oscillates (which defines the transmit cycle).

Burst of reactive oxygen species in pedicel-mediated fruit abscission after carbohydrate supply was cut off in longan (Dimocarpus longan)

PubMed Central

Yang, Ziqin; Zhong, Xiumei; Fan, Yan; Wang, Huicong; Li, Jianguo; Huang, Xuming

2015-01-01

Cutting off carbohydrate supply to longan (Dimocarpus longan Lour.) fruit by girdling and defoliation or by detachment induced 100% abscission within a few days. We used these treatments to study the involvement of reactive oxygen species (ROS) in fruit abscission. Girdling plus defoliation decreased sugar concentrations in the fruit and pedicel and depleted starch grains in the chloroplasts in the cells of abscission zone. Prior to the occurrence of intensive fruit abscission, there was a burst in ROS in the pedicel, which peaked at 1 day after treatment (DAT), when H2O2 in the abscission zone was found to be chiefly located along the plasma membrane (PM). H2O2 was found exclusively in the cell walls 2 DAT, almost disappeared 3 DAT, and reappeared in the mitochondria and cell walls 4 DAT. Signs of cell death such as cytoplasm breakdown were apparent from 3 DAT. The burst of ROS coincided with a sharp increase in the activity of PM-bound NADPH oxidase in the pedicel. At the same time, activities of antioxidant enzymes including superoxide dismutase (SOD), catalase, and peroxidase (POD) were all increased by the treatment and maintained higher than those in the control. Accompanying the reduction in H2O2 abundance, there was a sharp decrease in PM-bound NADPH oxidase activity after 1 DAT in the treated fruit. H2O2 scavenger dimethylthiourea (DMTU, 1 g L–1) significantly inhibited fruit abscission in detached fruit clusters and suppressed the increase in cellulase activity in the abscission zone. These results suggest that fruit abscission induced by carbohydrate stress is mediated by ROS. Roles of ROS in regulating fruit abscission were discussed in relation to its subcellular distribution. PMID:26074931

Long-Lag, Wide-pulse Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Norris, J. P.; Bonnell, J. T.; Kazanas, D.; Scargle, . D.; Hakkila, J.; Giblin, T. W.

2004-01-01

Currently, the best available probe of the early phase of gamma-ray burst (GRB) jet attributes is the prompt gamma-ray emission, in which several intrinsic and extrinsic variables determine GRB pulse evolution. Bright, usually complex bursts have many narrow pulses that are difficult to model due to overlap. However, the relatively simple, long spectral lag, wide-pulse bursts may have simpler physics and are easier to model. In this work we analyze the temporal and spectral behavior of wide pulses in 24 long-lag bursts, using a pulse model with two shape parameters - width and asymmetry - and the Band spectral model with three shape parameters. We find that pulses in long-lag bursts are distinguished both temporally and spectrally from those in bright bursts: the pulses in long spectral lag bursts are few in number, and approximately 100 times wider (10s of seconds), have systematically lower peaks in vF(v), harder low-energy spectra and softer high-energy spectra. We find that these five pulse descriptors are essentially uncorrelated for our long-lag sample, suggesting that at least approximately 5 parameters are needed to model burst temporal and spectral behavior. However, pulse width is strongly correlated with spectral lag; hence these two parameters may be viewed as mutual surrogates. We infer that accurate formulations for estimating GRB luminosity and total energy will depend on several gamma-ray attributes, at least for long-lag bursts. The prevalence of long-lag bursts near the BATSE trigger threshold, their predominantly low vF(v) spectral peaks, and relatively steep upper power-law spectral indices indicate that Swift will detect many such bursts.

SGR J1550-5418 Bursts Detected with the Fermi Gamma-Ray Burst Monitor during Its Most Prolific Activity

NASA Technical Reports Server (NTRS)

vanderHorst, A. J.; Kouveliotou, C.; Gorgone, N. M.; Kaneko, Y.; Baring, M. G.; Guiriec, S.; Gogus, E,; Granot, J.; Watts, A. L.; Lin, L.;

Respiratory modulation of sympathetic nerve activity is enhanced in male rat offspring following uteroplacental insufficiency.

PubMed

Menuet, C; Wlodek, M E; Fong, A Y; Allen, A M

2016-06-01

Sympathetic nerve activity to the cardiovascular system displays prominent respiratory-related modulation which leads to the generation of rhythmic oscillations in blood pressure called Traube-Hering waves. An amplification of this respiratory modulation of sympathetic activity is observed in hypertension of both genetic, the spontaneously hypertensive rat, and induced, chronic intermittent hypoxia or maternal protein restriction during gestation, origin. Male offspring of mothers with uteroplacental insufficiency, induced by bilateral uterine vessel ligation at 18 days of gestation, are also hypertensive in adulthood. In this study we examined whether these male offspring display altered respiratory modulation of sympathetic activity at pre-hypertensive ages compared to controls. Respiratory, cardiovascular and sympathetic parameters were examined using the working heart-brainstem preparation in 35 day old male rats that had reduced birth weight due to uteroplacental insufficiency. Whilst all respiratory parameters were not different between groups, we observed an enhanced respiratory-related burst of thoracic sympathetic nerve activity and amplified Traube-Hering waves in the growth-restricted group. This group also showed an increased sympathetic and bradycardic response to activation of peripheral chemoreceptors. The observations add support to the view that altered respiratory modulation of sympathetic activity represents a common mechanism involved in the development of several forms of hypertension. Copyright © 2015 Elsevier B.V. All rights reserved.

Trichinella spiralis infection enhances protein kinase C phosphorylation in guinea pig alveolar macrophages.

PubMed

Dzik, J M; Zieliński, Z; Cieśla, J; Wałajtys-Rode, E

2010-03-01

To learn more about the signalling pathways involved in superoxide anion production in guinea pig alveolar macrophages, triggered by Trichinella spiralis infection, protein level and phosphorylation of mitogen activated protein (MAP) kinases and protein kinase C (PKC) were investigated. Infection with T. spiralis, the nematode having 'lung phase' during colonization of the host, enhances PKC phosphorylation in guinea pig alveolar macrophages. Isoenzymes beta and delta of PKC have been found significantly phosphorylated, although their location was not changed as a consequence of T. spiralis infection. Neither in macrophages from T. spiralis-infected guinea pig nor in platelet-activating factor (PAF)-stimulated macrophages from uninfected animals, participation of MAP kinases in respiratory burst activation was statistically significant. The parasite antigens seem to act through macrophage PAF receptors, transducing a signal for enhanced NADPH oxidase activity, as stimulating effect of newborn larvae homogenate on respiratory burst was abolished by specific PAF receptor antagonist CV 6209. A suppressive action of T. spiralis larvae on host alveolar macrophage innate immunological response was reflected by diminished protein level of ERK2 kinase and suppressed superoxide anion production, in spite of high level of PKC phosphorylation.

Gamma Ray Bursts-Afterglows and Counterparts

NASA Technical Reports Server (NTRS)

Fishman, Gerald J

1998-01-01

Several breakthrough discoveries were made last year of x-ray, optical and radio afterglows and counterparts to gamma-ray bursts, and a redshift has been associated with at least one of these. These discoveries were made possible by the fast, accurate gamma-ray burst locations of the BeppoSAX satellite. It is now generally believed that the burst sources are at cosmological distances and that they represent the most powerful explosions in the Universe. These observations also open new possibilities for the study of early star formation, the physics of extreme conditions and perhaps even cosmology. This session will concentrate on recent x-ray, optical and radio afterglow observations of gamma-ray bursts, associated redshift measurements, and counterpart observations. Several review and theory talks will also be presented, along with a summary of the astrophysical implications of the observations. There will be additional poster contributions on observations of gamma-ray burst source locations at wavelengths other than gamma rays. Posters are also solicited that describe new observational capabilities for rapid follow-up observations of gamma-ray bursts.

An assay of optimal cytochrome c oxidase activity in fish gills.

PubMed

Hu, Yau-Chung; Chung, Meng-Han; Lee, Tsung-Han

2018-07-15

Cytochrome c oxidase (COX) catalyzes the terminal oxidation reaction in the electron transport chain (ETC) of aerobic respiratory systems. COX activity is an important indicator for the evaluation of energy production by aerobic respiration in various tissues. On the basis of the respiratory characteristics of muscle, we established an optimal method for the measurement of maximal COX activity. To validate the measurement of cytochrome c absorbance, different ionic buffer concentrations and tissue homogenate protein concentrations were used to investigate COX activity. The results showed that optimal COX activity is achieved when using 50-100 μg fish gill homogenate in conjunction with 75-100 mM potassium phosphate buffer. Furthermore, we compared branchial COX activities among three species of euryhaline teleost (Chanos chanos, Oreochromis mossambicus, and Oryzias dancena) to investigate differences in aerobic respiration of osmoregulatory organs. COX activities in the gills of these three euryhaline species were compared with COX subunit 4 (COX4) protein levels. COX4 protein abundance and COX activity patterns in the three species occurring in environments with various salinities increased when fish encountered salinity challenges. This COX activity assay therefore provides an effective and accurate means of assessing aerobic metabolism in fish. Copyright © 2018 Elsevier Inc. All rights reserved.

Ubiquinol-binding site in the alternative oxidase: mutagenesis reveals features important for substrate binding and inhibition.

PubMed

Albury, Mary S; Elliott, Catherine; Moore, Anthony L

2010-12-01

The alternative oxidase (AOX) is a non-protonmotive ubiquinol oxidase that is found in all plants, some fungi, green algae, bacteria and pathogenic protozoa. The lack of AOX in the mammalian host renders this protein an important potential therapeutic target in the treatment of pathogenic protozoan infections. Bioinformatic searches revealed that, within a putative ubiquinol-binding crevice in AOX, Gln242, Asn247, Tyr253, Ser256, His261 and Arg262 were highly conserved. To confirm that these amino-acid residues are important for ubiquinol-binding and hence activity substitution mutations were generated and characterised. Assessment of AOX activity in isolated Schizosaccharomyces pombe mitochondria revealed that mutation of either Gln242, Ser256, His261 and Arg262 resulted in >90% inhibition of antimycin A-insensitive respiration suggesting that hydroxyl, guanidino, imidazole groups, polar and charged residues in addition to the size of the amino-acid chain are important for ubiquinone-binding. Substitution of Asn247 with glutamine or Tyr253 with phenylalanine had little effect upon the respiratory rate indicating that these residues are not critical for AOX activity. However replacement of Tyr253 by alanine resulted in a 72% loss of activity suggesting that the benzoquinone group and not hydroxyl group is important for quinol binding. These results provide important new insights into the ubiquinol-binding site of the alternative oxidase, the identity of which maybe important for future rational drug design. Copyright © 2010 Elsevier B.V. All rights reserved.

Quantitation of immunoadsorbed flavoprotein oxidases by luminol-mediated chemiluminescence.

PubMed

Hinkkanen, A; Maly, F E; Decker, K

1983-04-01

The detection of the flavoenzymes 6-hydroxy-L-nicotine oxidase and 6-hydroxy-D-nicotine oxidase at the sub-femtomol level was achieved by coupling the reaction of the immunoadsorbed proteins to the peroxidase-catalysed oxidation of luminol. The H2O2-producing oxidases retained their full activity when bound to the respective immobilized antibodies. This fact allowed the concentration of the enzymes from very dilute solutions and the quantitative assay of their activities in the microU range. Due to strict stereoselectivity and the absence of immunological cross-reactivity, the two flavoproteins could be determined in the same solution. This method was used to measure the 6-hydroxy-D-nicotine oxidase and 6-hydroxy-L-nicotine oxidase activities in Escherichia coli RR1 and different Arthrobacter strains cultured under non-inducing conditions. The same activity ratio of 6-hydroxy-L-nicotine oxidase/6-hydroxy-D-nicotine oxidase as in D L-nicotine-induced cells of A. oxidans was observed in non-induced wild type and in riboflavin-requiring (rf-) mutant cells of this aerob.

Homologous and Homologous like Microwave Solar Radio Bursts

NASA Astrophysics Data System (ADS)

Trevisan, R. H.; Sawant, H. S.; Kalman, B.; Gesztelyi, L.

1990-11-01

ABSTRACT. Solar radio observations at 1.6 GHz were carried out in the month of July, 1985 by using 13.7 m diameter Itapetinga antenna with time resolution of 3 ms. Homologous Bursts, with total duration of about couple of seconds and repeated by some seconds were observed associated with Homologous H- flares. These H- flares were having periodicities of about 40 min. Observed long periodicities were attributed to oscillation of prominences, and small periods were attributed to removal of plasma from the field interaction zone. Also observed are "Homologous-Like" bursts. These bursts are double peak bursts with same time profile repeating in time. In addition to this, the ratio of the total duration of the bursts to time difference in the peaks of bursts remain constant. Morphological studies of these bursts have been presented. Keq tuoit : SUN-BURSTS - SUN-FLARE

Absence of regulation of human polymorphonuclear oxidative burst by interleukin-10, interleukin-4, interleukin-13 and transforming growth factor-beta in whole blood.

PubMed

Réglier-Poupet, H; Hakim, J; Gougerot-Pocidalo, M A; Elbim, C

1998-12-01

Cytokines such as IL-10, IL-4, IL-13 and TGF-beta play a major role in the regulation of immune responses and are considered as anti-inflammatory agents mainly due to their actions on monocytes. These cytokines are also known to participate in the regulation of PMN activities. However, few and contradictory results have been reported on their direct and priming effects on the PMN oxidative burst, which is essential for killing bacteria. We used a flow cytometry method to study the effects of these cytokines on the PMN oxidative burst; we also used whole blood to avoid PMN activation related to isolation procedures and in order to simulate the in vivo situation more closely. None of the cytokines tested had direct or priming effects on PMN H2O2 production. We also show for the first time that these cytokines do not modulate TNF priming of the PMN oxidative burst in response to N-formyl peptides (fMLP). These results show that the anti-bacterial activity of PMN, in terms of the PMN respiratory burst, is not down regulated by these anti-inflammatory cytokines in whole blood.

FRBCAT: The Fast Radio Burst Catalogue

NASA Astrophysics Data System (ADS)

Petroff, E.; Barr, E. D.; Jameson, A.; Keane, E. F.; Bailes, M.; Kramer, M.; Morello, V.; Tabbara, D.; van Straten, W.

2016-09-01

Here, we present a catalogue of known Fast Radio Burst sources in the form of an online catalogue, FRBCAT. The catalogue includes information about the instrumentation used for the observations for each detected burst, the measured quantities from each observation, and model-dependent quantities derived from observed quantities. To aid in consistent comparisons of burst properties such as width and signal-to-noise ratios, we have re-processed all the bursts for which we have access to the raw data, with software which we make available. The originally derived properties are also listed for comparison. The catalogue is hosted online as a Mysql database which can also be downloaded in tabular or plain text format for off-line use. This database will be maintained for use by the community for studies of the Fast Radio Burst population as it grows.

Effects of glutamate, substance P and eledoisin-related peptide on solitary tract neurones involved in respiration and respiratory reflexes.

PubMed

Henry, J L; Sessle, B J

1985-03-01

Recent studies have implicated glutamate and substance P in synaptic transmission in the nuclei tractus solitarii and in central regulation of cardiorespiratory functions. Consequently, in chloralose-anaesthetized cats that were artificially ventilated, we examined the effects of the microiontophoretic application of both chemicals (and the substance P homologue, eledoisin-related peptide) on single neurones of the nuclei tractus solitarii implicated in the control of respiration and respiratory tract reflexes. These neurones were functionally identified as either respiratory neurones or presumed reflex interneurones, and showed functional properties comparable to those previously documented for each of these two types. The iontophoretic application of glutamate produced an excitation of rapid onset in 23 or 25 reflex interneurones tested, but the respiratory neurones showed a differential sensitivity: one type (n = 32) was "glutamate-sensitive" and showed rapid excitation with glutamate applications of less than 30 nA, the other type of respiratory neurone (n = 26) was termed "glutamate-insensitive" since it either showed excitation only with applications of 60 nA or more or showed no response even with currents up to 94 nA. Each neurone studied was clearly of one type or the other. Glutamate could increase the number of spikes per rhythmic burst and the burst duration of respiratory neurones, it facilitated evoked activity in the reflex interneurones and in those respiratory neurones having a superior laryngeal nerve or vagus nerve afferent input, and the magnitude of the excitatory responses to glutamate varied directly with the amount of ejecting current. Substance P and eledoisin-related peptide also had excitatory effects on respiratory neurones and reflex interneurones, but compared with glutamate-induced effects the excitation was slower in onset and more prolonged in after-discharge. Both rhythmic and evoked activity could be facilitated, and the magnitude

The Five Year Fermi/GBM Magnetar Burst Catalog

NASA Astrophysics Data System (ADS)

Collazzi, A. C.; Kouveliotou, C.; van der Horst, A. J.; Younes, G. A.; Kaneko, Y.; Göğüş, E.; Lin, L.; Granot, J.; Finger, M. H.; Chaplin, V. L.; Huppenkothen, D.; Watts, A. L.; von Kienlin, A.; Baring, M. G.; Gruber, D.; Bhat, P. N.; Gibby, M. H.; Gehrels, N.; McEnery, J.; van der Klis, M.; Wijers, R. A. M. J.

2015-05-01

Since launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has detected many hundreds of bursts from magnetar sources. While the vast majority of these bursts have been attributed to several known magnetars, there is also a small sample of magnetar-like bursts of unknown origin. Here, we present the Fermi/GBM magnetar catalog, providing the results of the temporal and spectral analyses of 440 magnetar bursts with high temporal and spectral resolution. This catalog covers the first five years of GBM magnetar observations, from 2008 July to 2013 June. We provide durations, spectral parameters for various models, fluences, and peak fluxes for all the bursts, as well as a detailed temporal analysis for SGR J1550-5418 bursts. Finally, we suggest that some of the bursts of unknown origin are associated with the newly discovered magnetar 3XMM J185246.6+0033.7.

X-ray observations of the burst source MXB 1728 - 34

NASA Technical Reports Server (NTRS)

Basinska, E. M.; Lewin, W. H. G.; Sztajno, M.; Cominsky, L. R.; Marshall, F. J.

1984-01-01

Where sufficient information has been obtained, attention is given to the maximum burst flux, integrated burst flux, spectral hardness, rise time, etc., of 96 X-ray bursts observed from March 1976 to March 1979. The integrated burst flux and the burst frequency appear to be correlated; the longer the burst interval, the larger the integrated burst flux, as expected on the basis of simple thermonuclear flash models. The maximum burst flux and the integrated burst flux are strongly correlated; for low flux levels their dependence is approximately linear, while for increasing values of the integrated burst flux, the flux at burst maximum saturates and reaches a plateau.

Correlation Between Monoamine Oxidase Inhibitors and Anticonvulsants

PubMed Central

Dwivedi, Chandradhar; Misra, Radhey S.; Chaudhari, Anshumali; Parmar, Surendra S.

1980-01-01

Monoamine oxidase inhibitory and anticonvulsant properties of 2-substituted styryl-6-bromo-3-(4-ethylbenzoate/4 benzhydrazide)-4-quinazoles are studied. All styryl quinazolone esters except compound number 9 exhibited monoamine oxidase inhibitory properties during oxidative deamination of kynuramine. Corresponding hydrazides were found to have relatively higher activity. All these quinazolones were able to protect against pentylenetetrazol induced seizures. These observations in general do not prove that monoamine oxidase inhibitory properties represent the biochemical basis for the anticonvulsant activity of these compounds. PMID:7420438

Bioenergetics at extreme temperature: Thermus thermophilus ba(3)- and caa(3)-type cytochrome c oxidases.

PubMed

Radzi Noor, Mohamed; Soulimane, Tewfik

2012-04-01

Seven years into the completion of the genome sequencing projects of the thermophilic bacterium Thermus thermophilus strains HB8 and HB27, many questions remain on its bioenergetic mechanisms. A key fact that is occasionally overlooked is that oxygen has a very limited solubility in water at high temperatures. The HB8 strain is a facultative anaerobe whereas its relative HB27 is strictly aerobic. This has been attributed to the absence of nitrate respiration genes from the HB27 genome that are carried on a mobilizable but highly-unstable plasmid. In T. thermophilus, the nitrate respiration complements the primary aerobic respiration. It is widely known that many organisms encode multiple biochemically-redundant components of the respiratory complexes. In this minireview, the presence of the two cytochrome c oxidases (CcO) in T. thermophilus, the ba(3)- and caa(3)-types, is outlined along with functional considerations. We argue for the distinct evolutionary histories of these two CcO including their respective genetic and molecular organizations, with the caa(3)-oxidase subunits having been initially 'fused'. Coupled with sequence analysis, the ba(3)-oxidase crystal structure has provided evolutionary and functional information; for example, its subunit I is more closely related to archaeal sequences than bacterial and the substrate-enzyme interaction is hydrophobic as the elevated growth temperature weakens the electrostatic interactions common in mesophiles. Discussion on the role of cofactors in intra- and intermolecular electron transfer and proton pumping mechanism is also included. Copyright © 2011 Elsevier B.V. All rights reserved.

SOME COMMENTS ON TYPE IV BURSTS

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

Tanaka, H.; Kakinuma, T.

1962-01-01

It has become clear that a large continuum burst is composed of 4 distinctive types, CM/sub 1/, CM/sub 2/, DM, and IV, which originate from different altitudes over the photosphere. The observational characters of each type are given. CM/sub 1/ is the main phase of a centimeter-wave burst originating from about 0.02-0.05 R/sub S/ in height. DM burst is polarized in the ordinary sense, which is the cause of reversal of polarization with frequency. Its center frequency lies between about 1000 and 200 Mc/s, and is often misunderstood as the original Type IV burst. The movement of magnetic field duringmore » a burst is suggested. CM/sub 2/ may be considered as an enhancement of the upper part of the source of S-component caused by this movement of the field. (auth)« less

Mam33 promotes cytochrome c oxidase subunit I translation in Saccharomyces cerevisiae mitochondria.

PubMed

Roloff, Gabrielle A; Henry, Michael F

2015-08-15

Three mitochondrial DNA-encoded proteins, Cox1, Cox2, and Cox3, comprise the core of the cytochrome c oxidase complex. Gene-specific translational activators ensure that these respiratory chain subunits are synthesized at the correct location and in stoichiometric ratios to prevent unassembled protein products from generating free oxygen radicals. In the yeast Saccharomyces cerevisiae, the nuclear-encoded proteins Mss51 and Pet309 specifically activate mitochondrial translation of the largest subunit, Cox1. Here we report that Mam33 is a third COX1 translational activator in yeast mitochondria. Mam33 is required for cells to adapt efficiently from fermentation to respiration. In the absence of Mam33, Cox1 translation is impaired, and cells poorly adapt to respiratory conditions because they lack basal fermentative levels of Cox1. © 2015 Roloff and Henry. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Herringbone bursts associated with type II solar radio emission

NASA Technical Reports Server (NTRS)

Cairns, I. H.; Robinson, R. D.

1987-01-01

Detailed observations of the herringbone (HB) fine structure on type II solar radio bursts are presented. Data from the Culgoora radiospectrograph, radiometer and radioheliograph are analyzed. The characteristic spectral profiles, frequency drift rates and exciter velocities, fluxes, source sizes, brightness temperatures, and polarizations of individual HB bursts are determined. Correlations between individual bursts within the characteristic groups of bursts and the properties of the associated type II bursts are examined. These data are compatible with HB bursts being radiation at multiples of the plasma frequency generated by electron streams accelerated by the type II shock. HB bursts are physically distinct phenomena from type II and type III bursts, differing significantly in emission processes and/or source conditions; this conclusion indicates that many of the presently available theoretical ideas for HB bursts are incorrect.

An Ephemeral Burst-Buffer File System for Scientific Applications

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

Wang, Teng; Moody, Adam; Yu, Weikuan

BurstFS is a distributed file system for node-local burst buffers on high performance computing systems. BurstFS presents a shared file system space across the burst buffers so that applications that use shared files can access the highly-scalable burst buffers without changing their applications.

Regulation of tyramine oxidase synthesis in Klebsiella aerogenes.

PubMed Central

Okamura, H; Murooka, Y; Harada, T

1976-01-01

Tyramine oxidase in Klebsiella aerogenes is highly specific for tyramine, dopamine, octopamine, and norepinephrine, and its synthesis is induced specifically by these compounds. The enzyme is present in a membrane-bound form. The Km value for tyramine is 9 X 10(-4) M. Tyramine oxidase synthesis was subjected to catabolite repression by glucose in the presence of ammonium salts. Addition of cyclic adenosine 3',5'-monophosphate (cAMP) overcame the catabolite repression. A mutant strain, K711, which can produce a high level of beta-galactosidase in the presence of glucose and ammonium chloride, can also synthesize tyramine oxidase and histidase in the presence of inducer in glucose ammonium medium. Catabolite repression of tyramine oxidase synthesis was relieved when the cells were grown under conditions of nitrogen limitation, whereas beta-galactosidase was strongly repressed under these conditions. A cAMP-requiring mutant, MK54, synthesized tyramine oxidase rapidly when tyramine was used as the sole source of nitrogen in the absence of cAMP. However, a glutamine synthetase-constitutive mutant, MK94, failed to synthesize tyramine oxidase in the presence of glucose and ammonium chloride, although it synthesized histidase rapidly under these conditions. These results suggest that catabolite repression of tyramine oxidase synthesis in K. aerogenes is regulated by the intracellular level of cAMP and an unknown cytoplasmic factor that acts independently of cAMP and is formed under conditions of nitrogen limitation. PMID:179974

Gating of proton and water transfer in the respiratory enzyme cytochrome c oxidase.

PubMed

Wikström, Mårten; Ribacka, Camilla; Molin, Mika; Laakkonen, Liisa; Verkhovsky, Michael; Puustinen, Anne

2005-07-26

The membrane-bound enzyme cytochrome c oxidase is responsible for cell respiration in aerobic organisms and conserves free energy from O2 reduction into an electrochemical proton gradient by coupling the redox reaction to proton-pumping across the membrane. O2 reduction produces water at the bimetallic heme a3/CuB active site next to a hydrophobic cavity deep within the membrane. Water molecules in this cavity have been suggested to play an important role in the proton-pumping mechanism. Here, we show by molecular dynamics simulations that the conserved arginine/heme a3 delta-propionate ion pair provides a gate, which exhibits reversible thermal opening that is governed by the redox state and the water molecules in the cavity. An important role of this gate in the proton-pumping mechanism is supported by site-directed mutagenesis experiments. Transport of the product water out of the enzyme must be rigidly controlled to prevent water-mediated proton leaks that could compromise the proton-pumping function. Exit of product water is observed through the same arginine/propionate gate, which provides an explanation for the observed extraordinary spatial specificity of water expulsion from the enzyme.

Dark gamma-ray bursts

NASA Astrophysics Data System (ADS)

Brdar, Vedran; Kopp, Joachim; Liu, Jia

2017-03-01

Many theories of dark matter (DM) predict that DM particles can be captured by stars via scattering on ordinary matter. They subsequently condense into a DM core close to the center of the star and eventually annihilate. In this work, we trace DM capture and annihilation rates throughout the life of a massive star and show that this evolution culminates in an intense annihilation burst coincident with the death of the star in a core collapse supernova. The reason is that, along with the stellar interior, also its DM core heats up and contracts, so that the DM density increases rapidly during the final stages of stellar evolution. We argue that, counterintuitively, the annihilation burst is more intense if DM annihilation is a p -wave process than for s -wave annihilation because in the former case, more DM particles survive until the supernova. If among the DM annihilation products are particles like dark photons that can escape the exploding star and decay to standard model particles later, the annihilation burst results in a flash of gamma rays accompanying the supernova. For a galactic supernova, this "dark gamma-ray burst" may be observable in the Čerenkov Telescope Array.

Long-Lag, Wide-pulse Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Norris, J. P.; Bonnell, J. T.; Kazanas, D.; Scargie, J. D.; Hakkila, J.; Giblin, T. W.

