Effect of α-p-chlorophenoxyisobutyrate on the metabolism of isoprenoid compounds in the rat

PubMed Central

Krishnaiah, K. V.; Ramasarma, T.

1970-01-01

1. Feeding of α-p-chlorophenoxyisobutyrate (CPIB) to rats increased ubiquinone concentration in the liver but not in other tissues. The increase was progressive with the time of feeding and related to the concentration of CPIB in the diet. 2. Incorporation of [1-14C]acetate, but not of [2-14C]mevalonate, into sterols in the liver in vivo or by liver slices in vitro was decreased on feeding the rats with CPIB. However, incorporation of mevalonate into ubiquinone increased. 3. CPIB, when added in low concentrations to liver slices, had no effect on isoprene synthesis from acetate; higher concentrations, however, were inhibitory. 4. No activation of ubiquinone synthesis from mevalonate was observed when CPIB was added to the liver slices synthesizing ubiquinone. 5. The increase in ubiquinone in CPIB-fed animals appears to be due to increased synthesis in the initial stages and to decreased catabolism in the later stages. 6. An inverse relationship was found between the concentration of ubiquinone in the liver and the serum sterol concentration in CPIB-fed rats. PMID:5435680

The Role of Glycine Residues 140 and 141 of Subunit B in the Functional Ubiquinone Binding Site of the Na+-pumping NADH:quinone Oxidoreductase from Vibrio cholerae*

PubMed Central

Juárez, Oscar; Neehaul, Yashvin; Turk, Erin; Chahboun, Najat; DeMicco, Jessica M.; Hellwig, Petra; Barquera, Blanca

2012-01-01

The Na+-pumping NADH:quinone oxidoreductase (Na+-NQR) is the main entrance for electrons into the respiratory chain of many marine and pathogenic bacteria. The enzyme accepts electrons from NADH and donates them to ubiquinone, and the free energy released by this redox reaction is used to create an electrochemical gradient of sodium across the cell membrane. Here we report the role of glycine 140 and glycine 141 of the NqrB subunit in the functional binding of ubiquinone. Mutations at these residues altered the affinity of the enzyme for ubiquinol. Moreover, mutations in residue NqrB-G140 almost completely abolished the electron transfer to ubiquinone. Thus, NqrB-G140 and -G141 are critical for the binding and reaction of Na+-NQR with its electron acceptor, ubiquinone. PMID:22645140

The mitochondrial outer membrane protein mitoNEET is a redox enzyme catalyzing electron transfer from FMNH2 to oxygen or ubiquinone.

PubMed

Wang, Yiming; Landry, Aaron P; Ding, Huangen

2017-06-16

Increasing evidence suggests that mitoNEET, a target of the type II diabetes drug pioglitazone, is a key regulator of energy metabolism in mitochondria. MitoNEET is anchored to the mitochondrial outer membrane via its N-terminal α helix domain and hosts a redox-active [2Fe-2S] cluster in its C-terminal cytosolic region. The mechanism by which mitoNEET regulates energy metabolism in mitochondria, however, is not fully understood. Previous studies have shown that mitoNEET specifically interacts with the reduced flavin mononucleotide (FMNH 2 ) and that FMNH 2 can quickly reduce the mitoNEET [2Fe-2S] clusters. Here we report that the reduced mitoNEET [2Fe-2S] clusters can be readily oxidized by oxygen. In the presence of FMN, NADH, and flavin reductase, which reduces FMN to FMNH 2 using NADH as the electron donor, mitoNEET mediates oxidation of NADH with a concomitant reduction of oxygen. Ubiquinone-2, an analog of ubiquinone-10, can also oxidize the reduced mitoNEET [2Fe-2S] clusters under anaerobic or aerobic conditions. Compared with oxygen, ubiquinone-2 is more efficient in oxidizing the mitoNEET [2Fe-2S] clusters, suggesting that ubiquinone could be an intrinsic electron acceptor of the reduced mitoNEET [2Fe-2S] clusters in mitochondria. Pioglitazone or its analog NL-1 appears to inhibit the electron transfer activity of mitoNEET by forming a unique complex with mitoNEET and FMNH 2 The results suggest that mitoNEET is a redox enzyme that may promote oxidation of NADH to facilitate enhanced glycolysis in the cytosol and that pioglitazone may regulate energy metabolism in mitochondria by inhibiting the electron transfer activity of mitoNEET. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a water molecule mediated binding feature.

PubMed

Zhou, Qiangjun; Zhai, Yujia; Lou, Jizhong; Liu, Man; Pang, Xiaoyun; Sun, Fei

2011-07-01

The mitochondrial respiratory complex II or succinate: ubiquinone oxidoreductase (SQR) is a key membrane complex in both the tricarboxylic acid cycle and aerobic respiration. Five disinfectant compounds were investigated with their potent inhibition effects on the ubiquinone reduction activity of the porcine mitochondrial SQR by enzymatic assay and crystallography. Crystal structure of the SQR bound with thiabendazole (TBZ) reveals a different inhibitor-binding feature at the ubiquinone binding site where a water molecule plays an important role. The obvious inhibitory effect of TBZ based on the biochemical data (IC(50) ~100 μmol/L) and the significant structure-based binding affinity calculation (~94 μmol/L) draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage.

Ubiquinone modified printed carbon electrodes for cell culture pH monitoring.

PubMed

McBeth, Craig; Dughaishi, Rajaa Al; Paterson, Andrew; Sharp, Duncan

2018-08-15

The measurement of pH is important throughout many biological systems, but there are limited available technologies to enable its periodical monitoring in the complex, small volume, media often used in cell culture experiments across a range of disciplines. Herein, pad printed electrodes are developed and characterised through modification with: a commercially available fullerene multiwall carbon nanotube composite applied in Nafion, casting of hydrophobic ubiquinone as a pH probe to provide the electrochemical signal, and coated in Polyethylene glycol to reduce fouling and potentially enhance biocompatibility, which together are proven to enable the determination of pH in cell culture media containing serum. The ubiquinone oxidation peak position (E pa ) provided an indirect marker of pH across the applicable range of pH 6-9 (R 2 = 0.9985, n = 15) in complete DMEM. The electrochemical behaviour of these sensors was also proven to be robust; retaining their ability to measure pH in cell culture media supplemented with serum up to 20% (v/v) [encompassing the range commonly employed in cell culture], cycled > 100 times in 10% serum containing media and maintain > 60% functionality after 5 day incubation in a 10% serum containing medium. Overall, this proof of concept research highlights the potential applicability of this, or similar, electrochemical approaches to enable to detection or monitoring of pH in complex cell culture media. Copyright © 2018 Elsevier B.V. All rights reserved.

Current Advances on the Structure, Bioactivity, Synthesis, and Metabolic Regulation of Novel Ubiquinone Derivatives in the Edible and Medicinal Mushroom Antrodia cinnamomea.

PubMed

Zhang, Bo-Bo; Hu, Peng-Fei; Huang, Jing; Hu, Yong-Dan; Chen, Lei; Xu, Gan-Rong

2017-12-06

In recent years, Antrodia cinnamomea has attracted great attention around the world as an extremely precious edible and medicinal mushroom. Ubiquinone derivatives, which are characteristic metabolites of A. cinnamomea, have shown great bioactivities. Some of them have been regarded as promising therapeutic agents and approved into clinical trial by the U.S. Food and Drug Administration. Although some excellent reviews have been published covering different aspects of A. cinnamomea, this review brings, for the first time, complete information about the structure, bioactivity, chemical synthesis, biosynthesis, and metabolic regulation of ubiquinone derivatives in A. cinnamomea. It not only advances our knowledge on the bioactive metabolites, especially the ubiquinone derivatives, in A. cinnamomea but also provides valuable information for the investigation on other edible and medicinal mushrooms.

Converting NADH to NAD+ by nicotinamide nucleotide transhydrogenase as a novel strategy against mitochondrial pathologies during aging.

PubMed

Olgun, Abdullah

2009-08-01

Mitochondrial DNA defects are involved supposedly via free radicals in many pathologies including aging and cancer. But, interestingly, free radical production was not found increased in prematurely aging mice having higher mutation rate in mtDNA. Therefore, some other mechanisms like the increase of mitochondrial NADH/NAD(+) and ubiquinol/ubiquinone ratios, can be in action in respiratory chain defects. NADH/NAD(+) ratio can be normalized by the activation or overexpression of nicotinamide nucleotide transhydrogenase (NNT), a mitochondrial enzyme catalyzing the following very important reaction: NADH + NADP(+ )<--> NADPH + NAD(+). The products NAD(+) and NADPH are required in many critical biological processes, e.g., NAD(+) is used by histone deacetylase Sir2 which regulates longevity in different species. NADPH is used in a number of biosynthesis reactions (e.g., reduced glutathione synthesis), and processes like apoptosis. Increased ubiquinol/ubiquinone ratio interferes the function of dihydroorotate dehydrogenase, the only mitochondrial enzyme involved in ubiquinone mediated de novo pyrimidine synthesis. Uridine and its prodrug triacetyluridine are used to compensate pyrimidine deficiency but their bioavailability is limited. Therefore, the normalization of the ubiquinol/ubiquinone ratio can be accomplished by allotopic expression of alternative oxidase, a mitochondrial ubiquinol oxidase which converts ubiquinol to ubiquinone.

Conformational differences between the methoxy groups of QA and QB site ubisemiquinones in bacterial reaction centers: a key role for methoxy group orientation in modulating ubiquinone redox potential.

PubMed

Taguchi, Alexander T; O'Malley, Patrick J; Wraight, Colin A; Dikanov, Sergei A

2013-07-09

Ubiquinone is an almost universal, membrane-associated redox mediator. Its ability to accept either one or two electrons allows it to function in critical roles in biological electron transport. The redox properties of ubiquinone in vivo are determined by its environment in the binding sites of proteins and by the dihedral angle of each methoxy group relative to the ring plane. This is an attribute unique to ubiquinone among natural quinones and could account for its widespread function with many different redox complexes. In this work, we use the photosynthetic reaction center as a model system for understanding the role of methoxy conformations in determining the redox potential of the ubiquinone/semiquinone couple. Despite the abundance of X-ray crystal structures for the reaction center, quinone site resolution has thus far been too low to provide a reliable measure of the methoxy dihedral angles of the primary and secondary quinones, QA and QB. We performed 2D ESEEM (HYSCORE) on isolated reaction centers with ubiquinones (13)C-labeled at the headgroup methyl and methoxy substituents, and have measured the (13)C isotropic and anisotropic components of the hyperfine tensors. Hyperfine couplings were compared to those derived by DFT calculations as a function of methoxy torsional angle allowing estimation of the methoxy dihedral angles for the semiquinones in the QA and QB sites. Based on this analysis, the orientation of the 2-methoxy groups are distinct in the two sites, with QB more out of plane by 20-25°. This corresponds to an ≈50 meV larger electron affinity for the QB quinone, indicating a substantial contribution to the experimental difference in redox potentials (60-75 mV) of the two quinones. The methods developed here can be readily extended to ubiquinone-binding sites in other protein complexes.

Identification of the binding sites for ubiquinone and inhibitors in the Na+-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae by photoaffinity labeling

PubMed Central

Ito, Takeshi; Ninokura, Satoshi; Kitazumi, Yuki; Mezic, Katherine G.; Cress, Brady F.; Koffas, Mattheos A. G.; Morgan, Joel E.; Barquera, Blanca; Miyoshi, Hideto

2017-01-01

The Na+-pumping NADH-quinone oxidoreductase (Na+-NQR) is the first enzyme of the respiratory chain and the main ion transporter in many marine and pathogenic bacteria, including Vibrio cholerae. The V. cholerae Na+-NQR has been extensively studied, but its binding sites for ubiquinone and inhibitors remain controversial. Here, using a photoreactive ubiquinone PUQ-3 as well as two aurachin-type inhibitors [125I]PAD-1 and [125I]PAD-2 and photoaffinity labeling experiments on the isolated enzyme, we demonstrate that the ubiquinone ring binds to the NqrA subunit in the regions Leu-32–Met-39 and Phe-131–Lys-138, encompassing the rear wall of a predicted ubiquinone-binding cavity. The quinolone ring and alkyl side chain of aurachin bound to the NqrB subunit in the regions Arg-43–Lys-54 and Trp-23–Gly-89, respectively. These results indicate that the binding sites for ubiquinone and aurachin-type inhibitors are in close proximity but do not overlap one another. Unexpectedly, although the inhibitory effects of PAD-1 and PAD-2 were almost completely abolished by certain mutations in NqrB (i.e. G140A and E144C), the binding reactivities of [125I]PAD-1 and [125I]PAD-2 to the mutated enzymes were unchanged compared with those of the wild-type enzyme. We also found that photoaffinity labeling by [125I]PAD-1 and [125I]PAD-2, rather than being competitively suppressed in the presence of other inhibitors, is enhanced under some experimental conditions. To explain these apparently paradoxical results, we propose models for the catalytic reaction of Na+-NQR and its interactions with inhibitors on the basis of the biochemical and biophysical results reported here and in previous work. PMID:28298441

Effect of ubiquinol-10 on citral stability and off-flavor formation in oil-in-water (O/W) nanoemulsions.

PubMed

Zhao, Qin; Ho, Chi-Tang; Huang, Qingrong

2013-08-07

The effects of different concentrations of ubiquinol-10 (Q10H2) on citral's stability were systematically investigated and compared in citral-loaded oil-in-water (O/W) nanoemulsions. Solid phase microextraction gas chromatography (SPME-GC) was employed to monitor the degradation of citral and the formation of off-flavor compounds throughout storage at 25 and 45 °C. The optimum concentration of Q10H2 in the current formulation was determined to be around 0.10 wt % in the system (Q10H2/citral ratio 1:1), which can effectively protect citral from chemical degradation and oxidation. Results suggested, however, that a low concentration of Q10H2 may induce the majority of the ubisemiquinone (Q10(•-))/ubiquinone (Q10) redox transition, which possibly endowed Q10H2 with pro-oxidant properties. Further increase in Q10H2 concentration beyond a certain value also hindered its effect due to the complex properties of radicals involved and the overall environment encountered. With appropriate concentrations of Q10H2 presented in the system, major citral oxidation off-flavor compounds (p-cresol, α,p-dimethylstyrene, p-methylacetophenone), and some of the lipid degradation products can be inhibited to lower levels. In contrast, ubiquinone-10 (Q10) had a negligible effect on citral's chemical stability and off-flavor generation.

Atpenins, potent and specific inhibitors of mitochondrial complex II (succinate-ubiquinone oxidoreductase)

PubMed Central

Miyadera, Hiroko; Shiomi, Kazuro; Ui, Hideaki; Yamaguchi, Yuichi; Masuma, Rokuro; Tomoda, Hiroshi; Miyoshi, Hideto; Osanai, Arihiro; Kita, Kiyoshi; Ōmura, Satoshi

2003-01-01

Enzymes in the mitochondrial respiratory chain are involved in various physiological events in addition to their essential role in the production of ATP by oxidative phosphorylation. The use of specific and potent inhibitors of complex I (NADH-ubiquinone reductase) and complex III (ubiquinol-cytochrome c reductase), such as rotenone and antimycin, respectively, has allowed determination of the role of these enzymes in physiological processes. However, unlike complexes I, III, and IV (cytochrome c oxidase), there are few potent and specific inhibitors of complex II (succinate-ubiquinone reductase) that have been described. In this article, we report that atpenins potently and specifically inhibit the succinate-ubiquinone reductase activity of mitochondrial complex II. Therefore, atpenins may be useful tools for clarifying the biochemical and structural properties of complex II, as well as for determining its physiological roles in mammalian tissues. PMID:12515859

The electron transfer flavoprotein: ubiquinone oxidoreductases.

PubMed

Watmough, Nicholas J; Frerman, Frank E

2010-12-01

Electron transfer flavoprotein: ubiqionone oxidoreductase (ETF-QO) is a component of the mitochondrial respiratory chain that together with electron transfer flavoprotein (ETF) forms a short pathway that transfers electrons from 11 different mitochondrial flavoprotein dehydrogenases to the ubiquinone pool. The X-ray structure of the pig liver enzyme has been solved in the presence and absence of a bound ubiquinone. This structure reveals ETF-QO to be a monotopic membrane protein with the cofactors, FAD and a [4Fe-4S](+1+2) cluster, organised to suggests that it is the flavin that serves as the immediate reductant of ubiquinone. ETF-QO is very highly conserved in evolution and the recombinant enzyme from the bacterium Rhodobacter sphaeroides has allowed the mutational analysis of a number of residues that the structure suggested are involved in modulating the reduction potential of the cofactors. These experiments, together with the spectroscopic measurement of the distances between the cofactors in solution have confirmed the intramolecular pathway of electron transfer from ETF to ubiquinone. This approach can be extended as the R. sphaeroides ETF-QO provides a template for investigating the mechanistic consequences of single amino acid substitutions of conserved residues that are associated with a mild and late onset variant of the metabolic disease multiple acyl-CoA dehydrogenase deficiency (MADD). Copyright © 2010 Elsevier B.V. All rights reserved.

Characterization of a Plasmodium falciparum Orthologue of the Yeast Ubiquinone-Binding Protein, Coq10p.

PubMed

Jenkins, Bethany J; Daly, Thomas M; Morrisey, Joanne M; Mather, Michael W; Vaidya, Akhil B; Bergman, Lawrence W

2016-01-01

Coenzyme Q (CoQ, ubiquinone) is a central electron carrier in mitochondrial respiration. CoQ is synthesized through multiple steps involving a number of different enzymes. The prevailing view that the CoQ used in respiration exists as a free pool that diffuses throughout the mitochondrial inner membrane bilayer has recently been challenged. In the yeast Saccharomyces cerevisiae, deletion of the gene encoding Coq10p results in respiration deficiency without inhibiting the synthesis of CoQ, suggesting that the Coq10 protein is critical for the delivery of CoQ to the site(s) of respiration. The precise mechanism by which this is achieved remains unknown at present. We have identified a Plasmodium orthologue of Coq10 (PfCoq10), which is predominantly expressed in trophozoite-stage parasites, and localizes to the parasite mitochondrion. Expression of PfCoq10 in the S. cerevisiae coq10 deletion strain restored the capability of the yeast to grow on respiratory substrates, suggesting a remarkable functional conservation of this protein over a vast evolutionary distance, and despite a relatively low level of amino acid sequence identity. As the antimalarial drug atovaquone acts as a competitive inhibitor of CoQ, we assessed whether over-expression of PfCoq10 altered the atovaquone sensitivity in parasites and in yeast mitochondria, but found no alteration of its activity.

Identification of bottlenecks in Escherichia coli engineered for the production of CoQ(10).

PubMed

Cluis, Corinne P; Ekins, Andrew; Narcross, Lauren; Jiang, Heng; Gold, Nicholas D; Burja, Adam M; Martin, Vincent J J

2011-11-01

In this work, Escherichia coli was engineered to produce a medically valuable cofactor, coenzyme Q(10) (CoQ(10)), by removing the endogenous octaprenyl diphosphate synthase gene and functionally replacing it with a decaprenyl diphosphate synthase gene from Sphingomonas baekryungensis. In addition, by over-expressing genes coding for rate-limiting enzymes of the aromatic pathway, biosynthesis of the CoQ(10) precursor para-hydroxybenzoate (PHB) was increased. The production of isoprenoid precursors of CoQ(10) was also improved by the heterologous expression of a synthetic mevalonate operon, which permits the conversion of exogenously supplied mevalonate to farnesyl diphosphate. The over-expression of these precursors in the CoQ(10)-producing E. coli strain resulted in an increase in CoQ(10) content, as well as in the accumulation of an intermediate of the ubiquinone pathway, decaprenylphenol (10P-Ph). In addition, the over-expression of a PHB decaprenyl transferase (UbiA) encoded by a gene from Erythrobacter sp. NAP1 was introduced to direct the flux of DPP and PHB towards the ubiquinone pathway. This further increased CoQ(10) content in engineered E. coli, but decreased the accumulation of 10P-Ph. Finally, we report that the combined over-production of isoprenoid precursors and over-expression of UbiA results in the decaprenylation of para-aminobenzoate, a biosynthetic precursor of folate, which is structurally similar to PHB. Copyright © 2011 Elsevier Inc. All rights reserved.

Real-time electron transfer in respiratory complex I

PubMed Central

Verkhovskaya, Marina L.; Belevich, Nikolai; Euro, Liliya; Wikström, Mårten; Verkhovsky, Michael I.

2008-01-01

Electron transfer in complex I from Escherichia coli was investigated by an ultrafast freeze-quench approach. The reaction of complex I with NADH was stopped in the time domain from 90 μs to 8 ms and analyzed by electron paramagnetic resonance (EPR) spectroscopy at low temperatures. The data show that after binding of the first molecule of NADH, two electrons move via the FMN cofactor to the iron–sulfur (Fe/S) centers N1a and N2 with an apparent time constant of ≈90 μs, implying that these two centers should have the highest redox potential in the enzyme. The rate of reduction of center N2 (the last center in the electron transfer sequence) is close to that predicted by electron transfer theory, which argues for the absence of coupled proton transfer or conformational changes during electron transfer from FMN to N2. After fast reduction of N1a and N2, we observe a slow, ≈1-ms component of reduction of other Fe/S clusters. Because all elementary electron transfer rates between clusters are several orders of magnitude higher than this observed rate, we conclude that the millisecond component is limited by a single process corresponding to dissociation of the oxidized NAD+ molecule from its binding site, where it prevents entry of the next NADH molecule. Despite the presence of approximately one ubiquinone per enzyme molecule, no transient semiquinone formation was observed, which has mechanistic implications, suggesting a high thermodynamic barrier for ubiquinone reduction to the semiquinone radical. Possible consequences of these findings for the proton translocation mechanism are discussed. PMID:18316732

Electron Transport in Paracoccus Halodenitrificans and the Role of Ubiquinone

NASA Technical Reports Server (NTRS)

Hochstein, L. I.; Cronin, S. E.

1983-01-01

The membrane-bound NADH oxidase of Paracoccus halodenitrificans was inhibited by dicoumarol, 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO), and exposure to ultraviolet light (at 366 nm). When the membranes were extracted with n-pentane, NADH oxidase activity was lost. Partial restoration was achieved by adding the ubiquinone fraction extracted from the membranes. Succinate oxidation was not inhibited by dicoumarol or HQNO but was affected by ultraviolet irradiation or n-pentane extraction. However, the addition of the ubiquinone fraction to the n-pentane-extracted membranes did not restore enzyme activity. These observations suggested the reducing equivalents from succinate entered the respiratory chain on the oxygen side of the HQNO-sensitive site and probably did not proceed through a quinone.

Electron transport in Paracoccus halodenitrificans and the role of Ubiquinone

NASA Technical Reports Server (NTRS)

Hochstein, L. I.; Cronin, S. E.

1984-01-01

The membrane-bound NADH oxidase of Paracoccus halodenitrificans was inhibited by dicoumarol, 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO), and exposure to ultraviolet light (at 366 nm). When the membranes were extracted with n-pentane, NADH oxidase activity was lost. Partial restoration was achieved by adding the ubiquinone fraction extracted from the membranes. Succinate oxidation was not inhibited by dicoumarol or HQNO but was affected by ultraviolet irradiation or n-pentane extraction. However, the addition of the ubiquinone fraction to the n-pentane-extracted membranes did not restore enzyme activity. These observations suggested the reducing equivalents from succinate entered the respiratory chain on the oxygen side of the HQNO-sensitive site and probably did not proceed through a quinone.

NMR Reveals Double Occupancy of Quinone-type Ligands in the Catalytic Quinone Binding Site of the Na+-translocating NADH:Quinone Oxidoreductase from Vibrio cholerae*

PubMed Central

Nedielkov, Ruslan; Steffen, Wojtek; Steuber, Julia; Möller, Heiko M.

2013-01-01

The sodium ion-translocating NADH:quinone oxidoreductase (Na+-NQR) from the pathogen Vibrio cholerae exploits the free energy liberated during oxidation of NADH with ubiquinone to pump sodium ions across the cytoplasmic membrane. The Na+-NQR consists of four membrane-bound subunits NqrBCDE and the peripheral NqrF and NqrA subunits. NqrA binds ubiquinone-8 as well as quinones with shorter prenyl chains (ubiquinone-1 and ubiquinone-2). Here we show that the quinone derivative 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), a known inhibitor of the bc1 and b6f complexes found in mitochondria and chloroplasts, also inhibits quinone reduction by the Na+-NQR in a mixed inhibition mode. Tryptophan fluorescence quenching and saturation transfer difference NMR experiments in the presence of Na+-NQR inhibitor (DBMIB or 2-n-heptyl-4-hydroxyquinoline N-oxide) indicate that two quinone analog ligands are bound simultaneously by the NqrA subunit with very similar interaction constants as observed with the holoenzyme complex. We conclude that the catalytic site of quinone reduction is located on NqrA. The two ligands bind to an extended binding pocket in direct vicinity to each other as demonstrated by interligand Overhauser effects between ubiquinone-1 and DBMIB or 2-n-heptyl-4-hydroxyquinoline N-oxide, respectively. We propose that a similar spatially close arrangement of the native quinone substrates is also operational in vivo, enhancing the catalytic efficiency during the final electron transfer steps in the Na+-NQR. PMID:24003222

[Vitamin E activity of some alpha-tocopherol derivatives and their effect on the ubiquinone level in rat liver in vitro].

PubMed

Donchenko, G V; Kovalenko, V N; Zolotashko, O M; Makovetskiĭ, V P; Basalkevich, E D; Sivachek, T E; Svishchuk, A A; Khalmuradov, A G

1979-01-01

An addition of alpha-tocopherol (I) and its synthetic derivatives (alpha-tocopheryl quinone (II), its short-chained analog (III), alpha-tocopherol lactone (IV), and short-chained alpha-tocopheryl acetate (V)) to the homogenized liver of vitamin E deficient rats resulted in a significant increase of ubiquinone after 2 hour incubation. Activity of the above derivatives (II-V) was not associated directly with their transformation into I or with a noticeable increase of the I content. There is a certain correlation between the chemical structure and the level of vitamin E activity of alpha-tocopherol derivatives that led to an increase in the ubiquinone content and prevented the decrease of tissue respiration and termination of pregnancy in rats.

CoQ(10) deficiencies and MNGIE: two treatable mitochondrial disorders.

PubMed

Hirano, Michio; Garone, Caterina; Quinzii, Catarina M

2012-05-01

Although causative mutations have been identified for numerous mitochondrial disorders, few disease-modifying treatments are available. Two examples of treatable mitochondrial disorders are coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Here, we describe clinical and molecular features of CoQ(10) deficiencies and MNGIE and explain how understanding their pathomechanisms have led to rationale therapies. Primary CoQ(10) deficiencies, due to mutations in genes required for ubiquinone biosynthesis, and secondary deficiencies, caused by genetic defects not directly related to CoQ(10) biosynthesis, often improve with CoQ(10) supplementation. In vitro and in vivo studies of CoQ(10) deficiencies have revealed biochemical alterations that may account for phenotypic differences among patients and variable responses to therapy. In contrast to the heterogeneous CoQ(10) deficiencies, MNGIE is a single autosomal recessive disease due to mutations in the TYMP gene encoding thymidine phosphorylase (TP). In MNGIE, loss of TP activity causes toxic accumulations of the nucleosides thymidine and deoxyuridine that are incorporated by the mitochondrial pyrimidine salvage pathway and cause deoxynucleoside triphosphate pool imbalances, which, in turn cause mtDNA instability. Allogeneic hematopoetic stem cell transplantation to restore TP activity and eliminate toxic metabolites is a promising therapy for MNGIE. CoQ(10) deficiencies and MNGIE demonstrate the feasibility of treating specific mitochondrial disorders through replacement of deficient metabolites or via elimination of excessive toxic molecules. Studies of CoQ(10) deficiencies and MNGIE illustrate how understanding the pathogenic mechanisms of mitochondrial diseases can lead to meaningful therapies. This article is part of a Special Issue entitled: Biochemistry of Mitochondria, Life and Intervention 2010. Copyright © 2012 Elsevier B.V. All rights reserved.

In Silico Discovery of a Substituted 6-Methoxy-quinalidine with Leishmanicidal Activity in Leishmania infantum.

PubMed

Stevanović, Strahinja; Perdih, Andrej; Senćanski, Milan; Glišić, Sanja; Duarte, Margarida; Tomás, Ana M; Sena, Filipa V; Sousa, Filipe M; Pereira, Manuela M; Solmajer, Tom

2018-03-27

There is an urgent need for the discovery of new antileishmanial drugs with a new mechanism of action. Type 2 NADH dehydrogenase from Leishmania infantum ( Li NDH2) is an enzyme of the parasite's respiratory system, which catalyzes the electron transfer from NADH to ubiquinone without coupled proton pumping. In previous studies of the related NADH: ubiquinone oxidoreductase crystal structure from Saccharomyces cerevisiae , two ubiquinone-binding sites (UQ I and UQ II ) were identified and shown to play an important role in the NDH-2-catalyzed oxidoreduction reaction. Based on the available structural data, we developed a three-dimensional structural model of Li NDH2 using homology detection methods and performed an in silico virtual screening campaign to search for potential inhibitors targeting the Li NDH2 ubiquinone-binding site 1-UQ I . Selected compounds displaying favorable properties in the computational screening experiments were assayed for inhibitory activity in the structurally similar recombinant NDH-2 from S. aureus and leishmanicidal activity was determined in the wild-type axenic amastigotes and promastigotes of L. infantum . The identified compound, a substituted 6-methoxy-quinalidine, showed promising nanomolar leishmanicidal activity on wild-type axenic promastigotes and amastigotes of L. infantum and the potential for further development.

Coenzyme Q10 and statins: biochemical and clinical implications.

PubMed

Littarru, Gian Paolo; Langsjoen, Peter

2007-06-01

Statins are drugs of known and undisputed efficacy in the treatment of hypercholesterolemia, usually well tolerated by most patients. In some cases treatment with statins produces skeletal muscle complaints, and/or mild serum CK elevation; the incidence of rhabdomyolysis is very low. As a result of the common biosynthetic pathway Coenzyme Q (ubiquinone) and dolichol levels are also affected, to a certain degree, by the treatment with these HMG-CoA reductase inhibitors. Plasma levels of CoQ10 are lowered in the course of statin treatment. This could be related to the fact that statins lower plasma LDL levels, and CoQ10 is mainly transported by LDL, but a decrease is also found in platelets and in lymphocytes of statin treated patients, therefore it could truly depend on inhibition of CoQ10 synthesis. There are also some indications that statin treatment affects muscle ubiquinone levels, although it is not yet clear to which extent this depends on some effect on mitochondrial biogenesis. Some papers indicate that CoQ10 depletion during statin therapy might be associated with subclinical cardiomyopathy and this situation is reversed upon CoQ10 treatment. We can reasonably hypothesize that in some conditions where other CoQ10 depleting situations exist treatment with statins may seriously impair plasma and possible tissue levels of coenzyme Q10. While waiting for a large scale clinical trial where patients treated with statins are also monitored for their CoQ10 status, with a group also being given CoQ10, physicians should be aware of this drug-nutrient interaction and be vigilant to the possibility that statin drugs may, in some cases, impair skeletal muscle and myocardial bioenergetics.

Five rules for the evolution of cooperation.

PubMed

Nowak, Martin A

2006-12-08

Cooperation is needed for evolution to construct new levels of organization. Genomes, cells, multicellular organisms, social insects, and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity, and group selection. For each mechanism, a simple rule is derived that specifies whether natural selection can lead to cooperation.

Five Rules for the Evolution of Cooperation

NASA Astrophysics Data System (ADS)

Nowak, Martin A.

2006-12-01

Cooperation is needed for evolution to construct new levels of organization. Genomes, cells, multicellular organisms, social insects, and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity, and group selection. For each mechanism, a simple rule is derived that specifies whether natural selection can lead to cooperation.

Assignment of electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) to human chromosome 4q33 by fluorescence in situ hybridization and somatic cell hybridization.

PubMed

Spector, E B; Seltzer, W K; Goodman, S I

1999-08-01

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a nuclear-encoded protein located in the inner mitochondrial membrane. Inherited defects of ETF-QO cause glutaric acidemia type II. We here describe the localization of the ETF-QO gene to human chromosome 4q33 by somatic cell hybridization and fluorescence in situ hybridization. Copyright 1999 Academic Press.

Ubiquinone and Menaquinone Electron Carriers Represent the Yin and Yang in the Redox Regulation of the ArcB Sensor Kinase

PubMed Central

Alvarez, Adrián F.; Rodriguez, Claudia

2013-01-01

The Arc two-component system, comprising the ArcB sensor kinase and the ArcA response regulator, modulates the expression of numerous genes in response to respiratory growth conditions. Under aerobic growth conditions, the ubiquinone electron carriers were proposed to silence the kinase activity of ArcB by oxidizing two cytosol-located redox-active cysteine residues that participate in intermolecular disulfide bond formation. Here, we confirm the role of the ubiquinone electron carriers as the silencing signal of ArcB in vivo, we show that the redox potential of ArcB is about −41 mV, and we demonstrate that the menaquinols are required for proper ArcB activation upon a shift from aerobic to anaerobic growth conditions. Thus, an essential link in the Arc signal transduction pathway connecting the redox state of the quinone pool to the transcriptional apparatus is elucidated. PMID:23645604

Crystal structure of mitochondrial respiratory membrane protein complex II.

PubMed

Sun, Fei; Huo, Xia; Zhai, Yujia; Wang, Aojin; Xu, Jianxing; Su, Dan; Bartlam, Mark; Rao, Zihe

2005-07-01

The mitochondrial respiratory Complex II or succinate:ubiquinone oxidoreductase (SQR) is an integral membrane protein complex in both the tricarboxylic acid cycle and aerobic respiration. Here we report the first crystal structure of Complex II from porcine heart at 2.4 A resolution and its complex structure with inhibitors 3-nitropropionate and 2-thenoyltrifluoroacetone (TTFA) at 3.5 A resolution. Complex II is comprised of two hydrophilic proteins, flavoprotein (Fp) and iron-sulfur protein (Ip), and two transmembrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone. The structure correlates the protein environments around prosthetic groups with their unique midpoint redox potentials. Two ubiquinone binding sites are discussed and elucidated by TTFA binding. The Complex II structure provides a bona fide model for study of the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex.

Working dogs cooperate among one another by generalised reciprocity.

PubMed

Gfrerer, Nastassja; Taborsky, Michael

2017-03-06

Cooperation by generalised reciprocity implies that individuals apply the decision rule "help anyone if helped by someone". This mechanism has been shown to generate evolutionarily stable levels of cooperation, but as yet it is unclear how widely this cooperation mechanism is applied among animals. Dogs (Canis familiaris) are highly social animals with considerable cognitive potential and the ability to differentiate between individual social partners. But although dogs can solve complex problems, they may use simple rules for behavioural decisions. Here we show that dogs trained in an instrumental cooperative task to provide food to a social partner help conspecifics more often after receiving help from a dog before. Remarkably, in so doing they show no distinction between partners that had helped them before and completely unfamiliar conspecifics. Apparently, dogs use the simple decision rule characterizing generalised reciprocity, although they are probably capable of using the more complex decision rule of direct reciprocity: "help someone who has helped you". However, generalized reciprocity involves lower information processing costs and is therefore a cheaper cooperation strategy. Our results imply that generalised reciprocity might be applied more commonly than direct reciprocity also in other mutually cooperating animals.

Working dogs cooperate among one another by generalised reciprocity

PubMed Central

Gfrerer, Nastassja; Taborsky, Michael

2017-01-01

Cooperation by generalised reciprocity implies that individuals apply the decision rule “help anyone if helped by someone”. This mechanism has been shown to generate evolutionarily stable levels of cooperation, but as yet it is unclear how widely this cooperation mechanism is applied among animals. Dogs (Canis familiaris) are highly social animals with considerable cognitive potential and the ability to differentiate between individual social partners. But although dogs can solve complex problems, they may use simple rules for behavioural decisions. Here we show that dogs trained in an instrumental cooperative task to provide food to a social partner help conspecifics more often after receiving help from a dog before. Remarkably, in so doing they show no distinction between partners that had helped them before and completely unfamiliar conspecifics. Apparently, dogs use the simple decision rule characterizing generalised reciprocity, although they are probably capable of using the more complex decision rule of direct reciprocity: “help someone who has helped you”. However, generalized reciprocity involves lower information processing costs and is therefore a cheaper cooperation strategy. Our results imply that generalised reciprocity might be applied more commonly than direct reciprocity also in other mutually cooperating animals. PMID:28262722

Solanesyl Diphosphate Synthase, an Enzyme of the Ubiquinone Synthetic Pathway, Is Required throughout the Life Cycle of Trypanosoma brucei

PubMed Central

Lai, De-Hua; Poropat, Estefanía; Pravia, Carlos; Landoni, Malena; Couto, Alicia S.; Pérez Rojo, Fernando G.; Fuchs, Alicia G.; Dubin, Marta; Elingold, Igal; Rodríguez, Juan B.; Ferella, Marcela; Esteva, Mónica I.

2014-01-01

Ubiquinone 9 (UQ9), the expected product of the long-chain solanesyl diphosphate synthase of Trypanosoma brucei (TbSPPS), has a central role in reoxidation of reducing equivalents in the mitochondrion of T. brucei. The ablation of TbSPPS gene expression by RNA interference increased the generation of reactive oxygen species and reduced cell growth and oxygen consumption. The addition of glycerol to the culture medium exacerbated the phenotype by blocking its endogenous generation and excretion. The participation of TbSPPS in UQ synthesis was further confirmed by growth rescue using UQ with 10 isoprenyl subunits (UQ10). Furthermore, the survival of infected mice was prolonged upon the downregulation of TbSPPS and/or the addition of glycerol to drinking water. TbSPPS is inhibited by 1-[(n-oct-1-ylamino)ethyl] 1,1-bisphosphonic acid, and treatment with this compound was lethal for the cells. The findings that both UQ9 and ATP pools were severely depleted by the drug and that exogenous UQ10 was able to fully rescue growth of the inhibited parasites strongly suggest that TbSPPS and UQ synthesis are the main targets of the drug. These two strategies highlight the importance of TbSPPS for T. brucei, justifying further efforts to validate it as a new drug target. PMID:24376001

Multispectral and colour analysis for ubiquinone solutions and biological samples

NASA Astrophysics Data System (ADS)

Timofeeva, Elvira O.; Gorbunova, Elena V.; Chertov, Aleksandr N.

2017-02-01

An oxidative damage in cell structures is a basis of most mechanisms that lead to health diseases and senescence of human body. The presence of antioxidant issues such as redox potential imbalance in human body is a very important question for modern clinical diagnostics. Implementation of multispectral and colour analysis of the human skin into optical diagnostics of such wide distributed in a human body antioxidant as ubiquinone can be one of the steps for development of the device with a view to clinical diagnostics of redox potential or quality control of the cosmetics. The recording of multispectral images of the hand skin with monochromatic camera and a set of coloured filters was provided in the current research. Recording data of the multispectral imaging technique was processed using principal component analysis. Also colour characteristics of the skin before and after the skin treatment with facial mask which contains ubiquinone were calculated. The results of the mask treatment were compared with the treatment using oily ubiquinone solution. Despite the fact that results did not give clear explanation about healthy skin or skin stressed by reactive oxygen species, methods which were described in this research are able to identify how skin surface is changing after the antioxidant treatment. In future it is important to provide biomedical tests during the optical tests of the human skin.

Five rules for the evolution of cooperation

PubMed Central

Nowak, Martin A.

2011-01-01

Cooperation is needed for evolution to construct new levels of organization. The emergence of genomes, cells, multi-cellular organisms, social insects and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity and group selection. For each mechanism, a simple rule is derived which specifies whether natural selection can lead to cooperation. PMID:17158317

Coenzyme Q10 quantification in muscle, fibroblasts and cerebrospinal fluid by liquid chromatography/tandem mass spectrometry using a novel deuterated internal standard.

PubMed

Duberley, Kate E C; Hargreaves, Iain P; Chaiwatanasirikul, Korn-Anong; Heales, Simon J R; Land, John M; Rahman, Shamima; Mills, Kevin; Eaton, Simon

2013-05-15

Neurological dysfunction is common in primary coenzyme Q10 (2,3-dimethoxy, 5-methyl, 6-polyisoprene parabenzoquinone; CoQ10 ; ubiquinone) deficiencies, the most readily treatable subgroup of mitochondrial disorders. Therapeutic benefit from CoQ10 supplementation has also been noted in other neurodegenerative diseases. CoQ10 can be measured by high-performance liquid chromatography (HPLC) in plasma, muscle or leucocytes; however, there is no reliable method to quantify CoQ10 in cerebrospinal fluid (CSF). Additionally, many methods use CoQ9 , an endogenous ubiquinone in humans, as an internal standard. Deuterated CoQ10 (d6 -CoQ10 ) was synthesised by a novel, simple, method. Total CoQ10 was measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) using d6 -CoQ10 as internal standard and 5 mM methylamine as an ion-pairing reagent. Chromatography was performed using a Hypsersil GOLD C4 column (150 × 3 mm, 3 µm). CoQ10 levels were linear over a concentration range of 0-200 nM (R(2) = 0.9995). The lower limit of detection was 2 nM. The inter-assay coefficient of variation (CV) was 3.6% (10 nM) and 4.3% (20 nM), and intra-assay CV 3.4% (10 nM) and 3.6% (20 nM). Reference ranges were established for CoQ10 in CSF (5.7-8.7 nM; n = 17), fibroblasts (57.0-121.6 pmol/mg; n = 50) and muscle (187.3-430.1 pmol/mg; n = 15). Use of d6 -CoQ10 internal standard has enabled the development of a sensitive LC/MS/MS method to accurately determine total CoQ10 levels. Clinical applications of CSF CoQ10 determination include identification of patients with cerebral CoQ10 deficiency, and monitoring CSF CoQ10 levels following supplementation. Copyright © 2013 John Wiley & Sons, Ltd.

The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: A phase IIa, randomized, double-blind, and placebo-controlled study.

PubMed

Rodríguez-Carrizalez, Adolfo Daniel; Castellanos-González, José Alberto; Martínez-Romero, Esaú César; Miller-Arrevillaga, Guillermo; Pacheco-Moisés, Fermín Paul; Román-Pintos, Luis Miguel; Miranda-Díaz, Alejandra Guillermina

2016-07-01

Objective To evaluate the effect of ubiquinone (Coenzyme Q10) and combined antioxidant therapy (CAT) on oxidative stress markers in non-proliferative diabetic retinopathy (NPDR) under clinical management. Study design In a randomized, double-blind, phase IIa, placebo-controlled, clinical trial, three study groups were formed and administered medications as follows: Group 1, Coenzyme Q10; Group 2, CAT; and Group 3, placebo. Methods Serum levels of the products of lipid peroxidation (LPO) and nitrites/nitrates, as markers of oxidative/nitrosative stress, were measured. As antioxidants, the total antioxidant capacity (TAC), catalase activity, and glutathione peroxidase (GPx) activity were measured. Results Baseline serum levels of LPO and nitrites/nitrates were significantly elevated in the three groups vs. healthy group (P < 0.0001), while final levels in the Coenzyme Q10 and CAT groups were decreased vs. normal levels (P < 0.0001). The baseline TAC was consumed in the three groups (P < 0.0001), while final results in the Coenzyme Q10 and CAT groups improved (P < 0.0001). Baseline catalase activity was increased in all groups vs. normal values (P < 0.001), while final levels in the Coenzyme Q10 (P < 0.001) and CAT groups (P < 0.0001) were decreased. GPx behaved similarly to catalase and improved in the final results (P < 0.0001). Discussion Adjunctive antioxidant treatment for 6 months was effective and safe for improving the oxidative stress in NPDR.

The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein.

PubMed

Swanson, Michael A; Usselman, Robert J; Frerman, Frank E; Eaton, Gareth R; Eaton, Sandra S

2008-08-26

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) accepts electrons from electron transfer flavoprotein (ETF) and reduces ubiquinone from the ubiquinone pool. It contains one [4Fe-4S] (2+,1+) and one FAD, which are diamagnetic in the isolated oxidized enzyme and can be reduced to paramagnetic forms by enzymatic donors or dithionite. In the porcine protein, threonine 367 is hydrogen bonded to N1 and O2 of the flavin ring of the FAD. The analogous site in Rhodobacter sphaeroides ETF-QO is asparagine 338. Mutations N338T and N338A were introduced into the R. sphaeroides protein by site-directed mutagenesis to determine the impact of hydrogen bonding at this site on redox potentials and activity. The mutations did not alter the optical spectra, EPR g-values, spin-lattice relaxation rates, or the [4Fe-4S] (2+,1+) to FAD point-dipole interspin distances. The mutations had no impact on the reduction potential for the iron-sulfur cluster, which was monitored by changes in the continuous wave EPR signals of the [4Fe-4S] (+) at 15 K. For the FAD semiquinone, significantly different potentials were obtained by monitoring the titration at 100 or 293 K. Based on spectra at 293 K the N338T mutation shifted the first and second midpoint potentials for the FAD from +47 and -30 mV for wild type to -11 and -19 mV, respectively. The N338A mutation decreased the potentials to -37 and -49 mV. Lowering the midpoint potentials resulted in a decrease in the quinone reductase activity and negligible impact on disproportionation of ETF 1e (-) catalyzed by ETF-QO. These observations indicate that the FAD is involved in electron transfer to ubiquinone but not in electron transfer from ETF to ETF-QO. Therefore, the iron-sulfur cluster is the immediate acceptor from ETF.

The Iron-Sulfur Cluster of Electron Transfer Flavoprotein-Ubiquinone Oxidoreductase Is the Electron Acceptor for Electron Transfer Flavoprotein†

PubMed Central

Swanson, Michael A.; Usselman, Robert J.; Frerman, Frank E.; Eaton, Gareth R.; Eaton, Sandra S.

2009-01-01

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) accepts electrons from electron transfer flavoprotein (ETF) and reduces ubiquinone from the ubiquinone pool. It contains one [4Fe-4S]2+,1+ and one FAD, which are diamagnetic in the isolated oxidized enzyme and can be reduced to paramagnetic forms by enzymatic donors or dithionite. In the porcine protein, threonine 367 is hydrogen bonded to N1 and O2 of the flavin ring of the FAD. The analogous site in Rhodobacter sphaeroides ETF-QO is asparagine 338. Mutations N338T and N338A were introduced into the R. sphaeroides protein by site-directed mutagenesis to determine the impact of hydrogen bonding at this site on redox potentials and activity. The mutations did not alter the optical spectra, EPR g-values, spin-lattice relaxation rates, or the [4Fe-4S]2+,1+ to FAD point-dipole interspin distances. The mutations had no impact on the reduction potential for the iron-sulfur cluster, which was monitored by changes in the continuous wave EPR signals of the [4Fe-4S]+ at 15 K. For the FAD semiquinone, significantly different potentials were obtained by monitoring the titration at 100 or 293 K. Based on spectra at 293 K the N338T mutation shifted the first and second midpoint potentials for the FAD from +47 and -30 mV for wild type to -11 and -19 mV, respectively. The N338A mutation decreased the potentials to -37 and -49 mV. Lowering the midpoint potentials resulted in a decrease in the quinone reductase activity and negligible impact on disproportionation of ETF1e- catalyzed by ETF-QO. These observations indicate that the FAD is involved in electron transfer to ubiquinone but not in electron transfer from ETF to ETF-QO. Therefore, the iron-sulfur cluster is the immediate acceptor from ETF. PMID:9585549

Reactions of electron-transfer flavoprotein and electron-transfer flavoprotein: ubiquinone oxidoreductase.

PubMed Central

Ramsay, R R; Steenkamp, D J; Husain, M

1987-01-01

Electron-transfer flavoprotein:ubiquinone oxidoreductase (ETF-Q oxidoreductase) catalyses the re-oxidation of reduced electron-transfer flavoprotein (ETF) with ubiquinone-1 (Q-1) as the electron acceptor. A kinetic assay for the enzyme was devised in which glutaryl-CoA in the presence of glutaryl-CoA dehydrogenase was used to reduce ETFox. and the reduction of Q-1 was monitored at 275 nm. The partial reactions involved in the overall assay system were examined. Glutaryl-CoA dehydrogenase catalyses the rapid reduction of ETFox. to the anionic semiquinone (ETF.-), but reduces ETF.- to the fully reduced form (ETFhq) at a rate that is about 6-fold lower. ETF.-, but not ETFhq, is directly re-oxidized by Q-1 at a rate that, depending on the steady-state concentration of ETF.-, may contribute significantly to the overall reaction. ETF-Q oxidoreductase catalyses rapid disproportionation of ETF.- with an equilibrium constant of about 1.0 at pH 7.8. In the presence of Q-1 it also catalyses the re-oxidation of ETFhq at a rate that is faster than that of the overall reaction. Rapid-scan experiments indicated the formation of ETF.-, but its fractional concentration in the early stages of the re-oxidation of ETFhq is low. The data indicate that the re-oxidation of ETFhq proceeds at a rate that is adequate to account for the overall rate of electron transfer from glutaryl-CoA to Q-1. An unusual property of ETF-Q oxidoreductase seems to be that it not only catalyses the re-oxidation of the reduced forms of ETF but also facilitates the complete reduction of ETFox. to ETFhq by disproportionation of the radical. PMID:3593226

Elucidation of roles for vitamin B12 in regulation of folate, ubiquinone, and methionine metabolism

PubMed Central

Romine, Margaret F.; Rodionov, Dmitry A.; Maezato, Yukari; Anderson, Lindsey N.; Nandhikonda, Premchendar; Rodionova, Irina A.; Carre, Alexandre; Li, Xiaoqing; Xu, Chengdong; Clauss, Therese R. W.; Metz, Thomas O.; Wright, Aaron T.

2017-01-01

Only a small fraction of vitamin B12-requiring organisms are able to synthesize B12 de novo, making it a common commodity in microbial communities. Initially recognized as an enzyme cofactor of a few enzymes, recent studies have revealed additional B12-binding enzymes and regulatory roles for B12. Here we report the development and use of a B12-based chemical probe to identify B12-binding proteins in a nonphototrophic B12-producing bacterium. Two unexpected discoveries resulted from this study. First, we identified a light-sensing B12-binding transcriptional regulator and demonstrated that it controls folate and ubiquinone biosynthesis. Second, our probe captured proteins involved in folate, methionine, and ubiquinone metabolism, suggesting that it may play a role as an allosteric effector of these processes. These metabolic processes produce precursors for synthesis of DNA, RNA, and protein. Thereby, B12 likely modulates growth, and by limiting its availability to auxotrophs, B12-producing organisms may facilitate coordination of community metabolism. PMID:28137868

The insecticide target in the PSST subunit of complex I.

PubMed

Schuler, F; Casida, J E

2001-10-01

Current insecticides have been selected by sifting and winnowing hundreds of thousands of synthetic chemicals and natural products to obtain commercial preparations of optimal effectiveness and safety. This process has often ended up with compounds of high potency as inhibitors of the electron transport chain and more specifically of complex I (NADH:ubiquinone oxidoreductase). Many classes of chemicals are involved and the enzyme is one of the most complicated known, with 43 subunits catalyzing electron transfer from NADH to ubiquinone through flavin mononucleotide and up to eight iron-sulfur clusters. We used a potent photoaffinity ligand, (trifluoromethyl)diazirinyl[3H]pyridaben, to localize the insecticide target to a single high-affinity site in the PSST subunit that couples electron transfer from iron-sulfur cluster N2 to ubiquinone. Most importantly, all of the potent complex I-inhibiting pesticides, despite their great structural diversity, compete for this same specific binding domain in PSST. Finding their common mode of action and target provides insight into shared toxicological features and potential selection for resistant pests.

Fluorescence analysis of ubiquinone and its application in quality control of medical supplies

NASA Astrophysics Data System (ADS)

Timofeeva, Elvira O.; Gorbunova, Elena V.; Chertov, Aleksandr N.

2017-02-01

The presence of antioxidant issues such as redox potential imbalance in human body is a very important question for modern clinical diagnostics. Implementation of fluorescence analysis into optical diagnostics of such wide distributed in a human body antioxidant as ubiquinone is one of the steps for development of the device with a view to clinical diagnostics of redox potential. Recording of fluorescence was carried out with spectrometer using UV irradiation source with thin band (max at 287 and 330 nm) as a background radiation. Concentrations of ubiquinone from 0.25 to 2.5 mmol/l in explored samples were used for investigation. Recording data was processed using correlation analysis and differential analytical technique. The fourth derivative spectrum of fluorescence spectrum provided the basis for a multicomponent analysis of the solutions. As a technique in clinical diagnostics fluorescence analysis with processing method including differential spectrophotometry, it is step forward towards redox potential calculation and quality control in pharmacy for better health care.

Structure of the Deactive State of Mammalian Respiratory Complex I.

PubMed

Blaza, James N; Vinothkumar, Kutti R; Hirst, Judy

2018-02-06

Complex I (NADH:ubiquinone oxidoreductase) is central to energy metabolism in mammalian mitochondria. It couples NADH oxidation by ubiquinone to proton transport across the energy-conserving inner membrane, catalyzing respiration and driving ATP synthesis. In the absence of substrates, active complex I gradually enters a pronounced resting or deactive state. The active-deactive transition occurs during ischemia and is crucial for controlling how respiration recovers upon reperfusion. Here, we set a highly active preparation of Bos taurus complex I into the biochemically defined deactive state, and used single-particle electron cryomicroscopy to determine its structure to 4.1 Å resolution. We show that the deactive state arises when critical structural elements that form the ubiquinone-binding site become disordered, and we propose reactivation is induced when substrate binding to the NADH-reduced enzyme templates their reordering. Our structure both rationalizes biochemical data on the deactive state and offers new insights into its physiological and cellular roles. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Synthetic Ubiquinones Specifically Bind to Mitochondrial Voltage-Dependent Anion Channel 1 (VDAC1) in Saccharomyces cerevisiae Mitochondria.

PubMed

Murai, Masatoshi; Okuda, Ayaka; Yamamoto, Takenori; Shinohara, Yasuo; Miyoshi, Hideto

2017-01-31

The role of the voltage-dependent anion channel (VDAC) as a metabolic gate of the mitochondrial outer membrane has been firmly established; however, its involvement in the regulation of mitochondrial permeability transition (PT) remains extremely controversial. Although some low-molecular-weight chemicals have been proposed to modulate the regulatory role of VDAC in the induction of PT, direct binding between these chemicals and VDAC has not yet been demonstrated. In the present study, we investigated whether the ubiquinone molecule directly binds to VDAC in Saccharomyces cerevisiae mitochondria through a photoaffinity labeling technique using two photoreactive ubiquinones (PUQ-1 and PUQ-2). The results of the labeling experiments demonstrated that PUQ-1 and PUQ-2 specifically bind to VDAC1 and that the labeled position is located in the C-terminal region Phe221-Lys234, connecting the 15th and 16th β-strand sheets. Mutations introduced in this region (R224A, Y225A, D228A, and Y225A/D228A) hardly affected the binding affinity of PUQ-1. PUQ-1 and PUQ-2 both significantly suppressed the Ca 2+ -induced mitochondrial PT (monitored by mitochondrial swelling) at the one digit μM level. Thus, the results of the present study provided, for the first time to our knowledge, direct evidence indicating that the ubiquinone molecule specifically binds to VDAC1 through its quinone-head ring.

Cooperation and Contagion in Web-Based, Networked Public Goods Experiments

PubMed Central

Suri, Siddharth; Watts, Duncan J.

2011-01-01

A longstanding idea in the literature on human cooperation is that cooperation should be reinforced when conditional cooperators are more likely to interact. In the context of social networks, this idea implies that cooperation should fare better in highly clustered networks such as cliques than in networks with low clustering such as random networks. To test this hypothesis, we conducted a series of web-based experiments, in which 24 individuals played a local public goods game arranged on one of five network topologies that varied between disconnected cliques and a random regular graph. In contrast with previous theoretical work, we found that network topology had no significant effect on average contributions. This result implies either that individuals are not conditional cooperators, or else that cooperation does not benefit from positive reinforcement between connected neighbors. We then tested both of these possibilities in two subsequent series of experiments in which artificial seed players were introduced, making either full or zero contributions. First, we found that although players did generally behave like conditional cooperators, they were as likely to decrease their contributions in response to low contributing neighbors as they were to increase their contributions in response to high contributing neighbors. Second, we found that positive effects of cooperation were contagious only to direct neighbors in the network. In total we report on 113 human subjects experiments, highlighting the speed, flexibility, and cost-effectiveness of web-based experiments over those conducted in physical labs. PMID:21412431

Cooperation and contagion in web-based, networked public goods experiments.

PubMed

Suri, Siddharth; Watts, Duncan J

2011-03-11

A longstanding idea in the literature on human cooperation is that cooperation should be reinforced when conditional cooperators are more likely to interact. In the context of social networks, this idea implies that cooperation should fare better in highly clustered networks such as cliques than in networks with low clustering such as random networks. To test this hypothesis, we conducted a series of web-based experiments, in which 24 individuals played a local public goods game arranged on one of five network topologies that varied between disconnected cliques and a random regular graph. In contrast with previous theoretical work, we found that network topology had no significant effect on average contributions. This result implies either that individuals are not conditional cooperators, or else that cooperation does not benefit from positive reinforcement between connected neighbors. We then tested both of these possibilities in two subsequent series of experiments in which artificial seed players were introduced, making either full or zero contributions. First, we found that although players did generally behave like conditional cooperators, they were as likely to decrease their contributions in response to low contributing neighbors as they were to increase their contributions in response to high contributing neighbors. Second, we found that positive effects of cooperation were contagious only to direct neighbors in the network. In total we report on 113 human subjects experiments, highlighting the speed, flexibility, and cost-effectiveness of web-based experiments over those conducted in physical labs.

Second-Order Free-Riding on Antisocial Punishment Restores the Effectiveness of Prosocial Punishment

NASA Astrophysics Data System (ADS)

Szolnoki, Attila; Perc, Matjaž

2017-10-01

Economic experiments have shown that punishment can increase public goods game contributions over time. However, the effectiveness of punishment is challenged by second-order free-riding and antisocial punishment. The latter implies that noncooperators punish cooperators, while the former implies unwillingness to shoulder the cost of punishment. Here, we extend the theory of cooperation in the spatial public goods game by considering four competing strategies, which are traditional cooperators and defectors, as well as cooperators who punish defectors and defectors who punish cooperators. We show that if the synergistic effects are high enough to sustain cooperation based on network reciprocity alone, antisocial punishment does not deter public cooperation. Conversely, if synergistic effects are low and punishment is actively needed to sustain cooperation, antisocial punishment does is viable, but only if the cost-to-fine ratio is low. If the costs are relatively high, cooperation again dominates as a result of spatial pattern formation. Counterintuitively, defectors who do not punish cooperators, and are thus effectively second-order free-riding on antisocial punishment, form an active layer around punishing cooperators, which protects them against defectors that punish cooperators. A stable three-strategy phase that is sustained by the spontaneous emergence of cyclic dominance is also possible via the same route. The microscopic mechanism behind the reported evolutionary outcomes can be explained by the comparison of invasion rates that determine the stability of subsystem solutions. Our results reveal an unlikely evolutionary escape from adverse effects of antisocial punishment, and they provide a rationale for why second-order free-riding is not always an impediment to the evolutionary stability of punishment.

mtDNA Mutagenesis Disrupts Pluripotent Stem Cell Function by Altering Redox Signaling

PubMed Central

Hämäläinen, Riikka H.; Ahlqvist, Kati J.; Ellonen, Pekka; Lepistö, Maija; Logan, Angela; Otonkoski, Timo; Murphy, Michael P.; Suomalainen, Anu

2015-01-01

Summary mtDNA mutagenesis in somatic stem cells leads to their dysfunction and to progeria in mouse. The mechanism was proposed to involve modification of reactive oxygen species (ROS)/redox signaling. We studied the effect of mtDNA mutagenesis on reprogramming and stemness of pluripotent stem cells (PSCs) and show that PSCs select against specific mtDNA mutations, mimicking germline and promoting mtDNA integrity despite their glycolytic metabolism. Furthermore, mtDNA mutagenesis is associated with an increase in mitochondrial H2O2, reduced PSC reprogramming efficiency, and self-renewal. Mitochondria-targeted ubiquinone, MitoQ, and N-acetyl-L-cysteine efficiently rescued these defects, indicating that both reprogramming efficiency and stemness are modified by mitochondrial ROS. The redox sensitivity, however, rendered PSCs and especially neural stem cells sensitive to MitoQ toxicity. Our results imply that stem cell compartment warrants special attention when the safety of new antioxidants is assessed and point to an essential role for mitochondrial redox signaling in maintaining normal stem cell function. PMID:26027936

The Iron-Sulfur Cluster of Electron Transfer Flavoprotein-ubiquinone Oxidoreductase (ETF-QO) is the Electron Acceptor for Electron Transfer Flavoprotein†

PubMed Central

Swanson, Michael A.; Usselman, Robert J.; Frerman, Frank E.; Eaton, Gareth R.; Eaton, Sandra S.