2005-01-01

The best available probe of the early phase of gamma-ray burst (GRB) jet attributes is the prompt gamma-ray emission, in which several intrinsic and extrinsic variables determine observed GRB pulse evolution, including at least: jet opening angle, profiles of Lorentz factor and matter/field density, distance of emission region from central source, and viewing angle. Bright, usually complex bursts have many narrow pulses that are difficult to model due to overlap. However, the relatively simple, long spectral lag, wide-pulse bursts may have simpler physics and are easier to model. We have analyzed the temporal and spectral behavior of wide pulses in 24 long-lag bursts from the BATSE sample, using a pulse model with two shape parameters - width and asymmetry - and the Band spectral model with three shape parameters. We find that pulses in long-lag bursts are distinguished both temporally and spectrally from those in bright bursts: the pulses in long spectral lag bursts are few in number, and approximately 100 times wider (10s of seconds), have systemtically lower peaks in nu*F(nu), harder low-energy spectra and softer high-energy spectra. These five pulse descriptors are essentially uncorrelated for our long-lag sample, suggesting that at least approximately 5 parameters are needed to model burst temporal and spectral behavior, roughly commensurate with the theoretical phase space. However, we do find that pulse width is strongly correlated with spectral lag; hence these two parameters may be viewed as mutual surrogates. The prevalence of long-lag bursts near the BATSE trigger threshold, their predominantly low nu*F(nu) spectral peaks, and relatively steep upper power-law spectral indices indicate that Swiift will detect many such bursts.

BURST AND OUTBURST CHARACTERISTICS OF MAGNETAR 4U 0142+61

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

Göğüş, Ersin; Chakraborty, Manoneeta; Kaneko, Yuki

2017-01-20

We have compiled the most comprehensive burst sample from magnetar 4U 0142+61, comprising 27 bursts from its three burst-active episodes in 2011, 2012 and the latest one in 2015 observed with Swift /Burst Alert Telescope and Fermi /Gamma-ray Burst Monitor. Bursts from 4U 0142+61 morphologically resemble typical short bursts from other magnetars. However, 4U 0142+61 bursts are less energetic compared to the bulk of magnetar bursts. We uncovered an extended tail emission following a burst on 2015 February 28, with a thermal nature, cooling over a timescale of several minutes. During this tail emission, we also uncovered pulse peak phasemore » aligned X-ray bursts, which could originate from the same underlying mechanism as that of the extended burst tail, or an associated and spatially coincident but different mechanism.« less

Burst-type noise mechanisms in bipolar transistors

NASA Astrophysics Data System (ADS)

Wu, X. L.; van der Ziel, A.; Birbas, A. N.; van Rheenen, A. D.

1989-11-01

Two types of burst noise have been observed in silicon bipolar transistors. They can be characterized by the typical frequency dependence of their current fluctuation spectra. Interestingly, observation of the noise signal in the time domain gives two distinctively different pictures of the bistable waveform. Also, amplification of the noise signal yields different sounds when fed to a speaker. One of the noise spectra is the superposition of 1/ƒ noise and a Lorentzian component (burst noise) and the other can be described mathematically as 1/ƒ noise modulated by the burst noise. The classification of those two types of burst noise and the mathematical explanation will lead to a better understanding of the bipolar transistor burst noise itself.

Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

PubMed Central

Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

2013-01-01

The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

In vivo and in vitro evidences that carotenoids could modulate the neutrophil respiratory burst during dietary manipulation.

PubMed

Walrand, Stéphane; Farges, Marie-Chantal; Dehaese, Olivier; Cardinault, Nicolas; Minet-Quinard, Régine; Grolier, Pascal; Bouteloup-Demange, Corinne; Ribalta, Josep; Winklhofer-Roob, Brigitte M; Rock, Edmond; Vasson, Marie-Paule

2005-03-01

The primary role of polymorphonuclear neutrophils (PMNs) is to destroy pathogenic microorganisms after phagocytosis by producing reactive oxygen species (ROS) and toxic molecules. However, PMNs produce sufficient amounts of ROS during an oxidative burst to be autotoxic and detrimental to their own functions and to possibly cause DNA damage, protein and lipid oxidation and cell membrane destructuration. The aim of this study was to investigate in vivo the role of the antioxidant capacities of carotenoids in modulating ROS content in PMNs during oxidative burst. Moreover to investigate the direct or indirect effect of carotenoids, the modification of PMN ROS content was explored after in vitro supplementation with beta-carotene or lycopene, chosen taking account of their vitamin A and no vitamin A precursor effect, respectively. In vivo study: Venous blood was collected from 10 healthy male volunteers and ROS production from phorbol myristate acetate (PMA)-stimulated PMNs was determined, by flow cytometry using the fluorescent dye dihydrorhodamine 123, at baseline, after 3 weeks of carotenoid depletion (carotenoid intake limited to 25% of usual intake) and after 5 weeks of carotenoid repletion (30 mg beta-carotene, 15 mg lycopene and 9 mg lutein per day). In vitro study: ROS content in PMA-stimulated PMNs isolated from carotenoid depleted subjects and controls was quantified after an in vitro enrichment with beta-carotene (1 micromol/L) or lycopene (0.3 micromol/L). In vivo carotenoid depletion increased PMN H2O2 content after PMA activation by 38% (p < 0.05 vs baseline),while supplementation for 5 weeks restored basal H2O2 generation (p < 0.05 vs depletion). Although H2O2 measurement in PMNs from non-depleted subjects was not affected by an in vitro supply with beta-carotene or lycopene, a significant decrease in H2O2 content by 78.9 % and 81.2%, respectively, was observed in PMNs from carotenoid depleted subjects (p < 0.01 vs depleted control subjects). The

Abdominal expiratory activity in the rat brainstem–spinal cord in situ: patterns, origins and implications for respiratory rhythm generation

PubMed Central

Abdala, A P L; Rybak, I A; Smith, J C; Paton, J F R

2009-01-01

We studied respiratory neural activity generated during expiration. Motoneuronal activity was recorded simultaneously from abdominal (AbN), phrenic (PN), hypoglossal (HN) and central vagus nerves from neonatal and juvenile rats in situ. During eupnoeic activity, low-amplitude post-inspiratory (post-I) discharge was only present in AbN motor outflow. Expression of AbN late-expiratory (late-E) activity, preceding PN bursts, occurred during hypercapnia. Biphasic expiratory (biphasic-E) activity with pre-inspiratory (pre-I) and post-I discharges occurred only during eucapnic anoxia or hypercapnic anoxia. Late-E activity generated during hypercapnia (7–10% CO2) was abolished with pontine transections or chemical suppression of retrotrapezoid nucleus/ventrolateral parafacial (RTN/vlPF). AbN late-E activity during hypercapnia is coupled with augmented pre-I discharge in HN, truncated PN burst, and was quiescent during inspiration. Our data suggest that the pons provides a necessary excitatory drive to an additional neural oscillatory mechanism that is only activated under conditions of high respiratory drive to generate late-E activity destined for AbN motoneurones. This mechanism may arise from neurons located in the RTN/vlPF or the latter may relay late-E activity generated elsewhere. We hypothesize that this oscillatory mechanism is not a necessary component of the respiratory central pattern generator but constitutes a defensive mechanism activated under critical metabolic conditions to provide forced expiration and reduced upper airway resistance simultaneously. Possible interactions of this oscillator with components of the brainstem respiratory network are discussed. PMID:19491247

The Double Firing Burst

NASA Astrophysics Data System (ADS)

2008-09-01

Astronomers from around the world combined data from ground- and space-based telescopes to paint a detailed portrait of the brightest explosion ever seen. The observations reveal that the jets of the gamma-ray burst called GRB 080319B were aimed almost directly at the Earth. Uncovering the disc ESO PR Photo 28/08 A Gamma-Ray Burst with Two Jets Read more on this illuminating blast in the additional story. GRB 080319B was so intense that, despite happening halfway across the Universe, it could have been seen briefly with the unaided eye (ESO 08/08). In a paper to appear in the 11 September issue of Nature, Judith Racusin of Penn State University, Pennsylvania (USA), and a team of 92 co-authors report observations across the electromagnetic spectrum that began 30 minutes before the explosion and followed it for months afterwards. "We conclude that the burst's extraordinary brightness arose from a jet that shot material almost directly towards Earth at almost the speed of light - the difference is only 1 part in 20 000," says Guido Chincarini, a member of the team. Gamma-ray bursts are the Universe's most luminous explosions. Most occur when massive stars run out of fuel. As a star collapses, it creates a black hole or neutron star that, through processes not fully understood, drives powerful gas jets outward. As the jets shoot into space, they strike gas previously shed by the star and heat it, thereby generating bright afterglows. The team believes the jet directed toward Earth contained an ultra-fast component just 0.4 degrees across (this is slightly smaller than the apparent size of the Full Moon). This jet is contained within another slightly less energetic jet about 20 times wider. The broad component is more typical of other bursts. "Perhaps every gamma-ray burst has a narrow jet, but astronomers miss it most of the time," says team member Stefano Covino. "We happened to view this monster down the barrel of the very narrow and energetic jet, and the chance for

Transcriptional coupling of synaptic transmission and energy metabolism: role of nuclear respiratory factor 1 in co-regulating neuronal nitric oxide synthase and cytochrome c oxidase genes in neurons.

PubMed

Dhar, Shilpa S; Liang, Huan Ling; Wong-Riley, Margaret T T

2009-10-01

Neuronal activity is highly dependent on energy metabolism; yet, the two processes have traditionally been regarded as independently regulated at the transcriptional level. Recently, we found that the same transcription factor, nuclear respiratory factor 1 (NRF-1) co-regulates an important energy-generating enzyme, cytochrome c oxidase, as well as critical subunits of glutamatergic receptors. The present study tests our hypothesis that the co-regulation extends to the next level of glutamatergic synapses, namely, neuronal nitric oxide synthase, which generates nitric oxide as a downstream signaling molecule. Using in silico analysis, electrophoretic mobility shift assay, chromatin immunoprecipitation, promoter mutations, and NRF-1 silencing, we documented that NRF-1 functionally bound to Nos1, but not Nos2 (inducible) and Nos3 (endothelial) gene promoters. Both COX and Nos1 transcripts were up-regulated by depolarizing KCl treatment and down-regulated by TTX-mediated impulse blockade in neurons. However, NRF-1 silencing blocked the up-regulation of both Nos1 and COX induced by KCl depolarization, and over-expression of NRF-1 rescued both Nos1 and COX transcripts down-regulated by TTX. These findings are consistent with our hypothesis that synaptic neuronal transmission and energy metabolism are tightly coupled at the molecular level.

Physics of Gamma Ray Burst Sources

NASA Technical Reports Server (NTRS)

Meszaros, Peter

2004-01-01

During this grant period, the physics of gamma-ray bursts was investigated. A number of new results have emerged. The importance of pair formation in high compactness burst spectra may help explain x-ray flashes; a universal jet shape is a likely explanation for the distribution of jet break times; gravitational waves may be copiously produced both in short bursts from compact mergers and in long bursts arising from collapsars; x-ray iron lines are likely to be due to interaction with the stellar atmosphere of the progenitor; prompt optical flashes from reverse shocks will give diagnostics on the Lorentz factor and the environment; GeV and TeV emission from bursts may be expected in the external shock; etc. The group working with the PI included postdocs Dr. Bing Zhang (now assistant professor at University of Nevada); Dr. Shiho Kobayashi; graduate student Lijun Gou; collaborators Drs. Tim Kallman and Martin Rees. Meszaros shared with Rees and Dr. Bohan Paczynsky the AAS Rossi Prize in 2000 for their work on the theory of gamma ray bursts. The refereed publications and conference proceedings resulting from this research are summarized below. The PI gave a number of invited talks at major conferences, also listed.

Gravity Responsive NADH Oxidase of the Plasma Membrane

NASA Technical Reports Server (NTRS)

Morre, D. James (Inventor)

2002-01-01

A method and apparatus for sensing gravity using an NADH oxidase of the plasma membrane which has been found to respond to unit gravity and low centrifugal g forces. The oxidation rate of NADH supplied to the NADH oxidase is measured and translated to represent the relative gravitational force exerted on the protein. The NADH oxidase of the plasma membrane may be obtained from plant or animal sources or may be produced recombinantly.

"Short, Hard Gamma-Ray Bursts - Mystery Solved?????"

NASA Technical Reports Server (NTRS)

Parsons, A.

2006-01-01

After over a decade of speculation about the nature of short-duration hard-spectrum gamma-ray bursts (GRBs), the recent detection of afterglow emission from a small number of short bursts has provided the first physical constraints on possible progenitor models. While the discovery of afterglow emission from long GRBs was a real breakthrough linking their origin to star forming galaxies, and hence the death of massive stars, the progenitors, energetics, and environments for short gamma-ray burst events remain elusive despite a few recent localizations. Thus far, the nature of the host galaxies measured indicates that short GRBs arise from an old (> 1 Gyr) stellar population, strengthening earlier suggestions and providing support for coalescing compact object binaries as the progenitors. On the other hand, some of the short burst afterglow observations cannot be easily explained in the coalescence scenario. These observations raise the possibility that short GRBs may have different or multiple progenitors systems. The study of the short-hard GRB afterglows has been made possible by the Swift Gamma-ray Burst Explorer, launched in November of 2004. Swift is equipped with a coded aperture gamma-ray telescope that can observe up to 2 steradians of the sky and can compute the position of a gamma-ray burst to within 2-3 arcmin in less than 10 seconds. The Swift spacecraft can slew on to this burst position without human intervention, allowing its on-board x ray and optical telescopes to study the afterglow within 2 minutes of the original GRB trigger. More Swift short burst detections and afterglow measurements are needed before we can declare that the mystery of short gamma-ray burst is solved.

GLAST's GBM Burst Trigger

NASA Technical Reports Server (NTRS)

Band, D.; Briggs, M.; Connaughton, V.; Kippen, M.; Preece, R.

2003-01-01

The GLAST Burst Monitor (GBM) will detect and localize bursts for the GLAST mission, and provide the spectral and temporal context in the traditional 10 keV to 25 MeV band for the high energy observations by the Large Area Telescope (LAT). The GBM will use traditional rate triggers in up to three energy bands, and on a variety of timescales between 16 ms and 16 s.

Acute morphine effects on respiratory activity in mice with target deletion of the tachykinin 1 gene (Tac1-/-).

PubMed

Shvarev, Yuri; Berner, Jonas; Bilkei-Gorzo, Andras; Lagercrantz, Hugo; Wickström, Ronny

2010-01-01

Search for physiological mechanisms which could antagonize the opioid-induced respiratory depression is of important clinical value. In this study, we investigated the acute effects of morphine on respiratory activity in genetically modified newborn (P2) mice with target deletion of the (Tac1 -/-) gene lacking substance P (SP) and neurokinin A (NKA). In vivo, as shown with whole-body flow barometric plethysmography technique, morphine induced significantly attenuated minute ventilation during intermittent hypoxia in control animals. In contrast, knockout mice revealed significant increase in minute ventilation. In vitro, in brainstem preparation, knockout mice demonstrated greater changes in burst frequency during intermittent anoxia challenge. The data suggest that hereditary deficiency in tachykinins, SP and NKA results in more robust hypoxic response in newborn Tac1-/- mice during respiratory depression induced by morphine.

Immobilization of Pichia pastoris cells containing alcohol oxidase activity

PubMed Central

Maleknia, S; Ahmadi, H; Norouzian, D

2011-01-01

Background and Objectives The attempts were made to describe the development of a whole cell immobilization of P. pastoris by entrapping the cells in polyacrylamide gel beads. The alcohol oxidase activity of the whole cell Pichia pastoris was evaluated in comparison with yeast biomass production. Materials and Methods Methylotrophic yeast P. pastoris was obtained from Collection of Standard Microorganisms, Department of Bacterial Vaccines, Pasteur Institute of Iran (CSMPI). Stock culture was maintained on YPD agar plates. Alcohol oxidase was strongly induced by addition of 0.5% methanol as the carbon source. The cells were harvested by centrifugation then permeabilized. Finally the cells were immobilized in polyacrylamide gel beads. The activity of alcohol oxidase was determined by method of Tane et al. Results At the end of the logarithmic phase of cell culture, the alcohol oxidase activity of the whole cell P. Pastoris reached the highest level. In comparison, the alcohol oxidase activity was measured in an immobilized P. pastoris when entrapped in polyacrylamide gel beads. The alcohol oxidase activity of cells was induced by addition of 0.5% methanol as the carbon source. The cells were permeabilized by cetyltrimethylammonium bromide (CTAB) and immobilized. CTAB was also found to increase the gel permeability. Alcohol oxidase activity of immobilized cells was then quantitated by ABTS/POD spectrophotometric method at OD 420. There was a 14% increase in alcohol oxidase activity in immobilized cells as compared with free cells. By addition of 2-butanol as a substrate, the relative activity of alcohol oxidase was significantly higher as compared with other substrates added to the reaction media. Conclusion Immobilization of cells could eliminate lengthy and expensive procedures of enzyme separation and purification, protect and stabilize enzyme activity, and perform easy separation of the enzyme from the reaction media. PMID:22530090

Optimal Codes for the Burst Erasure Channel

NASA Technical Reports Server (NTRS)

Hamkins, Jon

2010-01-01

Deep space communications over noisy channels lead to certain packets that are not decodable. These packets leave gaps, or bursts of erasures, in the data stream. Burst erasure correcting codes overcome this problem. These are forward erasure correcting codes that allow one to recover the missing gaps of data. Much of the recent work on this topic concentrated on Low-Density Parity-Check (LDPC) codes. These are more complicated to encode and decode than Single Parity Check (SPC) codes or Reed-Solomon (RS) codes, and so far have not been able to achieve the theoretical limit for burst erasure protection. A block interleaved maximum distance separable (MDS) code (e.g., an SPC or RS code) offers near-optimal burst erasure protection, in the sense that no other scheme of equal total transmission length and code rate could improve the guaranteed correctible burst erasure length by more than one symbol. The optimality does not depend on the length of the code, i.e., a short MDS code block interleaved to a given length would perform as well as a longer MDS code interleaved to the same overall length. As a result, this approach offers lower decoding complexity with better burst erasure protection compared to other recent designs for the burst erasure channel (e.g., LDPC codes). A limitation of the design is its lack of robustness to channels that have impairments other than burst erasures (e.g., additive white Gaussian noise), making its application best suited for correcting data erasures in layers above the physical layer. The efficiency of a burst erasure code is the length of its burst erasure correction capability divided by the theoretical upper limit on this length. The inefficiency is one minus the efficiency. The illustration compares the inefficiency of interleaved RS codes to Quasi-Cyclic (QC) LDPC codes, Euclidean Geometry (EG) LDPC codes, extended Irregular Repeat Accumulate (eIRA) codes, array codes, and random LDPC codes previously proposed for burst erasure

Modification of medullary respiratory-related discharge patterns by behaviors and states of arousal.

PubMed

Chang, F C

1992-02-07

The modulatory influences of behaviors and states of arousal on bulbar respiratory-related unit (RRU) discharge patterns were studied in an unanesthetized, freely behaving guinea pig respiratory model system. When fully instrumented, this model system permits concurrent monitoring and recording of (i) single units from either Bötzinger complex or nucleus para-ambiguus; (ii) electrocorticogram; and, (iii) diaphragmatic EMG. In addition to being used in surveys of RRU discharge patterns in freely behaving states, the model system also offered a unique opportunity in investigating the effects of pentobarbital on RRU discharge patterns before, throughout the course of, and during recovery from anesthesia. In anesthetized preparations, a particular RRU discharge pattern (such as tonic, incrementing or decrementing) typically displayed little, if any notable variation. The most striking development following pentobarbital was a state of progressive bradypnea attributable to a significantly augmented RRU cycle duration, burst duration and an increase in the RRU spike frequencies during anesthesia. In freely behaving states, medullary RRU activities rarely adhered to a fixed, immutable discharge pattern. More specifically, the temporal organization (such as burst duration, cycle duration, and the extent of modulation of within-burst spike frequencies) of RRU discharge patterns regularly showed complex and striking variations, not only with states of arousal (sleep/wakefulness, anesthesia) but also with discrete alterations in electrocorticogram (ECoG) activities and a multitude of on-going behavioral repertoires such as volitional movement, postural modification, phonation, mastication, deglutition, sniffing/exploratory behavior, alerting/startle reflexes. Only during sleep, and on occasions when the animal assumed a motionless, resting posture, could burst patterns of relatively invariable periodicity and uniform temporal attributes be observed. RRU activities during

Chondrocyte burst promotes space for mineral expansion.

PubMed

Hara, Emilio Satoshi; Okada, Masahiro; Nagaoka, Noriyuki; Hattori, Takako; Iida, Letycia Mary; Kuboki, Takuo; Nakano, Takayoshi; Matsumoto, Takuya

2018-01-22

Analysis of tissue development from multidisciplinary approaches can result in more integrative biological findings, and can eventually allow the development of more effective bioengineering methods. In this study, we analyzed the initial steps of mineral formation during secondary ossification of mouse femur based on biological and bioengineering approaches. We first found that some chondrocytes burst near the mineralized area. External factors that could trigger chondrocyte burst were then investigated. Chondrocyte burst was shown to be modulated by mechanical and osmotic pressure. A hypotonic solution, as well as mechanical stress, significantly induced chondrocyte burst. We further hypothesized that chondrocyte burst could be associated with space-making for mineral expansion. In fact, ex vivo culture of femur epiphysis in hypotonic conditions, or under mechanical pressure, enhanced mineral formation, compared to normal culture conditions. Additionally, the effect of mechanical pressure on bone formation in vivo was investigated by immobilization of mouse lower limbs to decrease the body pressure onto the joints. The results showed that limb immobilization suppressed bone formation. Together, these results suggest chondrocyte burst as a novel fate of chondrocytes, and that manipulation of chondrocyte burst with external mechano-chemical stimuli could be an additional approach for cartilage and bone tissue engineering.

Observations of energitic radiation bursts from thunder activities

NASA Astrophysics Data System (ADS)

Tsuchiya, H.; Enoto, T.; Torii, T.; Yuasa, T.; Yamada, S.; Kitacuhi, T.; Nakazawa, K.; Kato, H.; Okano, M.; Makishima, K.

2009-04-01

Energetic radiation bursts have been observed during strong thunderstorms by ground-based detectors as well as high-mountain ones. Those radiation bursts are thought to result from runaway electrons originating from electrons accelerated by strong electric field in lightning discharges and thunderclouds, and hence provide a valuable key to understand particle acceleration in thunder activity. Interestingly, they can be categorized into two bursts by their duration. One consists of short bursts lasting for milli-seconds or less. The other comprises long bursts having duration of a few seconds. In order to better understand both short and long bursts, we have conducted experiments at coastal area of the Japan Sea and a 2770-m altitude observatory. In this talk, we will report on those experiments, showing the two experiments has successfully observed both short and long bursts. Especially, we will focus on high-energy radiations extending over MeV energies, and then discuss a plausible model to explain how those high-energy radiations are produced in thunder activity.

Stimulation of Respiratory Motor Output and Ventilation in a Murine Model of Pompe Disease by Ampakines.

PubMed

ElMallah, Mai K; Pagliardini, Silvia; Turner, Sara M; Cerreta, Anthony J; Falk, Darin J; Byrne, Barry J; Greer, John J; Fuller, David D

2015-09-01

Pompe disease results from a mutation in the acid α-glucosidase gene leading to lysosomal glycogen accumulation. Respiratory insufficiency is common, and the current U.S. Food and Drug Administration-approved treatment, enzyme replacement, has limited effectiveness. Ampakines are drugs that enhance α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor responses and can increase respiratory motor drive. Recent work indicates that respiratory motor drive can be blunted in Pompe disease, and thus pharmacologic stimulation of breathing may be beneficial. Using a murine Pompe model with the most severe clinical genotype (the Gaa(-/-) mouse), our primary objective was to test the hypothesis that ampakines can stimulate respiratory motor output and increase ventilation. Our second objective was to confirm that neuropathology was present in Pompe mouse medullary respiratory control neurons. The impact of ampakine CX717 on breathing was determined via phrenic and hypoglossal nerve recordings in anesthetized mice and whole-body plethysmography in unanesthetized mice. The medulla was examined using standard histological methods coupled with immunochemical markers of respiratory control neurons. Ampakine CX717 robustly increased phrenic and hypoglossal inspiratory bursting and reduced respiratory cycle variability in anesthetized Pompe mice, and it increased inspiratory tidal volume in unanesthetized Pompe mice. CX717 did not significantly alter these variables in wild-type mice. Medullary respiratory neurons showed extensive histopathology in Pompe mice. Ampakines stimulate respiratory neuromotor output and ventilation in Pompe mice, and therefore they have potential as an adjunctive therapy in Pompe disease.

EGRET observations of bursts at MeV energies

NASA Astrophysics Data System (ADS)

Catelli, J. R.; Dingus, B. L.; Schneid, E. J.

1998-05-01

We present preliminary results from the analysis of 16 bright bursts that have been observed by the EGRET NaI calorimeter, or TASC. Seven bursts have been imaged in the EGRET spark chamber above 30 MeV, but in most cases the TASC data gives the highest energy spectra available for these bursts. The TASC can obtain spectral and rate information for bursts well outside the field of view of the EGRET spark chambers, and is sensitive in the energy range from 1 to 200 MeV. The spectra for these bursts are mostly consistent with a simple power law with spectral index in the range from 1.7 to 3.7, with several of the brighter bursts showing emission past 100 MeV. No high energy cutoff has been observed. These high energy photons offer important clues to the physical processes involved at the origin of burst emission. For bursts at cosmological distances extremely high bulk Lorentz factors are implied by the presence of MeV and GeV photons which have not been attenuated by pair production with the lower energy photons from the source.

The Fermi-GBM Three-year X-Ray Burst Catalog

NASA Astrophysics Data System (ADS)

Jenke, P. A.; Linares, M.; Connaughton, V.; Beklen, E.; Camero-Arranz, A.; Finger, M. H.; Wilson-Hodge, C. A.

2016-08-01

The Fermi Gamma-ray Burst Monitor (GBM) is an all-sky gamma-ray monitor well known in the gamma-ray burst (GRB) community. Although GBM excels in detecting the hard, bright extragalactic GRBs, its sensitivity above 8 keV and its all-sky view make it an excellent instrument for the detection of rare, short-lived Galactic transients. In 2010 March, we initiated a systematic search for transients using GBM data. We conclude this phase of the search by presenting a three-year catalog of 1084 X-ray bursts. Using spectral analysis, location, and spatial distributions we classified the 1084 events into 752 thermonuclear X-ray bursts, 267 transient events from accretion flares and X-ray pulses, and 65 untriggered gamma-ray bursts. All thermonuclear bursts have peak blackbody temperatures broadly consistent with photospheric radius expansion (PRE) bursts. We find an average rate of 1.4 PRE bursts per day, integrated over all Galactic bursters within about 10 kpc. These include 33 and 10 bursts from the ultra-compact X-ray binaries 4U 0614+09 and 2S 0918-549, respectively. We discuss these recurrence times and estimate the total mass ejected by PRE bursts in our Galaxy.

Classification of Radiological Changes in Burst Fractures

PubMed Central

Şentürk, Salim; Öğrenci, Ahmet; Gürçay, Ahmet Gürhan; Abdioğlu, Ahmet Atilla; Yaman, Onur; Özer, Ali Fahir

2018-01-01

AIM: Burst fractures can occur with different radiological images after high energy. We aimed to simplify radiological staging of burst fractures. METHODS: Eighty patients whom exposed spinal trauma and had burst fracture were evaluated concerning age, sex, fracture segment, neurological deficit, secondary organ injury and radiological changes that occurred. RESULTS: We performed a new classification in burst fractures at radiological images. CONCLUSIONS: According to this classification system, secondary organ injury and neurological deficit can be an indicator of energy exposure. If energy is high, the clinical status will be worse. Thus, we can get an idea about the likelihood of neurological deficit and secondary organ injuries. This classification has simplified the radiological staging of burst fractures and is a classification that gives a very accurate idea about the neurological condition. PMID:29531604

Crystal Structure of Alcohol Oxidase from Pichia pastoris

PubMed Central

Valerius, Oliver; Feussner, Ivo; Ficner, Ralf

2016-01-01

FAD-dependent alcohol oxidases (AOX) are key enzymes of methylotrophic organisms that can utilize lower primary alcohols as sole source of carbon and energy. Here we report the crystal structure analysis of the methanol oxidase AOX1 from Pichia pastoris. The crystallographic phase problem was solved by means of Molecular Replacement in combination with initial structure rebuilding using Rosetta model completion and relaxation against an averaged electron density map. The subunit arrangement of the homo-octameric AOX1 differs from that of octameric vanillyl alcohol oxidase and other dimeric or tetrameric alcohol oxidases, due to the insertion of two large protruding loop regions and an additional C-terminal extension in AOX1. In comparison to other alcohol oxidases, the active site cavity of AOX1 is significantly reduced in size, which could explain the observed preference for methanol as substrate. All AOX1 subunits of the structure reported here harbor a modified flavin adenine dinucleotide, which contains an arabityl chain instead of a ribityl chain attached to the isoalloxazine ring. PMID:26905908

Calcium transport in vesicles energized by cytochrome oxidase

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

Rosier, Randy N.

1979-01-01

Experiments on the reconstitution of cytochrome oxidase into phospholipid vesicles were carried out using techniques of selectivity energizing the suspensions with ascorbate and cytochrome c or ascorbate, PMS, and internally trapped cytochrome c. It was found that the K + selective ionophore valinomycin stimulated the rate of respiration of cytochrome oxidase vesicles regardless of the direction of the K + flux across the vesicle membranes. The stimulation occurred in the presence of protonophoric uncouplers and in the complete absence of potassium or in detergent-lysed suspensions. Gramicidin had similar effects and it was determined that the ionophores acted by specific interactionmore » with cytochrome oxidase rather than by the previously assumed collapse of membrane potentials. When hydrophobic proteins and appropriate coupling factors were incorporated into the cytochrome oxidase, vesicles phosphorylation of ADP could be coupled to the oxidation reaction of cytochrome oxidase. Relatively low P:O, representing poor coupling of the system, were problematical and precluded measurements of protonmotive force. However the system was used to study ion translocation.« less

Importance of the alternative oxidase (AOX) pathway in regulating cellular redox and ROS homeostasis to optimize photosynthesis during restriction of the cytochrome oxidase pathway in Arabidopsis thaliana.

PubMed

Vishwakarma, Abhaypratap; Tetali, Sarada Devi; Selinski, Jennifer; Scheibe, Renate; Padmasree, Kollipara

2015-09-01

The importance of the alternative oxidase (AOX) pathway, particularly AOX1A, in optimizing photosynthesis during de-etiolation, under elevated CO2, low temperature, high light or combined light and drought stress is well documented. In the present study, the role of AOX1A in optimizing photosynthesis was investigated when electron transport through the cytochrome c oxidase (COX) pathway was restricted at complex III. Leaf discs of wild-type (WT) and aox1a knock-out mutants of Arabidopsis thaliana were treated with antimycin A (AA) under growth-light conditions. To identify the impact of AOX1A deficiency in optimizing photosynthesis, respiratory O2 uptake and photosynthesis-related parameters were measured along with changes in redox couples, reactive oxygen species (ROS), lipid peroxidation and expression levels of genes related to respiration, the malate valve and the antioxidative system. In the absence of AA, aox1a knock-out mutants did not show any difference in physiological, biochemical or molecular parameters compared with WT. However, after AA treatment, aox1a plants showed a significant reduction in both respiratory O2 uptake and NaHCO3-dependent O2 evolution. Chlorophyll fluorescence and P700 studies revealed that in contrast to WT, aox1a knock-out plants were incapable of maintaining electron flow in the chloroplastic electron transport chain, and thereby inefficient heat dissipation (low non-photochemical quenching) was observed. Furthermore, aox1a mutants exhibited significant disturbances in cellular redox couples of NAD(P)H and ascorbate (Asc) and consequently accumulation of ROS and malondialdehyde (MDA) content. By contrast, WT plants showed a significant increase in transcript levels of CSD1, CAT1, sAPX, COX15 and AOX1A in contrast to aox1a mutants. These results suggest that AOX1A plays a significant role in sustaining the chloroplastic redox state and energization to optimize photosynthesis by regulating cellular redox homeostasis and ROS

NICER Eyes on Bursting Stars

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2018-03-01

What happens to a neutron stars accretion disk when its surface briefly explodes? A new instrument recently deployed at the International Space Station (ISS) is now watching bursts from neutron stars and reporting back.Deploying a New X-Ray MissionLaunch of NICER aboard a Falcon 9 rocket in June 2017. [NASA/Tony Gray]In early June of 2017, a SpaceX Dragon capsule on a Falcon 9 rocket launched on a resupply mission to the ISS. The pressurized interior of the Dragon contained the usual manifest of crew supplies, spacewalk equipment, and vehicle hardware. But the unpressurized trunk of the capsule held something a little different: the Neutron star Interior Composition Explorer (NICER).In the two weeks following launch, NICER was extracted from the SpaceX Dragon capsule and installed on the ISS. And by the end of the month, the instrument was already collecting its first data set: observations of a bright X-ray burst from Aql X-1, a neutron star accreting matter from a low-mass binary companion.Impact of BurstsNICERs goal is to provide a new view of neutron-star physics at X-ray energies of 0.212 keV a window that allows us to explore bursts of energy that neutron stars sometimes emit from their surfaces.Artists impression of an X-ray binary, in which a compact object accretes material from a companion star. [ESA/NASA/Felix Mirabel]In X-ray burster systems, hydrogen- and helium-rich material from a low-mass companion star piles up in an accretion disk around the neutron star. This material slowly funnels onto the neutron stars surface, forming a layer that gravitationally compresses and eventually becomes so dense and hot that runaway nuclear fusion ignites.Within seconds, the layer of material is burned up, producing a burst of emission from the neutron star that outshines even the inner regions of the hot accretion disk. Then more material funnels onto the neutron star and the process begins again.Though we have a good picture of the physics that causes these bursts

The Third BATSE Gamma-Ray Burst Catalog

NASA Technical Reports Server (NTRS)

Meegan, Charles A.; Pendleton, Geoffrey N.; Briggs, Michael S.; Kouveliotou, Chryssa; Koshut, Thomas M.; Lestrade, John Patrick; Paciesas, William S.; McCollough, Michael L.; Brainerd, Jerome J.; Horack, John M.;

Prompt optical emission from gamma-ray bursts

NASA Astrophysics Data System (ADS)

Kehoe, Robert; Akerlof, Karl; Balsano, Richard; Barthelmy, Scott; Bloch, Jeff; Butterworth, Paul; Casperson, Don; Cline, Tom; Fletcher, Sandra; Frontera, Fillippo; Gisler, Galen; Heise, John; Hills, Jack; Hurley, Kevin; Lee, Brian; Marshall, Stuart; McKay, Tim; Pawl, Andrew; Piro, Luigi; Priedhorsky, Bill; Szymanski, John; Wren, Jim

The Robotic Optical Transient Search Experiment (ROTSE) seeks to measure contemporaneous and early afterglow optical emission from gamma-ray bursts (GRBs). The ROTSE-I telescope array has been fully automated and responding to burst alerts from the GRB Coordinates Network since March 1998, taking prompt optical data for 30 bursts in its first year. We will briefly review observations of GRB990123 which revealed the first detection of an optical burst occurring during the gamma-ray emission, reaching 9th magnitude at its peak. In addition, we present here preliminary optical results for seven other gamma-ray bursts. No other optical counterparts were seen in this analysis, and the best limiting senisitivities are mV > 13.0 at 14.7 seconds after the gamma-ray rise, and mmV > 16.4 at 62 minutes. These are the most stringent limits obtained for GRB optical counterpart brightness in the first hour after the burst. This analysis suggests that there is not a strong correlation between optical flux and gamma-ray emission.

Pressure vessel burst test program - Initial program paper

NASA Technical Reports Server (NTRS)

Cain, Maurice R.; Sharp, Douglas E.; Coleman, Michael D.; Webb, Bobby L.

1990-01-01

The current status of a pressure vessel burst test program, aimed at the study of the blast waves and fragmentation characteristics of ruptured gas-filled pressure vessels, is reported. The program includes a series of test plans, each involving multiple bursts with burst pressures ranging to 7500 psig. The discussion covers the identification of concerns and hazards, application of the data generated, and a brief review of the current methods for assessing vessel safety and burst parameters. Attention is also given to pretest activities, including completed vessel and facility/instrumentation preparation and results of completed preliminary burst tests.

An Early Tobacco Mosaic Virus-Induced Oxidative Burst in Tobacco Indicates Extracellular Perception of the Virus Coat Protein1

PubMed Central

Allan, Andrew C.; Lapidot, Moshe; Culver, James N.; Fluhr, Robert

2001-01-01

Induction of reactive oxygen species (ROS) was observed within seconds of the addition of exogenous tobacco mosaic virus (TMV) to the outside of tobacco (Nicotiana tabacum cv Samsun NN, EN, or nn) epidermal cells. Cell death was correlated with ROS production. Infectivity of the TMV virus was not a prerequisite for this elicitation and isolated coat protein (CP) subunits could also elicit the fast oxidative burst. The rapid induction of ROS was prevented by both inhibitors of plant signal transduction and inhibitors of NAD(P)H oxidases, suggesting activation of a multi-step signal transduction pathway. Induction of intracellular ROS by TMV was detected in TMV-resistant and -susceptible tobacco cultivars isogenic for the N allele. The burst was also detected with strains of virus that either elicit (ToMV) or fail to elicit (TMV U1) N′ gene-mediated responses. Hence, early ROS generation is independent or upstream of known genetic systems in tobacco that can mediate hypersensitive responses. Analysis of other viruses and TMV CP mutants showed marked differences in their ability to induce ROS showing specificity of the response. Thus, initial TMV-plant cell interactions that lead to early ROS induction occur outside the plasma membrane in an event requiring specific CP epitopes. PMID:11351074

A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I.

PubMed Central

Brown, M D; Yang, C C; Trounce, I; Torroni, A; Lott, M T; Wallace, D C

1992-01-01

A G-to-A transition at nucleotide pair (np) 7444 in the mtDNA was found to correlate with Leber hereditary optic neuropathy (LHON). The mutation eliminates the termination codon of the cytochrome c oxidase subunit I (COI) gene, extending the COI polypeptide by three amino acids. The mutation was discovered as an XbaI restriction-endonuclease-site loss present in 2 (9.1%) of 22 LHON patients who lacked the np 11778 LHON mutation and in 6 (1.1%) of 545 unaffected controls. The mutant polypeptide has an altered mobility on SDS-PAGE, suggesting a structural alteration, and the cytochrome c oxidase enzyme activity of patient lymphocytes is reduced approximately 40% relative to that in controls. These data suggest that the np 7444 mutation results in partial respiratory deficiency and thus contributes to the onset of LHON. Images Figure 1 Figure 3 PMID:1322638

Swift Gamma-Ray Burst Explorer: Mission Design for Rapid, Accurate Location of Gamma-ray Bursts

NASA Technical Reports Server (NTRS)

Bundas, David J.

2004-01-01

The Swift Gamma-ray Burst Explorer is a NASA Mid-sized Explorer (MIDEX) with the primary mission of determining the origins of Gamma-Ray Bursts (GRBs). It will be the first mission to autonomously respond to newly-discovered GRBs and provide immediate follow-up with narrow field instruments capable of multi-wavelength (UV, Optical, X-ray) observations. The characteristics of GRBs that are the key mission design drivers, are their non-repeating and brief duration bursts of multi-wavelength photons. In addition, rapid notification of the location and characteristics of the GRBs to ground-and-space-based observatories drive the end-to-end data analysis and distribution requirements.

Swift Gamma-ray Burst Explorer: Mission Design for Rapid, Accurate Location of Gamma-ray Bursts

NASA Technical Reports Server (NTRS)

Bundas, David J.

2005-01-01

The Swift Gamma-ray Burst Explorer is a NASA Mid-sized Explorer (MIDEX) with the primary mission of determining the origins of Gamma-Ray Bursts (GRBs). It will be the first mission to autonomously respond to newly-discovered GRBs and provide immediate follow-up with narrow field instruments capable of multi-wavelength (UT, Optical, X-ray) observations. The characteristics of GRBs that are the key mission design drivers, are their non-repeating and brief duration bursts of multi-wavelength photons. In addition, rapid notification of the location and characteristics of the GRBs to ground-and-space-based observatories drive the end-to-end data analysis and distribution requirements.

A Novel QKD-based Secure Edge Router Architecture Design for Burst Confidentiality in Optical Burst Switched Networks

NASA Astrophysics Data System (ADS)

Balamurugan, A. M.; Sivasubramanian, A.

2014-06-01

The Optical Burst Switching (OBS) is an emergent result to the technology issue that could achieve a viable network in future. They have the ability to meet the bandwidth requisite of those applications that call for intensive bandwidth. The field of optical transmission has undergone numerous advancements and is still being researched mainly due to the fact that optical data transmission can be done at enormous speeds. The concept of OBS is still far from perfection facing issues in case of security threat. The transfer of optical switching paradigm to optical burst switching faces serious downfall in the fields of burst aggregation, routing, authentication, dispute resolution and quality of service (QoS). This paper proposes a framework based on QKD based secure edge router architecture design to provide burst confidentiality. The QKD protocol offers high level of confidentiality as it is indestructible. The design architecture was implemented in FPGA using diverse models and the results were taken. The results show that the proposed model is suitable for real time secure routing applications of the Optical burst switched networks.

Selenium delays tomato fruit ripening by inhibiting ethylene biosynthesis and enhancing the antioxidant defense system.

PubMed

Zhu, Zhu; Chen, Yanli; Shi, Guoqing; Zhang, Xueji

2017-03-15

The antioxidant activity of selenium (Se) detoxifies reactive oxygen species (ROS) in plants and animals. In the present study, we elucidated the mechanism underlying Se induced fruit development and ripening. Our study showed that foliar pretreatment with 1mgL -1 sodium selenate effectively delayed fruit ripening and maintained fruit quality. Gene expression studies revealed that the repression of ethylene biosynthetic genes 1-aminocyclopropane-1-carboxylic acid (ACC) synthase and ACC oxidase decreased ethylene production and respiration rate. Moreover, Se treatment probably boosted the antioxidant defense system to reduce ROS generation and membrane damage. The enhanced antioxidative effect was attributed to higher glutathione content and increased activity of enzymes such as glutathione peroxidase and glutathione reductase. The upregulation of respiratory burst oxidase homologue genes in tomato fruit may also contribute to the enhanced antioxidative effect. Selenium treatment represents a promising strategy for delaying ripening and extending the shelf life of tomato fruit. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pacific oyster polyamine oxidase: a protein missing link in invertebrate evolution.

PubMed

Cervelli, Manuela; Polticelli, Fabio; Angelucci, Emanuela; Di Muzio, Elena; Stano, Pasquale; Mariottini, Paolo

2015-05-01

Polyamine oxidases catalyse the oxidation of polyamines and acetylpolyamines and are responsible for the polyamine interconversion metabolism in animal cells. Polyamine oxidases from yeast can oxidize spermine, N(1)-acetylspermine, and N(1)-acetylspermidine, while in vertebrates two different enzymes, namely spermine oxidase and acetylpolyamine oxidase, specifically catalyse the oxidation of spermine, and N(1)-acetylspermine/N(1)-acetylspermidine, respectively. In this work we proved that the specialized vertebrate spermine and acetylpolyamine oxidases have arisen from an ancestor invertebrate polyamine oxidase with lower specificity for polyamine substrates, as demonstrated by the enzymatic activity of the mollusc polyamine oxidase characterized here. This is the first report of an invertebrate polyamine oxidase, the Pacific oyster Crassostrea gigas (CgiPAO), overexpressed as a recombinant protein. This enzyme was biochemically characterized and demonstrated to be able to oxidase both N(1)-acetylspermine and spermine, albeit with different efficiency. Circular dichroism analysis gave an estimation of the secondary structure content and modelling of the three-dimensional structure of this protein and docking studies highlighted active site features. The availability of this pluripotent enzyme can have applications in crystallographic studies and pharmaceutical biotechnologies, including anticancer therapy as a source of hydrogen peroxide able to induce cancer cell death.

3rd Interplanetary Network Gamma-Ray Burst Website

NASA Astrophysics Data System (ADS)

Hurley, Kevin

1998-05-01

We announce the opening of the 3rd Interplanetary Network web site at http://ssl.berkeley.edu/ipn3/index.html This site presently has four parts: 1. A bibliography of over 3000 publications on gamma-ray bursts, 2. IPN data on all bursts triangulated up to February 1998, 3. A master list showing which spacecraft observed which bursts, 4. Preliminary IPN data on the latest bursts observed.

Evolution of cytochrome oxidase, an enzyme older than atmospheric oxygen.

PubMed

Castresana, J; Lübben, M; Saraste, M; Higgins, D G

1994-06-01

Cytochrome oxidase is a key enzyme in aerobic metabolism. All the recorded eubacterial (domain Bacteria) and archaebacterial (Archaea) sequences of subunits 1 and 2 of this protein complex have been used for a comprehensive evolutionary analysis. The phylogenetic trees reveal several processes of gene duplication. Some of these are ancient, having occurred in the common ancestor of Bacteria and Archaea, whereas others have occurred in specific lines of Bacteria. We show that eubacterial quinol oxidase was derived from cytochrome c oxidase in Gram-positive bacteria and that archaebacterial quinol oxidase has an independent origin. A considerable amount of evidence suggests that Proteobacteria (Purple bacteria) acquired quinol oxidase through a lateral gene transfer from Gram-positive bacteria. The prevalent hypothesis that aerobic metabolism arose several times in evolution after oxygenic photosynthesis, is not sustained by two aspects of the molecular data. First, cytochrome oxidase was present in the common ancestor of Archaea and Bacteria whereas oxygenic photosynthesis appeared in Bacteria. Second, an extant cytochrome oxidase in nitrogen-fixing bacteria shows that aerobic metabolism is possible in an environment with a very low level of oxygen, such as the root nodules of leguminous plants. Therefore, we propose that aerobic metabolism in organisms with cytochrome oxidase has a monophyletic and ancient origin, prior to the appearance of eubacterial oxygenic photosynthetic organisms.

Observational properties of decameter type IV bursts

NASA Astrophysics Data System (ADS)

Melnik, Valentin; Brazhenko, Anatoly; Rucker, Helmut; Konovalenko, Alexander; Briand, Carine; Dorovskyy, Vladimir; Zarka, Philippe; Frantzusenko, Anatoly; Panchenko, Michael; Poedts, Stefan; Zaqarashvili, Teimuraz; Shergelashvili, Bidzina

2013-04-01

Oscillations of decameter type IV bursts were registered during observations of solar radio emission by UTR-2, URAN-2 and NDA in 2011-2012. Large majority of these bursts were accompanied by coronal mass ejections (CMEs), which were observed by SOHO and STEREO in the visible light. Only in some cases decameter type IV bursts were not associated with CMEs. The largest periods of oscillations P were some tens of minutes. There were some modes of long periods of oscillations simultaneously. Periods of oscillations in flux and in polarization profiles were close. Detailed properties of oscillations at different frequencies were analyzed on the example of two type IV bursts. One of them was observed on April 7, 2011 when a CME happened. Another one (August 1, 2011) was registered without any CME. The 7 April type IV burst had two periods in the frames 75-85 and 35-85 minutes. Interesting feature of these oscillations is decreasing periods with time. The observed decreasing rates dP/dt equaled 0.03-0.07. Concerning type IV burst observed on August 1, 2011 the period of its oscillations increases from 17 min. at 30 MHz to 44 min. at 10 MHz. Connection of type IV burst oscillations with oscillations of magnetic arches and CMEs at corresponding altitudes are discussed. The work is fulfilled in the frame of FP7 project "SOLSPANET".

The hemibiotrophic cacao pathogen Moniliophthora perniciosa depends on a mitochondrial alternative oxidase for biotrophic development

PubMed Central

Thomazella, Daniela P T; Teixeira, Paulo José P L; Oliveira, Halley C; Saviani, Elzira E; Rincones, Johana; Toni, Isabella M; Reis, Osvaldo; Garcia, Odalys; Meinhardt, Lyndel W; Salgado, Ione; Pereira, Gonçalo A G

2012-01-01

The tropical pathogen Moniliophthora perniciosa causes witches’ broom disease in cacao. As a hemibiotrophic fungus, it initially colonizes the living host tissues (biotrophic phase), and later grows over the dead plant (necrotrophic phase). Little is known about the mechanisms that promote these distinct fungal phases or mediate the transition between them. An alternative oxidase gene (Mp-aox) was identified in the M. perniciosa genome and its expression was analyzed througout the fungal life cycle. In addition, the effects of inhibitors of the cytochrome-dependent respiratory chain (CRC) and alternative oxidase (AOX) were evaluated on the in vitro development of M. perniciosa. Larger numbers of Mp-aox transcripts were observed in the biotrophic hyphae, which accordingly showed elevated sensitivity to AOX inhibitors. More importantly, the inhibition of CRC prevented the transition from the biotrophic to the necrotrophic phase, and the combined use of a CRC and AOX inhibitor completely halted fungal growth. On the basis of these results, a novel mechanism is presented in which AOX plays a role in the biotrophic development of M. perniciosa and regulates the transition to its necrotrophic stage. Strikingly, this model correlates well with the infection strategy of animal pathogens, particularly Trypanosoma brucei, which uses AOX as a strategy for pathogenicity. PMID:22443281

The human burst suppression electroencephalogram of deep hypothermia.

PubMed

Westover, M Brandon; Ching, Shinung; Kumaraswamy, Vishakhadatta M; Akeju, Seun Oluwaseun; Pierce, Eric; Cash, Sydney S; Kilbride, Ronan; Brown, Emery N; Purdon, Patrick L

2015-10-01

Deep hypothermia induces 'burst suppression' (BS), an electroencephalogram pattern with low-voltage 'suppressions' alternating with high-voltage 'bursts'. Current understanding of BS comes mainly from anesthesia studies, while hypothermia-induced BS has received little study. We set out to investigate the electroencephalogram changes induced by cooling the human brain through increasing depths of BS through isoelectricity. We recorded scalp electroencephalograms from eleven patients undergoing deep hypothermia during cardiac surgery with complete circulatory arrest, and analyzed these using methods of spectral analysis. Within patients, the depth of BS systematically depends on the depth of hypothermia, though responses vary between patients except at temperature extremes. With decreasing temperature, burst lengths increase, and burst amplitudes and lengths decrease, while the spectral content of bursts remains constant. These findings support an existing theoretical model in which the common mechanism of burst suppression across diverse etiologies is the cyclical diffuse depletion of metabolic resources, and suggest the new hypothesis of local micro-network dropout to explain decreasing burst amplitudes at lower temperatures. These results pave the way for accurate noninvasive tracking of brain metabolic state during surgical procedures under deep hypothermia, and suggest new testable predictions about the network mechanisms underlying burst suppression. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Inhibition of Human Vascular NADPH Oxidase by Apocynin Derived Oligophenols

PubMed Central

Mora-Pale, Mauricio; Weïwer, Michel; Yu, Jingjing; Linhardt, Robert J.; Dordick, Jonathan S.

2009-01-01

Enzymatic oxidation of apocynin, which may mimic in vivo metabolism, affords a large number of oligomers (apocynin oxidation products, AOP) that inhibit vascular NADPH oxidase. In vitro studies of NADPH oxidase activity were performed to identify active inhibitors, resulting in a trimer hydroxylated quinone (IIIHyQ) that inhibited NADPH oxidase with an IC50 = 31 nM. Apocynin itself possessed minimal inhibitory activity. NADPH oxidase is believed to be inhibited through prevention of the interaction between two NADPH oxidase subunits, p47phox and p22phox. To that end, while apocynin was unable to block the interaction of his-tagged p47phox with a surface immobilized biotinalyted p22phox peptide, the IIIHyQ product strongly interfered with this interaction (apparent IC50 = 1.6 μM). These results provide evidence that peroxidase-catalyzed AOP, which consist of oligomeric phenols and quinones, inhibit critical interactions that are involved in the assembly and activation of human vascular NADPH oxidase. PMID:19523836

Molecular-clinical correlation in a family with a novel heteroplasmic Leigh syndrome missense mutation in the mitochondrial cytochrome c oxidase III gene.

PubMed

Mkaouar-Rebai, Emna; Ellouze, Emna; Chamkha, Imen; Kammoun, Fatma; Triki, Chahnez; Fakhfakh, Faiza

2011-01-01

Cytochrome c oxidase is an essential component of the mitochondrial respiratory chain that catalyzes the reduction of molecular oxygen by reduced cytochrome c. In this study, the authors report the second mutation associated with Leigh syndrome in the blood and buccal mucosa of 2 affected members of a Tunisian family. It was a novel heteroplasmic missense mitochondrial mutation at nucleotide 9478 in the gene specifying subunit III of cytochrome c oxidase substituting the valine at position 91 to alanine in a highly conserved amino acid. It was found with a high mutant load in tissues derived from endoderm (buccal mucosa) and mesoderm (blood). However, it was nearly absent in tissue derived from ectoderm (hair follicles). It was absent in 120 healthy controls, and PolyPhen analysis showed that the hydropathy index changed from +1.276 to +0.242, and the number of structures of the 3D protein decreased from 39 to 32.

Current status of NADPH oxidase research in cardiovascular pharmacology.

PubMed

Rodiño-Janeiro, Bruno K; Paradela-Dobarro, Beatriz; Castiñeiras-Landeira, María Isabel; Raposeiras-Roubín, Sergio; González-Juanatey, José R; Alvarez, Ezequiel

2013-01-01

The implications of reactive oxygen species in cardiovascular disease have been known for some decades. Rationally, therapeutic antioxidant strategies combating oxidative stress have been developed, but the results of clinical trials have not been as good as expected. Therefore, to move forward in the design of new therapeutic strategies for cardiovascular disease based on prevention of production of reactive oxygen species, steps must be taken on two fronts, ie, comprehension of reduction-oxidation signaling pathways and the pathophysiologic roles of reactive oxygen species, and development of new, less toxic, and more selective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors, to clarify both the role of each NADPH oxidase isoform and their utility in clinical practice. In this review, we analyze the value of NADPH oxidase as a therapeutic target for cardiovascular disease and the old and new pharmacologic agents or strategies to prevent NADPH oxidase activity. Some inhibitors and different direct or indirect approaches are available. Regarding direct NADPH oxidase inhibition, the specificity of NADPH oxidase is the focus of current investigations, whereas the chemical structure-activity relationship studies of known inhibitors have provided pharmacophore models with which to search for new molecules. From a general point of view, small-molecule inhibitors are preferred because of their hydrosolubility and oral bioavailability. However, other possibilities are not closed, with peptide inhibitors or monoclonal antibodies against NADPH oxidase isoforms continuing to be under investigation as well as the ongoing search for naturally occurring compounds. Likewise, some different approaches include inhibition of assembly of the NADPH oxidase complex, subcellular translocation, post-transductional modifications, calcium entry/release, electron transfer, and genetic expression. High-throughput screens for any of these activities could provide new

Current status of NADPH oxidase research in cardiovascular pharmacology

PubMed Central

Rodiño-Janeiro, Bruno K; Paradela-Dobarro, Beatriz; Castiñeiras-Landeira, María Isabel; Raposeiras-Roubín, Sergio; González-Juanatey, José R; Álvarez, Ezequiel

2013-01-01

The implications of reactive oxygen species in cardiovascular disease have been known for some decades. Rationally, therapeutic antioxidant strategies combating oxidative stress have been developed, but the results of clinical trials have not been as good as expected. Therefore, to move forward in the design of new therapeutic strategies for cardiovascular disease based on prevention of production of reactive oxygen species, steps must be taken on two fronts, ie, comprehension of reduction-oxidation signaling pathways and the pathophysiologic roles of reactive oxygen species, and development of new, less toxic, and more selective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors, to clarify both the role of each NADPH oxidase isoform and their utility in clinical practice. In this review, we analyze the value of NADPH oxidase as a therapeutic target for cardiovascular disease and the old and new pharmacologic agents or strategies to prevent NADPH oxidase activity. Some inhibitors and different direct or indirect approaches are available. Regarding direct NADPH oxidase inhibition, the specificity of NADPH oxidase is the focus of current investigations, whereas the chemical structure-activity relationship studies of known inhibitors have provided pharmacophore models with which to search for new molecules. From a general point of view, small-molecule inhibitors are preferred because of their hydrosolubility and oral bioavailability. However, other possibilities are not closed, with peptide inhibitors or monoclonal antibodies against NADPH oxidase isoforms continuing to be under investigation as well as the ongoing search for naturally occurring compounds. Likewise, some different approaches include inhibition of assembly of the NADPH oxidase complex, subcellular translocation, post-transductional modifications, calcium entry/release, electron transfer, and genetic expression. High-throughput screens for any of these activities could provide new

Testing the Gamma-Ray Burst Energy Relationships

NASA Technical Reports Server (NTRS)

Band, David L.; Preece, Robert D.