2011-01-01

Electron-transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) accepts electrons from electron-transfer flavoprotein (ETF) and reduces ubiquinone from the ubiquinone-pool. It contains one [4Fe-4S]2+,1+ and one FAD, which are diamagnetic in the isolated oxidized enzyme and can be reduced to paramagnetic forms by enzymatic donors or dithionite. In the porcine protein, threonine 367 is hydrogen bonded to N1 and O2 of the flavin ring of the FAD. The analogous site in Rhodobacter sphaeroides ETF-QO is asparagine 338. Mutations N338T and N338A were introduced into the R. sphaeroides protein by site-directed mutagenesis to determine the impact of hydrogen bonding at this site on redox potentials and activity. The mutations did not alter the optical spectra, EPR g-values, spin-lattice relaxation rates, or the [4Fe-4S]2+,1+ to FAD point-dipole interspin distances. The mutations had no impact on the reduction potential for the iron-sulfur cluster, which was monitored by changes in the continuous wave EPR signals of the [4Fe-4S]+ at 15 K. For the FAD semiquinone, significantly different potentials were obtained by monitoring the titration at 100 or 293 K. Based on spectra at 293 K the N338T mutation shifted the first and second midpoint potentials for the FAD from +47 mV and −30 mV for wild type to −11 mV and −19 mV, respectively. The N338A mutation decreased the potentials to −37 mV and −49 mV. Lowering the midpoint potentials resulted in a decrease in the quinone reductase activity and negligible impact on disproportionation of ETF1e− catalyzed by ETF-QO. These observations indicate that the FAD is involved in electron transfer to ubiquinone, but not in electron transfer from ETF to ETF-QO. Therefore the iron-sulfur cluster is the immediate acceptor from ETF. PMID:18672901

Sites of electron transfer to membrane-bound copper and hydroperoxide-induced damage in the respiratory chain of Escherichia coli.

PubMed

Rodríguez-Montelongo, L; Farías, R N; Massa, E M

1995-10-20

Previous studies in Escherichia coli as a model system for peroxide toxicity (L. Rodríguez-Montelongo, L. C. De la Cruz-Rodríguez, R. N. Farías, and E. M. Massa, 1993, Biochim. Biophys. Acta 1144, 77-84) have shown that electron flow through the respiratory chain supports a membrane-associated Cu(II)/Cu(I) redox cycle involved in irreversible impairment of the respiratory system by tert-butyl hydroperoxide (t-BOOH). In this paper, E. coli mutants deficient in specific respiratory chain components have been used to determine the sites of copper reduction and the targets inactivated by t-BOOH. Two sites of electron transfer to membrane-bound copper were identified: one in the region between NADH and ubiquinone supported by NADH as electron donor and another localized between ubiquinone and the cytochromes supported by electrons coming from NADH, succinate, or D-lactate. Electron flow through the former site in the presence of t-BOOH led to inactivation of NADH dehydrogenase II, whereas electron flow through the latter site in the presence of the hydroperoxide led to damage of ubiquinone. In agreement with the above in vitro results with isolated membranes, copper-dependent inactivation of NADH dehydrogenase and ubiquinone was demonstrated in E. coli cells exposed to t-BOOH. It is proposed that the t-BOOH-induced damage is a consequence of t-butylalkoxy radical generation through a Fenton-type reaction mediated by redox cycling of membrane-bound copper at those two loci of the respiratory chain.

Lambda Red-mediated mutagenesis and efficient large scale affinity purification of the Escherichia coli NADH:ubiquinone oxidoreductase (complex I).

PubMed

Pohl, Thomas; Uhlmann, Mareike; Kaufenstein, Miriam; Friedrich, Thorsten

2007-09-18

The proton-pumping NADH:ubiquinone oxidoreductase, the respiratory complex I, couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane. The Escherichia coli complex I consists of 13 different subunits named NuoA-N (from NADH:ubiquinone oxidoreductase), that are coded by the genes of the nuo-operon. Genetic manipulation of the operon is difficult due to its enormous size. The enzymatic activity of variants is obscured by an alternative NADH dehydrogenase, and purification of the variants is hampered by their instability. To overcome these problems the entire E. coli nuo-operon was cloned and placed under control of the l-arabinose inducible promoter ParaBAD. The exposed N-terminus of subunit NuoF was chosen for engineering the complex with a hexahistidine-tag by lambda-Red-mediated recombineering. Overproduction of the complex from this construct in a strain which is devoid of any membrane-bound NADH dehydrogenase led to the assembly of a catalytically active complex causing the entire NADH oxidase activity of the cytoplasmic membranes. After solubilization with dodecyl maltoside the engineered complex binds to a Ni2+-iminodiacetic acid matrix allowing the purification of approximately 11 mg of complex I from 25 g of cells. The preparation is pure and monodisperse and comprises all known subunits and cofactors. It contains more lipids than earlier preparations due to the gentle and fast purification procedure. After reconstitution in proteoliposomes it couples the electron transfer with proton translocation in an inhibitor sensitive manner, thus meeting all prerequisites for structural and functional studies.

Elucidation of roles for vitamin B 12 in regulation of folate, ubiquinone, and methionine metabolism

DOE PAGES

Romine, Margaret F.; Rodionov, Dmitry A.; Maezato, Yukari; ...

2017-01-30

Only a small fraction of vitamin B12-requiring organisms are able to synthesize B12 de novo, making it a common commodity in microbial communities. Initially recognized as an enzyme cofactor of a few enzymes, recent studies have revealed additional B12-binding enzymes and regulatory roles for B12. Here we report the development and use of a B12-based chemical probe to identify B12-binding proteins in a nonphototrophic B12-producing bacterium. Two unexpected discoveries resulted from this study. First, we identified a new light-sensing B12-binding transcriptional regulator and demonstrated that it controls folate and ubiquinone biosynthesis. Second, our probe captured proteins involved in folate, methionine,more » and ubiquinone metabolism suggesting that it may play a role as an allosteric effector of these processes. These metabolic processes produce precursors for synthesis of DNA, RNA, and protein. Thereby, B12 modulates growth, and by limiting its availability to auxotrophs, B12-producing organisms may facilitate coordination of community metabolism.« less

Elucidation of roles for vitamin B 12 in regulation of folate, ubiquinone, and methionine metabolism

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

Romine, Margaret F.; Rodionov, Dmitry A.; Maezato, Yukari

Only a small fraction of vitamin B 12-requiring organisms are able to synthesize B 12 de novo, making it a common commodity in microbial communities. Initially recognized as an enzyme cofactor of a few enzymes, recent studies have revealed additional B 12-binding enzymes and regulatory roles for B 12. Here we report the development and use of a B 12-based chemical probe to identify B 12-binding proteins in a nonphototrophic B 12-producing bacterium. Two unexpected discoveries resulted from this study. First, we identified a new light-sensing B 12-binding transcriptional regulator and demonstrated that it controls folate and ubiquinone biosynthesis. Second,more » our probe captured proteins involved in folate, methionine, and ubiquinone metabolism suggesting that it may play a role as an allosteric effector of these processes. These metabolic processes produce precursors for synthesis of DNA, RNA, and protein. Furthermore, B 12 modulates growth, and by limiting its availability to auxotrophs, B 12-producing organisms may facilitate coordination of community metabolism.« less

Sphingomonas and Related Genera

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

Balkwill, David L.; Fredrickson, Jim K.; Romine, Margaret F.

INTRODUCTION-The genus Sphingomonas was defined by Yabuuchi et al. (1990) as a group of Gram-negative, rod-shaped, chemoheterotrophic, strictly aerobic bacteria that possess ubiquinone 10 as the major respiratory quinone, contain glycosphingolipids (GSLs) instead of lipopolysaccharide in their cell envelopes, and typically produce yellow-pigmented colonies. By 2001, the genus included more than 20 species that were quite diverse in terms of their phylogenetic, ecological, and physiological properties. As a result, Takeuchi et al. (2001) subdivided Sphingomonas into four genera: Sphingomonas, Sphingobium, Novosphingobium and Sphingopyxis...

Glutaric acidemia type II: gene structure and mutations of the electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) gene.

PubMed

Goodman, Stephen I; Binard, Robert J; Woontner, Michael R; Frerman, Frank E

2002-01-01

Glutaric acidemia type II is a human inborn error of metabolism which can be due to defects in either subunit of electron transfer flavoprotein (ETF) or in ETF:ubiquinone oxidoreductase (ETF:QO), but few disease-causing mutations have been described. The ETF:QO gene is located on 4q33, and contains 13 exons. Primers to amplify these exons are presented, together with mutations identified by molecular analysis of 20 ETF:QO-deficient patients. Twenty-one different disease-causing mutations were identified on 36 of the 40 chromosomes.

Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool

PubMed Central

Zhang, Jian; Frerman, Frank E.; Kim, Jung-Ja P.

2006-01-01

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a 4Fe4S flavoprotein located in the inner mitochondrial membrane. It catalyzes ubiquinone (UQ) reduction by ETF, linking oxidation of fatty acids and some amino acids to the mitochondrial respiratory chain. Deficiencies in ETF or ETF-QO result in multiple acyl-CoA dehydrogenase deficiency, a human metabolic disease. Crystal structures of ETF-QO with and without bound UQ were determined, and they are essentially identical. The molecule forms a single structural domain. Three functional regions bind FAD, the 4Fe4S cluster, and UQ and are closely packed and share structural elements, resulting in no discrete structural domains. The UQ-binding pocket consists mainly of hydrophobic residues, and UQ binding differs from that of other UQ-binding proteins. ETF-QO is a monotopic integral membrane protein. The putative membrane-binding surface contains an α-helix and a β-hairpin, forming a hydrophobic plateau. The UQ—flavin distance (8.5 Å) is shorter than the UQ—cluster distance (18.8 Å), and the very similar redox potentials of FAD and the cluster strongly suggest that the flavin, not the cluster, transfers electrons to UQ. Two possible electron transfer paths can be envisioned. First, electrons from the ETF flavin semiquinone may enter the ETF-QO flavin one by one, followed by rapid equilibration with the cluster. Alternatively, electrons may enter via the cluster, followed by equilibration between centers. In both cases, when ETF-QO is reduced to a two-electron reduced state (one electron at each redox center), the enzyme is primed to reduce UQ to ubiquinol via FAD. PMID:17050691

Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool.

PubMed

Zhang, Jian; Frerman, Frank E; Kim, Jung-Ja P

2006-10-31

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a 4Fe4S flavoprotein located in the inner mitochondrial membrane. It catalyzes ubiquinone (UQ) reduction by ETF, linking oxidation of fatty acids and some amino acids to the mitochondrial respiratory chain. Deficiencies in ETF or ETF-QO result in multiple acyl-CoA dehydrogenase deficiency, a human metabolic disease. Crystal structures of ETF-QO with and without bound UQ were determined, and they are essentially identical. The molecule forms a single structural domain. Three functional regions bind FAD, the 4Fe4S cluster, and UQ and are closely packed and share structural elements, resulting in no discrete structural domains. The UQ-binding pocket consists mainly of hydrophobic residues, and UQ binding differs from that of other UQ-binding proteins. ETF-QO is a monotopic integral membrane protein. The putative membrane-binding surface contains an alpha-helix and a beta-hairpin, forming a hydrophobic plateau. The UQ-flavin distance (8.5 A) is shorter than the UQ-cluster distance (18.8 A), and the very similar redox potentials of FAD and the cluster strongly suggest that the flavin, not the cluster, transfers electrons to UQ. Two possible electron transfer paths can be envisioned. First, electrons from the ETF flavin semiquinone may enter the ETF-QO flavin one by one, followed by rapid equilibration with the cluster. Alternatively, electrons may enter via the cluster, followed by equilibration between centers. In both cases, when ETF-QO is reduced to a two-electron reduced state (one electron at each redox center), the enzyme is primed to reduce UQ to ubiquinol via FAD.

Attributes and National Behavior, Part 2: Modern International Relations Monograph Series. Patterns of Cooperation: Distance Theory.

ERIC Educational Resources Information Center

Vincent, Jack E.

Part of a large scale research project to test various theories with regard to their ability to analyze international relations, this monograph presents data on the application of distance theory to patterns of cooperation among nations. Distance theory implies that international relations systems (nations, organizations, individuals, etc.) can be…

Some studies on the biosynthesis of ubiquinone, isoprenoid alcohols, squalene and sterols by marine invertebrates

PubMed Central

Walton, M. J.; Pennock, J. F.

1972-01-01

The ability of fourteen marine invertebrates to utilize [14C]mevalonate for the biosynthesis of isoprenoid compounds was investigated. Several of the animals, in particular crustaceans, bivalve molluscs, a coelenterate and a sponge, were unable to synthesize squalene and sterols, whereas gastropod molluscs, echinoderms, an annelid and a sponge could. Regardless of sterol-synthesizing ability the animals (with the exception of a sponge) always made dolichol and ubiquinone, and thus a specific block in squalene and sterol synthesis was indicated in some animals. Radioactivity accumulated in relatively large amounts in farnesol and geranylgeraniol in those animals incapable of making sterols. PMID:4403925

Photodegradation of avobenzone: stabilization effect of antioxidants.

PubMed

Afonso, S; Horita, K; Sousa e Silva, J P; Almeida, I F; Amaral, M H; Lobão, P A; Costa, P C; Miranda, Margarida S; Esteves da Silva, Joaquim C G; Sousa Lobo, J M

2014-11-01

Avobenzone is one of the most common UVA-filters in sunscreens, and is known to be photounstable. Some of the strategies used to stabilize this filter present some drawbacks like photosensitization reactions. Antioxidants are widely used as cosmetic ingredients that prevent photoageing and complement the photoprotection offered by the UV-filters preventing or reducing photogenerated reactive species. The purpose of this work was to study the effect of antioxidants in the photostabilization of avobenzone. The filter dissolved in dimethyl sulfoxide or incorporated in a sunscreen formulation was irradiated with simulated solar radiation (750 W/m(2)). The tested antioxidants were vitamin C, vitamin E, and ubiquinone. The area under the curve of the absorption spectrum for UVA range and the sun protection factor (SPF) were calculated. Vitamin E (1:2), vitamin C (1:0.5) and ubiquinone (1:0.5) were the more effective concentrations increasing the photostability of avobenzone. In sunscreen formulations, the most effective photostabilizer was ubiquinone which also promoted an increase in SPF. This knowledge is important to improve effectiveness of sunscreen formulation. Antioxidants can be valuable ingredients for sunscreens with a triple activity of filter stabilization, SPF boosting and photoageing prevention. Copyright © 2014 Elsevier B.V. All rights reserved.

Modification of quinone electrochemistry by the proteins in the biological electron transfer chains: examples from photosynthetic reaction centers

PubMed Central

Gunner, M. R.; Madeo, Jennifer; Zhu, Zhenyu

2009-01-01

Quinones such as ubiquinone are the lipid soluble electron and proton carriers in the membranes of mitochondria, chloroplasts and oxygenic bacteria. Quinones undergo controlled redox reactions bound to specific sites in integral membrane proteins such as the cytochrome bc1 oxidoreductase. The quinone reactions in bacterial photosynthesis are amongst the best characterized, presenting a model to understand how proteins modulate cofactor chemistry. The free energy of ubiquinone redox reactions in aqueous solution and in the QA and QB sites of the bacterial photosynthetic reaction centers (RCs) are compared. In the primary QA site ubiquinone is reduced only to the anionic semiquinone (Q•−) while in the secondary QB site the product is the doubly reduced, doubly protonated quinol (QH2). The ways in which the protein modifies the relative energy of each reduced and protonated intermediate are described. For example, the protein stabilizes Q•− while destabilizing Q= relative to aqueous solution through electrostatic interactions. In addition, kinetic and thermodynamic mechanisms for stabilizing the intermediate semiquinones are compared. Evidence for the protein sequestering anionic compounds by slowing both on and off rates as well as by binding the anion more tightly is reviewed. PMID:18979192

The UbiI (VisC) Aerobic Ubiquinone Synthase Is Required for Expression of Type 1 Pili, Biofilm Formation, and Pathogenesis in Uropathogenic Escherichia coli

PubMed Central

Floyd, Kyle A.; Mitchell, Courtney A.; Eberly, Allison R.; Colling, Spencer J.; Zhang, Ellisa W.; DePas, William; Chapman, Matthew R.; Conover, Matthew; Rogers, Bridget R.; Hultgren, Scott J.

2016-01-01

ABSTRACT Uropathogenic Escherichia coli (UPEC), which causes the majority of urinary tract infections (UTI), uses pilus-mediated adherence to initiate biofilm formation in the urinary tract. Oxygen gradients within E. coli biofilms regulate expression and localization of adhesive type 1 pili. A transposon mutant screen for strains defective in biofilm formation identified the ubiI (formerly visC) aerobic ubiquinone synthase gene as critical for UPEC biofilm formation. In this study, we characterized a nonpolar ubiI deletion mutant and compared its behavior to that of wild-type bacteria grown under aerobic and anoxic conditions. Consistent with its function as an aerobic ubiquinone-8 synthase, deletion of ubiI in UPEC resulted in reduced membrane potential, diminished motility, and reduced expression of chaperone-usher pathway pili. Loss of aerobic respiration was previously shown to negatively impact expression of type 1 pili. To determine whether this reduction in type 1 pili was due to an energy deficit, wild-type UPEC and the ubiI mutant were compared for energy-dependent phenotypes under anoxic conditions, in which quinone synthesis is undertaken by anaerobic quinone synthases. Under anoxic conditions, the two strains exhibited wild-type levels of motility but produced diminished numbers of type 1 pili, suggesting that the reduction of type 1 pilus expression in the absence of oxygen is not due to a cellular energy deficit. Acute- and chronic-infection studies in a mouse model of UTI revealed a significant virulence deficit in the ubiI mutant, indicating that UPEC encounters enough oxygen in the bladder to induce aerobic ubiquinone synthesis during infection. IMPORTANCE The majority of urinary tract infections are caused by uropathogenic E. coli, a bacterium that can respire in the presence and absence of oxygen. The bladder environment is hypoxic, with oxygen concentrations ranging from 4% to 7%, compared to 21% atmospheric oxygen. This work provides evidence that aerobic ubiquinone synthesis must be engaged during bladder infection, indicating that UPEC bacteria sense and use oxygen as a terminal electron acceptor in the bladder and that this ability drives infection potential despite the fact that UPEC is a facultative anaerobe. PMID:27161114

The UbiI (VisC) Aerobic Ubiquinone Synthase Is Required for Expression of Type 1 Pili, Biofilm Formation, and Pathogenesis in Uropathogenic Escherichia coli.

PubMed

Floyd, Kyle A; Mitchell, Courtney A; Eberly, Allison R; Colling, Spencer J; Zhang, Ellisa W; DePas, William; Chapman, Matthew R; Conover, Matthew; Rogers, Bridget R; Hultgren, Scott J; Hadjifrangiskou, Maria

2016-10-01

Uropathogenic Escherichia coli (UPEC), which causes the majority of urinary tract infections (UTI), uses pilus-mediated adherence to initiate biofilm formation in the urinary tract. Oxygen gradients within E. coli biofilms regulate expression and localization of adhesive type 1 pili. A transposon mutant screen for strains defective in biofilm formation identified the ubiI (formerly visC) aerobic ubiquinone synthase gene as critical for UPEC biofilm formation. In this study, we characterized a nonpolar ubiI deletion mutant and compared its behavior to that of wild-type bacteria grown under aerobic and anoxic conditions. Consistent with its function as an aerobic ubiquinone-8 synthase, deletion of ubiI in UPEC resulted in reduced membrane potential, diminished motility, and reduced expression of chaperone-usher pathway pili. Loss of aerobic respiration was previously shown to negatively impact expression of type 1 pili. To determine whether this reduction in type 1 pili was due to an energy deficit, wild-type UPEC and the ubiI mutant were compared for energy-dependent phenotypes under anoxic conditions, in which quinone synthesis is undertaken by anaerobic quinone synthases. Under anoxic conditions, the two strains exhibited wild-type levels of motility but produced diminished numbers of type 1 pili, suggesting that the reduction of type 1 pilus expression in the absence of oxygen is not due to a cellular energy deficit. Acute- and chronic-infection studies in a mouse model of UTI revealed a significant virulence deficit in the ubiI mutant, indicating that UPEC encounters enough oxygen in the bladder to induce aerobic ubiquinone synthesis during infection. The majority of urinary tract infections are caused by uropathogenic E. coli, a bacterium that can respire in the presence and absence of oxygen. The bladder environment is hypoxic, with oxygen concentrations ranging from 4% to 7%, compared to 21% atmospheric oxygen. This work provides evidence that aerobic ubiquinone synthesis must be engaged during bladder infection, indicating that UPEC bacteria sense and use oxygen as a terminal electron acceptor in the bladder and that this ability drives infection potential despite the fact that UPEC is a facultative anaerobe. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Role of generosity and forgiveness: Return to a cooperative society

NASA Astrophysics Data System (ADS)

Park, Hye Jin; Kim, Beom Jun; Jeong, Hyeong-Chai

2017-04-01

One's reputation in human society depends on what and how one did in the past. If the reputation of a counterpart is too bad, we often avoid interacting with the individual. We introduce a selective cooperator called the goodie, who participates in the prisoner's dilemma game dependent on the opponent's reputation, and study its role in forming a cooperative society. We observe enhanced cooperation when goodies have a small but nonzero probability of playing the game with an individual who defected in previous rounds. Our finding implies that even this small generosity of goodies can provide defectors chances of encountering the better world of cooperation, encouraging them to escape from their isolated world of selfishness.

Role of generosity and forgiveness: Return to a cooperative society.

PubMed

Park, Hye Jin; Kim, Beom Jun; Jeong, Hyeong-Chai

2017-04-01

One's reputation in human society depends on what and how one did in the past. If the reputation of a counterpart is too bad, we often avoid interacting with the individual. We introduce a selective cooperator called the goodie, who participates in the prisoner's dilemma game dependent on the opponent's reputation, and study its role in forming a cooperative society. We observe enhanced cooperation when goodies have a small but nonzero probability of playing the game with an individual who defected in previous rounds. Our finding implies that even this small generosity of goodies can provide defectors chances of encountering the better world of cooperation, encouraging them to escape from their isolated world of selfishness.

Structural insights into the methyl donor recognition model of a novel membrane-binding protein UbiG.

PubMed

Zhu, Yuwei; Jiang, Xuguang; Wang, Chongyuan; Liu, Yang; Fan, Xiaojiao; Zhang, Linjuan; Niu, Liwen; Teng, Maikun; Li, Xu

2016-03-15

UbiG is a SAM-dependent O-methyltransferase, catalyzing two O-methyl transfer steps for ubiquinone biosynthesis in Escherichia coli. UbiG possesses a unique sequence insertion between β4 and α10, which is used for membrane lipid interaction. Interestingly, this sequence insertion also covers the methyl donor binding pocket. Thus, the relationship between membrane binding and entrance of the methyl donor of UbiG during the O-methyl transfer process is a question that deserves further exploration. In this study, we reveal that the membrane-binding region of UbiG gates the entrance of methyl donor. When bound with liposome, UbiG displays an enhanced binding ability toward the methyl donor product S-adenosylhomocysteine. We further employ protein engineering strategies to design UbiG mutants by truncating the membrane interacting region or making it more flexible. The ITC results show that the binding affinity of these mutants to SAH increases significantly compared with that of the wild-type UbiG. Moreover, we determine the structure of UbiG∆(165-187) in complex with SAH. Collectively, our results provide a new angle to cognize the relationship between membrane binding and entrance of the methyl donor of UbiG, which is of benefit for better understanding the O-methyl transfer process for ubiquinone biosynthesis.

Isoprenoid quinones of the genus Legionella.

PubMed Central

Karr, D E; Bibb, W F; Moss, C W

1982-01-01

Representative strains of each of the named species of Legionella were examined for isoprenoid quinones by reverse-phase thin-layer chromatography. All strains contained three or more ubiquinones (Q9, Q10, Q11, Q12, Q13) which were useful for placing the species into one of three distinct groups. Group 1 contained L. longbeachae, L. bozemanii, L. dumoffi, and L. gormanii; group 2 contained only L. micdadei; and group 3 contained only L. pneumophila. The identities of the quinones were established by UV spectroscopy and mass spectrometry. PMID:7107837

Localization of Ubiquinone-8 in the Na+-pumping NADH:Quinone Oxidoreductase from Vibrio cholerae*

PubMed Central

Casutt, Marco S.; Nedielkov, Ruslan; Wendelspiess, Severin; Vossler, Sara; Gerken, Uwe; Murai, Masatoshi; Miyoshi, Hideto; Möller, Heiko M.; Steuber, Julia

2011-01-01

Na+ is the second major coupling ion at membranes after protons, and many pathogenic bacteria use the sodium-motive force to their advantage. A prominent example is Vibrio cholerae, which relies on the Na+-pumping NADH:quinone oxidoreductase (Na+-NQR) as the first complex in its respiratory chain. The Na+-NQR is a multisubunit, membrane-embedded NADH dehydrogenase that oxidizes NADH and reduces quinone to quinol. Existing models describing redox-driven Na+ translocation by the Na+-NQR are based on the assumption that the pump contains four flavins and one FeS cluster. Here we show that the large, peripheral NqrA subunit of the Na+-NQR binds one molecule of ubiquinone-8. Investigations of the dynamic interaction of NqrA with quinones by surface plasmon resonance and saturation transfer difference NMR reveal a high affinity, which is determined by the methoxy groups at the C-2 and C-3 positions of the quinone headgroup. Using photoactivatable quinone derivatives, it is demonstrated that ubiquinone-8 bound to NqrA occupies a functional site. A novel scheme of electron transfer in Na+-NQR is proposed that is initiated by NADH oxidation on subunit NqrF and leads to quinol formation on subunit NqrA. PMID:21885438

Intramolecular electron transport in quinoprotein alcohol dehydrogenase of Acetobacter methanolicus: a redox-titration study

PubMed

Frébortova; Matsushita; Arata; Adachi

1998-01-27

Quinohemoprotein-cytochrome c complex alcohol dehydrogenase (ADH) of acetic acid bacteria consists of three subunits, of which subunit I contains pyrroloquinoline quinone (PQQ) and heme c, and subunit II contains three heme c components. The PQQ and heme c components are believed to be involved in the intramolecular electron transfer from ethanol to ubiquinone. To study the intramolecular electron transfer in ADH of Acetobacter methanolicus, the redox potentials of heme c components were determined with ADH complex and the isolated subunits I and II of A. methanolicus, as well as hybrid ADH consisting of the subunit I/III complex of Gluconobacter suboxydans ADH and subunit II of A. methanolicus ADH. The redox potentials of hemes c in ADH complex were -130, 49, 188, and 188 mV at pH 7.0 and 24, 187, 190, and 255 mV at pH 4.5. In hybrid ADH, one of these heme c components was largely changed in the redox potential. Reduced ADH was fully oxidized with potassium ferricyanide, while ubiquinone oxidized the enzyme partially. The results indicate that electrons extracted from ethanol at PQQ site are transferred to ubiquinone via heme c in subunit I and two of the three hemes c in subunit II. Copyright 1998 Elsevier Science B.V.

Hypothalamic digoxin and hemispheric chemical dominance--relation to the pathogenesis of senile osteoporosis, degenerative osteoarthritis, and spondylosis.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-03-01

The isoprenoid pathway produces three key metabolites: i) digoxin (a membrane sodium-potassium ATPase inhibitor which can regulate intracellular calcium/magnesium ratios), ii) dolichol (which regulates N-glycosylation of proteins), and iii) ubiquinone (a free radical scavenger), all of which are important in bone and joint metabolism. The pathway was assessed in senile osteoporosis, spondylosis, and osteoarthritis. Digoxin could possibly play a role in the genesis of cerebral dominance because it can regulate multiple neurotransmitter systems. The pathway was also assessed in individuals of differing hemispheric dominance for comparison and to find out the role of cerebral dominance in the pathogenesis of these diseases. The plasma/serum-activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone, and tryptophan/tyrosine catabolic patterns, as well as RBC Na(+)-K+ ATPase activity, were measured in the above mentioned groups. The glycoconjugate metabolism, free radical metabolism, and membrane composition were also studied. The pathway was upregulated with increased digoxin synthesis in patients with spondylosis and osteoarthritis. In this group of patients, the glycoconjugate levels and dolichol levels were increased and lysosomal stability reduced. The ubiquinone levels were low and free radicals increased in spondylosis and osteoarthritis. On the other hand, in senile osteoporosis, the isoprenoid pathway was downregulated and digoxin synthesis reduced. The glycoconjugate and dolichol levels were low and lysosomal stability increased. The ubiquinone levels were increased and free radical production increased in senile osteoporosis. The significance of these changes in the pathogenesis of osteoarthritis, spondylosis, and osteoporosis is discussed. The hyperdigoxinemic state is seen in osteoarthritis and spondylosis and in right hemispheric dominance. The hypodigoxinemic state is seen in left hemispheric dominance and senile osteoporosis. Hemispheric dominance plays a crucial role in deciding the predisposition to bone and joint diseases. Right hemispheric chemical dominance predisposes to spondylosis and osteoarthritis. Left hemispheric chemical dominance predisposes to osteoporosis.