2005-01-01

Building on Nakar & Piran's analysis of the Amati relation relating gamma-ray burst peak energies E(sub p) and isotropic energies E(sub iso ) we test the consistency of a large sample of BATSE bursts with the Amati and Ghirlanda (which relates peak energies and actual gamma-ray energies E(sub gamma)) relations. Each of these relations can be exp ressed as a ratio of the different energies that is a function of red shift (for both the Amati and Ghirlanda relations) and beaming fraction f(sub B) (for the Ghirlanda relation). The most rigorous test, whic h allows bursts to be at any redshift, corroborates Nakar & Piran's r esult - 88% of the BATSE bursts are inconsistent with the Amati relat ion - while only l.6% of the bursts are inconsistent with the Ghirlan da relation if f(sub B) = 1. Modelling the redshift distribution resu lts in an energy ratio distribution for the Amati relation that is sh ifted by an order of magnitude relative to the observed distributions; any sub-population satisfying the Amati relation can comprise at mos t approx. 18% of our burst sample. A similar analysis of the Ghirland a relation depends sensitively on the beaming fraction distribution f or small values of f(sub B); for reasonable estimates of this distrib ution about a third of the burst sample is inconsistent with the Ghir landa relation. Our results indicate that these relations are an artifact of the selection effects of the burst sample in which they were f ound; these selection effects may favor sub-populations for which the se relations are valid.

New decoding methods of interleaved burst error-correcting codes

NASA Astrophysics Data System (ADS)

Nakano, Y.; Kasahara, M.; Namekawa, T.

1983-04-01

A probabilistic method of single burst error correction, using the syndrome correlation of subcodes which constitute the interleaved code, is presented. This method makes it possible to realize a high capability of burst error correction with less decoding delay. By generalizing this method it is possible to obtain probabilistic method of multiple (m-fold) burst error correction. After estimating the burst error positions using syndrome correlation of subcodes which are interleaved m-fold burst error detecting codes, this second method corrects erasure errors in each subcode and m-fold burst errors. The performance of these two methods is analyzed via computer simulation, and their effectiveness is demonstrated.

The supernova-gamma-ray burst-jet connection.

PubMed

Hjorth, Jens

2013-06-13

The observed association between supernovae and gamma-ray bursts represents a cornerstone in our understanding of the nature of gamma-ray bursts. The collapsar model provides a theoretical framework for this connection. A key element is the launch of a bipolar jet (seen as a gamma-ray burst). The resulting hot cocoon disrupts the star, whereas the (56)Ni produced gives rise to radioactive heating of the ejecta, seen as a supernova. In this discussion paper, I summarize the observational status of the supernova-gamma-ray burst connection in the context of the 'engine' picture of jet-driven supernovae and highlight SN 2012bz/GRB 120422A--with its luminous supernova but intermediate high-energy luminosity--as a possible transition object between low-luminosity and jet gamma-ray bursts. The jet channel for supernova explosions may provide new insights into supernova explosions in general.

Flash photoionization of gamma-ray burst environments

NASA Technical Reports Server (NTRS)

Band, David L.; Hartmann, Dieter H.

1992-01-01

The H-alpha line emission that a flash-photoionized region emits is calculated. Archival transients, as well as various theoretical predictions, suggest that there may be significant ionizing flux. The limits on the line flux which might be observable indicate that the density must be fairly high for the recombination radiation to be observable. The intense burst radiation is insufficient to melt the dust which will be present in such a dense medium. This dust may attenuate the observable line emission, but does not attenuate the ionizing radiation before it ionizes the neutral medium surrounding the burst source. The dust can also produce a light echo. If there are indeed gamma-ray bursts in dense clouds, then it is possible that the burst was triggered by Bondi-Hoyle accretion from the dense medium, although it is unlikely on statistical grounds that all bursts occur in clouds.

Kilometric shock-associated events and microwave bursts

NASA Technical Reports Server (NTRS)

Kundu, M. R.; Macdowall, R. J.; Stone, R. G.

1990-01-01

The peak times of impulsive microwaves bursts are compared with those of shock-associated (SA) kilometric radio events. The first peaks in these two frequency regimes are usually well-correlated in time, but the last peaks of the SA events observed at 1 MHz occur an average of 20 min after the last impulsive microwave peaks. In some cases, the SA events overlap in time with the post-burst increases of microwave bursts; sometimes there is general correspondence in their intensity time profiles. These observations suggest that the earlier components of the SA events are usually caused by electrons accelerated in or near the microwave source region. The possibility that the later components of some SA events could be associated with nonthermal electrons responsible for microwave post-burst increases, although they have traditionally been attributed to electrons accelerated at type II burst producing shocks in the upper corona is discussed.

Oxygen activation in flavoprotein oxidases: the importance of being positive.

PubMed

Gadda, Giovanni

2012-04-03

The oxidation of flavin hydroquinones by O(2) in solution is slow, with second-order rate constants of ~250 M(-1) s(-1). This is due to the obligatory, single-electron transfer that initiates the reaction being thermodynamically unfavored and poorly catalyzed. Notwithstanding considerations of O(2) accessibility to the reaction site, its desolvation and geometry and other factors that can also contribute to further rate acceleration, flavoprotein oxidases must activate O(2) for reaction with flavin hydroquinones to be able to achieve the 100-1000-fold rate enhancements typically observed. Protein positive charges have been identified in glucose oxidase, monomeric sarcosine oxidase, N-methyltryptophan oxidase and fructosamine oxidase that electrostatically stabilize the transition state for the initial single electron transfer that generates the O(2)(-•)/flavin semiquinone radical pair. In choline oxidase despite the presence of three histidines in the active site, the trimethylammonium group of the reaction product provides such an electrostatic stabilization. A nonpolar site proximal to the flavin C(4a) atom in choline oxidase has also been identified, which contributes to the geometry and desolvation of the O(2) reaction site. The relevance of O(2) activation by product charges to other flavoprotein oxidases, such as for example those catalyzing amine oxidations, is discussed in this review. A nonpolar site close to the flavin C(4a) atom and a positive charge is identified through structural analysis in several flavoprotein oxidases. Mutagenesis has disclosed nonpolar sites in O(2)-reducing enzymes that utilize copper/TPQ or iron. It is predicted that classes of O(2)-reducing enzymes utilizing other cofactors also contain a similar catalytic motif.

Simulating X-ray bursts during a transient accretion event

NASA Astrophysics Data System (ADS)

Johnston, Zac; Heger, Alexander; Galloway, Duncan K.

2018-06-01

Modelling of thermonuclear X-ray bursts on accreting neutron stars has to date focused on stable accretion rates. However, bursts are also observed during episodes of transient accretion. During such events, the accretion rate can evolve significantly between bursts, and this regime provides a unique test for burst models. The accretion-powered millisecond pulsar SAX J1808.4-3658 exhibits accretion outbursts every 2-3 yr. During the well-sampled month-long outburst of 2002 October, four helium-rich X-ray bursts were observed. Using this event as a test case, we present the first multizone simulations of X-ray bursts under a time-dependent accretion rate. We investigate the effect of using a time-dependent accretion rate in comparison to constant, averaged rates. Initial results suggest that using a constant, average accretion rate between bursts may underestimate the recurrence time when the accretion rate is decreasing, and overestimate it when the accretion rate is increasing. Our model, with an accreted hydrogen fraction of X = 0.44 and a CNO metallicity of ZCNO = 0.02, reproduces the observed burst arrival times and fluences with root mean square (rms) errors of 2.8 h, and 0.11× 10^{-6} erg cm^{-2}, respectively. Our results support previous modelling that predicted two unobserved bursts and indicate that additional bursts were also missed by observations.

The First Mammalian Aldehyde Oxidase Crystal Structure

PubMed Central

Coelho, Catarina; Mahro, Martin; Trincão, José; Carvalho, Alexandra T. P.; Ramos, Maria João; Terao, Mineko; Garattini, Enrico; Leimkühler, Silke; Romão, Maria João

2012-01-01

Aldehyde oxidases (AOXs) are homodimeric proteins belonging to the xanthine oxidase family of molybdenum-containing enzymes. Each 150-kDa monomer contains a FAD redox cofactor, two spectroscopically distinct [2Fe-2S] clusters, and a molybdenum cofactor located within the protein active site. AOXs are characterized by broad range substrate specificity, oxidizing different aldehydes and aromatic N-heterocycles. Despite increasing recognition of its role in the metabolism of drugs and xenobiotics, the physiological function of the protein is still largely unknown. We have crystallized and solved the crystal structure of mouse liver aldehyde oxidase 3 to 2.9 Å. This is the first mammalian AOX whose structure has been solved. The structure provides important insights into the protein active center and further evidence on the catalytic differences characterizing AOX and xanthine oxidoreductase. The mouse liver aldehyde oxidase 3 three-dimensional structure combined with kinetic, mutagenesis data, molecular docking, and molecular dynamics studies make a decisive contribution to understand the molecular basis of its rather broad substrate specificity. PMID:23019336

CotA, a Multicopper Oxidase from Bacillus pumilus WH4, Exhibits Manganese-Oxidase Activity

PubMed Central

Su, Jianmei; Bao, Peng; Bai, Tenglong; Deng, Lin; Wu, Hui; Liu, Fan; He, Jin

2013-01-01

Multicopper oxidases (MCOs) are a family of enzymes that use copper ions as cofactors to oxidize various substrates. Previous research has demonstrated that several MCOs such as MnxG, MofA and MoxA can act as putative Mn(II) oxidases. Meanwhile, the endospore coat protein CotA from Bacillus species has been confirmed as a typical MCO. To study the relationship between CotA and the Mn(II) oxidation, the cotA gene from a highly active Mn(II)-oxidizing strain Bacillus pumilus WH4 was cloned and overexpressed in Escherichia coli strain M15. The purified CotA contained approximately four copper atoms per molecule and showed spectroscopic properties typical of blue copper oxidases. Importantly, apart from the laccase activities, the CotA also displayed substantial Mn(II)-oxidase activities both in liquid culture system and native polyacrylamide gel electrophoresis. The optimum Mn(II) oxidase activity was obtained at 53°C in HEPES buffer (pH 8.0) supplemented with 0.8 mM CuCl2. Besides, the addition of o-phenanthroline and EDTA both led to a complete suppression of Mn(II)-oxidizing activity. The specific activity of purified CotA towards Mn(II) was 0.27 U/mg. The Km, Vmax and kcat values towards Mn(II) were 14.85±1.17 mM, 3.01×10−6±0.21 M·min−1 and 0.32±0.02 s−1, respectively. Moreover, the Mn(II)-oxidizing activity of the recombinant E. coli strain M15-pQE-cotA was significantly increased when cultured both in Mn-containing K liquid medium and on agar plates. After 7-day liquid cultivation, M15-pQE-cotA resulted in 18.2% removal of Mn(II) from the medium. Furthermore, the biogenic Mn oxides were clearly observed on the cell surfaces of M15-pQE-cotA by scanning electron microscopy. To our knowledge, this is the first report that provides the direct observation of Mn(II) oxidation with the heterologously expressed protein CotA, Therefore, this novel finding not only establishes the foundation for in-depth study of Mn(II) oxidation mechanisms, but also offers a

Generating disulfides with the quiescin sulfhydryl oxidases

PubMed Central

Heckler, Erin J.; Rancy, Pumtiwitt C.; Kodali, Vamsi K.; Thorpe, Colin

2008-01-01

The Quiescin-sulfhydryl oxidase (QSOX) family of flavoenzymes catalyzes the direct and facile insertion of disulfide bonds into unfolded reduced proteins with concomitant reduction of oxygen to hydrogen peroxide. This review discusses the chemical mechanism of these enzymes and the involvement of thioredoxin and flavin-binding domains in catalysis. The variability of CxxC motifs in the QSOX family is highlighted and attention is drawn to the steric factors that may promote efficient thiol/disulfide exchange during oxidative protein folding. The varied cellular location of these multi-domain sulfhydryl oxidases is reviewed and potential intracellular and extracellular roles are summarized. Finally, this review identifies important unresolved questions concerning this ancient family of sulfhydryl oxidases. PMID:17980160

Gamma-Ray Burst Host Galaxies Have "Normal" Luminosities.

PubMed

Schaefer

2000-04-10

The galactic environment of gamma-ray bursts can provide good evidence about the nature of the progenitor system, with two old arguments implying that the burst host galaxies are significantly subluminous. New data and new analysis have now reversed this picture: (1) Even though the first two known host galaxies are indeed greatly subluminous, the next eight hosts have absolute magnitudes typical for a population of field galaxies. A detailed analysis of the 16 known hosts (10 with redshifts) shows them to be consistent with a Schechter luminosity function with R*=-21.8+/-1.0, as expected for normal galaxies. (2) Bright bursts from the Interplanetary Network are typically 18 times brighter than the faint bursts with redshifts; however, the bright bursts do not have galaxies inside their error boxes to limits deeper than expected based on the luminosities for the two samples being identical. A new solution to this dilemma is that a broad burst luminosity function along with a burst number density varying as the star formation rate will require the average luminosity of the bright sample (>6x1058 photons s-1 or>1.7x1052 ergs s-1) to be much greater than the average luminosity of the faint sample ( approximately 1058 photons s-1 or approximately 3x1051 ergs s-1). This places the bright bursts at distances for which host galaxies with a normal luminosity will not violate the observed limits. In conclusion, all current evidence points to gamma-ray burst host galaxies being normal in luminosity.

Spontaneously regulated vs. controlled ventilation of acute lung injury/acute respiratory distress syndrome.

PubMed

Marini, John J

2011-02-01

To present an updated discussion of those aspects of controlled positive pressure breathing and retained spontaneous regulation of breathing that impact the management of patients whose tissue oxygenation is compromised by acute lung injury. The recent introduction of ventilation techniques geared toward integrating natural breathing rhythms into even the earliest phase of acute respiratory distress syndrome support (e.g., airway pressure release, proportional assist ventilation, and neurally adjusted ventilatory assist), has stimulated a burst of new investigations. Optimizing gas exchange, avoiding lung injury, and preserving respiratory muscle strength and endurance are vital therapeutic objectives for managing acute lung injury. Accordingly, comparing the physiology and consequences of breathing patterns that preserve and eliminate breathing effort has been a theme of persisting investigative interest throughout the several decades over which it has been possible to sustain cardiopulmonary life support outside the operating theater.

Inhibitory effect of heparin on neutrophil phagocytosis and burst production using a new whole-blood cytofluorometric method for determination.

PubMed

Salih, H; Husfeld, L; Adam, D

1997-12-31

The influence of heparin on Polymorphonuclear (PMN s) leukocytes was investigated using a new whole-blood cytofluorometric method (patent granted for the test with the number P 4334935.8-41) with Candida albicans and Staphylococcus aureus as test microorganisms. After comparing the effect of equal volumes of two widely used heparins we examined the influence of 5 different heparin-concentrations. Using both yeasts and bacteria, we found a significant, dose-depending decrease of the percentage of phagocyting PMN's and of phagocytized microorganisms as well as of the resulting percentage of PMN s producing respiratory burst along the kinetics. Furthermore we could demonstrate that heparin independently of phagocytosis produces a dose-dependent decrease of burst production of PMN's. Our results indicate that the use of heparins as anticoagulant for immunological investigations as well as clinically with patients under immunosuppressive therapy should be critically reconsidered. This applies even more because due to the evaluated dose-dependent decrease of phagocyte function no boundary for the inhibiting effect can be declared.

Eddington-limited X-Ray Bursts as Distance Indicators. I. Systematic Trends and Spherical Symmetry in Bursts from 4U 1728-34

NASA Astrophysics Data System (ADS)

Galloway, Duncan K.; Psaltis, Dimitrios; Chakrabarty, Deepto; Muno, Michael P.

2003-06-01

We investigate the limitations of thermonuclear X-ray bursts as a distance indicator for the weakly magnetized accreting neutron star 4U 1728-34. We measured the unabsorbed peak flux of 81 bursts in public data from the Rossi X-Ray Timing Explorer (RXTE). The distribution of peak fluxes was bimodal: 66 bursts exhibited photospheric radius expansion (presumably reaching the local Eddington limit) and were distributed about a mean bolometric flux of 9.2×10-8ergscm-2s-1, while the remaining (non-radius expansion) bursts reached 4.5×10-8ergscm-2s-1, on average. The peak fluxes of the radius expansion bursts were not constant, exhibiting a standard deviation of 9.4% and a total variation of 46%. These bursts showed significant correlations between their peak flux and the X-ray colors of the persistent emission immediately prior to the burst. We also found evidence for quasi-periodic variation of the peak fluxes of radius expansion bursts, with a timescale of ~=40 days. The persistent flux observed with RXTE/ASM over 5.8 yr exhibited quasi-periodic variability on a similar timescale. We suggest that these variations may have a common origin in reflection from a warped accretion disk. Once the systematic variation of the peak burst fluxes is subtracted, the residual scatter is only ~=3%, roughly consistent with the measurement uncertainties. The narrowness of this distribution strongly suggests that (1) the radiation from the neutron star atmosphere during radius expansion episodes is nearly spherically symmetric and (2) the radius expansion bursts reach a common peak flux that may be interpreted as a standard candle intensity. Adopting the minimum peak flux for the radius expansion bursts as the Eddington flux limit, we derive a distance for the source of 4.4-4.8 kpc (assuming RNS=10 km), with the uncertainty arising from the probable range of the neutron star mass MNS=1.4-2 Msolar.

THE PREPARATION AND PROPERTIES OF HIGHLY PURIFIED ASCORBIC ACID OXIDASE

PubMed Central

Powers, Wendell H.; Lewis, Stanley; Dawson, Charles R.

1944-01-01

1. A method is described for the preparation of a highly purified ascorbic acid oxidase containing 0.24 per cent copper. 2. Using comparable activity measurements, this oxidase is about one and a half times as active on a dry weight basis as the hitherto most highly purified preparation described by Lovett-Janison and Nelson. The latter contained 0.15 per cent copper. 3. The oxidase activity is proportional to the copper content and the proportionality factor is the same as that reported by Lovett-Janison and Nelson. 4. When dialyzed free of salt, the blue concentrated oxidase solutions precipitate a dark green-blue protein which carries the activity. This may be prevented by keeping the concentrated solutions about 0.1 M in Na2HPO4. 5. When highly diluted for activity measurements the oxidase rapidly loses activity (irreversibly) previous to the measurement, unless the dilution is made with a dilute inert protein (gelatin) solution. Therefore activity values obtained using such gelatin-stabilized dilute solutions of the oxidase run considerably higher than values obtained by the Lovett-Janison and Nelson technique. 6. The effect of pH and substrate concentration on the activity of the purified oxidase in the presence and absence of inert protein was studied. PMID:19873382

Amine oxidases as important agents of pathological processes of rhabdomyolysis in rats.

PubMed

Gudkova, O O; Latyshko, N V; Shandrenko, S G

2016-01-01

In this study we have tested an idea on the important role of amine oxidases (semicarbazide-sensitive amine oxidase, diamine oxidase, polyamine oxidase) as an additional source of oxidative/carbonyl stress under glycerol-induced rhabdomyolysis, since the enhanced formation of reactive oxygen species and reactive carbonyl species in a variety of tissues is linked to various diseases. In our experiments we used the sensitive fluorescent method devised for estimation of amine oxidases activity in the rat kidney and thymus as targeted organs under rhabdomyolysis. We have found in vivo the multiple rises in activity of semicarbazide-sensitive amine oxidase, diamine oxidase, polyamine oxidase (2-4.5 times) in the corresponding cell fractions, whole cells or their lysates at the 3-6th day after glycerol injection. Aberrant antioxidant activities depended on rhabdomyolysis stage and had organ specificity. Additional treatment of animals with metal chelator ‘Unithiol’ adjusted only the activity of antioxidant enzymes but not amine oxidases in both organs. Furthermore the in vitro experiment showed that Fenton reaction (hydrogen peroxide in the presence of iron) products alone had no effect on semicarbazide-sensitive amine oxidase activity in rat liver cell fraction whereas supplementation with methylglyoxal resulted in its significant 2.5-fold enhancement. Combined action of the both agents had additive effect on semicarbazide-sensitive amine oxidase activity. We can assume that biogenic amine and polyamine catabolism by amine oxidases is upregulated by oxidative and carbonyl stress factors directly under rhabdomyolysis progression, and the increase in catabolic products concentration contributes to tissue damage in glycerol-induced acute renal failure and apoptosis stimulation in thymus.

Post-Launch Analysis of Swift's Gamma-Ray Burst Detection Sensitivity

NASA Technical Reports Server (NTRS)

Band, David L.

2005-01-01

The dependence of Swift#s detection sensitivity on a burst#s temporal and spectral properties shapes the detected burst population. Using s implified models of the detector hardware and the burst trigger syste m I find that Swift is more sensitive to long, soft bursts than CGRO# s BATSE, a reference mission because of its large burst database. Thu s Swift has increased sensitivity in the parameter space region into which time dilation and spectral redshifting shift high redshift burs ts.

ASKAP Joins the Hunt for Mysterious Bursts

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2017-05-01

A new telescope, the Australian Square Kilometre Array Pathfinder (ASKAP), has joined the search for energetic and elusive fast radio bursts. And in just a few days of looking, its already had success!Elusive TransientsThe Parkes radio telescope, which has detected all but five of the fast radio bursts published to date, has a very narrow field of view. [CSIRO]Fast radio bursts are mysterious millisecond-duration radio pulses that were first discovered around a decade ago. Since that time particularly in recent years weve made some progress toward the goal of localizing them. Were now fairly convinced that fast radio bursts come from outside of the galaxy, and yet theyre enormously bright orders of magnitude more luminous than any pulse seen from the Milky Way.Better identification of where these mysterious bursts come from would help us to determine what they are. But so far, weve discovered only around 30 such bursts, despite the fact that theyre estimated to occur at a rate of 3,000 events per day across the whole sky.Why are they so hard to find? Due to their short duration, effective detection would require instantaneous coverage of a very large fraction of the sky. The Parkes radio telescope which has detected all but five of the fast radio bursts published to date has a field of view spanning less than a square degree,significantly limiting our ability to rapidly survey for these transients.FRB 170107s band-averaged pulse (top) and dynamic spectrum (bottom). [Bannister et al. 2017]A New Array in TownA new player is now on the scene, however, and its already had huge success. ASKAP is a wide-field radio telescope made up of an array of 12-meter antennas. Using phased-array-feed technology, ASKAP is able to instantaneously observe an effective area of 160 square degrees an enormous field compared to Parkes 0.6 square degrees! This capability significantly increases our chances of being able to detect fast radio bursts.In a new study led by Keith Bannister

Theoretical investigations of X-ray bursts

NASA Technical Reports Server (NTRS)

Taam, Ronald E.

1987-01-01

Current theoretical understanding of the X-ray burst phenomenon is reviewed, providing a framework in which the burst radiation can be used as a diagnostic of the fundamental properties of the underlying neutron star. The typical Type I X-ray burst is detected as a rapid increase in emission to a level about a factor of 10 above that seen during the quiescent state and recurs on time scales which range from several hours to several days. The thermonuclear flash model has successfully reproduced the basic features of the X-ray burst phenomenon and thereby provided strong theoretical evidence that neutron stars are involved. Topics covered include: theory of the emission spectrum; oscillation modes and prospects for diagnosing the thermal state of neutron stars through experiments on board the X-Ray Timing Explorer or the Advanced X-Ray Astrophysics Facility; applications to the mass and radius of a neutron star.

Light Dawns on Dark Gamma-ray Bursts

NASA Astrophysics Data System (ADS)

2010-12-01

Gamma-ray bursts are among the most energetic events in the Universe, but some appear curiously faint in visible light. The biggest study to date of these so-called dark gamma-ray bursts, using the GROND instrument on the 2.2-metre MPG/ESO telescope at La Silla in Chile, has found that these gigantic explosions don't require exotic explanations. Their faintness is now fully explained by a combination of causes, the most important of which is the presence of dust between the Earth and the explosion. Gamma-ray bursts (GRBs), fleeting events that last from less than a second to several minutes, are detected by orbiting observatories that can pick up their high energy radiation. Thirteen years ago, however, astronomers discovered a longer-lasting stream of less energetic radiation coming from these violent outbursts, which can last for weeks or even years after the initial explosion. Astronomers call this the burst's afterglow. While all gamma-ray bursts [1] have afterglows that give off X-rays, only about half of them were found to give off visible light, with the rest remaining mysteriously dark. Some astronomers suspected that these dark afterglows could be examples of a whole new class of gamma-ray bursts, while others thought that they might all be at very great distances. Previous studies had suggested that obscuring dust between the burst and us might also explain why they were so dim. "Studying afterglows is vital to further our understanding of the objects that become gamma-ray bursts and what they tell us about star formation in the early Universe," says the study's lead author Jochen Greiner from the Max-Planck Institute for Extraterrestrial Physics in Garching bei München, Germany. NASA launched the Swift satellite at the end of 2004. From its orbit above the Earth's atmosphere it can detect gamma-ray bursts and immediately relay their positions to other observatories so that the afterglows could be studied. In the new study, astronomers combined Swift

Dexamethasone but not indomethacin inhibits human phagocyte nicotinamide adenine dinucleotide phosphate oxidase activity by down-regulating expression of genes encoding oxidase components.

PubMed

Condino-Neto, A; Whitney, C; Newburger, P E

1998-11-01

We investigated the effects of dexamethasone or indomethacin on the NADPH oxidase activity, cytochrome b558 content, and expression of genes encoding the components gp91-phox and p47-phox of the NADPH oxidase system in the human monocytic THP-1 cell line, differentiated with IFN-gamma and TNF-alpha, alone or in combination, for up to 7 days. IFN-gamma and TNF-alpha, alone or in combination, caused a significant up-regulation of the NADPH oxidase system as reflected by an enhancement of the PMA-stimulated superoxide release, cytochrome b558 content, and expression of gp91-phox and p47-phox genes on both days 2 and 7 of cell culture. Noteworthy was the tremendous synergism between IFN-gamma and TNF-alpha for all studied parameters. Dexamethasone down-regulated the NADPH oxidase system of cytokine-differentiated THP-1 cells as assessed by an inhibition on the PMA-stimulated superoxide release, cytochrome b558 content, and expression of the gp91-phox and p47-phox genes. The nuclear run-on assays indicated that dexamethasone down-regulated the NADPH oxidase system at least in part by inhibiting the transcription of gp91-phox and p47-phox genes. Indomethacin inhibited only the PMA-stimulated superoxide release of THP-1 cells differentiated with IFN-gamma and TNF-alpha during 7 days. None of the other parameters was affected by indomethacin. We conclude that dexamethasone down-regulates the NADPH oxidase system at least in part by inhibiting the expression of genes encoding the gp91-phox and p47-phox components of the NADPH oxidase system.

A commercial mixture of the brominated flame retardant pentabrominated diphenyl ether (DE-71) induces respiratory burst in human neutrophil granulocytes in vitro.

PubMed

Reistad, Trine; Mariussen, Espen

2005-09-01

Polybrominated diphenyl ethers (PBDEs) are widely used brominated flame retardants (BFRs), which have become ubiquitous in the environment. This study investigates the effects of the pentabrominated diphenyl ether mixture, DE-71, on human neutrophil granulocytes in vitro. DE-71 enhanced production of reactive oxygen species (ROS) in a concentration-dependent manner measured as lucigenin-amplified chemiluminescence. Octabrominated diphenyl ether (OBDE), decabrominated diphenyl ether (DBDE), and the non-brominated diphenyl ether did not induce ROS formation at the concentrations tested. DPI (4 microM), an inhibitor of the NADPH oxidase completely inhibited DE-71 induced ROS formation, highlighting a role for NADPH oxidase activation. The protein kinase C inhibitor BIM (0.25 microM) and the selective chelator of intracellular calcium, BAPTA-AM (5 microM), also inhibited NADPH oxidase activation, indicating a calcium-dependent activation of PKC. ROS formation was also inhibited by the tyrosine kinase inhibitor tyrphostin (1 microM), the phospholipase C inhibitor ET-18-OCH3 (5 microM), and the phosphatidylinositol-3 kinase inhibitor LY294002 (25 microM). Alterations in intracellular calcium were measured using fura-2/AM, and a significant increase was measured after exposure to DE-71 both with and without extracellular calcium. The tetra brominated compound BDE-47 also enhanced ROS formation in a concentration dependent manner. The combination of DE-71 with the bacteria-derived N-formyl peptide fMLP and PCB153 induced an additive effect in the lucigenin assay. We suggest that tyrosine kinase mediated activation of PI3K could result in enhanced activation of calcium-dependent PKC by enhanced PLC activity, followed by intracellular calcium release leading to ROS formation in neutrophil granulocytes.

The role of alternative oxidase in tomato fruit ripening and its regulatory interaction with ethylene

PubMed Central

Lin, Hong-Hui

2012-01-01

Although the alternative oxidase (AOX) has been proposed to play a role in fruit development, the function of AOX in fruit ripening is unclear. To gain further insight into the role of AOX in tomato fruit ripening, transgenic tomato plants 35S-AOX1a and 35S-AOX-RNAi were generated. Tomato plants with reduced LeAOX levels exhibited retarded ripening; reduced carotenoids, respiration, and ethylene production; and the down-regulation of ripening-associated genes. Moreover, no apparent respiratory climacteric occurred in the AOX-reduced tomato fruit, indicating that AOX might play an important role in climacteric respiration. In contrast, the fruit that overexpressed LeAOX1a accumulated more lycopene, though they displayed a similar pattern of ripening to wild-type fruit. Ethylene application promoted fruit ripening and anticipated ethylene production and respiration, including the alternative pathway respiration. Interestingly, the transgenic plants with reduced LeAOX levels failed to ripen after 1-methylcyclopropene (1-MCP) treatment, while such inhibition was notably less effective in 35S-AOX1a fruit. These findings indicate that AOX is involved in respiratory climacteric and ethylene-mediated fruit ripening of tomato. PMID:22915749

Gamma-Ray Bursts and Cosmology

NASA Technical Reports Server (NTRS)

Norris, Jay P.

2003-01-01

The unrivalled, extreme luminosities of gamma-ray bursts (GRBs) make them the favored beacons for sampling the high redshift Universe. To employ GRBs to study the cosmic terrain -- e.g., star and galaxy formation history -- GRB luminosities must be calibrated, and the luminosity function versus redshift must be measured or inferred. Several nascent relationships between gamma-ray temporal or spectral indicators and luminosity or total energy have been reported. These measures promise to further our understanding of GRBs once the connections between the luminosity indicators and GRB jets and emission mechanisms are better elucidated. The current distribution of 33 redshifts determined from host galaxies and afterglows peaks near z $\\sim$ 1, whereas for the full BATSE sample of long bursts, the lag-luminosity relation predicts a broad peak z $\\sim$ 1--4 with a tail to z $\\sim$ 20, in rough agreement with theoretical models based on star formation considerations. For some GRB subclasses and apparently related phenomena -- short bursts, long-lag bursts, and X-ray flashes -- the present information on their redshift distributions is sparse or entirely lacking, and progress is expected in Swift era when prompt alerts become numerous.

Heterologous expression and characterization of mouse spermine oxidase.

PubMed

Cervelli, Manuela; Polticelli, Fabio; Federico, Rodolfo; Mariottini, Paolo

2003-02-14

Polyamine oxidases are key enzymes responsible of the polyamine interconversion metabolism in animal cells. Recently, a novel enzyme belonging to this class of enzymes has been characterized for its capability to oxidize preferentially spermine and designated as spermine oxidase. This is a flavin adenine dinucleotide-containing enzyme, and it has been expressed both in vitro and in vivo systems. The primary structure of mouse spermine oxidase (mSMO) was deduced from a cDNA clone (Image Clone 264769) recovered by a data base search utilizing the human counterpart of polyamine oxidases, PAOh1. The open reading frame predicts a 555-amino acid protein with a calculated M(r) of 61,852.30, which shows a 95.1% identity with PAOh1. To understand the biochemical properties of mSMO and its structure/function relationship, the mSMO cDNA has been subcloned and expressed in secreted and secreted-tagged forms into Escherichia coli BL21 DE3 cells. The recombinant enzyme shows an optimal pH value of 8.0 and is able to oxidize rapidly spermine to spermidine and 3-aminopropanal and fails to act upon spermidine and N(1)-acetylpolyamines. The purified recombinant-tagged form enzyme (M(r) approximately 68,000) has K(m) and k(cat) values of 90 microm and 4.5 s(-1), respectively, using spermine as substrate at pH 8.0. Molecular modeling of mSMO protein based on maize polyamine oxidase three-dimensional structure suggests that the general features of maize polyamine oxidase active site are conserved in mSMO.

On the Theory of Type 1 X-Ray Bursts: The Energetics of Bursts and the Nuclear Fuel Reservoir in the Envelope

NASA Technical Reports Server (NTRS)

Fujimoto, Masayuki Y.; Sztajno, Mirek; Lewin, Walter H. G.; Vanparadijs, Jan

1986-01-01

The observed properties of type 1 X-ray bursts from 4U/MXB 1636-53 and those of models of thermonuclear flashes on accreting neutron stars are compared. Ways to explain variations in the burst recurrence properties without an apparent correlation with the accretion rate, including the rapid succession of bursts at intervals 10 min are discussed. The strongest X-ray bursts, which occur after a very long interval, are well described by thermonuclear flash models with simple accumulation of accreted fuel, and a spherically symmetric structure in the burning shell. The majority of observed bursts, however, occur after much shorter intervals, and radiate much smaller amounts of energy, by a factor of up to 10 times that predicted by the spherical models. An ignition mechanism of the bursts is proposed in terms of elemental mixing and dissipative heating associated with hydrodynamical instabilities in the neutron star envelope caused by angular momentum carried inward by accreted gas.

Burst Oscillations: Watching Neutron Stars Spin

NASA Technical Reports Server (NTRS)

Strohmayer, Tod

2010-01-01

It is now almost 15 years since the first detection of rotationally modulated emission from X-ray bursting neutron stars, "burst oscillations," This phenomenon enables us to see neutron stars spin, as the X-ray burst flux asymmetrically lights up the surface. It has enabled a new way to probe the neutron star spin frequency distribution, as well as to elucidate the multidimensional nature of nuclear burning on neutron stars. I will review our current observational understanding of the phenomenon, with an eye toward highlighting some of the interesting remaining puzzles, of which there is no shortage.

Putting together a plasma membrane NADH oxidase: a tale of three laboratories.

PubMed

Löw, Hans; Crane, Frederick L; Morré, D James

2012-11-01

The observation that high cellular concentrations of NADH were associated with low adenylate cyclase activity led to a search for the mechanism of the effect. Since cyclase is in the plasma membrane, we considered the membrane might have a site for NADH action, and that NADH might be oxidized at that site. A test for NADH oxidase showed very low activity, which could be increased by adding growth factors. The plasma membrane oxidase was not inhibited by inhibitors of mitochondrial NADH oxidase such as cyanide, rotenone or antimycin. Stimulation of the plasma membrane oxidase by iso-proterenol or triiodothyronine was different from lack of stimulation in endoplasmic reticulum. After 25 years of research, three components of a trans membrane NADH oxidase have been discovered. Flavoprotein NADH coenzyme Q reductases (NADH cytochrome b reductase) on the inside, coenzyme Q in the middle, and a coenzyme Q oxidase on the outside as a terminal oxidase. The external oxidase segment is a copper protein with unique properties in timekeeping, protein disulfide isomerase and endogenous NADH oxidase activity, which affords a mechanism for control of cell growth by the overall NADH oxidase and the remarkable inhibition of oxidase activity and growth of cancer cells by a wide range of anti-tumor drugs. A second trans plasma membrane electron transport system has been found in voltage dependent anion channel (VDAC), which has NADH ferricyanide reductase activity. This activity must be considered in relation to ferricyanide stimulation of growth and increased VDAC antibodies in patients with autism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Reverse effects of DPI administration combined with glutamine supplementation on function of rat neutrophils induced by overtraining.

PubMed

Dong, Jingmei; Chen, Peijie; Liu, Qing; Wang, Ru; Xiao, Weihua; Zhang, Yajun

2013-04-01

To examine the excessive reactive oxygen species (ROS) mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the combined effect of glutamine supplementation and diphenyleneiodonium (DPI) on the function of neutrophils induced by overtraining. Fifty male Wistar rats were randomly divided into 5 groups: control group (C), overtraining group (E), DPI-administration group (D), glutamine-supplementation group (G), and combined DPI and glutamine group (DG). Blood was sampled from the orbital vein after rats were trained on treadmill for 11 wk. Cytokine and lipid peroxidation in blood plasma were measured by enzyme-linked immunosorbent assay. The colocalization between gp91phox and p47phox of the NADPH oxidase was detected using immunocytochemistry and confocal microscopy. The activity of NADPH oxidase was assessed by chemiluminescence. Neutrophils' respiratory burst and phagocytosis function were measured by flow cytometry. NADPH oxidase was activated by overtraining. Cytokine and lipid peroxidation in blood plasma and the activity of NADPH oxidase were markedly increased in Group E compared with group C. Neutrophil function was lower in group E than group C. Both lower neutrophils function and higher ROS production were reversed in Group DG. The glutamine and DPI interference alone in group D and group G was less effective than DPI and glutamine combined in group DG. Activation of NADPH oxidase is responsible for the production of superoxide anions, which leads to excessive ROS and is related to the decrease in neutrophil function induced by overtraining. The combined DPI administration and glutamine supplementation reversed the decreased neutrophil function after overtraining.

In Situ Enzymatically Generated Photoswitchable Oxidase Mimetics and Their Application for Colorimetric Detection of Glucose Oxidase.

PubMed

Cao, Gen-Xia; Wu, Xiu-Ming; Dong, Yu-Ming; Li, Zai-Jun; Wang, Guang-Li

2016-07-09

In this study, a simple and amplified colorimetric assay is developed for the detection of the enzymatic activity of glucose oxidase (GOx) based on in situ formation of a photoswitchable oxidase mimetic of PO₄(3-)-capped CdS quantum dots (QDs). GOx catalyzes the oxidation of 1-thio-β-d-glucose to give 1-thio-β-d-gluconic acid which spontaneously hydrolyzes to β-d-gluconic acid and H₂S; the generated H₂S instantly reacts with Cd(2+) in the presence of Na₃PO₄ to give PO₄(3-)-stabilized CdS QDs in situ. Under visible-light (λ ≥ 400 nm) stimulation, the PO₄(3-)-capped CdS QDs are a new style of oxidase mimic derived by producing some active species, such as h⁺, (•)OH, O₂(•-) and a little H₂O₂, which can oxidize the typical substrate (3,3,5,5-tetramethylbenzydine (TMB)) with a color change. Based on the GOx-triggered growth of the oxidase mimetics of PO₄(3-)-capped CdS QDs in situ, we developed a simple and amplified colorimetric assay to probe the enzymatic activity of GOx. The proposed method allowed the detection of the enzymatic activity of GOx over the range from 25 μg/L to 50 mg/L with a low detection limit of 6.6 μg/L. We believe the PO₄(3-)-capped CdS QDs generated in situ with photo-stimulated enzyme-mimicking activity may find wide potential applications in biosensors.

Discovery of the short gamma-ray burst GRB 050709.

PubMed

Villasenor, J S; Lamb, D Q; Ricker, G R; Atteia, J-L; Kawai, N; Butler, N; Nakagawa, Y; Jernigan, J G; Boer, M; Crew, G B; Donaghy, T Q; Doty, J; Fenimore, E E; Galassi, M; Graziani, C; Hurley, K; Levine, A; Martel, F; Matsuoka, M; Olive, J-F; Prigozhin, G; Sakamoto, T; Shirasaki, Y; Suzuki, M; Tamagawa, T; Vanderspek, R; Woosley, S E; Yoshida, A; Braga, J; Manchanda, R; Pizzichini, G; Takagishi, K; Yamauchi, M

2005-10-06

Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, the energy scale and the progenitors of the short bursts have remained a mystery. Here we report the discovery of a short-hard burst whose accurate localization has led to follow-up observations that have identified the X-ray afterglow and (for the first time) the optical afterglow of a short-hard burst; this in turn led to the identification of the host galaxy of the burst as a late-type galaxy at z = 0.16 (ref. 10). These results show that at least some short-hard bursts occur at cosmological distances in the outskirts of galaxies, and are likely to be caused by the merging of compact binaries.

Gamma-Ray Burst Intensity Distributions

NASA Technical Reports Server (NTRS)

Band, David L.; Norris, Jay P.; Bonnell, Jerry T.

2004-01-01

We use the lag-luminosity relation to calculate self-consistently the redshifts, apparent peak bolometric luminosities L(sub B1), and isotropic energies E(sub iso) for a large sample of BATSE bursts. We consider two different forms of the lag-luminosity relation; for both forms the median redshift, for our burst database is 1.6. We model the resulting sample of burst energies with power law and Gaussian dis- tributions, both of which are reasonable models. The power law model has an index of a = 1.76 plus or minus 0.05 (95% confidence) as opposed to the index of a = 2 predicted by the simple universal jet profile model; however, reasonable refinements to this model permit much greater flexibility in reconciling predicted and observed energy distributions.

Capsule Influences the Deposition of Critical Complement C3 Levels Required for the Killing of Burkholderia pseudomallei via NADPH-Oxidase Induction by Human Neutrophils

PubMed Central

Woodman, Michael E.; Worth, Randall G.; Wooten, R. Mark

2012-01-01

Burkholderia pseudomallei is the causative agent of melioidosis and is a major mediator of sepsis in its endemic areas. Because of the low LD50 via aerosols and resistance to multiple antibiotics, it is considered a Tier 1 select agent by the CDC and APHIS. B. pseudomallei is an encapsulated bacterium that can infect, multiply, and persist within a variety of host cell types. In vivo studies suggest that macrophages and neutrophils are important for controlling B. pseudomallei infections, however few details are known regarding how neutrophils respond to these bacteria. Our goal is to describe the capacity of human neutrophils to control highly virulent B. pseudomallei compared to the relatively avirulent, acapsular B. thailandensis using in vitro analyses. B. thailandensis was more readily phagocytosed than B. pseudomallei, but both displayed similar rates of persistence within neutrophils, indicating they possess similar inherent abilities to escape neutrophil clearance. Serum opsonization studies showed that both were resistant to direct killing by complement, although B. thailandensis acquired significantly more C3 on its surface than B. pseudomallei, whose polysaccharide capsule significantly decreased the levels of complement deposition on the bacterial surface. Both Burkholderia species showed significantly enhanced uptake and killing by neutrophils after critical levels of C3 were deposited. Serum-opsonized Burkholderia induced a significant respiratory burst by neutrophils compared to unopsonized bacteria, and neutrophil killing was prevented by inhibiting NADPH-oxidase. In summary, neutrophils can efficiently kill B. pseudomallei and B. thailandensis that possess a critical threshold of complement deposition, and the relative differences in their ability to resist surface opsonization may contribute to the distinct virulence phenotypes observed in vivo. PMID:23251706

Limits of the memory coefficient in measuring correlated bursts

NASA Astrophysics Data System (ADS)

Jo, Hang-Hyun; Hiraoka, Takayuki

2018-03-01

Temporal inhomogeneities in event sequences of natural and social phenomena have been characterized in terms of interevent times and correlations between interevent times. The inhomogeneities of interevent times have been extensively studied, while the correlations between interevent times, often called correlated bursts, are far from being fully understood. For measuring the correlated bursts, two relevant approaches were suggested, i.e., memory coefficient and burst size distribution. Here a burst size denotes the number of events in a bursty train detected for a given time window. Empirical analyses have revealed that the larger memory coefficient tends to be associated with the heavier tail of the burst size distribution. In particular, empirical findings in human activities appear inconsistent, such that the memory coefficient is close to 0, while burst size distributions follow a power law. In order to comprehend these observations, by assuming the conditional independence between consecutive interevent times, we derive the analytical form of the memory coefficient as a function of parameters describing interevent time and burst size distributions. Our analytical result can explain the general tendency of the larger memory coefficient being associated with the heavier tail of burst size distribution. We also find that the apparently inconsistent observations in human activities are compatible with each other, indicating that the memory coefficient has limits to measure the correlated bursts.

The Human Burst Suppression Electroencephalogram of Deep Hypothermia

PubMed Central

Kumaraswamy, Vishakhadatta M.; Akeju, Seun Oluwaseun; Pierce, Eric; Cash, Sydney S.; Kilbride, Ronan; Brown, Emery N.; Purdon, Patrick L.

2015-01-01

Objective Deep hypothermia induces ‘burst suppression’ (BS), an electroencephalogram pattern with low-voltage ‘suppressions’ alternating with high-voltage ‘bursts’. Current understanding of BS comes mainly from anesthesia studies, while hypothermia-induced BS has received little study. We set out to investigate the electroencephalogram changes induced by cooling the human brain through increasing depths of BS through isoelectricity. Methods We recorded scalp electroencephalograms from eleven patients undergoing deep hypothermia during cardiac surgery with complete circulatory arrest, and analyzed these using methods of spectral analysis. Results Within patients, the depth of BS systematically depends on the depth of hypothermia, though responses vary between patients except at temperature extremes. With decreasing temperature, burst lengths increase, and burst amplitudes and lengths decrease, while the spectral content of bursts remains constant. Conclusions These findings support an existing theoretical model in which the common mechanism of burst suppression across diverse etiologies is the cyclical diffuse depletion of metabolic resources, and suggest the new hypothesis of local micro-network dropout to explain decreasing burst amplitudes at lower temperatures. Significance These results pave the way for accurate noninvasive tracking of brain metabolic state during surgical procedures under deep hypothermia, and suggest new testable predictions about the network mechanisms underlying burst suppression. PMID:25649968

R1, a novel repressor of the human monoamine oxidase A.

PubMed

Chen, Kevin; Ou, Xiao-Ming; Chen, Gao; Choi, Si Ho; Shih, Jean C

2005-03-25

Monoamine oxidase catalyzes the oxidative deamination of a number of neurotransmitters. A deficiency in monoamine oxidase A results in aggressive behavior in both humans and mice. Studies on the regulation of monoamine oxidase A gene expression have shown that the Sp1 family is important for monoamine oxidase A expression. To search for novel transcription factors, the sequences of three Sp1 sites in the monoamine oxidase A core promoter were used in the yeast one-hybrid system to screen a human cDNA library. A novel repressor, R1 (RAM2), has been cloned. The R1 cDNA encodes a protein with 454 amino acids and an open reading frame at the 5'-end. The transfection of R1 in a human neuroblastoma cell line, SK-N-BE (2)-C, inhibited the monoamine oxidase A promoter and enzymatic activity. The degree of inhibition of monoamine oxidase A by R1 correlated with the level of R1 protein expression. R1 was also found to repress monoamine oxidase A promoter activity within a natural chromatin environment. A gel-shift assay indicated that the endogenous R1 protein in SK-N-BE (2)-C cells interacted with the R1 binding sequence. R1 also bound directly to the natural monoamine oxidase A promoter in vivo as shown by chromatin immunoprecipitation assay. Immunocytochemical analysis showed that R1 was expressed in both cytosol and nucleus, which suggested a role for R1 in transcriptional regulation. Northern blot analysis revealed the presence of endogenous R1 mRNA in human brain and peripheral tissues. Taken together, this study shows that R1 is a novel repressor that inhibits monoamine oxidase A gene expression.

A novel proteolytic processing of prolysyl oxidase

PubMed Central

Atsawasuwan, Phimon; Mochida, Yoshiyuki; Katafuchi, Michitsuna; Tokutomi, Kentaro; Mocanu, Viorel; Parker, Carol E.; Yamauchi, Mitsuo

2012-01-01

Lysyl oxidase (LOX) is an amine oxidase that is critical for the stability of connective tissues. The secreted proLOX is enzymatically quiescent and is activated through proteolytic cleavage between residue Gly162 and Asp163 (residue numbers according to the mouse LOX) by bone morphogenetic protein (BMP)-1 gene products. Here we report a novel processing of proLOX identified in vitro and in vivo. Two forms of mature LOX were identified and characterized by their immunoreactivity to specific antibodies, amine oxidase activity and mass spectrometry. One form was identified as a well characterized BMP-1 processed LOX protein. Another was found to be a truncated form of LOX (tLOX) resulting from the cleavage at the carboxy terminus of Arg192. The tLOX still appeared to retain amine oxidase activity. The results from the proLOX gene deletion and mutation experiments indicated that the processing occurs independent of the cleavage of proLOX by BMP-1 gene products and likely requires the presence of LOX propeptide. These results indicate that proLOX could be processed by two different mechanisms producing two forms of active LOX. PMID:21591931

A novel proteolytic processing of prolysyl oxidase.

PubMed

Atsawasuwan, Phimon; Mochida, Yoshiyuki; Katafuchi, Michitsuna; Tokutomi, Kentaro; Mocanu, Viorel; Parker, Carol E; Yamauchi, Mitsuo

2011-01-01

Lysyl oxidase (LOX) is an amine oxidase that is critical for the stability of connective tissues. The secreted proLOX is enzymatically quiescent and is activated through proteolytic cleavage between residues Gly(162) and Asp(163) (residue numbers according to the mouse LOX) by bone morphogenetic protein (BMP)-1 gene products. Here we report a novel processing of proLOX identified in vitro and in vivo. Two forms of mature LOX were identified and characterized by their immunoreactivity to specific antibodies, amine oxidase activity, and mass spectrometry. One form was identified as a well-characterized BMP-1 processed LOX protein. Another was found to be a truncated form of LOX resulting from the cleavage at the carboxy terminus of Arg(192). The truncated form of LOX still appeared to retain amine oxidase activity. The results from the proLOX gene deletion and mutation experiments indicated that the processing occurs independent of the cleavage of proLOX by BMP-1 gene products and likely requires the presence of LOX propeptide. These results indicate that proLOX could be processed by two different mechanisms producing two forms of active LOX.

Exploiting algal NADPH oxidase for biophotovoltaic energy

DOE PAGES

Anderson, Alexander; Laohavisit, Anuphon; Blaby, Ian K.; ...

2015-01-29

Photosynthetic microbes exhibit light-dependent electron export across the cell membrane, which can generate electricity in biological photovoltaic (BPV) devices. How electrons are exported remains to be determined; the identification of mechanisms would help selection or generation of photosynthetic microbes capable of enhanced electrical output. We show that plasma membrane NADPH oxidase activity is a significant component of light-dependent generation of electricity by the unicellular green alga Chlamydomonas reinhardtii. NADPH oxidases export electrons across the plasma membrane to form superoxide anion from oxygen. The C. reinhardtii mutant lacking the NADPH oxidase encoded by RBO1 is impaired in both extracellular superoxide anionmore » production and current generation in a BPV device. Complementation with the wild-type gene restores both capacities, demonstrating the role of the enzyme in electron export. Monitoring light-dependent extracellular superoxide production with a colorimetric assay is shown to be an effective way of screening for electrogenic potential of candidate algal strains. Furthermore, the results show that algal NADPH oxidases are important for superoxide anion production and open avenues for optimizing the biological component of these devices.« less

NADPH oxidases: novel therapeutic targets for neurodegenerative diseases.

PubMed

Gao, Hui-Ming; Zhou, Hui; Hong, Jau-Shyong

2012-06-01

Oxidative stress is a key pathologic factor in neurodegenerative diseases such as Alzheimer and Parkinson diseases (AD, PD). The failure of free-radical-scavenging antioxidants in clinical trials pinpoints an urgent need to identify and to block major sources of oxidative stress in neurodegenerative diseases. As a major superoxide-producing enzyme complex in activated phagocytes, phagocyte NADPH oxidase (PHOX) is essential for host defense. However, recent preclinical evidence has underscored a pivotal role of overactivated PHOX in chronic neuroinflammation and progressive neurodegeneration. Deficiency in PHOX subunits mitigates neuronal damage induced by diverse insults/stresses relevant to neurodegenerative diseases. More importantly, suppression of PHOX activity correlates with reduced neuronal impairment in models of neurodegenerative diseases. The discovery of PHOX and non-phagocyte NADPH oxidases in astroglia and neurons further reinforces the crucial role of NADPH oxidases in oxidative stress-mediated chronic neurodegeneration. Thus, proper modulation of NADPH oxidase activity might hold therapeutic potential for currently incurable neurodegenerative diseases. Published by Elsevier Ltd.

Revealing degree distribution of bursting neuron networks.

PubMed

Shen, Yu; Hou, Zhonghuai; Xin, Houwen

2010-03-01

We present a method to infer the degree distribution of a bursting neuron network from its dynamics. Burst synchronization (BS) of coupled Morris-Lecar neurons has been studied under the weak coupling condition. In the BS state, all the neurons start and end bursting almost simultaneously, while the spikes inside the burst are incoherent among the neurons. Interestingly, we find that the spike amplitude of a given neuron shows an excellent linear relationship with its degree, which makes it possible to estimate the degree distribution of the network by simple statistics of the spike amplitudes. We demonstrate the validity of this scheme on scale-free as well as small-world networks. The underlying mechanism of such a method is also briefly discussed.

Bright x-ray flares in gamma-ray burst afterglows.

PubMed

Burrows, D N; Romano, P; Falcone, A; Kobayashi, S; Zhang, B; Moretti, A; O'brien, P T; Goad, M R; Campana, S; Page, K L; Angelini, L; Barthelmy, S; Beardmore, A P; Capalbi, M; Chincarini, G; Cummings, J; Cusumano, G; Fox, D; Giommi, P; Hill, J E; Kennea, J A; Krimm, H; Mangano, V; Marshall, F; Mészáros, P; Morris, D C; Nousek, J A; Osborne, J P; Pagani, C; Perri, M; Tagliaferri, G; Wells, A A; Woosley, S; Gehrels, N

2005-09-16

Gamma-ray burst (GRB) afterglows have provided important clues to the nature of these massive explosive events, providing direct information on the nearby environment and indirect information on the central engine that powers the burst. We report the discovery of two bright x-ray flares in GRB afterglows, including a giant flare comparable in total energy to the burst itself, each peaking minutes after the burst. These strong, rapid x-ray flares imply that the central engines of the bursts have long periods of activity, with strong internal shocks continuing for hundreds of seconds after the gamma-ray emission has ended.

Isolated cytochrome c oxidase deficiency in G93A SOD1 mice overexpressing CCS protein.