Impact of Mutations on the Midpoint Potential of the [4Fe-4S]+1,+2 Cluster and on Catalytic Activity in Electron Transfer Flavoprotein-ubiquinone Oxidoreductase (ETF-QO)†

PubMed Central

Usselman, Robert J.; Fielding, Alistair J.; Frerman, Frank E.; Watmough, Nicholas J.; Eaton, Gareth R.; Eaton, Sandra S.

2011-01-01

Electron transfer flavoprotein - ubiquinone oxidoreductase (ETF-QO) is an iron-sulfur flavoprotein that accepts electrons from electron-transfer flavoprotein (ETF) and reduces ubiquinone from the Q-pool. ETF-QO contains a single [4Fe-4S]2+,1+ cluster and one equivalent of FAD, which are diamagnetic in the isolated oxidized enzyme and can be reduced to paramagnetic forms by enzymatic donors or dithionite. Mutations were introduced by site-directed mutagenesis of amino acids in the vicinity of the iron-sulfur cluster of Rhodobacter sphaeroides ETF-QO. Y501 and T525 are equivalent to Y533 and T558 in the porcine ETF-QO. In the porcine protein, these residues are within hydrogen bonding distance of the Sγ of the cysteine ligands to the iron-sulfur cluster. Y501F, T525A, and Y501F/T525A substitutions were made to determine the effects on midpoint potential, activity, and EPR spectral properties of the cluster. The integrity of the mutated proteins was confirmed by optical spectra, EPR g-values, and spin-lattice relaxation rates, and the cluster to flavin point-dipole distance was determined by relaxation enhancement. Potentiometric titrations were monitored by changes in the CW EPR signals of the cluster and semiquinone. Single mutations decreased the mid-point potentials of the iron-sulfur cluster from +37 mV for wild type to −60 mV for Y501F and T525A and to −128 mV for Y501F/T525A. Lowering the midpoint potential resulted in a decrease in steady-state ubiquinone reductase activity and in ETF semiquinone disproportionation. The decrease in activity demonstrates that reduction of the iron-sulfur cluster is required for activity. There was no detectable effect of the mutations on the flavin midpoint potentials. PMID:18069858

Impact of mutations on the midpoint potential of the [4Fe-4S]+1,+2 cluster and on catalytic activity in electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO).

PubMed

Usselman, Robert J; Fielding, Alistair J; Frerman, Frank E; Watmough, Nicholas J; Eaton, Gareth R; Eaton, Sandra S

2008-01-08

Electron-transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is an iron-sulfur flavoprotein that accepts electrons from electron-transfer flavoprotein (ETF) and reduces ubiquinone from the Q-pool. ETF-QO contains a single [4Fe-4S]2+,1+ cluster and one equivalent of FAD, which are diamagnetic in the isolated oxidized enzyme and can be reduced to paramagnetic forms by enzymatic donors or dithionite. Mutations were introduced by site-directed mutagenesis of amino acids in the vicinity of the iron-sulfur cluster of Rhodobacter sphaeroides ETF-QO. Y501 and T525 are equivalent to Y533 and T558 in the porcine ETF-QO. In the porcine protein, these residues are within hydrogen-bonding distance of the Sgamma of the cysteine ligands to the iron-sulfur cluster. Y501F, T525A, and Y501F/T525A substitutions were made to determine the effects on midpoint potential, activity, and EPR spectral properties of the cluster. The integrity of the mutated proteins was confirmed by optical spectra, EPR g-values, and spin-lattice relaxation rates, and the cluster to flavin point-dipole distance was determined by relaxation enhancement. Potentiometric titrations were monitored by changes in the CW EPR signals of the cluster and semiquinone. Single mutations decreased the midpoint potentials of the iron-sulfur cluster from +37 mV for wild type to -60 mV for Y501F and T525A and to -128 mV for Y501F/T525A. Lowering the midpoint potential resulted in a decrease in steady-state ubiquinone reductase activity and in ETF semiquinone disproportionation. The decrease in activity demonstrates that reduction of the iron-sulfur cluster is required for activity. There was no detectable effect of the mutations on the flavin midpoint potentials.

Kin-selected cooperation without lifetime monogamy: human insights and animal implications.

PubMed

Kramer, Karen L; Russell, Andrew F

2014-11-01

Recent phylogenetic analyses suggest that monogamy precedes the evolution of cooperative breeding involving non-breeding helpers. The rationale: only through monogamy can helper-recipient relatedness coefficients match those of parent-offspring. Given that humans are cooperative breeders, these studies imply a monogamy bottleneck during hominin evolution. However, evidence from multiple sources is not compelling. In reconciliation, we propose that selection against cooperative breeding under alternative mating patterns will be mitigated by: (i) kin discrimination, (ii) reduced birth-intervals, and (iii) constraints on independent breeding, particularly for premature and post-fertile individuals. We suggest that such alternatives require consideration to derive a complete picture of the selection pressures acting on the evolution of cooperative breeding in humans and other animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impacts of extension access and cooperative membership on technology adoption and household welfare.

PubMed

Wossen, Tesfamicheal; Abdoulaye, Tahirou; Alene, Arega; Haile, Mekbib G; Feleke, Shiferaw; Olanrewaju, Adetunji; Manyong, Victor

2017-08-01

This paper examines the impacts of access to extension services and cooperative membership on technology adoption, asset ownership and poverty using household-level data from rural Nigeria. Using different matching techniques and endogenous switching regression approach, we find that both extension access and cooperative membership have a positive and statistically significant effect on technology adoption and household welfare. Moreover, we find that both extension access and cooperative membership have heterogeneous impacts. In particular, we find evidence of a positive selection as the average treatment effects of extension access and cooperative membership are higher for farmers with the highest propensity to access extension and cooperative services. The impact of extension services on poverty reduction and of cooperatives on technology adoption is significantly stronger for smallholders with access to formal credit than for those without access. This implies that expanding rural financial markets can maximize the potential positive impacts of extension and cooperative services on farmers' productivity and welfare.

Time Pressure Increases Cooperation in Competitively Framed Social Dilemmas

PubMed Central

Cone, Jeremy; Rand, David G.

2014-01-01

What makes people willing to pay costs to benefit others? Does such cooperation require effortful self-control, or do automatic, intuitive processes favor cooperation? Time pressure has been shown to increase cooperative behavior in Public Goods Games, implying a predisposition towards cooperation. Consistent with the hypothesis that this predisposition results from the fact that cooperation is typically advantageous outside the lab, it has further been shown that the time pressure effect is undermined by prior experience playing lab games (where selfishness is the more advantageous strategy). Furthermore, a recent study found that time pressure increases cooperation even in a game framed as a competition, suggesting that the time pressure effect is not the result of social norm compliance. Here, we successfully replicate these findings, again observing a positive effect of time pressure on cooperation in a competitively framed game, but not when using the standard cooperative framing. These results suggest that participants' intuitions favor cooperation rather than norm compliance, and also that simply changing the framing of the Public Goods Game is enough to make it appear novel to participants and thus to restore the time pressure effect. PMID:25551386

Time pressure increases cooperation in competitively framed social dilemmas.

PubMed

Cone, Jeremy; Rand, David G

2014-01-01

What makes people willing to pay costs to benefit others? Does such cooperation require effortful self-control, or do automatic, intuitive processes favor cooperation? Time pressure has been shown to increase cooperative behavior in Public Goods Games, implying a predisposition towards cooperation. Consistent with the hypothesis that this predisposition results from the fact that cooperation is typically advantageous outside the lab, it has further been shown that the time pressure effect is undermined by prior experience playing lab games (where selfishness is the more advantageous strategy). Furthermore, a recent study found that time pressure increases cooperation even in a game framed as a competition, suggesting that the time pressure effect is not the result of social norm compliance. Here, we successfully replicate these findings, again observing a positive effect of time pressure on cooperation in a competitively framed game, but not when using the standard cooperative framing. These results suggest that participants' intuitions favor cooperation rather than norm compliance, and also that simply changing the framing of the Public Goods Game is enough to make it appear novel to participants and thus to restore the time pressure effect.

Geranyl diphosphate:4-hydroxybenzoate geranyltransferase from Lithospermum erythrorhizon. Cloning and characterization of a ket enzyme in shikonin biosynthesis.

PubMed

Yazaki, Kazufumi; Kunihisa, Miyuki; Fujisaki, Takahiro; Sato, Fumihiko

2002-02-22

Two cDNAs encoding geranyl diphosphate:4-hy- droxybenzoate 3-geranyltransferase were isolated from Lithospermum erythrorhizon by nested PCR using the conserved amino acid sequences among polyprenyl- transferases for ubiquinone biosynthesis. They were functionally expressed in yeast COQ2 disruptant and showed a strict substrate specificity for geranyl diphosphate as the prenyl donor, in contrast to ubiquinone biosynthetic enzymes, suggesting that they are involved in the biosynthesis of shikonin, a naphthoquinone secondary metabolite. Regulation of their expression by various culture conditions coincided with that of geranyltransferase activity and the secondary metabolites biosynthesized via this enzyme. This is the first established plant prenyltransferase that transfers the prenyl chain to an aromatic substrate.

Screening of detergents for solubilization, purification and crystallization of membrane proteins: a case study on succinate:ubiquinone oxidoreductase from Escherichia coli

PubMed Central

Shimizu, Hironari; Nihei, Coh-ichi; Inaoka, Daniel Ken; Mogi, Tatushi; Kita, Kiyoshi; Harada, Shigeharu

2008-01-01

Succinate:ubiquinone oxidoreductase (SQR) was solubilized and purified from Escherichia coli inner membranes using several different detergents. The number of phospholipid molecules bound to the SQR molecule varied greatly depending on the detergent combination that was used for the solubilization and purification. Crystallization conditions were screened for SQR that had been solubilized and purified using 2.5%(w/v) sucrose monolaurate and 0.5%(w/v) Lubrol PX, respectively, and two different crystal forms were obtained in the presence of detergent mixtures composed of n-alkyl-oligoethylene glycol monoether and n-alkyl-maltoside. Crystallization took place before detergent phase separation occurred and the type of detergent mixture affected the crystal form. PMID:18765923

Screening of detergents for solubilization, purification and crystallization of membrane proteins: a case study on succinate:ubiquinone oxidoreductase from Escherichia coli.

PubMed

Shimizu, Hironari; Nihei, Coh-ichi; Inaoka, Daniel Ken; Mogi, Tatushi; Kita, Kiyoshi; Harada, Shigeharu

2008-09-01

Succinate:ubiquinone oxidoreductase (SQR) was solubilized and purified from Escherichia coli inner membranes using several different detergents. The number of phospholipid molecules bound to the SQR molecule varied greatly depending on the detergent combination that was used for the solubilization and purification. Crystallization conditions were screened for SQR that had been solubilized and purified using 2.5%(w/v) sucrose monolaurate and 0.5%(w/v) Lubrol PX, respectively, and two different crystal forms were obtained in the presence of detergent mixtures composed of n-alkyl-oligoethylene glycol monoether and n-alkyl-maltoside. Crystallization took place before detergent phase separation occurred and the type of detergent mixture affected the crystal form.

Redox potential tuning through differential quinone binding in the photosynthetic reaction center of Rhodobacter sphaeroides

DOE PAGES

Vermaas, Josh V.; Taguchi, Alexander T.; Dikanov, Sergei A.; ...

2015-03-03

Ubiquinone forms an integral part of the electron transport chain in cellular respiration and photosynthesis across a vast number of organisms. Prior experimental results have shown that the photosynthetic reaction center (RC) from Rhodobacter sphaeroides is only fully functional with a limited set of methoxy-bearing quinones, suggesting that specific interactions with this substituent are required to drive electron transport and the formation of quinol. The nature of these interactions has yet to be determined. Through parameterization of a CHARMM-compatible quinone force field and subsequent molecular dynamics simulations of the quinone-bound RC, in this paper we have investigated and characterized themore » interactions of the protein with the quinones in the Q A and Q B sites using both equilibrium simulation and thermodynamic integration. In particular, we identify a specific interaction between the 2-methoxy group of ubiquinone in the Q B site and the amide nitrogen of GlyL225 that we implicate in locking the orientation of the 2-methoxy group, thereby tuning the redox potential difference between the quinones occupying the Q A and Q B sites. Finally, disruption of this interaction leads to weaker binding in a ubiquinone analogue that lacks a 2-methoxy group, a finding supported by reverse electron transfer electron paramagnetic resonance experiments of the Q A–Q B– biradical and competitive binding assays.« less

Hypothalamic digoxin, hemispheric chemical dominance, and sarcoidosis.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-11-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with systemic sarcoidosis. All l5 patients with sarcoidosis were right-handed/left hemispheric dominant by the dichotic listening test. The pathway was also studied in normal right hemispheric, left hemispheric, and bihemispheric dominant individuals for comparison to find out the role of hemispheric dominance in the pathogenesis of sarcoidosis. In patients with sarcoidosis there was elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these patients. The neurotransmitter/digoxin-mediated increased intra cellular calcium induced immune activation, ubiquinone deficiency-related mitochondrial dysfunction/free radical generation, and increased dolichol-related altered glycoconjugate metabolism/endogenous self-glycoprotein antigen generation are crucial to the pathogenesis of sarcoidosis. The biochemical patterns obtained in sarcoidosis are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with sarcoidosis were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Sarcoidosis occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Redox potential tuning through differential quinone binding in the photosynthetic reaction center of Rhodobacter sphaeroides.

PubMed

Vermaas, Josh V; Taguchi, Alexander T; Dikanov, Sergei A; Wraight, Colin A; Tajkhorshid, Emad

2015-03-31

Ubiquinone forms an integral part of the electron transport chain in cellular respiration and photosynthesis across a vast number of organisms. Prior experimental results have shown that the photosynthetic reaction center (RC) from Rhodobacter sphaeroides is only fully functional with a limited set of methoxy-bearing quinones, suggesting that specific interactions with this substituent are required to drive electron transport and the formation of quinol. The nature of these interactions has yet to be determined. Through parameterization of a CHARMM-compatible quinone force field and subsequent molecular dynamics simulations of the quinone-bound RC, we have investigated and characterized the interactions of the protein with the quinones in the Q(A) and Q(B) sites using both equilibrium simulation and thermodynamic integration. In particular, we identify a specific interaction between the 2-methoxy group of ubiquinone in the Q(B) site and the amide nitrogen of GlyL225 that we implicate in locking the orientation of the 2-methoxy group, thereby tuning the redox potential difference between the quinones occupying the Q(A) and Q(B) sites. Disruption of this interaction leads to weaker binding in a ubiquinone analogue that lacks a 2-methoxy group, a finding supported by reverse electron transfer electron paramagnetic resonance experiments of the Q(A)⁻Q(B)⁻ biradical and competitive binding assays.

Identification of the ubiquinone-binding domain in the disulfide catalyst disulfide bond protein B.

PubMed

Xie, Tong; Yu, Linda; Bader, Martin W; Bardwell, James C A; Yu, Chang-An

2002-01-18

Disulfide bond (Dsb) formation is catalyzed in the periplasm of prokaryotes by the Dsb proteins. DsbB, a key enzyme in this process, generates disulfides de novo by using the oxidizing power of quinones. To explore the mechanism of this newly described enzymatic activity, we decided to study the ubiquinone-protein interaction and identify the ubiquinone-binding domain in DsbB by cross-linking to photoactivatable quinone analogues. When purified Escherichia coli DsbB was incubated with an azidoubiquinone derivative, 3-azido-2-methyl-5-[(3)H]methoxy-6-decyl-1,4-benzoquinone ([(3)H]azido-Q), and illuminated with long wavelength UV light, the decrease in enzymatic activity correlated with the amount of 3-azido-2-methyl-5-methoxy-6-decyl-1,4-benzoquinone (azido-Q) incorporated into the protein. One azido-Q-linked peptide with a retention time of 33.5 min was obtained by high performance liquid chromatography of the V8 digest of [(3)H]azido-Q-labeled DsbB. This peptide has a partial NH(2)-terminal amino acid sequence of NH(2)-HTMLQLY corresponding to residues 91-97. This sequence occurs in the second periplasmic domain of the inner membrane protein DsbB in a loop connecting transmembrane helices 3 and 4. We propose that the quinone-binding site is within or very near to this sequence.

Group Size Effect on Cooperation in One-Shot Social Dilemmas II: Curvilinear Effect.

PubMed

Capraro, Valerio; Barcelo, Hélène

2015-01-01

In a world in which many pressing global issues require large scale cooperation, understanding the group size effect on cooperative behavior is a topic of central importance. Yet, the nature of this effect remains largely unknown, with lab experiments insisting that it is either positive or negative or null, and field experiments suggesting that it is instead curvilinear. Here we shed light on this apparent contradiction by considering a novel class of public goods games inspired to the realistic scenario in which the natural output limits of the public good imply that the benefit of cooperation increases fast for early contributions and then decelerates. We report on a large lab experiment providing evidence that, in this case, group size has a curvilinear effect on cooperation, according to which intermediate-size groups cooperate more than smaller groups and more than larger groups. In doing so, our findings help fill the gap between lab experiments and field experiments and suggest concrete ways to promote large scale cooperation among people.

Primary coenzyme Q10 (CoQ 10) deficiencies and related nephropathies.

PubMed

Ozaltin, Fatih

2014-06-01

Oxidative phosphorylation (OXPHOS) is a metabolic pathway that uses energy released by the oxidation of nutrients to generate adenosine triphosphate (ATP). Coenzyme Q10 (CoQ10), also known as ubiquinone, plays an essential role in the human body not only by generating ATP in the mitochondrial respiratory chain but also by providing protection from reactive oxygen species (ROS) and functioning in the activation of many mitochondrial dehydrogenases and enzymes required in pyrimidine nucleoside biosynthesis. The presentations of primary CoQ10 deficiencies caused by genetic mutations are very heterogeneous. The phenotypes related to energy depletion or ROS production may depend on the content of CoQ10 in the cell, which is determined by the severity of the mutation. Primary CoQ10 deficiency is unique among mitochondrial disorders because early supplementation with CoQ10 can prevent the onset of neurological and renal manifestations. In this review I summarize primary CoQ10 deficiencies caused by various genetic abnormalities, emphasizing its nephropathic form.

[Ethics and esthetics in international cooperation].

PubMed

de Aranzabal Agudo, Maite; Hermana Tezanos, María Teresa

2011-09-01

Although more optimistic, the new report by the World Health Organization (WHO) continues to cast horrifying statistics on inequalities, not only in life expectancy but in many areas. Many Non-Governmental Organisations (NGOs) related to medicine seek to address this imbalance. To cooperate does not in any way appeal to the call of sentimentality. Cooperation moves money and is accountable. It requires a strong background in both professional and human values. It requires research on vaccines and diseases foreign to our society. To cooperate means "operate with" local counterparts, according to their needs and global health project. And finally, cooperation implies the demand for change in certain aspects of the global economic order. We reflect on these questions and describe the different ethical frameworks for the population and NGOs. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Characterization of the human SDHD gene encoding the small subunit of cytochrome b (cybS) in mitochondrial succinate-ubiquinone oxidoreductase.

PubMed

Hirawake, H; Taniwaki, M; Tamura, A; Amino, H; Tomitsuka, E; Kita, K

1999-08-04

We have mapped large (cybL) and small (cybS) subunits of cytochrome b in the succinate-ubiquinone oxidoreductase (complex II) of human mitochondria to chromosome 1q21 and 11q23, respectively (H. Hirawake et al., Cytogenet. Cell Genet. 79 (1997) 132-138). In the present study, the human SDHD gene encoding cybS was cloned and characterized. The gene comprises four exons and three introns extending over 19 kb. Sequence analysis of the 5' promoter region showed several motifs for the binding of transcription factors including nuclear respiratory factors NRF-1 and NRF-2 at positions -137 and -104, respectively. In addition to this gene, six pseudogenes of cybS were isolated and mapped on the chromosome.

Systematic study of the genus Acetobacter with descriptions of Acetobacter indonesiensis sp. nov., Acetobacter tropicalis sp. nov., Acetobacter orleanensis (Henneberg 1906) comb. nov., Acetobacter lovaniensis (Frateur 1950) comb. nov., and Acetobacter estunensis (Carr 1958) comb. nov.

PubMed

Lisdiyanti, Puspita; Kawasaki, Hiroko; Seki, Tatsuji; Yamada, Yuzo; Uchimura, Tai; Komagata, Kazuo

2000-06-01

Thirty-one Acetobacter strains obtained from culture collections and 45 Acetobacter strains isolated from Indonesian sources were investigated for their phenotypic characteristics, ubiquinone systems, DNA base compositions, and levels of DNA-DNA relatedness. Of 31 reference strains, six showed the presence of ubiquinone 10 (Q-10). These strains were eliminated from the genus Acetobacter. The other 25 reference strains and 45 Indonesian isolates were subjected to a systematic study and separated into 8 distinct groups on the basis of DNA-DNA relatedness. The known species, Acetobacter aceti, A. pasteurianus, and A. peroxydans are retained for three of these groups. New combinations, A. orleanensis (Henneberg 1906) comb. nov., A. lovaniensis (Frateur 1950) comb. nov., and A. estunensis (Carr 1958) comb. nov. are proposed for three other groups. Two new species, A. indonesiensis sp. nov. and A. tropicalis sp. nov. are proposed for the remaining two. No Indonesian isolates were identified as A. aceti, A. estunensis, and A. peroxydans. Phylogenetic analysis on the basis of 16S rDNA sequences was carried out for representative strains from each of the groups. This supported that the eight species belonged to the genus Acetobacter. Several strains previously assigned to the species of A. aceti and A. pasteurianus were scattered over the different species. It is evident that the value of DNA-DNA relatedness between strains comprising a new species should be determined for the establishment of the species. Thus current bacterial species without data of DNA-DNA relatedness should be reexamined for the stability of bacterial nomenclature.

Effects of dietary lipid, vitamins and minerals on total amounts and redox status of glutathione and ubiquinone in tissues of Atlantic salmon (Salmo salar): a multivariate approach.

PubMed

Hamre, Kristin; Torstensen, Bente E; Maage, Amund; Waagbø, Rune; Berge, Rolf K; Albrektsen, Sissel

2010-10-01

The hypothesis of the present study was that Atlantic salmon (Salmo salar) would respond to large variations in supplementation of dietary pro- and antioxidants, and marine lipid, with adjustment of the endogenously synthesised antioxidants, glutathione (GSH) and ubiquinone (UQ). An experiment with 2(7-3) reduced factorial design (the number of cases reduced systematically from 2(7) (full design) to 2(4) (reduced design)) was conducted, where vitamins, minerals and lipid were supplemented in the diet at high and low levels. For the vitamins and minerals the high levels were chosen to be just below anticipated toxic levels and the low levels were just above the requirement (vitamin C, 30 and 1000 mg/kg; vitamin E, 70 and 430 mg/kg; Fe, 70 and 1200 mg/kg; Cu, 8 and 110 mg/kg; Mn, 12 and 200 mg/kg). For astaxanthin, the dietary levels were 10 and 50 mg/kg and for lipid, 150 and 330 g/kg. The experiment was started with post-smolts (148 (sd 17 g)) and lasted for 5 months. The only effect on GSH was a minor increase ( < 10 %) in total concentration in the liver in response to high dietary lipid. GSH redox state was not affected. UQ responded to dietary lipid, astaxanthin and vitamin E, both with regard to total concentration and redox state. Except for an effect of Fe on plasma GSH, the trace elements and vitamin C had no effect on tissue levels and oxidation state of GSH and UQ. This shows that the endogenous redox state is quite robust with regard to variation of dietary pro- and antioxidants in Atlantic salmon.

Spatial structure favors cooperative behavior in the snowdrift game with multiple interactive dynamics

NASA Astrophysics Data System (ADS)

Su, Qi; Li, Aming; Wang, Long

2017-02-01

Spatial reciprocity is generally regarded as a positive rule facilitating the evolution of cooperation. However, a few recent studies show that, in the snowdrift game, spatial structure still could be detrimental to cooperation. Here we propose a model of multiple interactive dynamics, where each individual can cooperate and defect simultaneously against different neighbors. We realize individuals' multiple interactions simply by endowing them with strategies relevant to probabilities, and every one decides to cooperate or defect with a probability. With multiple interactive dynamics, the cooperation level in square lattices is higher than that in the well-mixed case for a wide range of cost-to-benefit ratio r, implying that spatial structure favors cooperative behavior in the snowdrift game. Moreover, in square lattices, the most favorable strategy follows a simple relation of r, which confers theoretically the average evolutionary frequency of cooperative behavior. We further extend our study to various homogeneous and heterogeneous networks, which demonstrates the robustness of our results. Here multiple interactive dynamics stabilizes the positive role of spatial structure on the evolution of cooperation and individuals' distinct reactions to different neighbors can be a new line in understanding the emergence of cooperation.

Indirect reciprocity provides a narrow margin of efficiency for costly punishment

PubMed Central

Iwasa, Yoh; Nowak, Martin A.

2008-01-01

Indirect reciprocity1-5 is a key mechanism for the evolution of human cooperation. Our behavior toward other people depends not only on what they have done to us, but also on what they have done to others. Indirect reciprocity works via reputation5-17. The standard model of indirect reciprocity offers a binary choice: people can either cooperate or defect. Cooperation implies a cost for the donor and a benefit for the recipient. Defection has no cost and yields no benefit. Currently there is considerable interest in studying the effect of costly (or altruistic) punishment on human behavior18-25. Punishment implies a cost for the punished person. Costly punishment means that the punisher also pays a cost. It has been suggested that costly punishment between individuals can promote cooperation. Here we study the role of costly punishment in an explicit model of indirect reciprocity. We analyze all social norms, which depend on the action of the donor and the reputation of the recipient. We allow errors in assigning reputation and study gossip as a mechanism for establishing coherence. We characterize all strategies that allow the evolutionary stability of cooperation. Some of those strategies use costly punishment, while others do not. We find that punishment strategies typically reduce the average payoff of the population. Consequently, there is only a small parameter region where costly punishment leads to an efficient equilibrium. In most cases, the population does better by not using costly punishment. The efficient strategy for indirect reciprocity is to withhold help for defectors rather than punish them. PMID:19122640

Mechanisms of cooperation and competition of two-species transport in narrow nanochannels

NASA Astrophysics Data System (ADS)

Bauer, Wolfgang Rudolf

2017-12-01

Flow of particles of two different species through a narrow channel with solely two discrete spatial positions is analyzed with respect to the species' capability to cooperate or compete for transport. The origin of the latter arises from particle-channel and interparticle interactions within the channel, i.e., blocking the position of a particle, and its interaction with its neighbors in the channel. The variety of occupation options within the channel defines the state space. The transition dynamics within is considered as a continuous Markov process, which, in contrast to mean-field approaches, conserves explicitly spatial correlations. A strong repulsive interaction between particles of the same kind and a very attractive empty channel imply a strong entanglement of transport of both species. In the limiting case of perfect coupling, flows in state space are restricted to a cyclic subspace, where they become all equivalent in the steady state. In particular, this implies equal particle flows of the two species. Entanglement of transport implies that the species mutually exert entropic forces on each other. For parallel directed concentration gradients this implies that the species' ability to cooperate increases with the degree of entanglement. Thus, the gradient of one species reciprocally induces a higher flow of the other species when compared to that in its absence. The opposite holds for antiparallel gradients where species mutually hamper their transport. For a sufficient strong coupling, the species under the influence of the stronger concentration gradient drives the other against its gradient, i.e., the positive mixing entropy production of the driving species becomes the motor for the negative mixing entropy production of the driven one. The degree of effectiveness by which negative entropy production emerges at the cost of positive entropy production increases with the coupling strength. This becomes evident from location and connectivity of the sources of entropy production in state space.

Effects of inhomogeneous activity of players and noise on cooperation in spatial public goods games

NASA Astrophysics Data System (ADS)

Guan, Jian-Yue; Wu, Zhi-Xi; Wang, Ying-Hai

2007-11-01

We study the public goods game in the noisy case by considering the players with inhomogeneous activity of teaching on a square lattice. It is shown that the introduction of the inhomogeneous activity of teaching the players can remarkably promote cooperation. By investigating the effects of noise on cooperative behavior in detail, we find that the variation of cooperator density ρC with the noise parameter κ displays several different behaviors: ρC monotonically increases (decreases) with κ ; ρC first increases (decreases) with κ and then it decreases (increases) monotonically after reaching its maximum (minimum) value, which depends on the amount of the multiplication factor r , on whether the system is homogeneous or inhomogeneous, and on whether the adopted updating is synchronous or asynchronous. These results imply that the noise plays an important and nontrivial role in the evolution of cooperation.

Nudging Cooperation in a Crowd Experiment

PubMed Central

Niella, Tamara; Stier-Moses, Nicolás; Sigman, Mariano

2016-01-01

We examine the hypothesis that driven by a competition heuristic, people don't even reflect or consider whether a cooperation strategy may be better. As a paradigmatic example of this behavior we propose the zero-sum game fallacy, according to which people believe that resources are fixed even when they are not. We demonstrate that people only cooperate if the competitive heuristic is explicitly overridden in an experiment in which participants play two rounds of a game in which competition is suboptimal. The observed spontaneous behavior for most players was to compete. Then participants were explicitly reminded that the competing strategy may not be optimal. This minor intervention boosted cooperation, implying that competition does not result from lack of trust or willingness to cooperate but instead from the inability to inhibit the competition bias. This activity was performed in a controlled laboratory setting and also as a crowd experiment. Understanding the psychological underpinnings of these behaviors may help us improve cooperation and thus may have vast practical consequences to our society. PMID:26797425

Nudging Cooperation in a Crowd Experiment.