PubMed

Son, Marjatta; Leary, Scot C; Romain, Nadine; Pierrel, Fabien; Winge, Dennis R; Haller, Ronald G; Elliott, Jeffrey L

2008-05-02

G93A SOD1 transgenic mice overexpressing CCS protein develop an accelerated disease course that is associated with enhanced mitochondrial pathology and increased mitochondrial localization of mutant SOD1. Because these results suggest an effect of mutant SOD1 on mitochondrial function, we assessed the enzymatic activities of mitochondrial respiratory chain complexes in the spinal cords of CCS/G93A SOD1 and control mice. CCS/G93A SOD1 mouse spinal cord demonstrates a 55% loss of complex IV (cytochrome c oxidase) activity compared with spinal cord from age-matched non-transgenic or G93A SOD1 mice. In contrast, CCS/G93A SOD1 spinal cord shows no reduction in the activities of complex I, II, or III. Blue native gel analysis further demonstrates a marked reduction in the levels of complex IV but not of complex I, II, III, or V in spinal cords of CCS/G93A SOD1 mice compared with non-transgenic, G93A SOD1, or CCS/WT SOD1 controls. With SDS-PAGE analysis, spinal cords from CCS/G93A SOD1 mice showed significant decreases in the levels of two structural subunits of cytochrome c oxidase, COX1 and COX5b, relative to controls. In contrast, CCS/G93A SOD1 mouse spinal cord showed no reduction in levels of selected subunits from complexes I, II, III, or V. Heme A analyses of spinal cord further support the existence of cytochrome c oxidase deficiency in CCS/G93A SOD1 mice. Collectively, these results establish that CCS/G93A SOD1 mice manifest an isolated complex IV deficiency which may underlie a substantial part of mutant SOD1-induced mitochondrial cytopathy.

Pulse-radiolysis studies on the interaction of one-electron reduced species with blue oxidases. Reduction of type-2-copper-depleted ascorbate oxidase.

PubMed

O'Neill, P; Fielden, E M; Avigliano, L; Marcozzi, G; Ballini, A; Agrò, F

1984-08-15

The interaction of one-electron reduced metronidazole (ArNO2.-) with native and Type-2-copper-depleted ascorbate oxidase were studied in buffered aqueous solution at pH 6.0 and 7.4 by using the technique of pulse radiolysis. With ArNO2.-, reduction of Type 1 copper of the native enzyme and of the Type-2-copper-depleted ascorbate oxidase occurs via a bimolecular step and at the same rate. Whereas the native protein accepts, in the absence of O2, 6-7 reducing equivalents, Type-2-copper-depleted ascorbate oxidase accepts only 3 reducing equivalents with stoichiometric reduction of Type 1 copper. On reaction of O2.- with ascorbate oxidase under conditions of [O2.-] much greater than [ascorbate oxidase], removal of Type 2 copper results in reduction of all the Type 1 copper atoms, in contrast with reduction of the equivalent of only one Type 1 copper atom in the holoprotein. From observations at 610 nm, the rate of reduction of ascorbate oxidase by O2.- is not dependent on the presence of Type 2 copper. For the holoprotein, no significant optical-absorption changes were observed at 330 nm. It is proposed that electrons enter the protein via Type 1 copper in a rate-determining step followed by a fast intramolecular transfer of electrons within the protein. For the Type-2-copper-depleted protein, intramolecular transfer within the protein, however, is slow or does not occur. In the presence of O2, it is also suggested that re-oxidation of the partially reduced holoprotein occurs at steady state, as inferred from the observations at 330 nm and 610 nm. The role of Type 2 copper in ascorbate oxidase is discussed in terms of its involvement in redistribution of electrons within the protein or structural considerations.

Peripheral oxygen-sensing cells directly modulate the output of an identified respiratory central pattern generating neuron.

PubMed

Bell, Harold J; Inoue, Takuya; Shum, Kelly; Luk, Collin; Syed, Naweed I

2007-06-01

Breathing is an essential homeostatic behavior regulated by central neuronal networks, often called central pattern generators (CPGs). Despite ongoing advances in our understanding of the neural control of breathing, the basic mechanisms by which peripheral input modulates the activities of the central respiratory CPG remain elusive. This lack of fundamental knowledge vis-à-vis the role of peripheral influences in the control of the respiratory CPG is due in large part to the complexity of mammalian respiratory control centres. We have therefore developed a simpler invertebrate model to study the basic cellular and synaptic mechanisms by which a peripheral chemosensory input affects the central respiratory CPG. Here we report on the identification and characterization of peripheral chemoreceptor cells (PCRCs) that relay hypoxia-sensitive chemosensory information to the known respiratory CPG neuron right pedal dorsal 1 in the mollusk Lymnaea stagnalis. Selective perfusion of these PCRCs with hypoxic saline triggered bursting activity in these neurons and when isolated in cell culture these cells also demonstrated hypoxic sensitivity that resulted in membrane depolarization and spiking activity. When cocultured with right pedal dorsal 1, the PCRCs developed synapses that exhibited a form of short-term synaptic plasticity in response to hypoxia. Finally, osphradial denervation in intact animals significantly perturbed respiratory activity compared with their sham counterparts. This study provides evidence for direct synaptic connectivity between a peripheral regulatory element and a central respiratory CPG neuron, revealing a potential locus for hypoxia-induced synaptic plasticity underlying breathing behavior.

Overview of Solar Radio Bursts and their Sources

NASA Astrophysics Data System (ADS)

Golla, Thejappa; MacDowall, Robert J.

2018-06-01

Properties of radio bursts emitted by the Sun at frequencies below tens of MHz are reviewed. In this frequency range, the most prominent radio emissions are those of solar type II, complex type III and solar type IV radio bursts, excited probably by the energetic electron populations accelerated in completely different environments: (1) type II bursts are due to non-relativistic electrons accelerated by the CME driven interplanetary shocks, (2) complex type III bursts are due to near-relativistic electrons accelerated either by the solar flare reconnection process or by the SEP shocks, and (3) type IV bursts are due to relativistic electrons, trapped in the post-eruption arcades behind CMEs; these relativistic electrons probably are accelerated by the continued reconnection processes occurring beneath the CME. These radio bursts, which can serve as the natural plasma probes traversing the heliosphere by providing information about various crucial space plasma parameters, are also an ideal instrument for investigating acceleration mechanisms responsible for the high energy particles. The rich collection of valuable high quality radio and high time resolution in situ wave data from the WAVES experiments of the STEREO A, STEREO B and WIND spacecraft has provided an unique opportunity to study these different radio phenomena and understand the complex physics behind their excitation. We have developed Monte Carlo simulation techniques to estimate the propagation effects on the observed characteristics of these low frequency radio bursts. We will present some of the new results and describe how one can use these radio burst observations for space weather studies. We will also describe some of the non-linear plasma processes detected in the source regions of both solar type III and type II radio bursts. The analysis and simulation techniques used in these studies will be of immense use for future space based radio observations.

Gamma Ray Burst Discoveries with the Swift Mission

NASA Technical Reports Server (NTRS)

Gehrels, Neil

2008-01-01

Gamma-ray bursts (GRBs) are among the most fascinating occurrences in the universe. They are powerful explosions, visible to high redshift, and thought to be the signature of black hole formation. The Swift Observatory has been detecting 100 bursts per year for 3 years and has greatly stimulated the field with new findings. Observations are made of the X-ray and optical afterglow from - 1 minute after the burst, continuing for days. Evidence is building that the long and short duration subcategories of GRBs have very different origins: massive star core collapse to a black hole for long bursts and binary neutron star coalescence to a black hole for short bursts. The similarity to Type I1 and Ia supernovae originating from young and old stellar progenitors is striking. Bursts are providing a new tool to study the high redshift universe. Swift has detected several events at z>5 and one at z=6.3 giving metallicity measurements and other data on galaxies at previously inaccessible distances. The talk will present the latest results from Swift in GRB astronomy.

Gamma Ray Burst Discoveries with the Swift Mission

NASA Technical Reports Server (NTRS)

Gehrels, Neil

2008-01-01

Gamma-ray bursts (GRBs) are among the most fascinating occurrences in the universe. They are powerful explosions, visible to high redshift, and thought to be the signature of black hole formation. The Swift Observatory has been detecting 100 bursts per year for 3 years and has greatly stimulated the field with new findings. Observations are made of the X-ray and optical afterglow from approximately 1 minute after the burst, continuing for days. Evidence is building that the long and short duration subcategories of GRBs have very different origins: massive star core collapse to a black hole for long bursts and binary neutron star coalescence to a black hole for short bursts. The similarity to Type II and Ia supernovae originating from young and old stellar progenitors is striking. Bursts are providing a new tool to study the high redshift universe. Swift has detected several events at z greater than 5 and one at z=6.3 giving metallicity measurements and other data on galaxies at previously inaccessible distances. The talk will present the latest results from Swift in GRB astronomy.

Gamma Ray Burst Discoveries with the Swift Mission

NASA Technical Reports Server (NTRS)

Gehrels, Neil

2009-01-01

Gamma-ray bursts (GRBs) are among the most fascinating occurrences in the universe. They are powerful explosions, visible to high redshift, and thought to be the signature of black hole formation. The Swift Observatory has been detecting 100 bursts per year for 4 years and has greatly stimulated the field with new findings. Observations are made of the X-ray and optical afterglow from approximately 1 minute after the burst, continuing for days. Evidence is building that the long and short duration subcategories of GRBs have very different origins: massive star core collapse to a black hole for long bursts and binary neutron star coalescence to a black hole for short bursts. The similarity to Type II and Ia supernovae originating from young and old stellar progenitors is striking. Bursts are providing a new tool to study the high redshift universe. Swift has detected several events at z>5 and one at z=6.7 giving metallicity measurements and other data on galaxies at previously inaccessible distances. The talk will present the latest results from Swift in GRB astronomy.

Broadband Spectral Investigations of Magnetar Bursts

NASA Astrophysics Data System (ADS)

Kırmızıbayrak, Demet; Şaşmaz Muş, Sinem; Kaneko, Yuki; Göğüş, Ersin

2017-09-01

We present our broadband (2-250 keV) time-averaged spectral analysis of 388 bursts from SGR J1550-5418, SGR 1900+14, and SGR 1806-20 detected with the Rossi X-ray Timing Explorer (RXTE) here and as a database in a companion web-catalog. We find that two blackbody functions (BB+BB), the sum of two modified blackbody functions (LB+LB), the sum of a blackbody function and a power-law function (BB+PO), and a power law with a high-energy exponential cutoff (COMPT) all provide acceptable fits at similar levels. We performed numerical simulations to constrain the best fitting model for each burst spectrum and found that 67.6% of burst spectra with well-constrained parameters are better described by the Comptonized model. We also found that 64.7% of these burst spectra are better described with the LB+LB model, which is employed in the spectral analysis of a soft gamma repeater (SGR) for the first time here, than with the BB+BB and BB+PO models. We found a significant positive lower bound trend on photon index, suggesting a decreasing upper bound on hardness, with respect to total flux and fluence. We compare this result with bursts observed from SGR and AXP (anomalous X-ray pulsar) sources and suggest that the relationship is a distinctive characteristic between the two. We confirm a significant anticorrelation between burst emission area and blackbody temperature, and find that it varies between the hot and cool blackbody temperatures differently than previously discussed. We expand on the interpretation of our results in the framework of a strongly magnetized neutron star.

Bursts of seizures in long-term recordings of human focal epilepsy

PubMed Central

Karoly, Philippa J.; Nurse, Ewan S.; Freestone, Dean R.; Ung, Hoameng; Cook, Mark J.; Boston, Ray

2017-01-01

Summary Objective We report on temporally clustered seizures detected from continuous long-term ambulatory human electroencephalographic data. The objective was to investigate short-term seizure clustering, which we have termed bursting, and consider implications for patient care, seizure prediction, and evaluating therapies. Methods Chronic ambulatory intracranial EEG data collected for the purpose of seizure prediction were annotated to identify seizure events. A detection algorithm was used to identify bursts of events. Burst events were compared to non-burst events to evaluate event dispersion, duration and dynamics. Results Bursts of seizures were present in six of fifteen patients, and detections were consistent over long term monitoring (> 2 years). Seizures within bursts are highly overdispersed compared to non-burst seizures. There was a complicated relationship between bursts and clinical seizures, although bursts were associated with multi-modal distributions of seizure duration, and poorer predictive outcomes. For three subjects, bursts demonstrated distinctive pre-ictal dynamics compared to clinical seizures. Significance We have previously hypothesized that there are distinct physiological pathways underlying short and long duration seizures. Here we show that burst seizures fall almost exclusively within the short population of seizure durations; however, a short duration was not sufficient to induce or imply bursting. We can therefore conclude that in addition to distinct mechanisms underlying seizure duration, there are separate factors regulating bursts of seizures. We show that bursts were a robust phenomenon in our patient cohort, which were consistent with overdispersed seizure rates, suggesting long-memory dynamics. PMID:28084639

In vitro study of 6-mercaptopurine oxidation catalysed by aldehyde oxidase and xanthine oxidase.

PubMed

Rashidi, Mohammad-Reza; Beedham, Christine; Smith, John S; Davaran, Soodabeh

2007-08-01

In spite of over 40 years of clinical use of 6-mercaptopurine, many aspects of complex pharmacology and metabolism of this drug remain unclear. It is thought that 6-mercaptopurine is oxidized to 6-thiouric acid through 6-thioxanthine or 8-oxo-6-mercaptopurine by one of two molybdenum hydroxylases, xanthine oxidase (XO), however, the role of other molybdenum hydroxylase, aldehyde oxidase (AO), in the oxidation of 6-mercaptopurine and possible interactions of AO substrates and inhibitors has not been investigated in more details. In the present study, the role of AO and XO in the oxidation of 6- mercaptopurine has been investigated. 6-mercaptopurine was incubated with bovine milk xanthine oxidase or partially purified guinea pig liver molybdenum hydroxylase fractions in the absence and presence of XO and AO inhibitor/substrates, and the reactions were monitored by spectrophotometric and HPLC methods. According to the results obtained from the inhibition studies, it is more likely that 6- mercaptopurine is oxidized to 6-thiouric acid via 6-thioxanthine rather than 8-oxo-6-mercaptopurine. The first step which is the rate limiting step is catalyzed solely by XO, whereas both XO and AO are involved in the oxidation of 6-thioxanthine to 6-thiouric acid.

Transient binding of CO to Cu(B) in cytochrome c oxidase is dynamically linked to structural changes around a carboxyl group: a time-resolved step-scan Fourier transform infrared investigation.

PubMed Central

Heitbrink, Dirk; Sigurdson, Håkan; Bolwien, Carsten; Brzezinski, Peter; Heberle, Joachim

2002-01-01

The redox-driven proton pump cytochrome c oxidase is that enzymatic machinery of the respiratory chain that transfers electrons from cytochrome c to molecular oxygen and thereby splits molecular oxygen to form water. To investigate the reaction mechanism of cytochrome c oxidase on the single vibrational level, we used time-resolved step-scan Fourier transform infrared spectroscopy and studied the dynamics of the reduced enzyme after photodissociation of bound carbon monoxide across the mid-infrared range (2300-950 cm(-1)). Difference spectra of the bovine complex were obtained at -20 degrees C with 5 micros time resolution. The data demonstrate a dynamic link between the transient binding of CO to Cu(B) and changes in hydrogen bonding at the functionally important residue E(I-286). Variation of the pH revealed that the pK(a) of E(I-286) is >9.3 in the fully reduced CO-bound oxidase. Difference spectra of cytochrome c oxidase from beef heart are compared with those of the oxidase isolated from Rhodobacter sphaeroides. The bacterial enzyme does not show the environmental change in the vicinity of E(I-286) upon CO dissociation. The characteristic band shape appears, however, in redox-induced difference spectra of the bacterial enzyme but is absent in redox-induced difference spectra of mammalian enzyme. In conclusion, it is demonstrated that the dynamics of a large protein complex such as cytochrome c oxidase can be resolved on the single vibrational level with microsecond Fourier transform infrared spectroscopy. The applied methodology provides the basis for future investigations of the physiological reaction steps of this important enzyme. PMID:11751290

Discovery of a Xylooligosaccharide Oxidase from Myceliophthora thermophila C1.

PubMed

Ferrari, Alessandro R; Rozeboom, Henriëtte J; Dobruchowska, Justyna M; van Leeuwen, Sander S; Vugts, Aniek S C; Koetsier, Martijn J; Visser, Jaap; Fraaije, Marco W

2016-11-04

By inspection of the predicted proteome of the fungus Myceliophthora thermophila C1 for vanillyl-alcohol oxidase (VAO)-type flavoprotein oxidases, a putative oligosaccharide oxidase was identified. By homologous expression and subsequent purification, the respective protein could be obtained. The protein was found to contain a bicovalently bound FAD cofactor. By screening a large number of carbohydrates, several mono- and oligosaccharides could be identified as substrates. The enzyme exhibits a strong substrate preference toward xylooligosaccharides; hence it is named xylooligosaccharide oxidase (XylO). Chemical analyses of the product formed upon oxidation of xylobiose revealed that the oxidation occurs at C1, yielding xylobionate as product. By elucidation of several XylO crystal structures (in complex with a substrate mimic, xylose, and xylobiose), the residues that tune the unique substrate specificity and regioselectivity could be identified. The discovery of this novel oligosaccharide oxidase reveals that the VAO-type flavoprotein family harbors oxidases tuned for specific oligosaccharides. The unique substrate profile of XylO hints at a role in the degradation of xylan-derived oligosaccharides by the fungus M. thermophila C1. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

MAXI observations of long X-ray bursts

NASA Astrophysics Data System (ADS)

Serino, Motoko; Iwakiri, Wataru; Tamagawa, Toru; Sakamoto, Takanori; Nakahira, Satoshi; Matsuoka, Masaru; Yamaoka, Kazutaka; Negoro, Hitoshi

2016-12-01

We report nine long X-ray bursts from neutron stars, detected with the Monitor of All-sky X-ray Image (MAXI). Some of these bursts lasted for hours, and hence are qualified as superbursts, which are prolonged thermonuclear flashes on neutron stars and are relatively rare events. MAXI observes roughly 85% of the whole sky every 92 minutes in the 2-20 keV energy band, and has detected nine bursts with a long e-folding decay time, ranging from 0.27 to 5.2 hr, since its launch in 2009 August until 2015 August. The majority of the nine events were found to originate from transient X-ray sources. The persistent luminosities of the sources, when these prolonged bursts were observed, were lower than 1% of the Eddington luminosity for five of them and lower than 20% for the rest. This trend is contrastive to the 18 superbursts observed before MAXI, all but two of which originated from bright persistent sources. The distribution of the total emitted energy, i.e., the product of e-folding time and luminosity, of these bursts clusters around 1041-1042 erg, whereas both the e-folding time and luminosity ranges for an order of magnitude. Among the nine events, two were from 4U 1850-086 during phases of relatively low persistent flux, whereas it usually exhibits standard short X-ray bursts during outbursts.

Stability of spermine oxidase to thermal and chemical denaturation: comparison with bovine serum amine oxidase.

PubMed

Cervelli, Manuela; Leonetti, Alessia; Cervoni, Laura; Ohkubo, Shinji; Xhani, Marla; Stano, Pasquale; Federico, Rodolfo; Polticelli, Fabio; Mariottini, Paolo; Agostinelli, Enzo

2016-10-01

Spermine oxidase (SMOX) is a flavin-containing enzyme that specifically oxidizes spermine to produce spermidine, 3-aminopropanaldehyde and hydrogen peroxide. While no crystal structure is available for any mammalian SMOX, X-ray crystallography showed that the yeast Fms1 polyamine oxidase has a dimeric structure. Based on this scenario, we have investigated the quaternary structure of the SMOX protein by native gel electrophoresis, which revealed a composite gel band pattern, suggesting the formation of protein complexes. All high-order protein complexes are sensitive to reducing conditions, showing that disulfide bonds were responsible for protein complexes formation. The major gel band other than the SMOX monomer is the covalent SMOX homodimer, which was disassembled by increasing the reducing conditions, while being resistant to other denaturing conditions. Homodimeric and monomeric SMOXs are catalytically active, as revealed after gel staining for enzymatic activity. An engineered SMOX mutant deprived of all but two cysteine residues was prepared and characterized experimentally, resulting in a monomeric species. High-sensitivity differential scanning calorimetry of SMOX was compared with that of bovine serum amine oxidase, to analyse their thermal stability. Furthermore, enzymatic activity assays and fluorescence spectroscopy were used to gain insight into the unfolding process.

Method and apparatus for coherent burst ranging

DOEpatents

Wachter, Eric A.; Fisher, Walter G.

1998-01-01

A high resolution ranging method is described utilizing a novel modulated waveform, hereafter referred to as coherent burst modulation. In the coherent burst method, high frequency modulation of an acoustic or electromagnetic transmitter, such as a laser, is performed at a modulation frequency. This modulation frequency is transmitted quasi-continuously in the form of interrupted bursts of radiation. Energy from the transmitter is directed onto a target, interacts with the target, and the returning energy is collected. The encoded burst pattern contained in the collected return signal is detected coherently by a receiver that is tuned so as to be principally sensitive to the modulation frequency. The receiver signal is processed to determine target range using both time-of-flight of the burst envelope and phase shift of the high frequency modulation. This approach effectively decouples the maximum unambiguous range and range resolution relationship of earlier methods, thereby allowing high precision ranging to be conducted at arbitrarily long distances using at least one burst of encoded energy. The use of a receiver tuned to the high frequency modulation contained within the coherent burst vastly improves both sensitivity in the detection of the target return signal and rejection of background interferences, such as ambient acoustic or electromagnetic noise. Simultaneous transmission at several energies (or wavelengths) is possible by encoding each energy with a separate modulation frequency or pattern; electronic demodulation at the receiver allows the return pattern for each energy to be monitored independently. Radial velocity of a target can also be determined by monitoring change in phase shift of the return signal as a function of time.

Method and apparatus for coherent burst ranging

DOEpatents

Wachter, E.A.; Fisher, W.G.

1998-04-28

A high resolution ranging method is described utilizing a novel modulated waveform, hereafter referred to as coherent burst modulation. In the coherent burst method, high frequency modulation of an acoustic or electromagnetic transmitter, such as a laser, is performed at a modulation frequency. This modulation frequency is transmitted quasi-continuously in the form of interrupted bursts of radiation. Energy from the transmitter is directed onto a target, interacts with the target, and the returning energy is collected. The encoded burst pattern contained in the collected return signal is detected coherently by a receiver that is tuned so as to be principally sensitive to the modulation frequency. The receiver signal is processed to determine target range using both time-of-flight of the burst envelope and phase shift of the high frequency modulation. This approach effectively decouples the maximum unambiguous range and range resolution relationship of earlier methods, thereby allowing high precision ranging to be conducted at arbitrarily long distances using at least one burst of encoded energy. The use of a receiver tuned to the high frequency modulation contained within the coherent burst vastly improves both sensitivity in the detection of the target return signal and rejection of background interferences, such as ambient acoustic or electromagnetic noise. Simultaneous transmission at several energies (or wavelengths) is possible by encoding each energy with a separate modulation frequency or pattern; electronic demodulation at the receiver allows the return pattern for each energy to be monitored independently. Radial velocity of a target can also be determined by monitoring change in phase shift of the return signal as a function of time. 12 figs.

Powerful Radio Burst Indicates New Astronomical Phenomenon

NASA Astrophysics Data System (ADS)

2007-09-01

Astronomers studying archival data from an Australian radio telescope have discovered a powerful, short-lived burst of radio waves that they say indicates an entirely new type of astronomical phenomenon. Region of Strong Radio Burst Visible-light (negative greyscale) and radio (contours) image of Small Magellanic Cloud and area where burst originated. CREDIT: Lorimer et al., NRAO/AUI/NSF Click on image for high-resolution file ( 114 KB) "This burst appears to have originated from the distant Universe and may have been produced by an exotic event such as the collision of two neutron stars or the death throes of an evaporating black hole," said Duncan Lorimer, Assistant Professor of Physics at West Virginia University (WVU) and the National Radio Astronomy Observatory (NRAO). The research team led by Lorimer consists of Matthew Bailes of Swinburne University in Australia, Maura McLaughlin of WVU and NRAO, David Narkevic of WVU, and Fronefield Crawford of Franklin and Marshall College in Lancaster, Pennsylvania. The astronomers announced their findings in the September 27 issue of the online journal Science Express. The startling discovery came as WVU undergraduate student David Narkevic re-analyzed data from observations of the Small Magellanic Cloud made by the 210-foot Parkes radio telescope in Australia. The data came from a survey of the Magellanic Clouds that included 480 hours of observations. "This survey had sought to discover new pulsars, and the data already had been searched for the type of pulsating signals they produce," Lorimer said. "We re-examined the data, looking for bursts that, unlike the usual ones from pulsars, are not periodic," he added. The survey had covered the Magellanic Clouds, a pair of small galaxies in orbit around our own Milky Way Galaxy. Some 200,000 light-years from Earth, the Magellanic Clouds are prominent features in the Southern sky. Ironically, the new discovery is not part of these galaxies, but rather is much more distant

Analysis of type II and type III solar radio bursts

NASA Astrophysics Data System (ADS)

Wijesekera, J. V.; Jayaratne, K. P. S. C.; Adassuriya, J.

2018-04-01

Solar radio burst is an arrangement of a frequency space that variation with time. Most of radio burst can be identified in low frequency range such as below 200 MHz and depending on frequencies. Solar radio bursts were the first phenomenon identified in the field of radio astronomy field. Solar radio frequency range is from 70 MHz to 2.2 GHz. Most of the radio burst can be identified in a low frequency range such as below 200 MHz. Properties of low-frequency radio were analyzed this research. There are two types of solar radio bursts were analyzed, named as type II and type III radio bursts. Exponential decay type could be seen in type II, and a linear could be indicated in type III solar radio bursts. The results of the drift rate graphs show the values of each chosen solar radio burst. High drift rate values can be seen in type III solar flares whereas low to medium drift rate values can be seen in type II solar flares. In the second part of the research the Newkirk model electron density model was used to estimate the drift velocities of the solar radio bursts. Although the special origin of the solar radio burst is not known clearly we assumed. The chosen solar radio bursts were originated within the solar radius of 0.9 - 1.3 range from the photosphere. We used power low in the form of (x) = A × 10‑bx were that the electron density related to the height of the solar atmosphere. The calculation of the plasma velocity of each solar radio burst was done using the electron density model and drift rates. Therefore velocity of chosen type II solar radio bursts indicates low velocities. The values are 233.2499 Km s‑1, 815.9522 Km s‑1 and 369.5425 Km s‑1. Velocity of chosen type III solar radio bursts were 1443.058 Km s‑1and 1205.05Km s ‑1.

POLYAMINE OXIDASE 1 from rice (Oryza sativa) is a functional ortholog of Arabidopsis POLYAMINE OXIDASE 5.

PubMed

Liu, Taibo; Wook Kim, Dong; Niitsu, Masaru; Berberich, Thomas; Kusano, Tomonobu

2014-01-01

POLYAMINE OXIDASE 1 (OsPAO1), from rice (Oryza sativa), and POLYAMINE OXIDASE 5 (AtPAO5), from Arabidopsis (Arabidopsis thaliana), are enzymes sharing high identity at the amino acid level and with similar characteristics, such as polyamine specificity and pH preference; furthermore, both proteins localize to the cytosol. A loss-of-function Arabidopsis mutant, Atpao5-2, was hypersensitive to low doses of exogenous thermospermine but this phenotype could be rescued by introduction of the wild-type AtPAO5 gene. Introduction of OsPAO1, under the control of a constitutive promoter, into Atpao5-2 mutants also restored normal thermospermine sensitivity, allowing growth in the presence of low levels of thermospermine, along with a concomitant decrease in thermospermine content in plants. By contrast, introduction of OsPAO3, which encodes a peroxisome-localized polyamine oxidase, into Atpao5-2 plants could not rescue any of the mutant phenotypes in the presence of thermospermine. These results suggest that OsPAO1 is the functional ortholog of AtPAO5.