PubMed

Niella, Tamara; Stier-Moses, Nicolás; Sigman, Mariano

2016-01-01

We examine the hypothesis that driven by a competition heuristic, people don't even reflect or consider whether a cooperation strategy may be better. As a paradigmatic example of this behavior we propose the zero-sum game fallacy, according to which people believe that resources are fixed even when they are not. We demonstrate that people only cooperate if the competitive heuristic is explicitly overridden in an experiment in which participants play two rounds of a game in which competition is suboptimal. The observed spontaneous behavior for most players was to compete. Then participants were explicitly reminded that the competing strategy may not be optimal. This minor intervention boosted cooperation, implying that competition does not result from lack of trust or willingness to cooperate but instead from the inability to inhibit the competition bias. This activity was performed in a controlled laboratory setting and also as a crowd experiment. Understanding the psychological underpinnings of these behaviors may help us improve cooperation and thus may have vast practical consequences to our society.

Hypothalamic digoxin, hemispheric chemical dominance, and interstitial lung disease.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-10-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with idiopathic pulmonary fibrosis and in individuals of differing hemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of idiopathic pulmonary fibrosis. All 15 cases of interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. The isoprenoidal metabolites--digoxin, dolichol, and ubiquinone, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, tyrosine/tryptophan catabolic patterns, free radical metabolism, glycoconjugate metabolism, and RBC membrane composition--were assessed in idiopathic pulmonary fibrosis as well as in individuals with differing hemispheric dominance. In patients with idiopathic pulmonary fibrosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in patients with idiopathic pulmonary fibrosis. Isoprenoid pathway dysfunction con tributes to the pathogenesis of idiopathic pulmonary fibrosis. The biochemical patterns obtained in interstitial lung disease are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. However, all the patients with interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Interstitial lung disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Diagnostic value of succinate ubiquinone reductase activity in the identification of patients with mitochondrial DNA depletion.

PubMed

Hargreaves, P; Rahman, S; Guthrie, P; Taanman, J W; Leonard, J V; Land, J M; Heales, S J R

2002-02-01

Mitochondrial DNA (mtDNA) depletion syndrome (McKusick 251880) is characterized by a progressive quantitative loss of mtDNA resulting in severe mitochondrial dysfunction. A diagnosis of mtDNA depletion can only be confirmed after Southern blot analysis of affected tissue. Only a limited number of centres have the facilities to offer this service, and this is frequently on an irregular basis. There is therefore a need for a test that can refine sample selection as well as complementing the molecular analysis. In this study we compared the activities of the nuclear-encoded succinate ubiquinone reductase (complex II) to the activities of the combined mitochondrial and nuclear-encoded mitochondrial electron transport chain (ETC) complexes; NADH:ubiquinone reductase (complex I), ubiquinol-cytochrome-c reductase (complex III), and cytochrome-c oxidase (complex IV), in skeletal muscle biopsies from 7 patients with confirmed mtDNA depletion. In one patient there was no evidence of an ETC defect. However, the remaining 6 patients exhibited reduced complex I and IV activities. Five of these patients also displayed reduced complex II-III (succinate:cytochrome-c reductase) activity. Individual measurement of complex II and complex III activities demonstrated normal levels of complex II activity compared to complex III, which was reduced in the 5 biopsies assayed. These findings suggest a possible diagnostic value for the detection of normal levels of complex II activity in conjunction with reduced complex I, III and IV activity in the identification of likely candidates for mtDNA depletion syndrome

UbiX is a flavin prenyltransferase required for bacterial ubiquinone biosynthesis

PubMed Central

White, Mark D.; Payne, Karl A.P.; Fisher, Karl; Marshall, Stephen A.; Parker, David; Rattray, Nicholas J.W.; Trivedi, Drupad K.; Goodacre, Royston; Rigby, Stephen E.J.; Scrutton, Nigel S.; Hay, Sam; Leys, David

2016-01-01

Ubiquinone, or coenzyme Q, is a ubiquitous lipid-soluble redox cofactor that is an essential component of electron transfer chains1. Eleven genes have been implicated in bacterial ubiquinone biosynthesis, including ubiX and ubiD, which are responsible for decarboxylation of the 3-octaprenyl-4-hydroxybenzoate precursor2. Despite structural and biochemical characterization of UbiX as an FMN-binding protein, no decarboxylase activity has been detected3–4. We report here that UbiX produces a novel flavin-derived cofactor required for the decarboxylase activity of UbiD5. UbiX acts as a flavin prenyltransferase, linking a dimethylallyl moiety to the flavin N5 and C6 atoms. This adds a fourth non-aromatic ring to the flavin isoalloxazine group. In contrast to other prenyltransferases6–7, UbiX is metal-independent and requires dimethylallyl-monophosphate as substrate. Kinetic crystallography reveals that the prenyl transferase mechanism of UbiX resembles that of the terpene synthases8. The active site environment is dominated by π-systems, which assist phosphate-C1’ bond breakage following FMN reduction, leading to formation of the N5-C1’ bond. UbiX then acts as a chaperone for adduct reorientation, via transient carbocation species, leading ultimately to formation of the dimethylallyl C3’-C6 bond. The study establishes the mechanism for formation of a new flavin-derived cofactor, extending both flavin and terpenoid biochemical repertoire. PMID:26083743

Coevolutionary, coexisting learning and teaching agents model for prisoner’s dilemma games enhancing cooperation with assortative heterogeneous networks

NASA Astrophysics Data System (ADS)

Tanimoto, Jun

2013-07-01

Unlike other natural network systems, assortativity can be observed in most human social networks, although it has been reported that a social dilemma situation represented by the prisoner’s dilemma favors dissortativity to enhance cooperation. We established a new coevolutionary model for both agents’ strategy and network topology, where teaching and learning agents coexist. Remarkably, this model enables agents’ enhancing cooperation more than a learners-only model on a time-frozen scale-free network and produces an underlying assortative network with a fair degree of power-law distribution. The model may imply how and why assortative networks are adaptive in human society.

Environmental stability and the evolution of cooperative breeding in hornbills

PubMed Central

Gonzalez, Juan-Carlos T.; Sheldon, Ben C.; Tobias, Joseph A.

2013-01-01

Reproductive cooperation in social animals has been the focus of intensive research, yet the role of environmental factors in promoting such cooperation remains uncertain. A recent global analysis suggested that cooperative breeding in birds is a ‘bet-hedging’ strategy associated with climatic uncertainty, but it is unclear whether this mechanism applies generally or is restricted to the insectivorous passerines that predominate as cooperative breeders at the global scale. Here, we use a phylogenetic framework to assess the effect of climate on the evolution of cooperation in hornbills (Bucerotidae), an avian family characterized by frugivory and carnivory. We show that, in contrast to the global pattern, cooperative reproduction is positively associated with both inter- and intra-annual climatic stability. This reversed relationship implies that hornbills are relatively insensitive to climatic fluctuations, perhaps because of their dietary niche or increased body mass, both of which may remove the need for bet-hedging. We conclude that the relationship between climatic variability and cooperative breeding is inconsistent across taxa, and potentially mediated by life-history variation. These findings help to explain the mixed results of previous studies and highlight the likely shortcomings of global datasets inherently biased towards particular categories. PMID:23926149

Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency.

PubMed

Sondheimer, Neal; Hewson, Stacy; Cameron, Jessie M; Somers, Gino R; Broadbent, Jane Dunning; Ziosi, Marcello; Quinzii, Catarina Maria; Naini, Ali B

2017-09-01

Coenzyme Q 10 (CoQ 10 ) or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ 10 synthesis are usually associated with the impaired function of CoQ 10 -dependent complexes I, II and III. The recessively transmitted CoQ 10 deficiency has been associated with a number of phenotypically and genetically heterogeneous groups of disorders manifesting at variable age of onset. The infantile, multisystemic presentation is usually caused by mutations in genes directly involved in CoQ 10 biosynthesis. To date, mutations in COQ1 ( PDSS1 and PDSS2 ), COQ2 , COQ4 , COQ6 , COQ7 , COQ8A / ADCK3 , COQ8B/ADCK4 , and COQ9 genes have been identified in patients with primary form of CoQ 10 deficiency. Here we report novel mutations in the COQ4 gene, which were identified in an infant with profound mitochondrial disease presenting with perinatal seizures, hypertrophic cardiomyopathy and severe muscle CoQ 10 deficiency.

Mitochondrial Ubiquinone Homologues, Superoxide Radical Generation, and Longevity in Different Mammalian Species*

PubMed Central

Lass, Achim; Agarwal, Sanjiv; Sohal, Rajindar S.

2010-01-01

Rates of mitochondrial superoxide anion radical ( O2·¯) generation are known to be inversely correlated with the maximum life span potential of different mammalian species. The objective of this study was to understand the possible mechanism(s) underlying such variations in the rate of O2·¯ generation. The hypothesis that the relative amounts of the ubiquinones or coenzyme Q (CoQ) homologues, CoQ9 and CoQ10, are related with the rate of O2·¯ generation was tested. A comparison of nine different mammalian species, namely mouse, rat, guinea pig, rabbit, pig, goat, sheep, cow, and horse, which vary from 3.5 to 46 years in their maximum longevity, indicated that the rate of O2·¯ generation in cardiac submitochondrial particles (SMPs) was directly related to the relative amount of CoQ9 and inversely related to the amount of CoQ10, extractable from their cardiac mitochondria. To directly test the relationship between CoQ homologues and the rate of O2·¯ generation, rat heart SMPs, naturally containing mainly CoQ9 and cow heart SMPs, with high natural CoQ10 content, were chosen for depletion/reconstitution experiments. Repeated extractions of rat heart SMPs with pentane exponentially depleted both CoQ homologues while the corresponding rates of O2·¯ generation and oxygen consumption were lowered linearly. Reconstitution of both rat and cow heart SMPs with different amounts of CoQ9 or CoQ10 caused an initial increase in the rates of O2·¯ generation, followed by a plateau at high concentrations. Within the physiological range of CoQ concentrations, there were no differences in the rates of O2·¯ generation between SMPs reconstituted with CoQ9 or CoQ10. Only at concentrations that were considerably higher than the physiological level, the SMPs reconstituted with CoQ9 exhibited higher rates of O2·¯ generation than those obtained with CoQ10. These in vitro findings do not support the hypothesis that differences in the distribution of CoQ homologues are responsible for the variations in the rates of mitochondrial O2·¯ generation in different mammalian species. PMID:9235911

Cooperative motion of intrinsic and actuated semiflexible swimmers

NASA Astrophysics Data System (ADS)

Llopis, I.; Pagonabarraga, I.; Cosentino Lagomarsino, M.; Lowe, C. P.

2013-03-01

We examine the phenomenon of hydrodynamic-induced cooperativity for pairs of flagellated micro-organism swimmers, of which spermatozoa cells are an example. We consider semiflexible swimmers, where inextensible filaments are driven by an internal intrinsic force and torque-free mechanism (intrinsic swimmers). The velocity gain for swimming cooperatively, which depends on both the geometry and the driving, develops as a result of the near-field coupling of bending and hydrodynamic stresses. We identify the regimes where hydrodynamic cooperativity is advantageous and quantify the change in efficiency. When the filaments' axes are parallel, hydrodynamic interaction induces a directional instability that causes semiflexible swimmers that profit from swimming together to move apart from each other. Biologically, this implies that flagella need to select different synchronized collective states and to compensate for directional instabilities (e.g., by binding) in order to profit from swimming together. By analyzing the cooperative motion of pairs of externally actuated filaments, we assess the impact that stress distribution along the filaments has on their collective displacements.

Functional characterization of LePGT1, a membrane-bound prenyltransferase involved in the geranylation of p-hydroxybenzoic acid.

PubMed

Ohara, Kazuaki; Muroya, Ayumu; Fukushima, Nobuhiro; Yazaki, Kazufumi

2009-06-26

The AS-PT (aromatic substrate prenyltransferase) family plays a critical role in the biosynthesis of important quinone compounds such as ubiquinone and plastoquinone, although biochemical characterizations of AS-PTs have rarely been carried out because most members are membrane-bound enzymes with multiple transmembrane alpha-helices. PPTs [PHB (p-hydroxybenzoic acid) prenyltransferases] are a large subfamily of AS-PTs involved in ubiquinone and naphthoquinone biosynthesis. LePGT1 [Lithospermum erythrorhizon PHB geranyltransferase] is the regulatory enzyme for the biosynthesis of shikonin, a naphthoquinone pigment, and was utilized in the present study as a representative of membrane-type AS-PTs to clarify the function of this enzyme family at the molecular level. Site-directed mutagenesis of LePGT1 with a yeast expression system indicated three out of six conserved aspartate residues to be critical to the enzymatic activity. A detailed kinetic analysis of mutant enzymes revealed the amino acid residues responsible for substrate binding were also identified. Contrary to ubiquinone biosynthetic PPTs, such as UBIA in Escherichia coli which accepts many prenyl substrates of different chain lengths, LePGT1 can utilize only geranyl diphosphate as its prenyl substrate. Thus the substrate specificity was analysed using chimeric enzymes derived from LePGT1 and UBIA. In vitro and in vivo analyses of the chimeras suggested that the determinant region for this specificity was within 130 amino acids of the N-terminal. A 3D (three-dimensional) molecular model of the substrate-binding site consistent with these biochemical findings was generated.

Detergent-dependent kinetics of truncated Plasmodium falciparum dihydroorotate dehydrogenase.

PubMed

Malmquist, Nicholas A; Baldwin, Jeffrey; Phillips, Margaret A

2007-04-27

The survival of the malaria parasite Plasmodium falciparum is dependent upon the de novo biosynthesis of pyrimidines. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the fourth step in this pathway in an FMN-dependent reaction. The full-length enzyme is associated with the inner mitochondrial membrane, where ubiquinone (CoQ) serves as the terminal electron acceptor. The lipophilic nature of the co-substrate suggests that electron transfer to CoQ occurs at the two-dimensional lipid-solution interface. Here we show that PfDHODH associates with liposomes even in the absence of the N-terminal transmembrane-spanning domain. The association of a series of ubiquinone substrates with detergent micelles was studied by isothermal titration calorimetry, and the data reveal that CoQ analogs with long decyl (CoQ(D)) or geranyl (CoQ(2)) tails partition into detergent micelles, whereas that with a short prenyl tail (CoQ(1)) remains in solution. PfDHODH-catalyzed reduction of CoQ(D) and CoQ(2), but not CoQ(1), is stimulated as detergent concentrations (Tween 80 or Triton X-100) are increased up to their critical micelle concentrations, beyond which activity declines. Steady-state kinetic data acquired for the reaction with CoQ(D) and CoQ(2) in substrate-detergent mixed micelles fit well to a surface dilution kinetic model. In contrast, the data for CoQ(1) as a substrate were well described by solution steady-state kinetics. Our results suggest that the partitioning of lipophilic ubiquinone analogues into detergent micelles needs to be an important consideration in the kinetic analysis of enzymes that utilize these substrates.

All three quinone species play distinct roles in ensuring optimal growth under aerobic and fermentative conditions in E. coli K12

PubMed Central

Nitzschke, Annika

2018-01-01

The electron transport chain of E. coli contains three different quinone species, ubiquinone (UQ), menaquinone (MK) and demethylmenaquinone (DMK). The content and ratio of the different quinone species vary depending on the external conditions. To study the function of the different quinone species in more detail, strains with deletions preventing UQ synthesis, as well as MK and/or DMK synthesis were cultured under aerobic and anaerobic conditions. The strains were characterized with respect to growth and product synthesis. As quinones are also involved in the control of ArcB/A activity, we analyzed the phosphorylation state of the response regulator as well as the expression of selected genes.The data show reduced aerobic growth coupled to lactate production in the mutants defective in ubiquinone synthesis. This confirms the current assumption that ubiquinone is the main quinone under aerobic growth conditions. In the UQ mutant strains the amount of MK and DMK is significantly elevated. The strain synthesizing only DMK is less affected in growth than the strain synthesizing MK as well as DMK. An inhibitory effect of MK on aerobic growth due to increased oxidative stress is postulated.Under fermentative growth conditions the mutant synthesizing only UQ is severely impaired in growth. Obviously, UQ is not able to replace MK and DMK during anaerobic growth. Mutations affecting quinone synthesis have an impact on ArcA phosphorylation only under anaerobic conditions. ArcA phosphorylation is reduced in strains synthesizing only MK or MK plus DMK. PMID:29614086

Defectors Can Create Conditions That Rescue Cooperation

PubMed Central

Waite, Adam James; Cannistra, Caroline; Shou, Wenying

2015-01-01

Cooperation based on the production of costly common goods is observed throughout nature. This is puzzling, as cooperation is vulnerable to exploitation by defectors which enjoy a fitness advantage by consuming the common good without contributing fairly. Depletion of the common good can lead to population collapse and the destruction of cooperation. However, population collapse implies small population size, which, in a structured population, is known to favor cooperation. This happens because small population size increases variability in cooperator frequency across different locations. Since individuals in cooperator-dominated locations (which are most likely cooperators) will grow more than those in defector-dominated locations (which are most likely defectors), cooperators can outgrow defectors globally despite defectors outgrowing cooperators in each location. This raises the possibility that defectors can lead to conditions that sometimes rescue cooperation from defector-induced destruction. We demonstrate multiple mechanisms through which this can occur, using an individual-based approach to model stochastic birth, death, migration, and mutation events. First, during defector-induced population collapse, defectors occasionally go extinct before cooperators by chance, which allows cooperators to grow. Second, empty locations, either preexisting or created by defector-induced population extinction, can favor cooperation because they allow cooperator but not defector migrants to grow. These factors lead to the counterintuitive result that the initial presence of defectors sometimes allows better survival of cooperation compared to when defectors are initially absent. Finally, we find that resource limitation, inducible by defectors, can select for mutations adaptive to resource limitation. When these mutations are initially present at low levels or continuously generated at a moderate rate, they can favor cooperation by further reducing local population size. We predict that in a structured population, small population sizes precipitated by defectors provide a “built-in” mechanism for the persistence of cooperation. PMID:26690946

Intelligent tit-for-tat in the iterated prisoner's dilemma game

NASA Astrophysics Data System (ADS)

Baek, Seung Ki; Kim, Beom Jun

2008-07-01

We seek a route to the equilibrium where all the agents cooperate in the iterated prisoner’s dilemma game on a two-dimensional plane, focusing on the role of tit-for-tat strategy. When a time horizon, within which a strategy can recall the past, is one time step, an equilibrium can be achieved as cooperating strategies dominate the whole population via proliferation of tit-for-tat. Extending the time horizon, we filter out poor strategies by simplified replicator dynamics and observe a similar evolutionary pattern to reach the cooperating equilibrium. In particular, the rise of a modified tit-for-tat strategy plays a central role, which implies how a robust strategy is adopted when provided with an enhanced memory capacity.

A Distributed Energy-Aware Trust Management System for Secure Routing in Wireless Sensor Networks

NASA Astrophysics Data System (ADS)

Stelios, Yannis; Papayanoulas, Nikos; Trakadas, Panagiotis; Maniatis, Sotiris; Leligou, Helen C.; Zahariadis, Theodore

Wireless sensor networks are inherently vulnerable to security attacks, due to their wireless operation. The situation is further aggravated because they operate in an infrastructure-less environment, which mandates the cooperation among nodes for all networking tasks, including routing, i.e. all nodes act as “routers”, forwarding the packets generated by their neighbours in their way to the sink node. This implies that malicious nodes (denying their cooperation) can significantly affect the network operation. Trust management schemes provide a powerful tool for the detection of unexpected node behaviours (either faulty or malicious). Once misbehaving nodes are detected, their neighbours can use this information to avoid cooperating with them either for data forwarding, data aggregation or any other cooperative function. We propose a secure routing solution based on a novel distributed trust management system, which allows for fast detection of a wide set of attacks and also incorporates energy awareness.

7 CFR 1.75 - General stipulations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 1 2013-01-01 2013-01-01 false General stipulations. 1.75 Section 1.75 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Cooperative Production of Television... direct or implied, by the U.S. Department of Agriculture or its agencies, of the sponsor's product. (d...

Globalization and Educational Policymaking: A Case Study.

ERIC Educational Resources Information Center

Taylor, Sandra; Henry, Miriam

2000-01-01

This case study illuminates the process of globalization in the public policy domain of vocational education, drawing on the relation between Australia and the Organization for Economic Cooperation and Development. The paper argues that educational globalization does not necessarily imply policy homogenization, but rather that tensions exist…

Gender Differences in Emotional Responses to Cooperative and Competitive Game Play

PubMed Central

Kivikangas, J. Matias; Kätsyri, Jari; Järvelä, Simo; Ravaja, Niklas

2014-01-01

Previous research indicates that males prefer competition over cooperation, and it is sometimes suggested that females show the opposite behavioral preference. In the present article, we investigate the emotions behind the preferences: Do males exhibit more positive emotions during competitive than cooperative activities, and do females show the opposite pattern? We conducted two experiments where we assessed the emotional responses of same-gender dyads (in total 130 participants, 50 female) during intrinsically motivating competitive and cooperative digital game play using facial electromyography (EMG), skin conductance, heart rate measures, and self-reported emotional experiences. We found higher positive emotional responses (as indexed by both physiological measures and self-reports) during competitive than cooperative play for males, but no differences for females. In addition, we found no differences in negative emotions, and heart rate, skin conductance, and self-reports yielded contradictory evidence for arousal. These results support the hypothesis that males not only prefer competitive over cooperative play, but they also exhibit more positive emotional responses during them. In contrast, the results suggest that the emotional experiences of females do not differ between cooperation and competition, which implies that less competitiveness does not mean more cooperativeness. Our results pertain to intrinsically motivated game play, but might be relevant also for other kinds of activities. PMID:24983952

Gender differences in emotional responses to cooperative and competitive game play.

PubMed

Kivikangas, J Matias; Kätsyri, Jari; Järvelä, Simo; Ravaja, Niklas

2014-01-01

Previous research indicates that males prefer competition over cooperation, and it is sometimes suggested that females show the opposite behavioral preference. In the present article, we investigate the emotions behind the preferences: Do males exhibit more positive emotions during competitive than cooperative activities, and do females show the opposite pattern? We conducted two experiments where we assessed the emotional responses of same-gender dyads (in total 130 participants, 50 female) during intrinsically motivating competitive and cooperative digital game play using facial electromyography (EMG), skin conductance, heart rate measures, and self-reported emotional experiences. We found higher positive emotional responses (as indexed by both physiological measures and self-reports) during competitive than cooperative play for males, but no differences for females. In addition, we found no differences in negative emotions, and heart rate, skin conductance, and self-reports yielded contradictory evidence for arousal. These results support the hypothesis that males not only prefer competitive over cooperative play, but they also exhibit more positive emotional responses during them. In contrast, the results suggest that the emotional experiences of females do not differ between cooperation and competition, which implies that less competitiveness does not mean more cooperativeness. Our results pertain to intrinsically motivated game play, but might be relevant also for other kinds of activities.

The antioxidant transcription factor Nrf2 negatively regulates autophagy and growth arrest induced by the anticancer redox agent mitoquinone.

PubMed

Rao, V Ashutosh; Klein, Sarah R; Bonar, Spencer J; Zielonka, Jacek; Mizuno, Naoko; Dickey, Jennifer S; Keller, Paul W; Joseph, Joy; Kalyanaraman, Balaraman; Shacter, Emily

2010-11-05

Mitoquinone (MitoQ) is a synthetically modified, redox-active ubiquinone compound that accumulates predominantly in mitochondria. We found that MitoQ is 30-fold more cytotoxic to breast cancer cells than to healthy mammary cells. MitoQ treatment led to irreversible inhibition of clonogenic growth of breast cancer cells through a combination of autophagy and apoptotic cell death mechanisms. Relatively limited cytotoxicity was seen with the parent ubiquinone coenzyme Q(10.) Inhibition of cancer cell growth by MitoQ was associated with G(1)/S cell cycle arrest and phosphorylation of the checkpoint kinases Chk1 and Chk2. The possible role of oxidative stress in MitoQ activity was investigated by measuring the products of hydroethidine oxidation. Increases in ethidium and dihydroethidium levels, markers of one-electron oxidation of hydroethidine, were observed at cytotoxic concentrations of MitoQ. Keap1, an oxidative stress sensor protein that regulates the antioxidant transcription factor Nrf2, underwent oxidation, degradation, and dissociation from Nrf2 in MitoQ-treated cells. Nrf2 protein levels, nuclear localization, and transcriptional activity also increased following MitoQ treatment. Knockdown of Nrf2 caused a 2-fold increase in autophagy and an increase in G(1) cell cycle arrest in response to MitoQ but had no apparent effect on apoptosis. The Nrf2-regulated enzyme NQO1 is partly responsible for controlling the level of autophagy. Keap1 and Nrf2 act as redox sensors for oxidative perturbations that lead to autophagy. MitoQ and similar compounds should be further evaluated for novel anticancer activity.

Devosia soli sp. nov., isolated from greenhouse soil in Korea.

PubMed

Yoo, Seung-Hee; Weon, Hang-Yeon; Kim, Byung-Yong; Hong, Seung-Beom; Kwon, Soon-Wo; Cho, Yang-Hee; Go, Seung-Joo; Stackebrandt, Erko

2006-11-01

A Gram-negative, obligately aerobic, rod-shaped bacterium was isolated from greenhouse soil used to cultivate lettuce. The strain, GH2-10T, was characterized on the basis of phenotypic and genotypic data. 16S rRNA gene sequence analysis revealed that the isolate belonged to the genus Devosia, with highest sequence similarity (98.5%) to Devosia riboflavina IFO 13584T. Sequence similarities with other strains tested were below 97.0%. Strain GH2-10T had Q-10 as the predominant ubiquinone and C18:1omega7c and C16:0 as the major fatty acids. The G+C content of the genomic DNA was 59.5 mol%. The results of DNA-DNA hybridization experiments (47% relatedness between D. riboflavina DSM 7230T and strain GH2-10T) and physiological and biochemical tests suggested that strain GH2-10T represents a novel species of the genus Devosia, for which the name Devosia soli sp. nov. is proposed. The type strain is GH2-10T (=KACC 11509T=DSM 17780T).

Asymmetric interaction and indeterminate fitness correlation between cooperative partners in the fig–fig wasp mutualism

PubMed Central

Wang, Rui-Wu; Sun, Bao-Fa; Zheng, Qi; Shi, Lei; Zhu, Lixing

2011-01-01

Empirical observations have shown that cooperative partners can compete for common resources, but what factors determine whether partners cooperate or compete remain unclear. Using the reciprocal fig–fig wasp mutualism, we show that nonlinear amplification of interference competition between fig wasps—which limits the fig wasps' ability to use a common resource (i.e. female flowers)—keeps the common resource unsaturated, making cooperation locally stable. When interference competition was manually prevented, the fitness correlation between figs and fig wasps went from positive to negative. This indicates that genetic relatedness or reciprocal exchange between cooperative players, which could create spatial heterogeneity or self-restraint, was not sufficient to maintain stable cooperation. Moreover, our analysis of field-collected data shows that the fitness correlation between cooperative partners varies stochastically, and that the mainly positive fitness correlation observed during the warm season shifts to a negative correlation during the cold season owing to an increase in the initial oviposition efficiency of each fig wasp. This implies that the discriminative sanction of less-cooperative wasps (i.e. by decreasing the egg deposition efficiency per fig wasp) but reward to cooperative wasps by fig, a control of the initial value, will facilitate a stable mutualism. Our finding that asymmetric interaction leading to an indeterminate fitness interaction between symbiont (i.e. cooperative actors) and host (i.e. recipient) has the potential to explain why conflict has been empirically observed in both well-documented intraspecific and interspecific cooperation systems. PMID:21490005

Child Trafficking and Formalisation: The Case of International Adoption from Ecuador

ERIC Educational Resources Information Center

Leifsen, Esben

2008-01-01

Child trafficking activity often draws on formal administrative and legal resources. Formalisation implies considerable cooperation between public functionaries, lawyers and external actors. I argue that child rights advocates are forceful policy formulators who tend to ignore the public-external link because they focus on the external…

The Importance of Teaching a Win-Win Philosophy.

ERIC Educational Resources Information Center

Brainard, Alan J.

Most people are raised in a traditional environment which teaches that someone-winning implies that someone-loses. However, psychology and the examples provided in the Watergate scandal demonstrate that such a philosophy is neither productive nor beneficial. A "win-win" philosophy of cooperation, not competition, is needed for…

Methylobacterium frigidaeris sp. nov., isolated from an air conditioning system.

PubMed

Lee, Yunho; Jeon, Che Ok

2018-01-01

A reddish pink-pigmented, Gram-stain-negative, aerobic and methylotrophic bacterial strain, designated strain IER25-16 T , was isolated from a laboratory air conditioning system in the Republic of Korea. Cells were motile rods showing catalase- and oxidase-positive reactions. Strain IER25-16 T grew at 10-40 °C (optimum, 30 °C), at pH 4.0-7.0 (optimum, pH 5.0-7.0) and in the presence of 0-1.0 % (w/v) NaCl (optimum, 0 %). The major respiratory quinone was ubiquinone-10 and ubiquinone-9 was also detected as the minor respiratory quinone. Summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c) was detected as the predominant fatty acids. The genomic DNA G+C content of strain IER25-16 T was 70.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequence comparison revealed that strain IER25-16 T belonged to the genus Methylobacterium of the class Alphaproteobacteria. Strain IER25-16 T was most closely related to Methylobacterium platani PMB02 T (97.9 %), Methylobacterium aquaticum GR16 T (97.9 %) and Methylobacterium tarhaniae N4211 T (97.5 %). The average nucleotide identity and in silico DNA-DNA hybridization values between strain IER25-16 T and M. platani, M. aquaticum and M. tarhaniae were 88.3, 88.8 and 89.6 % and 36.2, 37.3 and 39.3 %, respectively. The phenotypic and chemotaxonomic features and the phylogenetic inference clearly suggested that strain IER25-16 T represents a novel species of the genus Methylobacterium, for which the name Methylobacteriumfrigidaeris sp. nov. is proposed. The type strain is strain IER25-16 T (=KACC 19280 T =JCM 32048 T ).