Aurone synthase is a catechol oxidase with hydroxylase activity and provides insights into the mechanism of plant polyphenol oxidases

PubMed Central

Molitor, Christian; Mauracher, Stephan Gerhard

2016-01-01

Tyrosinases and catechol oxidases belong to the family of polyphenol oxidases (PPOs). Tyrosinases catalyze the o-hydroxylation and oxidation of phenolic compounds, whereas catechol oxidases were so far defined to lack the hydroxylation activity and catalyze solely the oxidation of o-diphenolic compounds. Aurone synthase from Coreopsis grandiflora (AUS1) is a specialized plant PPO involved in the anabolic pathway of aurones. We present, to our knowledge, the first crystal structures of a latent plant PPO, its mature active and inactive form, caused by a sulfation of a copper binding histidine. Analysis of the latent proenzyme’s interface between the shielding C-terminal domain and the main core provides insights into its activation mechanisms. As AUS1 did not accept common tyrosinase substrates (tyrosine and tyramine), the enzyme is classified as a catechol oxidase. However, AUS1 showed hydroxylase activity toward its natural substrate (isoliquiritigenin), revealing that the hydroxylase activity is not correlated with the acceptance of common tyrosinase substrates. Therefore, we propose that the hydroxylase reaction is a general functionality of PPOs. Molecular dynamics simulations of docked substrate–enzyme complexes were performed, and a key residue was identified that influences the plant PPO’s acceptance or rejection of tyramine. Based on the evidenced hydroxylase activity and the interactions of specific residues with the substrates during the molecular dynamics simulations, a novel catalytic reaction mechanism for plant PPOs is proposed. The presented results strongly suggest that the physiological role of plant catechol oxidases were previously underestimated, as they might hydroxylate their—so far unknown—natural substrates in vivo. PMID:26976571

Ceramic Matrix Composite Vane Subelement Burst Testing

NASA Technical Reports Server (NTRS)

Brewer, David N.; Verrilli, Michael; Calomino, Anthony

2006-01-01

Burst tests were performed on Ceramic Matrix Composite (CMC) vane specimens, manufactured by two vendors, under the Ultra Efficient Engine Technology (UEET) project. Burst specimens were machined from the ends of 76mm long vane sub-elements blanks and from High Pressure Burner Rig (HPBR) tested specimens. The results of burst tests will be used to compare virgin specimens with specimens that have had an Environmental Barrier Coating (EBC) applied, both HPBR tested and untested, as well as a comparison between vendors.

Ballerina - pirouettes in search of gamma bursts

NASA Astrophysics Data System (ADS)

Brandt, S.; Lund, N.; Pedersen, H.; Hjorth, J.; BALLERINA Collaboration

1999-09-01

The cosmological origin of gamma ray bursts has now been established with reasonable certainty. Many more bursts will need to be studied to establish the typical distance scale, and to map out the large diversity in properties which have been indicated by the first handful of events. We are proposing Ballerina, a small satellite to provide accurate positions and new data on the gamma-ray bursts. We anticipate a detection rate an order of magnitude larger than obtained from Beppo-SAX.

Non-Equilibrium Thermodynamics of Transcriptional Bursts

NASA Astrophysics Data System (ADS)

Hernández-Lemus, Enrique

Gene transcription or Gene Expression (GE) is the process which transforms the information encoded in DNA into a functional RNA message. It is known that GE can occur in bursts or pulses. Transcription is irregular, with strong periods of activity, interspersed by long periods of inactivity. If we consider the average behavior over millions of cells, this process appears to be continuous. But at the individual cell level, there is considerable variability, and for most genes, very little activity at any one time. Some have claimed that GE bursting can account for the high variability in gene expression occurring between cells in isogenic populations. This variability has a big impact on cell behavior and thus on phenotypic conditions and disease. In view of these facts, the development of a thermodynamic framework to study gene expression and transcriptional regulation to integrate the vast amount of molecular biophysical GE data is appealing. Application of such thermodynamic formalism is useful to observe various dissipative phenomena in GE regulatory dynamics. In this chapter we will examine at some detail the complex phenomena of transcriptional bursts (specially of a certain class of anomalous bursts) in the context of a non-equilibrium thermodynamics formalism and will make some initial comments on the relevance of some irreversible processes that may be connected to anomalous transcriptional bursts.

Oscillations During Thermonuclear X-ray Bursts

NASA Technical Reports Server (NTRS)

Strohmayer, Tod E.; White, Nicholas E. (Technical Monitor)

2001-01-01

High amplitude, nearly coherent X-ray brightness oscillations during thermonuclear X-ray bursts were discovered with the Rossi X-ray Timing Explorer (RXTE) in early 1996. Spectral and timing evidence strongly supports the conclusion that these oscillations are caused by rotational modulation of the burst emission and that they reveal the spin frequency of neutron stars in low mass X-ray binaries, a long sought goal of X-ray astronomy. Studies carried out over the past year have led to the discovery of burst oscillations in four new sources, bringing to ten the number with confirmed burst oscillations. I review the status of our knowledge of these oscillations and indicate how they can be used to probe the physics of neutron stars. For a few burst oscillation sources it has been proposed that the strongest and most ubiquitous frequency is actually the first overtone of the spin frequency and hence that two nearly antipodal hot spots are present on the neutron star. This inference has important implications for both the physics of thermonuclear burning as well as the mass - radius relation for neutron stars, so its confirmation is crucial. I discuss recent attempts to confirm this hypothesis for 4U 1636-53, the source for which a signal at the putative fundamental (290Hz) has, been claimed.

Long Duration X-ray Bursts Observed by MAXI

NASA Astrophysics Data System (ADS)

Serino, Motoko; Iwakiri, Wataru; Tamagawa, Toru; Sakamoto, Takanori; Nakahira, Satoshi; Matsuoka, Masaru; Yamaoka, Kazutaka; Negoro, Hitoshi

Monitor of All-sky X-ray Image (MAXI) is X-ray mission on the International Space Station. MAXI scans all sky every 92 min and detects various X-ray transient events including X-ray bursts. Among the X-ray bursts observed by MAXI, eleven had long duration and were observed more than one scan. Six out of eleven long bursts have the e-folding time of >1 h, that should be classified as "superbursts", while the rest are "intermediate-duration bursts". The total emitted energy of these long X-ray bursts range from 1041 to 1042 ergs. The lower limits of the superburst recurrence time of 4U 0614+091 and Ser X-1 are calculated as 4400 and 59 days, which may be consistent with the observed recurrence time of 3523 and 1148 days, respectively.

Amplitude sorting of oscillatory burst signals by sampling

DOEpatents

Davis, Thomas J.

1977-01-01

A method and apparatus for amplitude sorting of oscillatory burst signals is described in which the burst signal is detected to produce a burst envelope signal and an intermediate or midportion of such envelope signal is sampled to provide a sample pulse output. The height of the sample pulse is proportional to the amplitude of the envelope signal and to the maximum burst signal amplitude. The sample pulses are fed to a pulse height analyzer for sorting. The present invention is used in an acoustic emission testing system to convert the amplitude of the acoustic emission burst signals into sample pulse heights which are measured by a pulse height analyzer for sorting the pulses in groups according to their height in order to identify the material anomalies in the test material which emit the acoustic signals.

Closest Gamma Ray Burst Providing Scientists With Crucial Test for Burst Physics

NASA Astrophysics Data System (ADS)

2003-05-01

The closest Gamma Ray Burst (GRB) yet known is providing astronomers with a rare opportunity to gain information vital to understanding these powerful cosmic explosions. Extremely precise radio-telescope observations already have ruled out one proposed mechanism for the bursts. "This is the closest and brightest GRB we've ever seen, and we can use it to decipher the physics of how these bursts work," said Greg Taylor of the National Radio Astronomy Observatory (NRAO) in Socorro, NM. Taylor worked with Dale Frail, also of the NRAO, along with Prof. Shri Kulkarni and graduate student Edo Berger of Caltech in studying a GRB detected on March 29, 2003. The scientists presented their findings to the American Astronomical Society's meeting in Nashville, TN. VLBA image of GRB 030329 VLBA IMAGE of GRB 030329 CREDIT: NRAO/AUI/NSF (Click on Image for Larger Version) Taylor and Frail used the National Science Foundation's (NSF) Very Long Baseline Array (VLBA) and other radio telescopes to study the burst, known as GRB 030329. In a series of observations from April 1 to May 19, they determined the size of the expanding "fireball" from the burst and measured its position in the sky with great precision. At a distance of about 2.6 billion light-years, GRB 030329 is hardly next door. However, compared to other GRBs at typical distances of 8-10 billion light-years, it presents an easier target for study. "We only expect to see one burst per decade this close," said Frail. The precise measurement of the object's position allowed the scientists to show that one theoretical model for GRBs can be ruled out. This model, proposed in 2000, says that the radio-wave energy emitted by the GRB comes from "cannonballs" of material shot from the explosion at extremely high speeds. "The 'cannonball model' predicted that we should see the radio-emitting object move across the sky by a specific amount. We have not seen that motion," Taylor said. The currently standard "fireball model" of GRBs

BALLERINA - doing Pirouettes for the Gamma-Bursts

NASA Astrophysics Data System (ADS)

Lund, Niels; Ballerina Consortium

1998-12-01

BALLERINA is a satellite project currently selected (together with 3 other candidates) for a five month phase-A study within the Danish Small-Satellite Programme. BALLERINA combines an all-sky monitor yielding instantaneous half-degree size error boxes with rapid maneuverability and a wide field X-ray telescope. The project aims to study the transition phase from the gamma-burst to the afterglow phase, and to distribute sub-arcminute positions for the bursts in near real time. We expect to be able to lock-on to the source with the X-ray telescope in less than 3 minutes from the trigger, and to provide the accurate burst position to the general astronomical community within 10 minutes. While waiting for the bursts we plan to study other transient and persistent X-ray sources .

Manifestation of peripherial coding in the effect of increasing loudness and enhanced discrimination of the intensity of tone bursts before and after tone burst noise

NASA Astrophysics Data System (ADS)

Rimskaya-Korsavkova, L. K.

2017-07-01

To find the possible reasons for the midlevel elevation of the Weber fraction in intensity discrimination of a tone burst, a comparison was performed for the complementary distributions of spike activity of an ensemble of space nerves, such as the distribution of time instants when spikes occur, the distribution of interspike intervals, and the autocorrelation function. The distribution properties were detected in a poststimulus histogram, an interspike interval histogram, and an autocorrelation histogram—all obtained from the reaction of an ensemble of model space nerves in response to an auditory noise burst-useful tone burst complex. Two configurations were used: in the first, the peak amplitude of the tone burst was varied and the noise amplitude was fixed; in the other, the tone burst amplitude was fixed and the noise amplitude was varied. Noise could precede or follow the tone burst. The noise and tone burst durations, as well as the interval between them, was 4 kHz and corresponded to the characteristic frequencies of the model space nerves. The profiles of all the mentioned histograms had two maxima. The values and the positions of the maxima in the poststimulus histogram corresponded to the amplitudes and mutual time position of the noise and the tone burst. The maximum that occurred in response to the tone burst action could be a basis for the formation of the loudness of the latter (explicit loudness). However, the positions of the maxima in the other two histograms did not depend on the positions of tone bursts and noise in the combinations. The first maximum fell in short intervals and united intervals corresponding to the noise and tone burst durations. The second maximum fell in intervals corresponding to a tone burst delay with respect to noise, and its value was proportional to the noise amplitude or tone burst amplitude that was smaller in the complex. An increase in tone burst or noise amplitudes was caused by nonlinear variations in the two

Beta burst dynamics in Parkinson's disease OFF and ON dopaminergic medication.

PubMed

Tinkhauser, Gerd; Pogosyan, Alek; Tan, Huiling; Herz, Damian M; Kühn, Andrea A; Brown, Peter

2017-11-01

Exaggerated basal ganglia beta activity (13-35 Hz) is commonly found in patients with Parkinson's disease and can be suppressed by dopaminergic medication, with the degree of suppression being correlated with the improvement in motor symptoms. Importantly, beta activity is not continuously elevated, but fluctuates to give beta bursts. The percentage number of longer beta bursts in a given interval is positively correlated with clinical impairment in Parkinson's disease patients. Here we determine whether the characteristics of beta bursts are dependent on dopaminergic state. Local field potentials were recorded from the subthalamic nucleus of eight Parkinson's disease patients during temporary lead externalization during surgery for deep brain stimulation. The recordings took place with the patient quietly seated following overnight withdrawal of levodopa and after administration of levodopa. Beta bursts were defined by applying a common amplitude threshold and burst characteristics were compared between the two drug conditions. The amplitude of beta bursts, indicative of the degree of local neural synchronization, progressively increased with burst duration. Treatment with levodopa limited this evolution leading to a relative increase of shorter, lower amplitude bursts. Synchronization, however, was not limited to local neural populations during bursts, but also, when such bursts were cotemporaneous across the hemispheres, was evidenced by bilateral phase synchronization. The probability of beta bursts and the proportion of cotemporaneous bursts were reduced by levodopa. The percentage number of longer beta bursts in a given interval was positively related to motor impairment, while the opposite was true for the percentage number of short duration beta bursts. Importantly, the decrease in burst duration was also correlated with the motor improvement. In conclusion, we demonstrate that long duration beta bursts are associated with an increase in local and

Local cortical dynamics of burst suppression in the anaesthetized brain.

PubMed

Lewis, Laura D; Ching, Shinung; Weiner, Veronica S; Peterfreund, Robert A; Eskandar, Emad N; Cash, Sydney S; Brown, Emery N; Purdon, Patrick L

2013-09-01

Burst suppression is an electroencephalogram pattern that consists of a quasi-periodic alternation between isoelectric 'suppressions' lasting seconds or minutes, and high-voltage 'bursts'. It is characteristic of a profoundly inactivated brain, occurring in conditions including hypothermia, deep general anaesthesia, infant encephalopathy and coma. It is also used in neurology as an electrophysiological endpoint in pharmacologically induced coma for brain protection after traumatic injury and during status epilepticus. Classically, burst suppression has been regarded as a 'global' state with synchronous activity throughout cortex. This assumption has influenced the clinical use of burst suppression as a way to broadly reduce neural activity. However, the extent of spatial homogeneity has not been fully explored due to the challenges in recording from multiple cortical sites simultaneously. The neurophysiological dynamics of large-scale cortical circuits during burst suppression are therefore not well understood. To address this question, we recorded intracranial electrocorticograms from patients who entered burst suppression while receiving propofol general anaesthesia. The electrodes were broadly distributed across cortex, enabling us to examine both the dynamics of burst suppression within local cortical regions and larger-scale network interactions. We found that in contrast to previous characterizations, bursts could be substantially asynchronous across the cortex. Furthermore, the state of burst suppression itself could occur in a limited cortical region while other areas exhibited ongoing continuous activity. In addition, we found a complex temporal structure within bursts, which recapitulated the spectral dynamics of the state preceding burst suppression, and evolved throughout the course of a single burst. Our observations imply that local cortical dynamics are not homogeneous, even during significant brain inactivation. Instead, cortical and, implicitly

Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide.

PubMed

Fischer, Anthony J; Lennemann, Nicholas J; Krishnamurthy, Sateesh; Pócza, Péter; Durairaj, Lakshmi; Launspach, Janice L; Rhein, Bethany A; Wohlford-Lenane, Christine; Lorentzen, Daniel; Bánfi, Botond; McCray, Paul B

2011-10-01

Recent reports postulate that the dual oxidase (DUOX) proteins function as part of a multicomponent oxidative pathway used by the respiratory mucosa to kill bacteria. The other components include epithelial ion transporters, which mediate the secretion of the oxidizable anion thiocyanate (SCN(-)) into airway surface liquid, and lactoperoxidase (LPO), which catalyzes the H(2)O(2)-dependent oxidation of the pseudohalide SCN(-) to yield the antimicrobial molecule hypothiocyanite (OSCN(-)). We hypothesized that this oxidative host defense system is also active against respiratory viruses. We evaluated the activity of oxidized LPO substrates against encapsidated and enveloped viruses. When tested for antiviral properties, the LPO-dependent production of OSCN(-) did not inactivate adenovirus or respiratory syncytial virus (RSV). However, substituting SCN(-) with the alternative LPO substrate iodide (I(-)) resulted in a marked reduction of both adenovirus transduction and RSV titer. Importantly, well-differentiated primary airway epithelia generated sufficient H(2)O(2) to inactivate adenovirus or RSV when LPO and I(-) were supplied. The administration of a single dose of 130 mg of oral potassium iodide to human subjects increased serum I(-) concentrations, and resulted in the accumulation of I(-) in upper airway secretions. These results suggest that the LPO/I(-)/H(2)O(2) system can contribute to airway antiviral defenses. Furthermore, the delivery of I(-) to the airway mucosa may augment innate antiviral immunity.

Three-dimensional organization of three-domain copper oxidases: A review

NASA Astrophysics Data System (ADS)

Zhukhlistova, N. E.; Zhukova, Yu. N.; Lyashenko, A. V.; Zaĭtsev, V. N.; Mikhaĭlov, A. M.

2008-01-01

“Blue” copper-containing proteins are multidomain proteins that utilize a unique redox property of copper ions. Among other blue multicopper oxidases, three-domain oxidases belong to the group of proteins that exhibit a wide variety of compositions in amino acid sequences, functions, and occurrences in organisms. This paper presents a review of the data obtained from X-ray diffraction investigations of the three-dimensional structures of three-domain multicopper oxidases, such as the ascorbate oxidase catalyzing oxidation of ascorbate to dehydroascorbate and its three derivatives; the multicopper oxidase CueO (the laccase homologue); the laccases isolated from the basidiomycetes Coprinus cinereus, Trametes versicolor, Coriolus zonatus, Cerrena maxima, and Rigidoporus lignosus and the ascomycete Melanocarpus albomyces; and the bacterial laccases CotA from the endospore coats of Bacillus subtilis. A comparison of the molecular structures of the laccases of different origins demonstrates that, structurally, these objects are highly conservative. This obviously indicates that the catalytic activity of the enzymes under consideration is characterized by similar mechanisms.

NADPH OXIDASE: STRUCTURE AND ACTIVATION MECHANISMS (REVIEW). NOTE I.

PubMed

Filip-Ciubotaru, Florina; Manciuc, Carmen; Stoleriu, Gabriela; Foia, Liliana

2016-01-01

NADPH oxidase (nicotinamide adenine dinucleotide phosphate-oxidase), with its generically termed NOX isoforms, is the major source of ROS (reactive oxigen species) in biological systems. ROS are small oxygen-derived molecules with an important role in various biological processes (physiological or pathological). If under physiological conditions some processes are beneficial and necessary for life, under pathophysiological conditions they are noxious, harmful. NADPH oxidases are present in phagocytes and in a wide variety of nonphagocytic cells. The enzyme generates superoxide by transferring electrons from NADPH inside the cell across the membrane and coupling them to molecular oxygen to produce superoxide anion, a reactive free-radical. Structurally, NADPH oxidase is a multicomponent enzyme which includes two integral membrane proteins, glycoprotein gp9 1 Phox and adaptor protein p22(phox), which together form the heterodimeric flavocytochrome b558 that constitutes the core of the enzyme. During the resting state, the multidomain regulatory subunits p40P(phox), p47(phox), p67(Phox) are located in the cytosol organized as a complex. The activation of phagocytic NADPH oxidase occurs through a complex series of protein interactions.

Solar U- and J- Bursts at the Frequencies 10-30MHz

NASA Astrophysics Data System (ADS)

Dorovskyy, V. V.; Melnik, V. N.; Konovalenko, A. A.; Abranin, E. P.; Rucker, H. O.; Lecacheux, A.

2006-08-01

In the present report we discuss the results of observations of solar U- and J- bursts over the frequency range 10-30MHz, which have been obtained within the framework of an international observational campaign in June - August, 2004 at the radio telescope UTR-2 (Kharkov, Ukraine). We succeed to observe these types of bursts for the first time at such a low frequencies due to combination of large effective area of the radio telescope and high sensitivity of the new back-end. During June - August, 2004 about 30 U- and J- bursts were registered, and only 5 of them were confidently identified as U-bursts that may speak about the relative sparsity of the latter at mentioned frequencies. Both the isolated bursts and their sequences were observed. On average the turning frequencies lay in the range 10-22 MHz that corresponds to the arches heliocentric heights of 1.6-2.2 solar radii. In some sequences the bursts turning frequency was stable that may indicate the arch stability, while in others the turning frequency had tendency to vary from burst to burst. Durations of U- and J- bursts did not differ from those of usual Type III bursts (3-7s), while the drift rates of an ascending arm (on the average -1MHz/ s) was a little bit lower, than those of ordinary Type III bursts in this range. The harmonic structure of U- and J- bursts, and also Jb-J pairs (analogous to IIIb-III pairs) were registered. Also L-shaped bursts (Leblanc and Hoyos, 1985) were recorded. A specific feature of L-shaped bursts is prolonged zero-drift region on their dynamic spectra. The sizes and configurations of the arches were estimated on the base of obtained data. Possible explanations of the observed properties of U- and J- bursts are discussed.

Reaction of oxygen with the respiratory chain in cells and tissues.

PubMed

Chance, B

1965-09-01

This paper considers the way in which the oxygen reaction described by Dr. Nicholls and the ADP control reactions described by Dr. Racker could cooperate to establish a purposeful metabolic control phenomenon in vivo. This has required an examination of the kinetic properties of the respiratory chain with particular reference to methods for determinations of oxygen affinity (K(m)). The constant parameter for tissue respiration is k(1), the velocity constant for the reaction of oxygen with cytochrome oxidase. Not only is this quantity a constant for a particular tissue or mitochondria; it appears to vary little over a wide range of biological material, and for practical purposes a value of 5 x 10(7) at 25 degrees close to our original value (20) is found to apply with adequate accuracy for calculation of K(m) for mammalia. The quantity which will depend upon the tissue and its metabolic state is the value of K(m) itself, and K(m) may be as large as 0.5 microM and may fall to 0.05 microM or less in resting, controlled, or inhibited states. The control characteristic for ADP may depend upon the electron flux due to the cytochrome chain (40); less ADP is required to activate the slower electron transport at lower temperatures than at higher temperatures. The affinity constants for ADP control appear to be less dependent upon substrate supplied to the system. The balance of ADP and oxygen control in vivo is amply demonstrated experimentally and is dependent on the oxygen concentration as follows. In the presence of excess oxygen, control may be due to the ADP or phosphate (or substrate), and the kinetics of oxygen utilization will be independent of the oxygen concentration. As the oxygen concentration is diminished, hemoglobin becomes disoxygenated, deep gradients of oxygen concentration develop in the tissue, and eventually cytochrome oxidase becomes partially and then completely reduced. DPN at this point will become reduced and the electron flow diminished. The rate

Burst synchronization transitions in a neuronal network of subnetworks

NASA Astrophysics Data System (ADS)

Sun, Xiaojuan; Lei, Jinzhi; Perc, Matjaž; Kurths, Jürgen; Chen, Guanrong

2011-03-01

In this paper, the transitions of burst synchronization are explored in a neuronal network consisting of subnetworks. The studied network is composed of electrically coupled bursting Hindmarsh-Rose neurons. Numerical results show that two types of burst synchronization transitions can be induced not only by the variations of intra- and intercoupling strengths but also by changing the probability of random links between different subnetworks and the number of subnetworks. Furthermore, we find that the underlying mechanisms for these two bursting synchronization transitions are different: one is due to the change of spike numbers per burst, while the other is caused by the change of the bursting type. Considering that changes in the coupling strengths and neuronal connections are closely interlaced with brain plasticity, the presented results could have important implications for the role of the brain plasticity in some functional behavior that are associated with synchronization.

Correlated bursts and the role of memory range

NASA Astrophysics Data System (ADS)

Jo, Hang-Hyun; Perotti, Juan I.; Kaski, Kimmo; Kertész, János

2015-08-01

Inhomogeneous temporal processes in natural and social phenomena have been described by bursts that are rapidly occurring events within short time periods alternating with long periods of low activity. In addition to the analysis of heavy-tailed interevent time distributions, higher-order correlations between interevent times, called correlated bursts, have been studied only recently. As the underlying mechanism behind such correlated bursts is far from being fully understood, we devise a simple model for correlated bursts using a self-exciting point process with a variable range of memory. Whether a new event occurs is stochastically determined by a memory function that is the sum of decaying memories of past events. In order to incorporate the noise and/or limited memory capacity of systems, we apply two memory loss mechanisms: a fixed number or a variable number of memories. By analysis and numerical simulations, we find that too much memory effect may lead to a Poissonian process, implying that there exists an intermediate range of memory effect to generate correlated bursts comparable to empirical findings. Our conclusions provide a deeper understanding of how long-range memory affects correlated bursts.

Galactic dual population models of gamma-ray bursts

NASA Technical Reports Server (NTRS)

Higdon, J. C.; Lingenfelter, R. E.

1994-01-01

We investigate in more detail the properties of two-population models for gamma-ray bursts in the galactic disk and halo. We calculate the gamma-ray burst statistical properties, mean value of (V/V(sub max)), mean value of cos Theta, and mean value of (sin(exp 2) b), as functions of the detection flux threshold for bursts coming from both Galactic disk and massive halo populations. We consider halo models inferred from the observational constraints on the large-scale Galactic structure and we compare the expected values of mean value of (V/V(sub max)), mean value of cos Theta, and mean value of (sin(exp 2) b), with those measured by Burst and Transient Source Experiment (BATSE) and other detectors. We find that the measured values are consistent with solely Galactic populations having a range of halo distributions, mixed with local disk distributions, which can account for as much as approximately 25% of the observed BATSE bursts. M31 does not contribute to these modeled bursts. We also demonstrate, contrary to recent arguments, that the size-frequency distributions of dual population models are quite consistent with the BATSE observations.

Statistical Properties of SGR J1550-5418 Bursts

NASA Technical Reports Server (NTRS)

Gorgone, Nicholas M.

2010-01-01

Magnetars are slowly rotating neutron stars with extreme magnetic fields, over 10(exp 15) Gauss. Only few have been discovered in the last 30 years. These sources are dormant most of their lifetimes and become randomly active emitting multiple soft gamma-ray bursts. We present here our results on the temporal analysis of 300 bursts from Soft Gamma Repeater SGR J1550-5418 recorded with the Gamma-ray Burst Monitor (GBM) onboard the Fermi Observatory during its activation on January 22-29, 2009. We employed an un-triggered burst search in the energy range 8-100keV to collect all events from the source, besides the ones that triggered GBM. For the entire sample of bursts we determined their durations, rise and decay times. We study here the statistical properties of these characteristics and discuss how these may help us better understand the physical characteristics of the magnetar model.

Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

PubMed Central

Sharma, Vivek; Enkavi, Giray; Vattulainen, Ilpo; Róg, Tomasz; Wikström, Mårten

2015-01-01

Molecular oxygen acts as the terminal electron sink in the respiratory chains of aerobic organisms. Cytochrome c oxidase in the inner membrane of mitochondria and the plasma membrane of bacteria catalyzes the reduction of oxygen to water, and couples the free energy of the reaction to proton pumping across the membrane. The proton-pumping activity contributes to the proton electrochemical gradient, which drives the synthesis of ATP. Based on kinetic experiments on the O–O bond splitting transition of the catalytic cycle (A → PR), it has been proposed that the electron transfer to the binuclear iron–copper center of O2 reduction initiates the proton pump mechanism. This key electron transfer event is coupled to an internal proton transfer from a conserved glutamic acid to the proton-loading site of the pump. However, the proton may instead be transferred to the binuclear center to complete the oxygen reduction chemistry, which would constitute a short-circuit. Based on atomistic molecular dynamics simulations of cytochrome c oxidase in an explicit membrane–solvent environment, complemented by related free-energy calculations, we propose that this short-circuit is effectively prevented by a redox-state–dependent organization of water molecules within the protein structure that gates the proton transfer pathway. PMID:25646428

Thalamic neuron models encode stimulus information by burst-size modulation

PubMed Central

Elijah, Daniel H.; Samengo, Inés; Montemurro, Marcelo A.

2015-01-01

Thalamic neurons have been long assumed to fire in tonic mode during perceptive states, and in burst mode during sleep and unconsciousness. However, recent evidence suggests that bursts may also be relevant in the encoding of sensory information. Here, we explore the neural code of such thalamic bursts. In order to assess whether the burst code is generic or whether it depends on the detailed properties of each bursting neuron, we analyzed two neuron models incorporating different levels of biological detail. One of the models contained no information of the biophysical processes entailed in spike generation, and described neuron activity at a phenomenological level. The second model represented the evolution of the individual ionic conductances involved in spiking and bursting, and required a large number of parameters. We analyzed the models' input selectivity using reverse correlation methods and information theory. We found that n-spike bursts from both models transmit information by modulating their spike count in response to changes to instantaneous input features, such as slope, phase, amplitude, etc. The stimulus feature that is most efficiently encoded by bursts, however, need not coincide with one of such classical features. We therefore searched for the optimal feature among all those that could be expressed as a linear transformation of the time-dependent input current. We found that bursting neurons transmitted 6 times more information about such more general features. The relevant events in the stimulus were located in a time window spanning ~100 ms before and ~20 ms after burst onset. Most importantly, the neural code employed by the simple and the biologically realistic models was largely the same, implying that the simple thalamic neuron model contains the essential ingredients that account for the computational properties of the thalamic burst code. Thus, our results suggest the n-spike burst code is a general property of thalamic neurons. PMID

Thalamic neuron models encode stimulus information by burst-size modulation.

PubMed

Elijah, Daniel H; Samengo, Inés; Montemurro, Marcelo A

2015-01-01

Thalamic neurons have been long assumed to fire in tonic mode during perceptive states, and in burst mode during sleep and unconsciousness. However, recent evidence suggests that bursts may also be relevant in the encoding of sensory information. Here, we explore the neural code of such thalamic bursts. In order to assess whether the burst code is generic or whether it depends on the detailed properties of each bursting neuron, we analyzed two neuron models incorporating different levels of biological detail. One of the models contained no information of the biophysical processes entailed in spike generation, and described neuron activity at a phenomenological level. The second model represented the evolution of the individual ionic conductances involved in spiking and bursting, and required a large number of parameters. We analyzed the models' input selectivity using reverse correlation methods and information theory. We found that n-spike bursts from both models transmit information by modulating their spike count in response to changes to instantaneous input features, such as slope, phase, amplitude, etc. The stimulus feature that is most efficiently encoded by bursts, however, need not coincide with one of such classical features. We therefore searched for the optimal feature among all those that could be expressed as a linear transformation of the time-dependent input current. We found that bursting neurons transmitted 6 times more information about such more general features. The relevant events in the stimulus were located in a time window spanning ~100 ms before and ~20 ms after burst onset. Most importantly, the neural code employed by the simple and the biologically realistic models was largely the same, implying that the simple thalamic neuron model contains the essential ingredients that account for the computational properties of the thalamic burst code. Thus, our results suggest the n-spike burst code is a general property of thalamic neurons.

On Burst Detection and Prediction in Retweeting Sequence

DTIC Science & Technology

2015-05-22

We conduct a comprehensive empirical analysis of a large microblogging dataset collected from the Sina Weibo and report our observations of burst...whether and how accurate we can predict bursts using classifiers based on the extracted features. Our empirical study of the Sina Weibo data shows the...feasibility of burst prediction using appropriately extracted features and classic classifiers. 1 Introduction Microblogging, such as Twitter and Sina

Optical recording from respiratory pattern generator of fetal mouse brainstem reveals a distributed network.

PubMed

Eugenin, J; Nicholls, J G; Cohen, L B; Muller, K J

2006-01-01

Unfailing respiration depends on neural mechanisms already present in mammals before birth. Experiments were made to determine how inspiratory and expiratory neurons are grouped in the brainstem of fetal mice. A further aim was to assess whether rhythmicity arises from a single pacemaker or is generated by multiple sites in the brainstem. To measure neuronal firing, a fluorescent calcium indicator dye was applied to embryonic central nervous systems isolated from mice. While respiratory commands were monitored electrically from third to fifth cervical ventral roots, activity was measured optically over areas containing groups of respiratory neurones, or single neurones, along the medulla from the facial nucleus to the pre-Bötzinger complex. Large optical signals allowed recordings to be made during individual respiratory cycles. Inspiratory and expiratory neurones were intermingled. A novel finding was that bursts of activity arose in a discrete area intermittently, occurring during some breaths, but failing in others. Raised CO2 partial pressure or lowered pH increased the frequency of respiration; neurons then fired reliably with every cycle. Movies of activity revealed patterns of activation of inspiratory and expiratory neurones during successive respiratory cycles; there was no evidence for waves spreading systematically from region to region. Our results suggest that firing of neurons in immature respiratory circuits is a stochastic process, and that the rhythm does not depend on a single pacemaker. Respiratory circuits in fetal mouse brainstem appear to possess a high safety factor for generating rhythmicity, which may or may not persist as development proceeds.

The application of network synthesis to repeating classical gamma-ray bursts

NASA Technical Reports Server (NTRS)

Hurley, K.; Kouveliotou, C.; Fishman, J.; Meegan, C.; Laros, J.; Klebesadel, R.

1995-01-01

It has been suggested that the Burst and Transient Source Experiment (BATSE) gamma-ray burst catalog contains several groups of bursts clustered in space or in space and time, which provide evidence that a substantial fraction of the classical gamma-ray burst sources repeat. Because many of the bursts in these groups are weak, they are not directly detected by the Ulysses GRB experiment. We apply the network synthesis method to these events to test the repeating burst hypothesis. Although we find no evidence for repeating sources, the method must be applied under more general conditions before reaching any definite conclusions about the existence of classical gamma-ray burst repeating sources.

Expression and Chloroplast Targeting of Cholesterol Oxidase in Transgenic Tobacco Plants

PubMed Central

Corbin, David R.; Grebenok, Robert J.; Ohnmeiss, Thomas E.; Greenplate, John T.; Purcell, John P.

2001-01-01

Cholesterol oxidase represents a novel type of insecticidal protein with potent activity against the cotton boll weevil (Anthonomus grandis grandis Boheman). We transformed tobacco (Nicotiana tabacum) plants with the cholesterol oxidase choM gene and expressed cytosolic and chloroplast-targeted versions of the ChoM protein. Transgenic leaf tissues expressing cholesterol oxidase exerted insecticidal activity against boll weevil larvae. Our results indicate that cholesterol oxidase can metabolize phytosterols in vivo when produced cytosolically or when targeted to chloroplasts. The transgenic plants exhibiting cytosolic expression accumulated low levels of saturated sterols known as stanols, and displayed severe developmental aberrations. In contrast, the transgenic plants expressing chloroplast-targeted cholesterol oxidase maintained a greater accumulation of stanols, and appeared phenotypically and developmentally normal. These results are discussed within the context of plant sterol distribution and metabolism. PMID:11457962

Effect of network architecture on burst and spike synchronization in a scale-free network of bursting neurons.

PubMed

Kim, Sang-Yoon; Lim, Woochang

2016-07-01

We investigate the effect of network architecture on burst and spike synchronization in a directed scale-free network (SFN) of bursting neurons, evolved via two independent α- and β-processes. The α-process corresponds to a directed version of the Barabási-Albert SFN model with growth and preferential attachment, while for the β-process only preferential attachments between pre-existing nodes are made without addition of new nodes. We first consider the "pure" α-process of symmetric preferential attachment (with the same in- and out-degrees), and study emergence of burst and spike synchronization by varying the coupling strength J and the noise intensity D for a fixed attachment degree. Characterizations of burst and spike synchronization are also made by employing realistic order parameters and statistical-mechanical measures. Next, we choose appropriate values of J and D where only burst synchronization occurs, and investigate the effect of the scale-free connectivity on the burst synchronization by varying (1) the symmetric attachment degree and (2) the asymmetry parameter (representing deviation from the symmetric case) in the α-process, and (3) the occurrence probability of the β-process. In all these three cases, changes in the type and the degree of population synchronization are studied in connection with the network topology such as the degree distribution, the average path length Lp, and the betweenness centralization Bc. It is thus found that just taking into consideration Lp and Bc (affecting global communication between nodes) is not sufficient to understand emergence of population synchronization in SFNs, but in addition to them, the in-degree distribution (affecting individual dynamics) must also be considered to fully understand for the effective population synchronization. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effect of Post-Burst Energy on Exploding Bridgewire Output

NASA Astrophysics Data System (ADS)

Lee, Elizabeth; Bowden, Mike

2015-06-01

For an EBW detonator, as the fireset energy is increased from threshold to all-fire level the post-burst energy delivered to the detonator increases, and the function times decrease. To gain an understanding of the processes through which the post-burst electrical energy influences the function times the effect of the post-burst energy on the explosion of bridgewires was studied. A fireset was developed which enabled the post-burst energy to be varied independent of the burst energy by terminating the current flow at pre-selected times. The effect of this on the bridgewires was characterised at a range of firing voltages and a range of termination times. The response of the bridgewire was characterised using Photonic Doppler Velocimetry. The velocimetry trace detected two families of velocities. The first family had initial velocities in the range 1-2 km.s-1 and the second family had velocities in the range 0-0.5 km.s-1. The relative position of the two families depended on the post burst energy. The results show that a reduction in the post-burst energy and therefore the total delivered energy, but for a constant energy delivered to burst, corresponds to a decrease in the acceleration and peak velocity of the bridgewire / plasma at burst.

Gamma Ray Bursts and the Birth of Black Holes

NASA Technical Reports Server (NTRS)

Gehrels, Neil

2009-01-01

Black holes have been predicted since the 1940's from solutions of Einstein's general relativity field equation. There is strong evidence of their existence from astronomical observations, but their origin has remained an open question of great interest. Gamma-ray bursts may the clue. They are powerful explosions, visible to high redshift, and appear to be the birth cries of black holes. The Swift and Fermi missions are two powerful NASA observatories currently in orbit that are discovering how gamma-ray bursts work. Evidence is building that the long and short duration subcategories of GRBs have very different origins: massive star core collapse to a black hole for long bursts and binary neutron star coalescence to a black hole for short bursts. The similarity to Type II and Ia supernovae originating from young and old stellar progenitors is striking. Bursts are tremendously luminous and are providing a new tool to study the high redshift universe. One Swift burst at z=8.3 is the most distant object known in the universe. The talk will present the latest gamma-ray burst results from Swift and Fermi and will highlight what they are teaching us about black holes and jet outflows.

Burst Firing is a Neural Code in an Insect Auditory System

PubMed Central

Eyherabide, Hugo G.; Rokem, Ariel; Herz, Andreas V. M.; Samengo, Inés

2008-01-01

Various classes of neurons alternate between high-frequency discharges and silent intervals. This phenomenon is called burst firing. To analyze burst activity in an insect system, grasshopper auditory receptor neurons were recorded in vivo for several distinct stimulus types. The experimental data show that both burst probability and burst characteristics are strongly influenced by temporal modulations of the acoustic stimulus. The tendency to burst, hence, is not only determined by cell-intrinsic processes, but also by their interaction with the stimulus time course. We study this interaction quantitatively and observe that bursts containing a certain number of spikes occur shortly after stimulus deflections of specific intensity and duration. Our findings suggest a sparse neural code where information about the stimulus is represented by the number of spikes per burst, irrespective of the detailed interspike-interval structure within a burst. This compact representation cannot be interpreted as a firing-rate code. An information-theoretical analysis reveals that the number of spikes per burst reliably conveys information about the amplitude and duration of sound transients, whereas their time of occurrence is reflected by the burst onset time. The investigated neurons encode almost half of the total transmitted information in burst activity. PMID:18946533

Self-Organization on Social Media: Endo-Exo Bursts and Baseline Fluctuations

PubMed Central

Oka, Mizuki; Hashimoto, Yasuhiro; Ikegami, Takashi

2014-01-01

A salient dynamic property of social media is bursting behavior. In this paper, we study bursting behavior in terms of the temporal relation between a preceding baseline fluctuation and the successive burst response using a frequency time series of 3,000 keywords on Twitter. We found that there is a fluctuation threshold up to which the burst size increases as the fluctuation increases and that above the threshold, there appears a variety of burst sizes. We call this threshold the critical threshold. Investigating this threshold in relation to endogenous bursts and exogenous bursts based on peak ratio and burst size reveals that the bursts below this threshold are endogenously caused and above this threshold, exogenous bursts emerge. Analysis of the 3,000 keywords shows that all the nouns have both endogenous and exogenous origins of bursts and that each keyword has a critical threshold in the baseline fluctuation value to distinguish between the two. Having a threshold for an input value for activating the system implies that Twitter is an excitable medium. These findings are useful for characterizing how excitable a keyword is on Twitter and could be used, for example, to predict the response to particular information on social media. PMID:25329610

Comparative Activity-Based Flavin-Dependent Oxidase Profiling.

PubMed

Krysiak, Joanna; Breinbauer, Rolf

2017-01-01

Activity-based protein profiling (ABPP) has become a powerful chemoproteomic technology allowing for the dissection of complex ligand-protein interactions in their native cellular environment. One of the biggest challenges for ABPP is the extension of the proteome coverage. In this chapter a new ABPP strategy dedicated to monoamine oxidases (MAO) is presented. These enzymes are representative examples of flavin-dependent oxidases, playing a crucial role in the regulation of nervous system signaling.

Multidomain flavin-dependent sulfhydryl oxidases.

PubMed

Coppock, Donald L; Thorpe, Colin

2006-01-01

Eukaryotic flavin-dependent sulfhydryl oxidases catalyze oxidative protein folding with the generation of disulfides and the reduction of oxygen to hydrogen peroxide. This review deals principally with the Quiescinsulfhydryl oxidases (QSOX) that are found in multiple forms in multicellular organisms and singly in a number of protozoan parasites. QSOX is an ancient fusion of thioredoxin domains and an FAD-binding module, ERV1/ALR. Interdomain disulfide exchanges transmit reducing equivalents from substrates to the flavin cofactor and thence to molecular oxygen. The in vitro substrate specificity of avian QSOX1 and the likely substrates of QSOXs in vivo are discussed. The location of QSOX immunoreactivity and mRNA expression levels in human cells and tissues is reviewed. Generally, there is a marked association of QSOX1 expression with cell types that have a high secretory load of disulfide-containing peptides and proteins. The abundance of sulfhydryl oxidases in the islets of Langerhans suggests that oxidative protein folding may directly contribute to the oxidative stress believed to be a factor in the progression to type II diabetes. Finally, the structure and mechanism of QSOX proteins is compared to their smaller stand-alone cousins: yeast ERV1p and ERV2p, the mammalian augmenter of liver regeneration (ALR), and the viral ALR homologs.

Effect of contraceptive steroids on monoamine oxidase activity

PubMed Central

Southgate, Jennifer; Collins, G. G. S.; Pryse-Davies, J.; Sandler, M.

1969-01-01

Cyclical variations in monoamine oxidase activity during the human menstrual cycle, specific to the endometrium and modified in women undergoing contraceptive steroid treatment, may reflect changes in hormonal environment. Treatment of rats with individual constituents of the contraceptive pill causes analogous changes: oestrogens inhibit and progestogens potentiate uterine monoamine oxidase activity. ImagesFig. 2Fig. 3

Interplanetary baseline observations of type III solar radio bursts

NASA Technical Reports Server (NTRS)

Weber, R. R.; Fitzenreiter, R. J.; Novaco, J. C.; Fainberg, J.

1977-01-01

Simultaneous observations of type III radio bursts from spacecraft separated by 0.43 AU have been made using the solar orbiters Helios-A and Helios-B. The burst beginning at 19:22 UT on March 28, 1976, has been located from the intersection of the source directions measured at each spacecraft and from burst arrival-time differences. The source positions range from 0.03 AU from the sun at 3000 kHz to 0.08 AU at 585 kHz. The electron density along the burst trajectory and the exciter velocity (0.13c) were determined directly without the need to assume a density model, as has been done with single-spacecraft observations. The separation of Helios-A and -B has also provided measurements of burst directivity at low frequencies. For the March 28 burst the intensity observed from near the source longitude (Helios-B) was 3-10dB greater than that from 60 deg west of the source (Helios-A)

Reliable WDM multicast in optical burst-switched networks

NASA Astrophysics Data System (ADS)

Jeong, Myoungki; Qiao, Chunming; Xiong, Yijun

2000-09-01

IN this paper,l we present a reliable WDM (Wavelength-Division Multiplexing) multicast protocol in optical burst-switched (OBS) networks. Since the burst dropping (loss) probability may be potentially high in a heavily loaded OBS backbone network, reliable multicast protocols that have developed for IP networks at the transport (or application) layer may incur heavy overheads such as a large number of duplicate retransmissions. In addition, it may take a longer time for an end host to detect and then recover from burst dropping (loss) occurred at the WDM layer. For efficiency reasons, we propose burst loss recovery within the OBS backbone (i.e., at the WDM link layer). The proposed protocol requires two additional functions to be performed by the WDM switch controller: subcasting and maintaining burst states, when the WDM switch has more than one downstream on the WDM multicast tree. We show that these additional functions are simple to implement and the overhead associated with them is manageable.

EXOGENOUS CYTOCHROME C RESTORES MYOCARDIAL CYTOCHROME OXIDASE ACTIVITY INTO THE LATE PHASE OF SEPSIS

PubMed Central

Piel, David A.; Deutschman, Clifford S.; Levy, Richard J.

2009-01-01

Mitochondrial dysfunction is thought to play a role in the pathogenesis of a variety of disease states, including sepsis. An acquired defect in oxidative phosphorylation potentially causes sepsis-induced organ dysfunction. Cytochrome oxidase (CcOX), the terminal oxidase of the respiratory chain, is competitively inhibited early in sepsis and progresses, becoming noncompetitive during the late phase. We have previously demonstrated that exogenous cytochrome c can overcome myocardial CcOX competitive inhibition and improve cardiac function during murine sepsis at the 24-h point. Here, we evaluate the effect of exogenous cytochrome c on CcOX activity and survival in mice at the later time points. Exogenous cytochrome c (800 μg) or saline was intravenously injected 24 h after cecal ligation and puncture (CLP) or sham operation. Steady-state mitochondrial cytochrome c levels and heme c content increased significantly 48 h post-CLP and remained elevated at 72 h in cytochrome c-injected mice compared with saline injection. Cecal ligation and puncture inhibited CcOX at 48 h in saline-injected mice. However, cytochrome c injection abrogated this inhibition and restored CcOX kinetic activity to sham values at 48 h. Survival after CLP to 96 h after cytochrome c injection approached 50% compared with only 15% after saline injection. Thus, a single injection of exogenous cytochrome c 24 h post-CLP repletes mitochondrial substrate levels for up to 72 h, restores myocardial COX activity, and significantly improves survival. PMID:18414235

Plasma diamine oxidase levels in pregnancy complicated by threatened abortion.

PubMed Central

Legge, M; Duff, G B

1981-01-01

Plasma diamine oxidase levels were assayed in 66 patients who presented with pregnancy complicated by threatened abortion. Levels within the normal range were associated with continuing pregnancies, whereas levels below the normal range were associated with subsequent abortion. Among those patients in whom gestation was greater than eight weeks, 66.6% of diamine oxidase levels correctly predicted the pregnancy outcome. Assay of the diamine oxidase levels at eight weeks of gestation or less gave little useful information. PMID:6785320

Plasma diamine oxidase levels in pregnancy complicated by threatened abortion.

PubMed

Legge, M; Duff, G B

1981-02-01

Plasma diamine oxidase levels were assayed in 66 patients who presented with pregnancy complicated by threatened abortion. Levels within the normal range were associated with continuing pregnancies, whereas levels below the normal range were associated with subsequent abortion. Among those patients in whom gestation was greater than eight weeks, 66.6% of diamine oxidase levels correctly predicted the pregnancy outcome. Assay of the diamine oxidase levels at eight weeks of gestation or less gave little useful information.

The Effect of Magnetic Fields on Gamma-Ray Bursts Inferred from Multi-Wavelength Observations of the Bursts of 23 January 1999

NASA Technical Reports Server (NTRS)

Galama, T. J.; Briggs, M. S.; Wijers, R. A. M. J.; Vreeswijk, P. M.; Rol, E.; Band, D.; vanParadijs, J.; Kouveliotou, C.; Preece, R. D.; Bremer, M.

1999-01-01

Gamma-ray bursts (GRBs) are thought to arise when an extremely relativistic outflow of particles from a massive explosion (the nature at which is still unclear) interacts with material surrounding the site of the explosion. Observations of the evolving changes in emission at many wavelengths allow us to investigate the origin of the photons, and so potentially determine the nature of the explosion. Here we report the results of gamma-ray, optical, infrared, submillimeter, millimeter and radio observations of the burst ORB990123 and its afterglow. Our interpretation of the data indicates that the initial and afterglow emissions are associated with three distinct regions in the fireball. The peak flux of the afterglow, one day after the burst, has a lower frequency than observed for other bursts; this explains the short-lived radio emission. We suggest that the differences between bursts reflect variations in the magnetic-field strength in the afterglow-emitting regions.

Periodic Bursts of Jovian Non-Io Decametric Radio Emission

NASA Technical Reports Server (NTRS)

Panchenko, M.; Rucker, H O.; Farrell, W. M.

2013-01-01

During the years 2000-2011 the radio instruments onboard Cassini, Wind and STEREO spacecraft have Recorded a large amount of the Jovian decametric radio emission (DAM). In this paper we report on the analysis of the new type of Jovian periodic radio bursts recently revealed in the decametric frequency range. These bursts, which are non-Io component of DAM, are characterized by a strong periodic reoccurrence over several Jovian days with a period approx. = 1:5% longer than the rotation rate of the planet's magnetosphere (System III). The bursts are typically observed between 4 and 12 MHz and their occurrence probability has been found to be significantly higher in the sector of Jovian Central Meridian Longitude between 300 deg. and 60 deg. (via 360 deg.). The stereoscopic multispacecraft observations have shown that the radio sources of the periodic bursts radiate in a non-axisymmetric hollow cone-like pattern and sub-corotate with Jupiter remaining active during several planet's rotations. The occurrence of the periodic non-Io DAM bursts is strongly correlated with pulses of the solar wind ram pressure at Jupiter. Moreover the periodic bursts exhibit a tendency to occur in groups every approx. 25 days. The polarization measurements have shown that the periodic bursts are right hand polarized radio emission associated with the Northern magnetic hemisphere of Jupiter. We suggest that periodic non-Io DAM bursts may be connected with the interchange instability in Io plasma torus triggered by the solar wind.

Periodic bursts of Jovian non-Io decametric radio emission

PubMed Central

Panchenko, M.; Rucker, H.O.; Farrell, W.M.

2013-01-01

During the years 2000–2011 the radio instruments onboard Cassini, Wind and STEREO spacecraft have recorded a large amount of the Jovian decametric radio emission (DAM). In this paper we report on the analysis of the new type of Jovian periodic radio bursts recently revealed in the decametric frequency range. These bursts, which are non-Io component of DAM, are characterized by a strong periodic reoccurrence over several Jovian days with a period ≈1.5% longer than the rotation rate of the planet's magnetosphere (System III). The bursts are typically observed between 4 and 12 MHz and their occurrence probability has been found to be significantly higher in the sector of Jovian Central Meridian Longitude between 300° and 60° (via 360°). The stereoscopic multispacecraft observations have shown that the radio sources of the periodic bursts radiate in a non-axisymmetric hollow cone-like pattern and sub-corotate with Jupiter remaining active during several planet's rotations. The occurrence of the periodic non-Io DAM bursts is strongly correlated with pulses of the solar wind ram pressure at Jupiter. Moreover the periodic bursts exhibit a tendency to occur in groups every ∼25 days. The polarization measurements have shown that the periodic bursts are right hand polarized radio emission associated with the Northern magnetic hemisphere of Jupiter. We suggest that periodic non-Io DAM bursts may be connected with the interchange instability in Io plasma torus triggered by the solar wind. PMID:23585696

Detection of Bursts and Pauses in Spike Trains

PubMed Central

Ko, D.; Wilson, C. J.; Lobb, C. J.; Paladini, C. A.

2012-01-01

Midbrain dopaminergic neurons in vivo exhibit a wide range of firing patterns. They normally fire constantly at a low rate, and speed up, firing a phasic burst when reward exceeds prediction, or pause when an expected reward does not occur. Therefore, the detection of bursts and pauses from spike train data is a critical problem when studying the role of phasic dopamine (DA) in reward related learning, and other DA dependent behaviors. However, few statistical methods have been developed that can identify bursts and pauses simultaneously. We propose a new statistical method, the Robust Gaussian Surprise (RGS) method, which performs an exhaustive search of bursts and pauses in spike trains simultaneously. We found that the RGS method is adaptable to various patterns of spike trains recorded in vivo, and is not influenced by baseline firing rate, making it applicable to all in vivo spike trains where baseline firing rates vary over time. We compare the performance of the RGS method to other methods of detecting bursts, such as the Poisson Surprise (PS), Rank Surprise (RS), and Template methods. Analysis of data using the RGS method reveals potential mechanisms underlying how bursts and pauses are controlled in DA neurons. PMID:22939922

Burst Firing in Bee Gustatory Neurons Prevents Adaptation.

PubMed

Miriyala, Ashwin; Kessler, Sébastien; Rind, F Claire; Wright, Geraldine A

2018-05-01

Animals detect changes in the environment using modality-specific, peripheral sensory neurons. The insect gustatory system encodes tastant identity and concentration through the independent firing of gustatory receptor neurons (GRNs) that spike rapidly at stimulus onset and quickly adapt. Here, we show the first evidence that concentrated sugar evokes a temporally structured burst pattern of spiking involving two GRNs within the gustatory sensilla of bumblebees. Bursts of spikes resulted when a sucrose-activated GRN was inhibited by another GRN at a frequency of ∼22 Hz during the first 1 s of stimulation. Pharmacological blockade of gap junctions abolished bursting, indicating that bee GRNs have electrical synapses that produce a temporal pattern of spikes when one GRN is activated by a sugar ligand. Bursting permitted bee GRNs to maintain a high rate of spiking and to exhibit the slowest rate of adaptation of any insect species. Feeding bout duration correlated with coherent bursting; only sugar concentrations that produced bursting evoked the bumblebee's feeding reflex. Volume of solution imbibed was a direct function of time in contact with food. We propose that gap junctions among GRNs enable a sustained rate of GRN spiking that is necessary to drive continuous feeding by the bee proboscis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of wear on the burst strength of l-80 steel casing

NASA Astrophysics Data System (ADS)

Irawan, S.; Bharadwaj, A. M.; Temesgen, B.; Karuppanan, S.; Abdullah, M. Z. B.

2015-12-01

Casing wear has recently become one of the areas of research interest in the oil and gas industry especially in extended reach well drilling. The burst strength of a worn out casing is one of the significantly affected mechanical properties and is yet an area where less research is done The most commonly used equations to calculate the resulting burst strength after wear are Barlow, the initial yield burst, the full yield burst and the rupture burst equations. The objective of this study was to estimate casing burst strength after wear through Finite Element Analysis (FEA). It included calculation and comparison of the different theoretical bursts pressures with the simulation results along with effect of different wear shapes on L-80 casing material. The von Misses stress was used in the estimation of the burst pressure. The result obtained shows that the casing burst strength decreases as the wear percentage increases. Moreover, the burst strength value of the casing obtained from the FEA has a higher value compared to the theoretical burst strength values. Casing with crescent shaped wear give the highest burst strength value when simulated under nonlinear analysis.

Expression of Ascorbic Acid Oxidase in Zucchini Squash (Cucurbita pepo L.).

PubMed

Lin, L S; Varner, J E

1991-05-01

The expression of ascorbic acid oxidase was studied in zucchini squash (Cucurbita pepo L.), one of the most abundant natural sources of the enzyme. In the developing fruit, specific activity of ascorbic acid oxidase was highest between 4 and 6 days after anthesis. Protein and mRNA levels followed the same trend as enzyme activity. Highest growth rate of the fruit occurred before 6 days after anthesis. Within a given fruit, ascorbic acid oxidase activity and mRNA level were highest in the epidermis, and lowest in the central placental region. In leaf tissue, ascorbic acid oxidase activity was higher in young leaves, and very low in old leaves. Within a given leaf, enzyme activity was highest in the fast-growing region (approximately the lower third of the blade), and lowest in the slow-growing region (near leaf apex). High expression of ascorbic acid oxidase at a stage when rapid growth is occurring (in both fruits and leaves), and localization of the enzyme in the fruit epidermis, where cells are under greatest tension during rapid growth in girth, suggest that ascorbic acid oxidase might be involved in reorganization of the cell wall to allow for expansion. Based on the known chemistry of dehydroascorbic acid, the end product of the ascorbic acid oxidase-catalyzed reaction, we have proposed several hypotheses to explain how dehydroascorbic acid might cause cell wall "loosening."