Evolution of cooperation on complex networks with synergistic and discounted group interactions

NASA Astrophysics Data System (ADS)

Zhou, Lei; Li, Aming; Wang, Long

2015-06-01

In the real world individuals often engage in group interactions and their payoffs are determined by many factors, including the typical nonlinear interactions, i.e., synergy and discounting. Previous literatures assume that individual payoffs are either synergistically enhanced or discounted with the additional cooperators. Such settings ignore the interplay of these two factors, which is in sharp contrast with the fact that they ubiquitously coexist. Here we investigate how the coexistence and periodical switching of synergistic and discounted group interactions affect the evolution of cooperation on various complex networks. We show that scale-free networks facilitate the emergence of cooperation in terms of fixation probability for group interactions. With nonlinear interactions the heterogeneity of the degree acts as a double-edged sword: below the neutral drift it is the best for cooperation while above the neutral drift it instead provides the least opportunity for cooperators to be fixed. The advantages of the heterogeneity fade as interactive attributes switch between synergy and discounting, which suggests that the heterogeneity of population structures cannot favor cooperators in group interactions even with simple nonlinear interactions. Nonetheless, scale-free networks always guarantee cooperators the fastest rate of fixation. Our work implies that even very simple nonlinear group interactions could greatly shape the fixation probability and fixation time of cooperators in structured populations indicated by complex networks.

Hypothalamic digoxin and hemispheric chemical dominance: relation to speech and language dysfunction.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-06-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. Since endogenous digoxin can regulate neurotransmitter transport and dolichols can modulate glycoconjugate synthesis important in synaptic connectivity, the pathway was assessed in patients with dyslexia, delayed recovery from global aphasia consequent to a dominant hemispheric thrombotic infarct, and developmental delay of speech milestone. The pathway was also studied in right hemispheric, left hemispheric, and bihemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of speech disorders. The plasma/serum--activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone--and tryptophan/tyrosine catabolic patterns, as well as RBC (Na+)-K+ ATPase activity, were measured in the above mentioned groups. The glycoconjugate metabolism and membrane composition was also studied. The study showed that in dyslexia, developmental delay of speech milestone, and delayed recovery from global aphasia there was an upregulated isoprenoidal pathway with increased digoxin and dolichol levels. The membrane (Na+)-K+ ATPase activity, serum magnesium and ubiquinone levels were low. The tryptophan catabolites were increased and the tyrosine catabolites including dopamine decreased in the serum contributing to a speech dysfunction. There was an increase in carbohydrate residues of glycoproteins, glycosaminoglycans, and glycolipids levels as well as an increased activity of GAG degrading enzymes and glyco hydrolases in the serum. The cholesterol:phospholipid ratio of RBC membrane increased and membrane glycoconjugates showed a decrease. All of these could contribute to altered synaptic inactivity in these disorders. The patterns correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance may play a role in the genesis of these disorders. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test.

Sites of superoxide and hydrogen peroxide production during fatty acid oxidation in rat skeletal muscle mitochondria

PubMed Central

Perevoshchikova, Irina V.; Quinlan, Casey L.; Orr, Adam L.; Gerencser, Akos A.; Brand, Martin D.

2013-01-01

H2O2 production by skeletal muscle mitochondria oxidizing palmitoylcarnitine was examined under two conditions: the absence of respiratory chain inhibitors and the presence of myxothiazol to inhibit complex III. Without inhibitors, respiration and H2O2 production were low unless carnitine or malate was added to limit acetyl-CoA accumulation. With palmitoylcarnitine alone, H2O2 production was dominated by complex II (44% from site IIF in the forward reaction); the remainder was mostly from complex I (34%, superoxide from site IF). With added carnitine, H2O2 production was about equally shared between complexes I, II, and III. With added malate, it was 75% from complex III (superoxide from site IIIQo) and 25% from site IF. Thus complex II (site IIF in the forward reaction) is a major source of H2O2 production during oxidation of palmitoylcarnitine ± carnitine. Under the second condition (myxothiazol present to keep ubiquinone reduced), the rates of H2O2 production were highest in the presence of palmitoylcarnitine ± carnitine and were dominated by complex II (site IIF in the reverse reaction). About half the rest was from site IF, but a significant portion, ~40 pmol H2O2 · min−1 · mg protein−1, was not from complex I, II, or III and was attributed to the proteins of β-oxidation (electron-transferring flavoprotein (ETF) and ETF-ubiquinone oxidoreductase). The maximum rate from the ETF system was ~200 pmol H2O2 · min−1 ~ mg protein−1 under conditions of compromised antioxidant defense and reduced ubiqui-none pool. Thus complex II and the ETF system both contribute to H2O2 production during fatty acid oxidation under appropriate conditions. PMID:23583329

Apoptosis-inducing Factor (AIF) and Its Family Member Protein, AMID, Are Rotenone-sensitive NADH:Ubiquinone Oxidoreductases (NDH-2)*

PubMed Central

Elguindy, Mahmoud M.; Nakamaru-Ogiso, Eiko

2015-01-01

Apoptosis-inducing factor (AIF) and AMID (AIF-homologous mitochondrion-associated inducer of death) are flavoproteins. Although AIF was originally discovered as a caspase-independent cell death effector, bioenergetic roles of AIF, particularly relating to complex I functions, have since emerged. However, the role of AIF in mitochondrial respiration and redox metabolism has remained unknown. Here, we investigated the redox properties of human AIF and AMID by comparing them with yeast Ndi1, a type 2 NADH:ubiquinone oxidoreductase (NDH-2) regarded as alternative complex I. Isolated AIF and AMID containing naturally incorporated FAD displayed no NADH oxidase activities. However, after reconstituting isolated AIF or AMID into bacterial or mitochondrial membranes, N-terminally tagged AIF and AMID displayed substantial NADH:O2 activities and supported NADH-linked proton pumping activities in the host membranes almost as efficiently as Ndi1. NADH:ubiquinone-1 activities in the reconstituted membranes were highly sensitive to 2-n-heptyl-4-hydroxyquinoline-N-oxide (IC50 = ∼1 μm), a quinone-binding inhibitor. Overexpressing N-terminally tagged AIF and AMID enhanced the growth of a double knock-out Escherichia coli strain lacking complex I and NDH-2. In contrast, C-terminally tagged AIF and NADH-binding site mutants of N-terminally tagged AIF and AMID failed to show both NADH:O2 activity and the growth-enhancing effect. The disease mutant AIFΔR201 showed decreased NADH:O2 activity and growth-enhancing effect. Furthermore, we surprisingly found that the redox activities of N-terminally tagged AIF and AMID were sensitive to rotenone, a well known complex I inhibitor. We propose that AIF and AMID are previously unidentified mammalian NDH-2 enzymes, whose bioenergetic function could be supplemental NADH oxidation in cells. PMID:26063804

Basic regulatory principles of Escherichia coli's electron transport chain for varying oxygen conditions.

PubMed

Henkel, Sebastian G; Ter Beek, Alexander; Steinsiek, Sonja; Stagge, Stefan; Bettenbrock, Katja; de Mattos, M Joost Teixeira; Sauter, Thomas; Sawodny, Oliver; Ederer, Michael

2014-01-01

For adaptation between anaerobic, micro-aerobic and aerobic conditions Escherichia coli's metabolism and in particular its electron transport chain (ETC) is highly regulated. Although it is known that the global transcriptional regulators FNR and ArcA are involved in oxygen response it is unclear how they interplay in the regulation of ETC enzymes under micro-aerobic chemostat conditions. Also, there are diverse results which and how quinones (oxidised/reduced, ubiquinone/other quinones) are controlling the ArcBA two-component system. In the following a mathematical model of the E. coli ETC linked to basic modules for substrate uptake, fermentation product excretion and biomass formation is introduced. The kinetic modelling focusses on regulatory principles of the ETC for varying oxygen conditions in glucose-limited continuous cultures. The model is based on the balance of electron donation (glucose) and acceptance (oxygen or other acceptors). Also, it is able to account for different chemostat conditions due to changed substrate concentrations and dilution rates. The parameter identification process is divided into an estimation and a validation step based on previously published and new experimental data. The model shows that experimentally observed, qualitatively different behaviour of the ubiquinone redox state and the ArcA activity profile in the micro-aerobic range for different experimental conditions can emerge from a single network structure. The network structure features a strong feed-forward effect from the FNR regulatory system to the ArcBA regulatory system via a common control of the dehydrogenases of the ETC. The model supports the hypothesis that ubiquinone but not ubiquinol plays a key role in determining the activity of ArcBA in a glucose-limited chemostat at micro-aerobic conditions.

A matter of trust? A study of coordination of Swedish stakeholders in return-to-work.

PubMed

Ståhl, Christian; Svensson, Tommy; Petersson, Gunilla; Ekberg, Kerstin

2010-09-01

Stakeholder cooperation in return-to-work has been increasingly emphasized over the last years. However, there is a lack of empirical studies on the subject. This study explores different public stakeholders' experiences of participating in Coordination Associations (CAs), a Swedish form of structured cooperation in return-to-work. The aim of the study is to determine the impact of stakeholder interests on the prerequisites for cooperation. Thirty-five representatives from two CAs in eastern Sweden were interviewed regarding the aim, structure and strategies for their common work. Stakeholders' actions are to a high degree determined by their institutional preferences and self-interest. In the CAs, the motives for cooperation differ, and although these differences supposedly could be overcome, they are in fact not. One of the stakeholders, the Public Employment Service, limit its interest to coordinating resources, while the other three wishes to engage in elaborated cooperative work forms, implying the crossing of organizational borders. This discrepancy can largely be attributed to the difficulties for representatives from state authorities in changing their priorities in order to make cooperation work. Stakeholders' interests have a high impact on the prerequisites for cooperation in return-to-work. By referring to organizational goals, stakeholders engage in non-cooperative behaviour, which threatens to spoil cooperative initiatives and to develop distrust in cooperative work forms. The results of this study expose the complexity of and threats to cooperation, and its conclusions may be used by return-to-work stakeholders in different jurisdictions to improve the possibilities for the development of cooperative structures.

Mitochondrial respiratory complex I probed by delayed luminescence spectroscopy

NASA Astrophysics Data System (ADS)

Baran, Irina; Ionescu, Diana; Privitera, Simona; Scordino, Agata; Mocanu, Maria Magdalena; Musumeci, Francesco; Grasso, Rosaria; Gulino, Marisa; Iftime, Adrian; Tofolean, Ioana Teodora; Garaiman, Alexandru; Goicea, Alexandru; Irimia, Ruxandra; Dimancea, Alexandru; Ganea, Constanta

2013-12-01

The role of mitochondrial complex I in ultraweak photon-induced delayed photon emission [delayed luminescence (DL)] of human leukemia Jurkat T cells was probed by using complex I targeting agents like rotenone, menadione, and quercetin. Rotenone, a complex I-specific inhibitor, dose-dependently increased the mitochondrial level of reduced nicotinamide adenine dinucleotide (NADH), decreased clonogenic survival, and induced apoptosis. A strong correlation was found between the mitochondrial levels of NADH and oxidized flavin mononucleotide (FMNox) in rotenone-, menadione- and quercetin-treated cells. Rotenone enhanced DL dose-dependently, whereas quercetin and menadione inhibited DL as well as NADH or FMNox. Collectively, the data suggest that DL of Jurkat cells originates mainly from mitochondrial complex I, which functions predominantly as a dimer and less frequently as a tetramer. In individual monomers, both pairs of pyridine nucleotide (NADH/reduced nicotinamide adenine dinucleotide phosphate) sites and flavin (FMN-a/FMN-b) sites appear to bind cooperatively their specific ligands. Enhancement of delayed red-light emission by rotenone suggests that the mean time for one-electron reduction of ubiquinone or FMN-a by the terminal Fe/S center (N2) is 20 or 284 μs, respectively. All these findings suggest that DL spectroscopy could be used as a reliable, sensitive, and robust technique to probe electron flow within complex I in situ.

Sulfur metabolism in Beggiatoa alba.

PubMed Central

Schmidt, T M; Arieli, B; Cohen, Y; Padan, E; Strohl, W R

1987-01-01

The metabolism of sulfide, sulfur, and acetate by Beggiatoa alba was investigated under oxic and anoxic conditions. B. alba oxidized acetate to carbon dioxide with the stoichiometric reduction of oxygen to water. In vivo acetate oxidation was suppressed by sulfide and by several classic respiratory inhibitors, including dibromothymoquinone, an inhibitor specific for ubiquinones. B. alba also carried out an oxygen-dependent conversion of sulfide to sulfur, a reaction that was inhibited by several electron transport inhibitors but not by dibromothymoquinone, indicating that the electrons released from sulfide oxidation were shuttled to oxygen without the involvement of ubiquinones. Intracellular sulfur stored by B. alba was not oxidized to sulfate or converted to an external soluble form under aerobic conditions. On the other hand, sulfur stored by filaments of Thiothrix nivea was oxidized to extracellular soluble oxidation products, including sulfate. Sulfur stored by filaments of B. alba, however, was reduced to sulfide under short-term anoxic conditions. This anaerobic reduction of sulfur was linked to the endogenous oxidation of stored carbon and to hydrogen oxidation. PMID:3316186

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

Romine, Margaret F.; Rodionov, Dmitry A.; Maezato, Yukari

Only a small fraction of vitamin B12-requiring organisms are able to synthesize B12 de novo, making it a common commodity in microbial communities. Initially recognized as an enzyme cofactor of a few enzymes, recent studies have revealed additional B12-binding enzymes and regulatory roles for B12. Here we report the development and use of a B12-based chemical probe to identify B12-binding proteins in a nonphototrophic B12-producing bacterium. Two unexpected discoveries resulted from this study. First, we identified a new light-sensing B12-binding transcriptional regulator and demonstrated that it controls folate and ubiquinone biosynthesis. Second, our probe captured proteins involved in folate, methionine,more » and ubiquinone metabolism suggesting that it may play a role as an allosteric effector of these processes. These metabolic processes produce precursors for synthesis of DNA, RNA, and protein. Thereby, B12 modulates growth, and by limiting its availability to auxotrophs, B12-producing organisms may facilitate coordination of community metabolism.« less

Mammalian complex I pumps 4 protons per 2 electrons at high and physiological proton motive force in living cells.

PubMed

Ripple, Maureen O; Kim, Namjoon; Springett, Roger

2013-02-22

Mitochondrial complex I couples electron transfer between matrix NADH and inner-membrane ubiquinone to the pumping of protons against a proton motive force. The accepted proton pumping stoichiometry was 4 protons per 2 electrons transferred (4H(+)/2e(-)) but it has been suggested that stoichiometry may be 3H(+)/2e(-) based on the identification of only 3 proton pumping units in the crystal structure and a revision of the previous experimental data. Measurement of proton pumping stoichiometry is challenging because, even in isolated mitochondria, it is difficult to measure the proton motive force while simultaneously measuring the redox potentials of the NADH/NAD(+) and ubiquinol/ubiquinone pools. Here we employ a new method to quantify the proton motive force in living cells from the redox poise of the bc(1) complex measured using multiwavelength cell spectroscopy and show that the correct stoichiometry for complex I is 4H(+)/2e(-) in mouse and human cells at high and physiological proton motive force.

Reward from punishment does not emerge at all costs.

PubMed

Vukov, Jeromos; Pinheiro, Flávio L; Santos, Francisco C; Pacheco, Jorge M

2013-01-01

The conundrum of cooperation has received increasing attention during the last decade. In this quest, the role of altruistic punishment has been identified as a mechanism promoting cooperation. Here we investigate the role of altruistic punishment on the emergence and maintenance of cooperation in structured populations exhibiting connectivity patterns recently identified as key elements of social networks. We do so in the framework of Evolutionary Game Theory, employing the Prisoner's Dilemma and the Stag-Hunt metaphors to model the conflict between individual and collective interests regarding cooperation. We find that the impact of altruistic punishment strongly depends on the ratio q/p between the cost of punishing a defecting partner (q) and the actual punishment incurred by the partner (p). We show that whenever q/p<1, altruistic punishment turns out to be detrimental for cooperation for a wide range of payoff parameters, when compared to the scenario without punishment. The results imply that while locally, the introduction of peer punishment may seem to reduce the chances of free-riding, realistic population structure may drive the population towards the opposite scenario. Hence, structured populations effectively reduce the expected beneficial contribution of punishment to the emergence of cooperation which, if not carefully dosed, may in fact hinder the chances of widespread cooperation.

Influence of Web Based Cooperative Learning Strategy and Achiever Motivation on Student Study Outcome

ERIC Educational Resources Information Center

Hariadi, Bambang; Wurijanto, Tutut

2016-01-01

The research aimed at examining the effect of instructional strategy (web-based STAD and text-based STAD) and achiever motivation toward student learning outcomes. The research implied quasi-experimental design with nonequivalent control group factorial version. The subjects were undergraduate students of Information Systems of academic year…

In-gap quasiparticle excitations induced by non-magnetic Cu impurities in Na(Fe0.96Co0.03Cu0.01)As revealed by scanning tunnelling spectroscopy

PubMed Central

Yang, Huan; Wang, Zhenyu; Fang, Delong; Deng, Qiang; Wang, Qiang-Hua; Xiang, Yuan-Yuan; Yang, Yang; Wen, Hai-Hu

2013-01-01

The origin of superconductivity in the iron pnictides remains unclear. One suggestion is that superconductivity in these materials has a magnetic origin, which would imply a sign-reversal s± pairing symmetry. Another suggests it is the result of orbital fluctuations, which would imply a sign-equal s++ pairing symmetry. There is no consensus yet which of these two distinct and contrasting pairing symmetries is the right one in iron pnictide superconductors. Here we explore the nature of the pairing symmetry in the superconducting state of Na(Fe0.97−xCo0.03Cux)As by probing the effect of scattering of Cooper pairs by non-magnetic Cu impurities. Using scanning tunnelling spectroscopy, we identify the in-gap quasiparticle states induced by the Cu impurities, showing signatures of Cooper pair breaking by these non-magnetic impurities–a process that is only consistent with s± pairing. This experiment provides strong evidence for the s± pairing. PMID:24248097

Interactive diversity promotes the evolution of cooperation in structured populations

NASA Astrophysics Data System (ADS)

Su, Qi; Li, Aming; Zhou, Lei; Wang, Long

2016-10-01

Evolutionary games on networks traditionally assume that each individual adopts an identical strategy to interact with all its neighbors in each generation. Considering the prevalent diversity of individual interactions in the real society, here we propose the concept of interactive diversity, which allows individuals to adopt different strategies against different neighbors in each generation. We investigate the evolution of cooperation based on the edge dynamics rather than the traditional nodal dynamics in networked systems. The results show that, without invoking any other mechanisms, interactive diversity drives the frequency of cooperation to a high level for a wide range of parameters in both well-mixed and structured populations. Even in highly connected populations, cooperation still thrives. When interactive diversity and large topological heterogeneity are combined together, however, in the relaxed social dilemma, cooperation level is lower than that with just one of them, implying that the combination of many promotive factors may make a worse outcome. By an analytical approximation, we get the condition under which interactive diversity provides more advantages for cooperation than traditional evolutionary dynamics does. Numerical simulations validating the approximation are also presented. Our work provides a new line to explore the latent relation between the ubiquitous cooperation and individuals’ distinct responses in different interactions. The presented results suggest that interactive diversity should receive more attention in pursuing mechanisms fostering cooperation.

The take-it-or-leave-it option allows small penalties to overcome social dilemmas

PubMed Central

Sasaki, Tatsuya; Brännström, Åke; Dieckmann, Ulf; Sigmund, Karl

2012-01-01

Self-interest frequently causes individuals engaged in joint enterprises to choose actions that are counterproductive. Free-riders can invade a society of cooperators, causing a tragedy of the commons. Such social dilemmas can be overcome by positive or negative incentives. Even though an incentive-providing institution may protect a cooperative society from invasion by free-riders, it cannot always convert a society of free-riders to cooperation. In the latter case, both norms, cooperation and defection, are stable: To avoid a collapse to full defection, cooperators must be sufficiently numerous initially. A society of free-riders is then caught in a social trap, and the institution is unable to provide an escape, except at a high, possibly prohibitive cost. Here, we analyze the interplay of (a) incentives provided by institutions and (b) the effects of voluntary participation. We show that this combination fundamentally improves the efficiency of incentives. In particular, optional participation allows institutions punishing free-riders to overcome the social dilemma at a much lower cost, and to promote a globally stable regime of cooperation. This removes the social trap and implies that whenever a society of cooperators cannot be invaded by free-riders, it will necessarily become established in the long run, through social learning, irrespective of the initial number of cooperators. We also demonstrate that punishing provides a “lighter touch” than rewarding, guaranteeing full cooperation at considerably lower cost. PMID:22232694

The role of coenzyme Q-10 in aging: a follow-up study on life-long oral supplementation Q-10 in rats.

PubMed

Lönnrot, K; Metsä-Ketelä, T; Alho, H

1995-01-01

The essential role of coenzyme Q--ubiquinone--in biological energy transduction is well established. Reduced Q--ubiquinol--has also been shown to act as an antioxidant and to decrease the action of free radicals, which in turn could cause damage to structural lipids or proteins. The accumulation of lipopigments during aging in several peripheral organs and in the nervous system is considered to be related to the peroxidation of unsaturated fatty acids. An age-related decline of Q-10 has been suggested to occur in man and rats. In this study we followed the effects of life-long oral supplementation of coenzyme Q-10 on the development and life-span and pigment accumulation in peripheral tissues and the nervous system of laboratory rats. The Q-10 supplemented group showed a significant increase in Q-10 in plasma and liver, while it was unchanged in other tissues. There was no significant difference between the two groups in the development and mortality of the animals. No differences were observed in lipopigment accumulation. Our results indicate that in rats, life-long supplementation of Q-10 has no beneficial effects on life-span or pigment accumulation.

29 CFR 1908.10 - Cooperative Agreements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 5 2012-07-01 2012-07-01 false Cooperative Agreements. 1908.10 Section 1908.10 Labor... CONSULTATION AGREEMENTS § 1908.10 Cooperative Agreements. (a) Who may make Agreements. The Assistant Secretary may make a Cooperative Agreement under this part with the Governor of a State or with any State agency...

29 CFR 1908.10 - Cooperative Agreements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 5 2010-07-01 2010-07-01 false Cooperative Agreements. 1908.10 Section 1908.10 Labor... CONSULTATION AGREEMENTS § 1908.10 Cooperative Agreements. (a) Who may make Agreements. The Assistant Secretary may make a Cooperative Agreement under this part with the Governor of a State or with any State agency...

29 CFR 1908.10 - Cooperative Agreements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 5 2014-07-01 2014-07-01 false Cooperative Agreements. 1908.10 Section 1908.10 Labor... CONSULTATION AGREEMENTS § 1908.10 Cooperative Agreements. (a) Who may make Agreements. The Assistant Secretary may make a Cooperative Agreement under this part with the Governor of a State or with any State agency...

The Antioxidant Transcription Factor Nrf2 Negatively Regulates Autophagy and Growth Arrest Induced by the Anticancer Redox Agent Mitoquinone*

PubMed Central

Rao, V. Ashutosh; Klein, Sarah R.; Bonar, Spencer J.; Zielonka, Jacek; Mizuno, Naoko; Dickey, Jennifer S.; Keller, Paul W.; Joseph, Joy; Kalyanaraman, Balaraman; Shacter, Emily

2010-01-01

Mitoquinone (MitoQ) is a synthetically modified, redox-active ubiquinone compound that accumulates predominantly in mitochondria. We found that MitoQ is 30-fold more cytotoxic to breast cancer cells than to healthy mammary cells. MitoQ treatment led to irreversible inhibition of clonogenic growth of breast cancer cells through a combination of autophagy and apoptotic cell death mechanisms. Relatively limited cytotoxicity was seen with the parent ubiquinone coenzyme Q10. Inhibition of cancer cell growth by MitoQ was associated with G1/S cell cycle arrest and phosphorylation of the checkpoint kinases Chk1 and Chk2. The possible role of oxidative stress in MitoQ activity was investigated by measuring the products of hydroethidine oxidation. Increases in ethidium and dihydroethidium levels, markers of one-electron oxidation of hydroethidine, were observed at cytotoxic concentrations of MitoQ. Keap1, an oxidative stress sensor protein that regulates the antioxidant transcription factor Nrf2, underwent oxidation, degradation, and dissociation from Nrf2 in MitoQ-treated cells. Nrf2 protein levels, nuclear localization, and transcriptional activity also increased following MitoQ treatment. Knockdown of Nrf2 caused a 2-fold increase in autophagy and an increase in G1 cell cycle arrest in response to MitoQ but had no apparent effect on apoptosis. The Nrf2-regulated enzyme NQO1 is partly responsible for controlling the level of autophagy. Keap1 and Nrf2 act as redox sensors for oxidative perturbations that lead to autophagy. MitoQ and similar compounds should be further evaluated for novel anticancer activity. PMID:20805228

Effect of ubiquinol supplementation on biochemical and oxidative stress indexes after intense exercise in young athletes.

PubMed

Orlando, Patrick; Silvestri, Sonia; Galeazzi, Roberta; Antonicelli, Roberto; Marcheggiani, Fabio; Cirilli, Ilenia; Bacchetti, Tiziana; Tiano, Luca

2018-12-01

Physical exercise significantly impacts the biochemistry of the organism. Ubiquinone is a key component of the mitochondrial respiratory chain and ubiquinol, its reduced and active form, is an emerging molecule in sport nutrition. The aim of this study was to evaluate the effect of ubiquinol supplementation on biochemical and oxidative stress indexes after an intense bout of exercise. 21 male young athletes (26 + 5 years of age) were randomized in two groups according to a double blind cross-over study, either supplemented with ubiquinol (200 mg/day) or placebo for 1 month. Blood was withdrawn before and after a single bout of intense exercise (40 min run at 85% maxHR). Physical performance, hematochemical parameters, ubiquinone/ubiquinol plasma content, intracellular reactive oxygen species (ROS) level, mitochondrial membrane depolarization, paraoxonase activity and oxidative DNA damage were analyzed. A single bout of intense exercise produced a significant increase in most hematochemical indexes, in particular CK and Mb while, on the contrary, normalized coenzyme Q 10 plasma content decreased significantly in all subjects. Ubiquinol supplementation prevented exercise-induced CoQ deprivation and decrease in paraoxonase activity. Moreover at a cellular level, in peripheral blood mononuclear cells, ubiquinol supplementation was associated with a significant decrease in cytosolic ROS while mitochondrial membrane potential and oxidative DNA damage remained unchanged. Data highlights a very rapid dynamic of CoQ depletion following intense exercise underlying an increased demand by the organism. Ubiquinol supplementation minimized exercise-induced depletion and enhanced plasma and cellular antioxidant levels but it was not able to improve physical performance indexes or markers of muscular damage.

Decay of superconducting correlations for gauged electrons in dimensions D ≤ 4

NASA Astrophysics Data System (ADS)

Tada, Yasuhiro; Koma, Tohru

2018-03-01

We study lattice superconductors coupled to gauge fields, such as an attractive Hubbard model in electromagnetic fields, with a standard gauge fixing. We prove upper bounds for a two-point Cooper pair correlation at finite temperatures in spatial dimensions D ≤ 4. The upper bounds decay exponentially in three dimensions and by power law in four dimensions. These imply the absence of the superconducting long-range order for the Cooper pair amplitude as a consequence of fluctuations of the gauge fields. Since our results hold for the gauge fixing Hamiltonian, they cannot be obtained as a corollary of Elitzur's theorem.

Sustainable Odds: Towards Quantitative Decision Support when Relevant Probabilities are not Available

NASA Astrophysics Data System (ADS)

Smith, L. A.

2012-04-01

There is, at present, no attractive foundation for quantitative probabilistic decision support in the face of model inadequacy, or given ambiguity (deep uncertainty) regarding the relative likelihood of various outcomes, known or unknown. True model error arguably precludes the extraction of objective probabilities from an ensemble of model runs drawn from an available (inadequate) model class, while the acknowledgement of incomplete understanding precludes the justified use of (if not the very formation of) an individual's subjective probabilities. An alternative approach based on Sustainable Odds is proposed and investigated. Sustainable Odds differ from "fair odds" (and are easily distinguished any claim which implying well defined probabilities) as the probabilities implied by sustainable odds summed over all outcomes is expected to exceed one. Traditionally, a person's fair odds are found by identifying the probability level at which one would happily accept either side of a bet, thus the probabilities implied by fair odds always sum to one. Knowing that one has incomplete information and perhaps even erroneous beliefs, there is no compelling reason a rational agent should accept the constraint implied by "fair odds" in any bet. Rather, a rational agent might insist on longer odds both on the event and against the event in order to account for acknowledged ignorance. Let probabilistic odds imply any set of odds for which the implied probabilities sum to one; once model error is acknowledged can one rationally demand non-probabilistic odds? The danger of using fair odds (or probabilities) in decision making is illustrated by considering the risk of ruin a cooperative insurance scheme using probabilistic odds is exposed to. Cases where knowing merely that the insurer's model is imperfect, and nothing else, is sufficient to place bets which drive the insurer to an unexpectedly early ruin are presented. Methodologies which allow the insurer to avoid this early ruin are explored; those which prevent early ruin are said to provide "sustainable odds", and it is suggested that these must be non-probabilistic. The aim here is not for the insurance cooperative to make a profit in the long run (or to form a book in any one round) but rather to increase the chance that the cooperative will not go bust, merely breaking even in the long run and thereby continuing to provide a service. In the perfect model scenario, with complete knowledge of all uncertainties and unlimited computational resources, fair odds may prove to be sustainable. The implications these results hold in the case of games against nature, which is perhaps a more relevant context for decision makers concerned with geophysical systems, are discussed. The claim that acknowledged model error makes fair (probabilistic) odds an irrational aim is considered, as are the challenges of working within the framework of sustainable (but non-probabilistic) odds.

Exploring Do-It-Yourself Approaches in Computational Quantum Chemistry: The Pedagogical Benefits of the Classical Boys Algorithm

ERIC Educational Resources Information Center

Orsini, Gabriele

2015-01-01

The ever-increasing impact of molecular quantum calculations over chemical sciences implies a strong and urgent need for the elaboration of proper teaching strategies in university curricula. In such perspective, this paper proposes an extensive project for a student-driven, cooperative, from-scratch implementation of a general Hartree-Fock…

Gravitoelectromagnetism and Dark Energy in Superconductors

NASA Astrophysics Data System (ADS)

de Matos, Clovis Jacinto

A gravitomagnetic analog of the London moment in superconductors could explain the anomalous Cooper pair mass excess reported by Janet Tate. Ultimately the gravitomagnetic London moment is attributed to the breaking of the principle of general covariance in superconductors. This naturally implies nonconservation of classical energy-momentum. A possible relation with the manifestation of dark energy in superconductors is questioned.

Does Coenzyme Q10 Supplementation Mitigate Statin-Associated Muscle Symptoms? Pharmacological and Methodological Considerations.

PubMed

Taylor, Beth A

2018-04-01

Statin drugs markedly reduce low-density lipoprotein cholesterol and consequently the incidence of cardiac events. In approximately 5-10% of adults, these drugs are associated with a range of muscle side effects such as muscle pain, cramping and weakness. Reduction in mitochondrial coenzyme Q10 (CoQ10), or ubiquinone, has been proposed as a mechanism for these statin-associated muscle symptoms (SAMS), and thus various formulations of CoQ10 are marketed and consumed for the prevention and treatment of SAMS. However, data supporting the efficacy of CoQ10 are equivocal, with some studies showing that CoQ10 supplementation reduces the incidence and severity of SAMS and others finding no beneficial effects of supplementation. Methodological and pharmacological issues may confound interpretation of data on this topic. For example, many patients who report SAMS, such as those who have been enrolled in previous CoQ10 studies, may be experiencing non-specific (non-statin-associated) muscle pain. In addition, the effectiveness of oral CoQ10 supplementation to increase mitochondrial CoQ10 in human skeletal muscle is not well established. This manuscript will critically evaluate the published data on the efficacy of CoQ10 supplements in the prevention and treatment of SAMS.

Globalization and human cooperation

PubMed Central

Buchan, Nancy R.; Grimalda, Gianluca; Wilson, Rick; Brewer, Marilynn; Fatas, Enrique; Foddy, Margaret

2009-01-01

Globalization magnifies the problems that affect all people and that require large-scale human cooperation, for example, the overharvesting of natural resources and human-induced global warming. However, what does globalization imply for the cooperation needed to address such global social dilemmas? Two competing hypotheses are offered. One hypothesis is that globalization prompts reactionary movements that reinforce parochial distinctions among people. Large-scale cooperation then focuses on favoring one's own ethnic, racial, or language group. The alternative hypothesis suggests that globalization strengthens cosmopolitan attitudes by weakening the relevance of ethnicity, locality, or nationhood as sources of identification. In essence, globalization, the increasing interconnectedness of people worldwide, broadens the group boundaries within which individuals perceive they belong. We test these hypotheses by measuring globalization at both the country and individual levels and analyzing the relationship between globalization and individual cooperation with distal others in multilevel sequential cooperation experiments in which players can contribute to individual, local, and/or global accounts. Our samples were drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. We find that as country and individual levels of globalization increase, so too does individual cooperation at the global level vis-à-vis the local level. In essence, “globalized” individuals draw broader group boundaries than others, eschewing parochial motivations in favor of cosmopolitan ones. Globalization may thus be fundamental in shaping contemporary large-scale cooperation and may be a positive force toward the provision of global public goods. PMID:19255433

Globalization and human cooperation.

PubMed

Buchan, Nancy R; Grimalda, Gianluca; Wilson, Rick; Brewer, Marilynn; Fatas, Enrique; Foddy, Margaret

2009-03-17

Globalization magnifies the problems that affect all people and that require large-scale human cooperation, for example, the overharvesting of natural resources and human-induced global warming. However, what does globalization imply for the cooperation needed to address such global social dilemmas? Two competing hypotheses are offered. One hypothesis is that globalization prompts reactionary movements that reinforce parochial distinctions among people. Large-scale cooperation then focuses on favoring one's own ethnic, racial, or language group. The alternative hypothesis suggests that globalization strengthens cosmopolitan attitudes by weakening the relevance of ethnicity, locality, or nationhood as sources of identification. In essence, globalization, the increasing interconnectedness of people worldwide, broadens the group boundaries within which individuals perceive they belong. We test these hypotheses by measuring globalization at both the country and individual levels and analyzing the relationship between globalization and individual cooperation with distal others in multilevel sequential cooperation experiments in which players can contribute to individual, local, and/or global accounts. Our samples were drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. We find that as country and individual levels of globalization increase, so too does individual cooperation at the global level vis-à-vis the local level. In essence, "globalized" individuals draw broader group boundaries than others, eschewing parochial motivations in favor of cosmopolitan ones. Globalization may thus be fundamental in shaping contemporary large-scale cooperation and may be a positive force toward the provision of global public goods.

Social Value Induction and Cooperation in the Centipede Game

PubMed Central

2016-01-01

The Centipede game provides a dynamic model of cooperation and competition in repeated dyadic interactions. Two experiments investigated psychological factors driving cooperation in 20 rounds of a Centipede game with significant monetary incentives and anonymous and random re-pairing of players after every round. The main purpose of the research was to determine whether the pattern of strategic choices observed when no specific social value orientation is experimentally induced—the standard condition in all previous investigations of behavior in the Centipede and most other experimental games—is essentially individualistic, the orthodox game-theoretic assumption being that players are individualistically motivated in the absence of any specific motivational induction. Participants in whom no specific state social value orientation was induced exhibited moderately non-cooperative play that differed significantly from the pattern found when an individualistic orientation was induced. In both experiments, the neutral treatment condition, in which no orientation was induced, elicited competitive behavior resembling behavior in the condition in which a competitive orientation was explicitly induced. Trait social value orientation, measured with a questionnaire, influenced cooperation differently depending on the experimentally induced state social value orientation. Cooperative trait social value orientation was a significant predictor of cooperation and, to a lesser degree, experimentally induced competitive orientation was a significant predictor of non-cooperation. The experimental results imply that the standard assumption of individualistic motivation in experimental games may not be valid, and that the results of such investigations need to take into account the possibility that players are competitively motivated. PMID:27010385

43 CFR 43.620 - Cooperative agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Cooperative agreement. 43.620 Section 43... DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 43.620 Cooperative agreement. Cooperative... activity contemplated by the award. The term does not include cooperative research and development...

10 CFR 745.114 - Cooperative research.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Cooperative research. 745.114 Section 745.114 Energy DEPARTMENT OF ENERGY PROTECTION OF HUMAN SUBJECTS § 745.114 Cooperative research. Cooperative research... of cooperative research projects, each institution is responsible for safeguarding the rights and...

10 CFR 745.114 - Cooperative research.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Cooperative research. 745.114 Section 745.114 Energy DEPARTMENT OF ENERGY PROTECTION OF HUMAN SUBJECTS § 745.114 Cooperative research. Cooperative research... of cooperative research projects, each institution is responsible for safeguarding the rights and...

10 CFR 745.114 - Cooperative research.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Cooperative research. 745.114 Section 745.114 Energy DEPARTMENT OF ENERGY PROTECTION OF HUMAN SUBJECTS § 745.114 Cooperative research. Cooperative research... of cooperative research projects, each institution is responsible for safeguarding the rights and...

10 CFR 745.114 - Cooperative research.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Cooperative research. 745.114 Section 745.114 Energy DEPARTMENT OF ENERGY PROTECTION OF HUMAN SUBJECTS § 745.114 Cooperative research. Cooperative research... of cooperative research projects, each institution is responsible for safeguarding the rights and...

10 CFR 745.114 - Cooperative research.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Cooperative research. 745.114 Section 745.114 Energy DEPARTMENT OF ENERGY PROTECTION OF HUMAN SUBJECTS § 745.114 Cooperative research. Cooperative research... of cooperative research projects, each institution is responsible for safeguarding the rights and...

Cucumber possesses a single terminal alternative oxidase gene that is upregulated by cold stress and in the mosaic (MSC) mitochondrial mutants

USDA-ARS?s Scientific Manuscript database

In plants alternative oxidase (AOX) is an important nuclear-encoded enzyme active in the mitochondrial electron-transport chain, transferring electrons from ubiquinol to alternative oxidase instead of the cytochrome pathway to yield ubiquinone and water. AOX protects against unexpected inhibition of...

Regulation of succinate-ubiquinone reductase and fumarate reductase activities in human complex II by phosphorylation of its flavoprotein subunit.

PubMed

Tomitsuka, Eriko; Kita, Kiyoshi; Esumi, Hiroyasu

2009-01-01

Complex II (succinate-ubiquinone reductase; SQR) is a mitochondrial respiratory chain enzyme that is directly involved in the TCA cycle. Complex II exerts a reverse reaction, fumarate reductase (FRD) activity, in various species such as bacteria, parasitic helminths and shellfish, but the existence of FRD activity in humans has not been previously reported. Here, we describe the detection of FRD activity in human cancer cells. The activity level was low, but distinct, and it increased significantly when the cells were cultured under hypoxic and glucose-deprived conditions. Treatment with phosphatase caused the dephosphorylation of flavoprotein subunit (Fp) with a concomitant increase in SQR activity, whereas FRD activity decreased. On the other hand, treatment with protein kinase caused an increase in FRD activity and a decrease in SQR activity. These data suggest that modification of the Fp subunit regulates both the SQR and FRD activities of complex II and that the phosphorylation of Fp might be important for maintaining mitochondrial energy metabolism within the tumor microenvironment.

Molecular Genetics of Ubiquinone Biosynthesis in Animals

PubMed Central

Wang, Ying; Hekimi, Siegfried

2014-01-01

Ubiquinone (UQ), also known as coenzyme Q (CoQ), is a redox-active lipid present in all cellular membranes where it functions in a variety of cellular processes. The best known functions of UQ are to act as a mobile electron carrier in the mitochondrial respiratory chain and to serve as a lipid soluble antioxidant in cellular membranes. All eukaryotic cells synthesize their own UQ. Most of the current knowledge on the UQ biosynthetic pathway was obtained by studying Escherichia coli and S. cerevisiae UQ-deficient mutants. The orthologues of all the genes known from yeast studies to be involved in UQ biosynthesis have subsequently been found in higher organisms. Animal mutants with different genetic defects in UQ biosynthesis display very different phenotypes, despite the fact that in all these mutants the same biosynthetic pathway is affected. This review summarizes the present knowledge of the eukaryotic biosynthesis of UQ, with focus on the biosynthetic genes identified in animals, including C. elegans, rodents and humans. Moreover, we review the phenotypes of mutants in these genes and discuss the functional consequences of UQ deficiency in general. PMID:23190198

Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II.

PubMed

Dong, L-F; Low, P; Dyason, J C; Wang, X-F; Prochazka, L; Witting, P K; Freeman, R; Swettenham, E; Valis, K; Liu, J; Zobalova, R; Turanek, J; Spitz, D R; Domann, F E; Scheffler, I E; Ralph, S J; Neuzil, J

2008-07-17

Alpha-tocopheryl succinate (alpha-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of alpha-TOS has not been identified. Here, we show that alpha-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ)-binding site (Q(P) and Q(D), respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of alpha-TOS compared to that of UbQ for the Q(P) and Q(D) sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and underwent apoptosis in the presence of alpha-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to alpha-TOS. We propose that alpha-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy.

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

PubMed Central

Dong, Lan-Feng; Low, Pauline; Dyason, Jeffrey C.; Wang, Xiu-Fang; Prochazka, Lubomir; Witting, Paul K.; Freeman, Ruth; Swettenham, Emma; Valis, Karel; Liu, Ji; Zobalova, Renata; Turanek, Jaroslav; Spitz, Doug R.; Domann, Frederick E.; Scheffler, Immo E.; Ralph, Stephen J.; Neuzil, Jiri

2009-01-01

α-Tocopheryl succinate (α-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of α-TOS has not been identified. Here we show that α-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ) binding site (QP and QD, respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of α-TOS compared to that of UbQ for the QP and QD sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and undergo apoptosis in the presence of α-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to α-TOS. We propose that α-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy. PMID:18372923

Mammalian Complex I Pumps 4 Protons per 2 Electrons at High and Physiological Proton Motive Force in Living Cells*

PubMed Central

Ripple, Maureen O.; Kim, Namjoon; Springett, Roger

2013-01-01

Mitochondrial complex I couples electron transfer between matrix NADH and inner-membrane ubiquinone to the pumping of protons against a proton motive force. The accepted proton pumping stoichiometry was 4 protons per 2 electrons transferred (4H+/2e−) but it has been suggested that stoichiometry may be 3H+/2e− based on the identification of only 3 proton pumping units in the crystal structure and a revision of the previous experimental data. Measurement of proton pumping stoichiometry is challenging because, even in isolated mitochondria, it is difficult to measure the proton motive force while simultaneously measuring the redox potentials of the NADH/NAD+ and ubiquinol/ubiquinone pools. Here we employ a new method to quantify the proton motive force in living cells from the redox poise of the bc1 complex measured using multiwavelength cell spectroscopy and show that the correct stoichiometry for complex I is 4H+/2e− in mouse and human cells at high and physiological proton motive force. PMID:23306206

50 CFR 15.24 - Permits for cooperative breeding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PLANTS WILD BIRD CONSERVATION ACT Permits and Approval of Cooperative Breeding Programs § 15.24 Permits for cooperative breeding. (a) Application requirements for permits for cooperative breeding. Each... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Permits for cooperative breeding. 15.24...

50 CFR 15.24 - Permits for cooperative breeding.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PLANTS WILD BIRD CONSERVATION ACT Permits and Approval of Cooperative Breeding Programs § 15.24 Permits for cooperative breeding. (a) Application requirements for permits for cooperative breeding. Each... 50 Wildlife and Fisheries 1 2011-10-01 2011-10-01 false Permits for cooperative breeding. 15.24...

49 CFR 32.620 - Cooperative agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Cooperative agreement. 32.620 Section 32.620... (FINANCIAL ASSISTANCE) Definitions § 32.620 Cooperative agreement. Cooperative agreement means an award of... term does not include cooperative research and development agreements as defined in 15 U.S.C. 3710a. ...

45 CFR 690.114 - Cooperative research.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Cooperative research. 690.114 Section 690.114... OF HUMAN SUBJECTS § 690.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research...

45 CFR 690.114 - Cooperative research.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Cooperative research. 690.114 Section 690.114... OF HUMAN SUBJECTS § 690.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research...

45 CFR 690.114 - Cooperative research.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Cooperative research. 690.114 Section 690.114... OF HUMAN SUBJECTS § 690.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research...

45 CFR 690.114 - Cooperative research.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Cooperative research. 690.114 Section 690.114... OF HUMAN SUBJECTS § 690.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research...

45 CFR 690.114 - Cooperative research.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 3 2012-10-01 2012-10-01 false Cooperative research. 690.114 Section 690.114... OF HUMAN SUBJECTS § 690.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research...

50 CFR 15.24 - Permits for cooperative breeding.

Code of Federal Regulations, 2012 CFR

2012-10-01

... PLANTS WILD BIRD CONSERVATION ACT Permits and Approval of Cooperative Breeding Programs § 15.24 Permits for cooperative breeding. (a) Application requirements for permits for cooperative breeding. Each... 50 Wildlife and Fisheries 1 2012-10-01 2012-10-01 false Permits for cooperative breeding. 15.24...

10 CFR 603.1240 - Cooperative agreement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Cooperative agreement. 603.1240 Section 603.1240 Energy... Used in this Part § 603.1240 Cooperative agreement. A legal instrument which, consistent with 31 U.S.C... carrying out the activity contemplated by the cooperative agreement. The term does not include “cooperative...

50 CFR 81.3 - Cooperative Agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Cooperative Agreement. 81.3 Section 81.3... SPECIES OF FISH, WILDLIFE, AND PLANTS-COOPERATION WITH THE STATES § 81.3 Cooperative Agreement. Upon... Secretary shall enter into an Agreement with the State. A Cooperative Agreement is necessary before a...

50 CFR 81.3 - Cooperative Agreement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Cooperative Agreement. 81.3 Section 81.3... SPECIES OF FISH, WILDLIFE, AND PLANTS-COOPERATION WITH THE STATES § 81.3 Cooperative Agreement. Upon... Secretary shall enter into an Agreement with the State. A Cooperative Agreement is necessary before a...

45 CFR 1155.620 - Cooperative agreement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Cooperative agreement. 1155.620 Section 1155.620... ASSISTANCE) Definitions § 1155.620 Cooperative agreement. Cooperative agreement means an award of financial... term does not include cooperative research and development agreements as defined in 15 U.S.C. 3710a. ...

45 CFR 1155.620 - Cooperative agreement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Cooperative agreement. 1155.620 Section 1155.620... ASSISTANCE) Definitions § 1155.620 Cooperative agreement. Cooperative agreement means an award of financial... term does not include cooperative research and development agreements as defined in 15 U.S.C. 3710a. ...

45 CFR 1155.620 - Cooperative agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Cooperative agreement. 1155.620 Section 1155.620... ASSISTANCE) Definitions § 1155.620 Cooperative agreement. Cooperative agreement means an award of financial... term does not include cooperative research and development agreements as defined in 15 U.S.C. 3710a. ...

45 CFR 1173.620 - Cooperative agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Cooperative agreement. 1173.620 Section 1173.620... (FINANCIAL ASSISTANCE) Definitions § 1173.620 Cooperative agreement. Cooperative agreement means an award of... award. The term does not include cooperative research and development agreements as defined in 15 U.S.C...

Hypothalamic digoxin, hemispheric chemical dominance, and oncogenesis: evidence from multiple myeloma.

PubMed

Kurup, Ravi Kumar; Kurup, Paramesware Achutha

2003-12-01

This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol, and ubiquinone in multiple myeloma. The isoprenoid pathway and digoxin status were also studied for comparison in individuals of differing hemispheric dominance to find out the rote of cerebral dominance in the genesis of multiple myeloma and neoplasms. The following parameters were assessed: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition, and free radical metabolism--in multiple myeloma, as well as in individuals of differing hemispheric dominance. There was elevation in plasma HMG CoA reductase activity, serum digoxin, and dolichol, and a reduction in RBC membrane Na(+)-K+ ATPase activity, serum ubiquinone, and magnesium levels. Serum tryptophan, serotonin, nicotine, strychnine, and quinolinic acid were elevated, while tyrosine, dopamine, noradrenaline, and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins, and serum glycolipids were elevated. The RBC membrane glycosaminoglycans, hexose, and fucose residues of glycoproteins, cholesterol, and phospholipids were reduced. The activity of all free-radical scavenging enzymes, concentration of glutathione, iron binding capacity, and ceruloplasmin decreased significantly, while the concentration of lipid peroxidation products and nitric oxide increased. Hyperdigoxinemia-related altered intracellular Ca++/Mg++ ratios mediated oncogene activation, dolichol-induced altered glycoconjugate metabolism, and ubiquinone deficiency-related mitochondrial dysfunction can contribute to the pathogenesis of multiple myeloma. The biochemical patterns obtained in multiple myeloma are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with multiple myeloma were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Multiple myeloma occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-09-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. It was considered pertinent to assess the pathway in inflammatory bowel disease (ulcerative colitis and regional ileitis). Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. All the patients with inflammatory bowel disease were right-handed/left hemispheric dominant by the dichotic listening test. The following parameters were measured in patients with inflammatory bowel disease and in individuals with differing hemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free-radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition and RBC membrane Na+-K+ ATPase activity. Statistical analysis was done by ANOVA. In patients with inflammatory bowel disease there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Inflammatory bowel disease is associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to immune activation, defective glycoprotein bowel antigen presentation, and autoimmunity and a schizophreniform psychosis important in its pathogenesis. The biochemical patterns obtained in inflammatory bowel disease is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Inflammatory bowel disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Change of subunit composition of mitochondrial complex II (succinate-ubiquinone reductase/quinol-fumarate reductase) in Ascaris suum during the migration in the experimental host.

PubMed

Iwata, Fumiko; Shinjyo, Noriko; Amino, Hisako; Sakamoto, Kimitoshi; Islam, M Khyrul; Tsuji, Naotoshi; Kita, Kiyoshi

2008-03-01

The mitochondrial metabolic pathway of the parasitic nematode Ascaris suum changes dramatically during its life cycle, to adapt to changes in the environmental oxygen concentration. We previously showed that A. suum mitochondria express stage-specific isoforms of complex II (succinate-ubiquinone reductase: SQR/quinol-fumarate reductase: QFR). The flavoprotein (Fp) and small subunit of cytochrome b (CybS) in adult complex II differ from those of infective third stage larval (L3) complex II. However, there is no difference in the iron-sulfur cluster (Ip) or the large subunit of cytochrome b (CybL) between adult and L3 isoforms of complex II. In the present study, to clarify the changes that occur in the respiratory chain of A. suum larvae during their migration in the host, we examined enzymatic activity, quinone content and complex II subunit composition in mitochondria of lung stage L3 (LL3) A. suum larvae. LL3 mitochondria showed higher QFR activity ( approximately 160 nmol/min/mg) than mitochondria of A. suum at other stages (L3: approximately 80 nmol/min/mg; adult: approximately 70 nmol/min/mg). Ubiquinone content in LL3 mitochondria was more abundant than rhodoquinone ( approximately 1.8 nmol/mg versus approximately 0.9 nmol/mg). Interestingly, the results of two-dimensional bule-native/sodium dodecyl sulfate polyacrylamide gel electrophoresis analyses showed that LL3 mitochondria contained larval Fp (Fp(L)) and adult Fp (Fp(A)) at a ratio of 1:0.56, and that most LL3 CybS subunits were of the adult form (CybS(A)). This clearly indicates that the rearrangement of complex II begins with a change in the isoform of the anchor CybS subunit, followed by a similar change in the Fp subunit.

Sites of superoxide and hydrogen peroxide production during fatty acid oxidation in rat skeletal muscle mitochondria.

PubMed

Perevoshchikova, Irina V; Quinlan, Casey L; Orr, Adam L; Gerencser, Akos A; Brand, Martin D

2013-08-01

H2O2 production by skeletal muscle mitochondria oxidizing palmitoylcarnitine was examined under two conditions: the absence of respiratory chain inhibitors and the presence of myxothiazol to inhibit complex III. Without inhibitors, respiration and H2O2 production were low unless carnitine or malate was added to limit acetyl-CoA accumulation. With palmitoylcarnitine alone, H2O2 production was dominated by complex II (44% from site IIF in the forward reaction); the remainder was mostly from complex I (34%, superoxide from site IF). With added carnitine, H2O2 production was about equally shared between complexes I, II, and III. With added malate, it was 75% from complex III (superoxide from site IIIQo) and 25% from site IF. Thus complex II (site IIF in the forward reaction) is a major source of H2O2 production during oxidation of palmitoylcarnitine ± carnitine. Under the second condition (myxothiazol present to keep ubiquinone reduced), the rates of H2O2 production were highest in the presence of palmitoylcarnitine ± carnitine and were dominated by complex II (site IIF in the reverse reaction). About half the rest was from site IF, but a significant portion, ∼40pmol H2O2·min(-1)·mg protein(-1), was not from complex I, II, or III and was attributed to the proteins of β-oxidation (electron-transferring flavoprotein (ETF) and ETF-ubiquinone oxidoreductase). The maximum rate from the ETF system was ∼200pmol H2O2·min(-1)·mg protein(-1) under conditions of compromised antioxidant defense and reduced ubiquinone pool. Thus complex II and the ETF system both contribute to H2O2 productionduring fatty acid oxidation under appropriate conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

Apoptosis-inducing Factor (AIF) and Its Family Member Protein, AMID, Are Rotenone-sensitive NADH:Ubiquinone Oxidoreductases (NDH-2).

PubMed

Elguindy, Mahmoud M; Nakamaru-Ogiso, Eiko

2015-08-21

Apoptosis-inducing factor (AIF) and AMID (AIF-homologous mitochondrion-associated inducer of death) are flavoproteins. Although AIF was originally discovered as a caspase-independent cell death effector, bioenergetic roles of AIF, particularly relating to complex I functions, have since emerged. However, the role of AIF in mitochondrial respiration and redox metabolism has remained unknown. Here, we investigated the redox properties of human AIF and AMID by comparing them with yeast Ndi1, a type 2 NADH:ubiquinone oxidoreductase (NDH-2) regarded as alternative complex I. Isolated AIF and AMID containing naturally incorporated FAD displayed no NADH oxidase activities. However, after reconstituting isolated AIF or AMID into bacterial or mitochondrial membranes, N-terminally tagged AIF and AMID displayed substantial NADH:O₂ activities and supported NADH-linked proton pumping activities in the host membranes almost as efficiently as Ndi1. NADH:ubiquinone-1 activities in the reconstituted membranes were highly sensitive to 2-n-heptyl-4-hydroxyquinoline-N-oxide (IC₅₀ = ∼1 μm), a quinone-binding inhibitor. Overexpressing N-terminally tagged AIF and AMID enhanced the growth of a double knock-out Escherichia coli strain lacking complex I and NDH-2. In contrast, C-terminally tagged AIF and NADH-binding site mutants of N-terminally tagged AIF and AMID failed to show both NADH:O₂ activity and the growth-enhancing effect. The disease mutant AIFΔR201 showed decreased NADH:O₂ activity and growth-enhancing effect. Furthermore, we surprisingly found that the redox activities of N-terminally tagged AIF and AMID were sensitive to rotenone, a well known complex I inhibitor. We propose that AIF and AMID are previously unidentified mammalian NDH-2 enzymes, whose bioenergetic function could be supplemental NADH oxidation in cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Q-Band Electron-Nuclear Double Resonance Reveals Out-of-Plane Hydrogen Bonds Stabilize an Anionic Ubisemiquinone in Cytochrome bo3 from Escherichia coli.

PubMed

Sun, Chang; Taguchi, Alexander T; Vermaas, Josh V; Beal, Nathan J; O'Malley, Patrick J; Tajkhorshid, Emad; Gennis, Robert B; Dikanov, Sergei A

2016-10-11

The respiratory cytochrome bo 3 ubiquinol oxidase from Escherichia coli has a high-affinity ubiquinone binding site that stabilizes the one-electron reduced ubisemiquinone (SQ H ), which is a transient intermediate during the electron-mediated reduction of O 2 to water. It is known that SQ H is stabilized by two strong hydrogen bonds from R71 and D75 to ubiquinone carbonyl oxygen O1 and weak hydrogen bonds from H98 and Q101 to O4. In this work, SQ H was investigated with orientation-selective Q-band (∼34 GHz) pulsed 1 H electron-nuclear double resonance (ENDOR) spectroscopy on fully deuterated cytochrome (cyt) bo 3 in a H 2 O solvent so that only exchangeable protons contribute to the observed ENDOR spectra. Simulations of the experimental ENDOR spectra provided the principal values and directions of the hyperfine (hfi) tensors for the two strongly coupled H-bond protons (H1 and H2). For H1, the largest principal component of the proton anisotropic hfi tensor T z' = 11.8 MHz, whereas for H2, T z' = 8.6 MHz. Remarkably, the data show that the direction of the H1 H-bond is nearly perpendicular to the quinone plane (∼70° out of plane). The orientation of the second strong hydrogen bond, H2, is out of plane by ∼25°. Equilibrium molecular dynamics simulations on a membrane-embedded model of the cyt bo 3 Q H site show that these H-bond orientations are plausible but do not distinguish which H-bond, from R71 or D75, is nearly perpendicular to the quinone ring. Density functional theory calculations support the idea that the distances and geometries of the H-bonds to the ubiquinone carbonyl oxygens, along with the measured proton anisotropic hfi couplings, are most compatible with an anionic (deprotonated) ubisemiquinone.

Doping dependence of the anisotropic quasiparticle interference in NaFe(1-x)Co(x)As iron-based superconductors.

PubMed

Cai, Peng; Ruan, Wei; Zhou, Xiaodong; Ye, Cun; Wang, Aifeng; Chen, Xianhui; Lee, Dung-Hai; Wang, Yayu

2014-03-28

We use scanning tunneling microscopy to investigate the doping dependence of quasiparticle interference (QPI) in NaFe1-xCoxAs iron-based superconductors. The goal is to study the relation between nematic fluctuations and Cooper pairing. In the parent and underdoped compounds, where fourfold rotational symmetry is broken macroscopically, the QPI patterns reveal strong rotational anisotropy. At optimal doping, however, the QPI patterns are always fourfold symmetric. We argue this implies small nematic susceptibility and, hence, insignificant nematic fluctuation in optimally doped iron pnictides. Since TC is the highest this suggests nematic fluctuation is not a prerequistite for strong Cooper pairing.

Humans expect generosity

NASA Astrophysics Data System (ADS)

Brañas-Garza, Pablo; Rodríguez-Lara, Ismael; Sánchez, Angel

2017-02-01

Mechanisms supporting human ultra-cooperativeness are very much subject to debate. One psychological feature likely to be relevant is the formation of expectations, particularly about receiving cooperative or generous behavior from others. Without such expectations, social life will be seriously impeded and, in turn, expectations leading to satisfactory interactions can become norms and institutionalize cooperation. In this paper, we assess people’s expectations of generosity in a series of controlled experiments using the dictator game. Despite differences in respective roles, involvement in the game, degree of social distance or variation of stakes, the results are conclusive: subjects seldom predict that dictators will behave selfishly (by choosing the Nash equilibrium action, namely giving nothing). The majority of subjects expect that dictators will choose the equal split. This implies that generous behavior is not only observed in the lab, but also expected by subjects. In addition, expectations are accurate, matching closely the donations observed and showing that as a society we have a good grasp of how we interact. Finally, correlation between expectations and actual behavior suggests that expectations can be an important ingredient of generous or cooperative behavior.

Marivita hallyeonensis sp. nov., isolated from seawater, reclassification of Gaetbulicola byunsanensis as Marivita byunsanensis comb. nov. and emended description of the genus Marivita Hwang et al. 2009.

PubMed

Yoon, Jung-Hoon; Kang, So-Jung; Lee, Soo-Young; Jung, Yong-Taek; Lee, Jung-Sook; Oh, Tae-Kwang

2012-04-01

A Gram-stain-negative, non-motile, non-spore-forming, aerobic, rod-shaped bacterial strain, designated DPG-28T, was isolated from seawater on the southern coast of Korea. Strain DPG-28T grew optimally at 30 °C and in the presence of 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain DPG-28T formed a coherent cluster with members of the genera Marivita and Gaetbulicola, with which it exhibited sequence similarity values of 97.8-98.5 %. The DNA G+C content of strain DPG-28T was 65.1 mol%. The predominant ubiquinone of strain DPG-28T was ubiquinone-10 (Q-10), consistent with data for the genera Marivita and Gaetbulicola. The cellular fatty acid profiles of strain DPG-28T and the type strains of Marivita cryptomonadis, Marivita litorea and Gaetbulicola byunsanensis were essentially similar in that the common predominant fatty acid was C18:1ω7c. Major polar lipids found in strain DPG-28T and the type strains of M. cryptomonadis, M. litorea and G. byunsanensis were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine and an unidentified aminolipid. From these data, it is proposed that Gaetbulicola byunsanensis be reclassified as a member of the genus Marivita, for which the name Marivita byunsanensis comb. nov. is proposed, with the type strain SMK-114T (=CCUG 57612T=KCTC 22632T), and that strain DPG-28T be classified in the genus Marivita. Differential phenotypic properties and genetic distinctiveness of strain DPG-28T demonstrated that this strain is distinguishable from M. cryptomonadis, M. litorea and G. byunsanensis. On the basis of the data presented, strain DPG-28T is considered to represent a novel species of the genus Marivita, for which the name Marivita hallyeonensis sp. nov. is proposed. The type strain is DPG-28T (=KCTC 23421T=CCUG 60522T). An emended description of the genus Marivita is also provided.

Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4

PubMed Central

Foresti, Ombretta; Ruggiano, Annamaria; Hannibal-Bach, Hans K; Ejsing, Christer S; Carvalho, Pedro

2013-01-01

Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR, a rate-limiting enzyme of the mevalonate pathway. As HMGR acts at the beginning of the pathway, its regulation affects the synthesis of sterols and of other essential mevalonate-derived metabolites, such as ubiquinone or dolichol. Here, we describe a novel, evolutionarily conserved feedback system operating at a sterol-specific step of the mevalonate pathway. This involves the sterol-dependent degradation of squalene monooxygenase mediated by the yeast Doa10 or mammalian Teb4, a ubiquitin ligase implicated in a branch of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway. Since the other branch of ERAD is required for HMGR regulation, our results reveal a fundamental role for ERAD in sterol homeostasis, with the two branches of this pathway acting together to control sterol biosynthesis at different levels and thereby allowing independent regulation of multiple products of the mevalonate pathway. DOI: http://dx.doi.org/10.7554/eLife.00953.001 PMID:23898401

Complementary and alternative medicine approaches to blood pressure reduction: An evidence-based review.

PubMed

Nahas, Richard

2008-11-01

ABSTRACTOBJECTIVETo review the evidence supporting complementary and alternative medicine approaches used in the treatment of hypertension.QUALITY OF EVIDENCEMEDLINE and EMBASE were searched from January 1966 to May 2008 combining the key words hypertension or blood pressure with acupuncture, chocolate, cocoa, coenzyme Q10, ubiquinone, melatonin, vitamin D, meditation, and stress reduction. Clinical trials, prospective studies, and relevant references were included.MAIN MESSAGEEvidence from systematic reviews supports the blood pressure-lowering effects of coenzyme Q10, polyphenol-rich dark chocolate, Qigong, slow breathing, and transcendental meditation. Vitamin D deficiency is associated with hypertension and cardiovascular risk; supplementation lowered blood pressure in 2 trials. Acupuncture reduced blood pressure in 3 trials; in 1 of these it was no better than an invasive placebo. Melatonin was effective in 2 small trials, but caution is warranted in patients taking pharmacotherapy.CONCLUSIONSeveral complementary and alternative medicine therapies can be considered as part of an evidence-based approach to the treatment of hypertension. The potential benefit of these interventions warrants further research using cardiovascular outcomes.

Microbial community in biofilm on membrane surface of submerged MBR: effect of in-line cleaning chemical agent.

PubMed

Lim, B R; Ahn, K H; Song, K G; Cho, J W

2005-01-01

The objective of this study was to investigate the change in microbial community pattern with the effect of cleaning agent using a quinone profile that is used for membrane in-line chemical cleaning in SMBR. The dominant quinone types of biofilm were ubiquinone (UQs)-8, -10, followed by menaquinone (MKs)-8(H4), -7 and UQ-9, but those of suspended microorganisms were UQ-8, UQ-10 followed by MKs-8(H4), -7 and -11. Both UQ and MK contents decreased with increasing NaCIO dosage and it seems that there is more resistance from UQ compared to MK. In addition, COD and DOC concentrations increased with increasing NaClO dosage up to 0.05 g-NaCIO/g-SS. The organic degradation performance of the microbial community in the presence of NaClO was impaired. The present study suggested that larger added amounts of NaClO caused an inhibition of organic degradation and cell lysis.

Tag-mediated cooperation with non-deterministic genotype-phenotype mapping

NASA Astrophysics Data System (ADS)

Zhang, Hong; Chen, Shu

2016-01-01

Tag-mediated cooperation provides a helpful framework for resolving evolutionary social dilemmas. However, most of the previous studies have not taken into account genotype-phenotype distinction in tags, which may play an important role in the process of evolution. To take this into consideration, we introduce non-deterministic genotype-phenotype mapping into a tag-based model with spatial prisoner's dilemma. By our definition, the similarity between genotypic tags does not directly imply the similarity between phenotypic tags. We find that the non-deterministic mapping from genotypic tag to phenotypic tag has non-trivial effects on tag-mediated cooperation. Although we observe that high levels of cooperation can be established under a wide variety of conditions especially when the decisiveness is moderate, the uncertainty in the determination of phenotypic tags may have a detrimental effect on the tag mechanism by disturbing the homophilic interaction structure which can explain the promotion of cooperation in tag systems. Furthermore, the non-deterministic mapping may undermine the robustness of the tag mechanism with respect to various factors such as the structure of the tag space and the tag flexibility. This observation warns us about the danger of applying the classical tag-based models to the analysis of empirical phenomena if genotype-phenotype distinction is significant in real world. Non-deterministic genotype-phenotype mapping thus provides a new perspective to the understanding of tag-mediated cooperation.

10 CFR 607.620 - Cooperative agreement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Cooperative agreement. 607.620 Section 607.620 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 607.620 Cooperative agreement. Cooperative agreement means an award of...

48 CFR 702.170-4 - Cooperating country.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Cooperating country. 702.170-4 Section 702.170-4 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT GENERAL DEFINITIONS OF WORDS AND TERMS Definitions 702.170-4 Cooperating country. Cooperating country...

76 FR 27386 - Agency Information Collection (Cooperative Studies Program (CSP): Site Survey and Meeting...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-New (VA Form 10-0511)] Agency Information.... 2900-New (VA Form 10-0511).'' SUPPLEMENTARY INFORMATION: Titles: a. Cooperative Studies Program (CSP) Site Survey, VA Form 10-0511. b. Cooperative Studies Program (CSP) Meeting Evaluation, VA Form 10...

49 CFR 11.114 - Cooperative research.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 1 2012-10-01 2012-10-01 false Cooperative research. 11.114 Section 11.114... research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research projects, each institution is responsible for...

49 CFR 11.114 - Cooperative research.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 false Cooperative research. 11.114 Section 11.114... research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research projects, each institution is responsible for...

49 CFR 11.114 - Cooperative research.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Cooperative research. 11.114 Section 11.114... research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research projects, each institution is responsible for...

49 CFR 11.114 - Cooperative research.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Cooperative research. 11.114 Section 11.114... research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research projects, each institution is responsible for...

49 CFR 11.114 - Cooperative research.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false Cooperative research. 11.114 Section 11.114... research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research projects, each institution is responsible for...

Clustering in large networks does not promote upstream reciprocity.

PubMed

Masuda, Naoki

2011-01-01

Upstream reciprocity (also called generalized reciprocity) is a putative mechanism for cooperation in social dilemma situations with which players help others when they are helped by somebody else. It is a type of indirect reciprocity. Although upstream reciprocity is often observed in experiments, most theories suggest that it is operative only when players form short cycles such as triangles, implying a small population size, or when it is combined with other mechanisms that promote cooperation on their own. An expectation is that real social networks, which are known to be full of triangles and other short cycles, may accommodate upstream reciprocity. In this study, I extend the upstream reciprocity game proposed for a directed cycle by Boyd and Richerson to the case of general networks. The model is not evolutionary and concerns the conditions under which the unanimity of cooperative players is a Nash equilibrium. I show that an abundance of triangles or other short cycles in a network does little to promote upstream reciprocity. Cooperation is less likely for a larger population size even if triangles are abundant in the network. In addition, in contrast to the results for evolutionary social dilemma games on networks, scale-free networks lead to less cooperation than networks with a homogeneous degree distribution.

Clustering in Large Networks Does Not Promote Upstream Reciprocity

PubMed Central

Masuda, Naoki

2011-01-01

Upstream reciprocity (also called generalized reciprocity) is a putative mechanism for cooperation in social dilemma situations with which players help others when they are helped by somebody else. It is a type of indirect reciprocity. Although upstream reciprocity is often observed in experiments, most theories suggest that it is operative only when players form short cycles such as triangles, implying a small population size, or when it is combined with other mechanisms that promote cooperation on their own. An expectation is that real social networks, which are known to be full of triangles and other short cycles, may accommodate upstream reciprocity. In this study, I extend the upstream reciprocity game proposed for a directed cycle by Boyd and Richerson to the case of general networks. The model is not evolutionary and concerns the conditions under which the unanimity of cooperative players is a Nash equilibrium. I show that an abundance of triangles or other short cycles in a network does little to promote upstream reciprocity. Cooperation is less likely for a larger population size even if triangles are abundant in the network. In addition, in contrast to the results for evolutionary social dilemma games on networks, scale-free networks lead to less cooperation than networks with a homogeneous degree distribution. PMID:21998641

Proposals of Sphingomonas paucimobilis gen. nov. and comb. nov., Sphingomonas parapaucimobilis sp. nov., Sphingomonas yanoikuyae sp. nov., Sphingomonas adhaesiva sp. nov., Sphingomonas capsulata comb. nov., and two genospecies of the genus Sphingomonas.

PubMed

Yabuuchi, E; Yano, I; Oyaizu, H; Hashimoto, Y; Ezaki, T; Yamamoto, H

1990-01-01

Based on the partial nucleotide sequence analysis of 16S ribosomal ribonucleic acid (rRNA), presence of unique sphingoglycolipids in cellular lipid, and the major type of ubiquinone (Q10), we propose Sphingomonas gen. nov. with the type species Sphingomonas paucimobilis (Holmes et al, 1977) comb. nov. From the homology values of deoxyribonucleic acid-deoxyribonucleic acid hybridization and the phenotypic characteristics, three new species, Sphingomonas parapaucimobilis, Sphingomonas yanoikuyae, Sphingomonas adhaesiva, and one new combination, Sphingomonas capsulata, are described. S. parapaucimobilis JCM 7510 (= GIFU 11387), S. yanoikuyae JCM 7371 (= GIFU 9882), and S. adhaesiva JCM 7370 (= GIFU 11458) are designated as the type strains of the three new species. Emended description of the type strain of S. capsulata is presented.

Impact of Oral Ubiquinol on Blood Oxidative Stress and Exercise Performance

PubMed Central

Bloomer, Richard J.; Canale, Robert E.; McCarthy, Cameron G.; Farney, Tyler M.

2012-01-01

Coenzyme Q10 (CoQ10) plays an important role in bioenergetic processes and has antioxidant activity. Fifteen exercise-trained individuals (10 men and 5 women; 30–65 years) received reduced CoQ10 (Kaneka QH ubiquinol; 300 mg per day) or a placebo for four weeks in a random order, double blind, cross-over design (3 week washout). After each four-week period, a graded exercise treadmill test and a repeated cycle sprint test were performed (separated by 48 hours). Blood samples were collected before and immediately following both exercise tests and analyzed for lactate, malondialdehyde, and hydrogen peroxide. Resting blood samples were analyzed for CoQ10 (ubiquinone and ubiquinol) profile before and after each treatment period. Treatment with CoQ10 resulted in a significant increase in total blood CoQ10 (138%; P = 0.02) and reduced blood CoQ10 (168%; P = 0.02), but did not improve exercise performance (with the exception of selected individuals) or impact oxidative stress. The relationship between the percentage change in total blood CoQ10 and the cycle sprint total work (R2 = 0.6009) was noted to be moderate to strong. We conclude that treatment with CoQ10 in healthy, exercise-trained subjects increases total and reduced blood CoQ10, but this increase does not translate into improved exercise performance or decreased oxidative stress. PMID:22966414

Coenzyme Q plays opposing roles on bacteria/fungi and viruses in Drosophila innate immunity.

PubMed

Cheng, W; Song, C; Anjum, K M; Chen, M; Li, D; Zhou, H; Wang, W; Chen, J

2011-08-01

Coenzyme Q (CoQ or ubiquinone) is a lipid-soluble component of virtually all types of cell membranes and has been shown to play multiple metabolic functions. Several clinical diseases including encephalomyopathy, cerebellar ataxia and isolated myopathy were shown to be associated with CoQ deficiency. However, the role of CoQ in immunity has not been defined. In the present study, we showed that flies defective in CoQ biosynthetic gene coq2 were more susceptible to bacterial and fungal infections, while were more resistant to viruses. We found that Drosophila contained both CoQ9 and CoQ10, and food supplement of CoQ10 could partially rescue the impaired immune functions of coq2 mutants. Surprisingly, wild-type flies fed CoQ10 became more susceptible to viral infection, which suggested that extra caution should be taken when using CoQ10 as a food supplement. We further showed that CoQ was essential for normal induction of anti-microbial peptides and amplification of viruses. Our work determined CoQ content in Drosophila and described its function in immunity for the first time. © 2011 Blackwell Publishing Ltd.

Charges on Strange Quark Nuggets in Space

NASA Technical Reports Server (NTRS)

Teplitz, v.; Bhatia, A.; Abers, E.; Dicus, D.; Repko, Wayne; Rosenbaum, D.

2008-01-01

Witten (1984): 3 quark flavors implies same P.E., but less K.E. by Pauli Principle. Farhi and Jaffe find SQN B.E./q rises to asymptotic value as N=A/3 rises. A. De Rujula and S. Glashow identify bunch of methods of detecting SQNs. M. Alford, K.Rajagopa1, and F.Wilczek find Cooper pairing of SQN q's. Primordial: depends on cooling by evaporation being less than cooling by neutrino emission and any other mechanisms. Evap approx. MA(sup 2/3); neutrinos NM. M>10{20} works. Collisions of SQS's from NS binaries. Explosive events could give trifecta: gamma absorption for E>2m(e); emission at 2m(e); and emission at m(e-) from e+ production. There are questions of e+ production in COG, and of pair instability Sne. SQM roles possible. Possible detection of SQN emission line from e- capture during X-ray flare needs estimate.

16 CFR 307.10 - Cooperative advertising.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Cooperative advertising. 307.10 Section 307... REGULATIONS UNDER THE COMPREHENSIVE SMOKELESS TOBACCO HEALTH EDUCATION ACT OF 1986 Advertising Disclosures § 307.10 Cooperative advertising. The Act prohibits any manufacturer, packager, or importer of smokeless...

42 CFR 411.23 - Beneficiary's cooperation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Beneficiary's cooperation. 411.23 Section 411.23... Medicare Payment: General Provisions § 411.23 Beneficiary's cooperation. (a) If CMS takes action to recover conditional payments, the beneficiary must cooperate in the action. (b) If CMS's recovery action is...

45 CFR 303.107 - Requirements for cooperative arrangements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false Requirements for cooperative arrangements. 303.107... HUMAN SERVICES STANDARDS FOR PROGRAM OPERATIONS § 303.107 Requirements for cooperative arrangements. The State must ensure that all cooperative arrangements: (a) Contain a clear description of the specific...

50 CFR 29.2 - Cooperative land management.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Cooperative land management. 29.2 Section... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM LAND USE MANAGEMENT General Rules § 29.2 Cooperative land management. Cooperative agreements with persons for crop cultivation, haying, grazing, or the harvest of...

Colwellia aestuarii sp. nov., isolated from a tidal flat sediment in Korea.

PubMed

Jung, Seo-Youn; Oh, Tae-Kwang; Yoon, Jung-Hoon

2006-01-01

A novel Colwellia-like bacterial strain, SMK-10T, was isolated from a tidal flat sediment in Korea and subjected to a polyphasic taxonomic analysis. Cells of strain SMK-10T were Gram-negative, motile, greyish yellow-pigmented, curved rods. Optimal growth occurred at 25-30 degrees C and in the presence of 2-3 % (w/v) NaCl. Strain SMK-10T contained Q-8 as the predominant ubiquinone and C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH, C(17 : 1), C(15 : 1) and iso-C(16 : 0) as major fatty acids. The DNA G+C content was 39.3 mol%. Phylogenetic trees based on 16S rRNA gene sequence analysis showed that strain SMK-10T belonged to the genus Colwellia. 16S rRNA gene sequence similarity values (94.7-96.7 %) to the type strains of all other Colwellia species and various differential phenotypic properties were sufficient to distinguish strain SMK-10T from recognized Colwellia species. On the basis of its phenotypic properties and phylogenetic distinctiveness, strain SMK-10T (= KCTC 12480T = DSM 17314T) is classified as the type strain of a novel Colwellia species, for which the name Colwellia aestuarii sp. nov. is proposed.

50 CFR 15.26 - Approval of cooperative breeding programs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... WILDLIFE AND PLANTS WILD BIRD CONSERVATION ACT Permits and Approval of Cooperative Breeding Programs § 15.26 Approval of cooperative breeding programs. Upon receipt of a complete application, the Director... 50 Wildlife and Fisheries 1 2011-10-01 2011-10-01 false Approval of cooperative breeding programs...

45 CFR 46.114 - Cooperative research.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Cooperative research. 46.114 Section 46.114 Public... HHS Policy for Protection of Human Research Subjects § 46.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the...

45 CFR 46.114 - Cooperative research.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Cooperative research. 46.114 Section 46.114 Public... HHS Policy for Protection of Human Research Subjects § 46.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the...

45 CFR 46.114 - Cooperative research.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Cooperative research. 46.114 Section 46.114 Public... HHS Policy for Protection of Human Research Subjects § 46.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the...

45 CFR 46.114 - Cooperative research.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Cooperative research. 46.114 Section 46.114 Public... HHS Policy for Protection of Human Research Subjects § 46.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the...

45 CFR 46.114 - Cooperative research.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Cooperative research. 46.114 Section 46.114 Public... HHS Policy for Protection of Human Research Subjects § 46.114 Cooperative research. Cooperative research projects are those projects covered by this policy which involve more than one institution. In the...

43 CFR 24.6 - Cooperative agreements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Cooperative agreements. 24.6 Section 24.6... WILDLIFE POLICY: STATE-FEDERAL RELATIONSHIPS § 24.6 Cooperative agreements. (a) By reason of the... cooperative agreements for a variety of fish and wildlife programs on Federal lands. This practice shall be...

43 CFR 24.6 - Cooperative agreements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Cooperative agreements. 24.6 Section 24.6... WILDLIFE POLICY: STATE-FEDERAL RELATIONSHIPS § 24.6 Cooperative agreements. (a) By reason of the... cooperative agreements for a variety of fish and wildlife programs on Federal lands. This practice shall be...

43 CFR 24.6 - Cooperative agreements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Cooperative agreements. 24.6 Section 24.6... WILDLIFE POLICY: STATE-FEDERAL RELATIONSHIPS § 24.6 Cooperative agreements. (a) By reason of the... cooperative agreements for a variety of fish and wildlife programs on Federal lands. This practice shall be...

42 CFR 493.567 - Refusal to cooperate with validation inspection.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Refusal to cooperate with validation inspection... § 493.567 Refusal to cooperate with validation inspection. (a) Laboratory with a certificate of accreditation. (1) A laboratory with a certificate of accreditation that refuses to cooperate with a validation...

42 CFR 493.567 - Refusal to cooperate with validation inspection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Refusal to cooperate with validation inspection... § 493.567 Refusal to cooperate with validation inspection. (a) Laboratory with a certificate of accreditation. (1) A laboratory with a certificate of accreditation that refuses to cooperate with a validation...

42 CFR 493.567 - Refusal to cooperate with validation inspection.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Refusal to cooperate with validation inspection... § 493.567 Refusal to cooperate with validation inspection. (a) Laboratory with a certificate of accreditation. (1) A laboratory with a certificate of accreditation that refuses to cooperate with a validation...

42 CFR 493.567 - Refusal to cooperate with validation inspection.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Refusal to cooperate with validation inspection... § 493.567 Refusal to cooperate with validation inspection. (a) Laboratory with a certificate of accreditation. (1) A laboratory with a certificate of accreditation that refuses to cooperate with a validation...

42 CFR 493.567 - Refusal to cooperate with validation inspection.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Refusal to cooperate with validation inspection... § 493.567 Refusal to cooperate with validation inspection. (a) Laboratory with a certificate of accreditation. (1) A laboratory with a certificate of accreditation that refuses to cooperate with a validation...

Identification and transcription profiling of NDUFS8 in Aedes taeniorhynchus (Diptera:Culididae): developmental regulation and environmental response

USDA-ARS?s Scientific Manuscript database

The cDNA of a NADH dehydrogenase -ubiquinone Fe-S protein 8 subunit (NDUFS8) gene from Aedes (Ochlerotatus) taeniorhynchus Wiedemann has been cloned and sequenced. The full-length mRNA sequence (824 bp) of AetNDUFS8 encodes an open reading region of 651 bp (i.e., 217 amino acids). To detect whether ...

The 2-Methoxy Group Orientation Regulates the Redox Potential Difference between the Primary (QA) and Secondary (QB) Quinones of Type II Bacterial Photosynthetic Reaction Centers.

PubMed

de Almeida, Wagner B; Taguchi, Alexander T; Dikanov, Sergei A; Wraight, Colin A; O'Malley, Patrick J

2014-08-07

Recent studies have shown that only quinones with a 2-methoxy group can act simultaneously as the primary (Q A ) and secondary (Q B ) electron acceptors in photosynthetic reaction centers from purple bacteria such as Rb. sphaeroides . 13 C HYSCORE measurements of the 2-methoxy group in the semiquinone states, SQ A and SQ B , were compared with DFT calculations of the 13 C hyperfine couplings as a function of the 2-methoxy dihedral angle. X-ray structure comparisons support 2-methoxy dihedral angle assignments corresponding to a redox potential gap (Δ E m ) between Q A and Q B of 175-193 mV. A model having a methyl group substituted for the 2-methoxy group exhibits no electron affinity difference. This is consistent with the failure of a 2-methyl ubiquinone analogue to function as Q B in mutant reaction centers with a Δ E m of ∼160-195 mV. The conclusion reached is that the 2-methoxy group is the principal determinant of electron transfer from Q A to Q B in type II photosynthetic reaction centers with ubiquinone serving as both acceptor quinones.

Hydroxynonenal-stimulated activity of the uncoupling protein in Acanthamoeba castellanii mitochondria under phosphorylating conditions.

PubMed

Woyda-Ploszczyca, Andrzej; Jarmuszkiewicz, Wieslawa

2013-05-01

The influence of 4-hydroxy-2-nonenal (HNE), a lipid peroxidation end product, on the activity of the amoeba Acanthamoeba castellanii uncoupling protein (AcUCP) in isolated phosphorylating mitochondria was studied. Under phosphorylating conditions, exogenously added HNE induced GTP-sensitive AcUCP-mediated mitochondrial uncoupling. The HNE-induced proton leak decreased the yield of oxidative phosphorylation in an HNE concentration-dependent manner. The present study describes how the contributions of ATP synthase and HNE-induced AcUCP in phosphorylating respiration vary when the rate of succinate oxidation is decreased by limiting succinate uptake or inhibiting complex III activity within the range of a constant membrane potential. In phosphorylating mitochondria, at a given HNE concentration (100 μM), the efficiency of AcUCP in mitochondrial uncoupling increased as the respiratory rate decreased because the AcUCP contribution remained constant while the ATP synthase contribution decreased with the respiratory rate. HNE-induced uncoupling can be inhibited by GTP only when ubiquinone is sufficiently oxidized, indicating that in phosphorylating A. castellanii mitochondria, the sensitivity of AcUCP activity to GTP depends on the redox state of the membranous ubiquinone.

Changes in isoprenoid lipid synthesis by gemfibrozil and clofibric acid in rat hepatocytes.

PubMed

Hashimoto, F; Taira, S; Hayashi, H

2000-05-15

We studied whether gemfibrozil and clofibric acid alter isoprenoid lipid synthesis in rat hepatocytes. After incubation of the cells with the agent for 74 hr, [(14)C]acetate or [(3)H]mevalonate was added, and the cells were further incubated for 4 hr. Gemfibrozil and clofibric acid increased ubiquinone synthesis from [(14)C]acetate and [(3)H]mevalonate. The effect of gemfibrozil was greater than that of clofibric acid. Also, gemfibrozil decreased dolichol synthesis from [(14)C]acetate and [(3)H]mevalonate. However, clofibric acid increased dolichol synthesis from [(3)H]mevalonate. Gemfibrozil decreased cholesterol synthesis from [(14)C]acetate and [(3)H]mevalonate. Clofibric acid decreased cholesterol synthesis from [(14)C]acetate, but did not affect synthesis from [(3)H]mevalonate. These results suggest that both agents, at different rates, activate the synthetic pathway of ubiquinone, at least from mevalonate. Gemfibrozil may inhibit the synthetic pathway of dolichol, at least from mevalonate. Contrary to gemfibrozil, clofibric acid may activate the synthetic pathway of dolichol from mevalonate. Gemfibrozil may inhibit the synthetic pathway of cholesterol from mevalonate in addition to the pathway from acetate to mevalonate inhibited by both agents.

Component identification of electron transport chains in curdlan-producing Agrobacterium sp. ATCC 31749 and its genome-specific prediction using comparative genome and phylogenetic trees analysis.

PubMed

Zhang, Hongtao; Setubal, Joao Carlos; Zhan, Xiaobei; Zheng, Zhiyong; Yu, Lijun; Wu, Jianrong; Chen, Dingqiang

2011-06-01

Agrobacterium sp. ATCC 31749 (formerly named Alcaligenes faecalis var. myxogenes) is a non-pathogenic aerobic soil bacterium used in large scale biotechnological production of curdlan. However, little is known about its genomic information. DNA partial sequence of electron transport chains (ETCs) protein genes were obtained in order to understand the components of ETC and genomic-specificity in Agrobacterium sp. ATCC 31749. Degenerate primers were designed according to ETC conserved sequences in other reported species. DNA partial sequences of ETC genes in Agrobacterium sp. ATCC 31749 were cloned by the PCR method using degenerate primers. Based on comparative genomic analysis, nine electron transport elements were ascertained, including NADH ubiquinone oxidoreductase, succinate dehydrogenase complex II, complex III, cytochrome c, ubiquinone biosynthesis protein ubiB, cytochrome d terminal oxidase, cytochrome bo terminal oxidase, cytochrome cbb (3)-type terminal oxidase and cytochrome caa (3)-type terminal oxidase. Similarity and phylogenetic analyses of these genes revealed that among fully sequenced Agrobacterium species, Agrobacterium sp. ATCC 31749 is closest to Agrobacterium tumefaciens C58. Based on these results a comprehensive ETC model for Agrobacterium sp. ATCC 31749 is proposed.

Localization and Function of the Membrane-bound Riboflavin in the Na+-translocating NADH:Quinone Oxidoreductase (Na+-NQR) from Vibrio cholerae*

PubMed Central

Casutt, Marco S.; Huber, Tamara; Brunisholz, René; Tao, Minli; Fritz, Günter; Steuber, Julia

2010-01-01

The sodium ion-translocating NADH:quinone oxidoreductase (Na+-NQR) from the human pathogen Vibrio cholerae is a respiratory membrane protein complex that couples the oxidation of NADH to the transport of Na+ across the bacterial membrane. The Na+-NQR comprises the six subunits NqrABCDEF, but the stoichiometry and arrangement of these subunits are unknown. Redox-active cofactors are FAD and a 2Fe-2S cluster on NqrF, covalently attached FMNs on NqrB and NqrC, and riboflavin and ubiquinone-8 with unknown localization in the complex. By analyzing the cofactor content and NADH oxidation activity of subcomplexes of the Na+-NQR lacking individual subunits, the riboflavin cofactor was unequivocally assigned to the membrane-bound NqrB subunit. Quantitative analysis of the N-terminal amino acids of the holo-complex revealed that NqrB is present in a single copy in the holo-complex. It is concluded that the hydrophobic NqrB harbors one riboflavin in addition to its covalently attached FMN. The catalytic role of two flavins in subunit NqrB during the reduction of ubiquinone to ubiquinol by the Na+-NQR is discussed. PMID:20558724

Genome Analysis of Structure–Function Relationships in Respiratory Complex I, an Ancient Bioenergetic Enzyme

PubMed Central

Degli Esposti, Mauro

2016-01-01

Respiratory complex I (NADH:ubiquinone oxidoreductase) is a ubiquitous bioenergetic enzyme formed by over 40 subunits in eukaryotes and a minimum of 11 subunits in bacteria. Recently, crystal structures have greatly advanced our knowledge of complex I but have not clarified the details of its reaction with ubiquinone (Q). This reaction is essential for bioenergy production and takes place in a large cavity embedded within a conserved module that is homologous to the catalytic core of Ni–Fe hydrogenases. However, how a hydrogenase core has evolved into the protonmotive Q reductase module of complex I has remained unclear. This work has exploited the abundant genomic information that is currently available to deduce structure–function relationships in complex I that indicate the evolutionary steps of Q reactivity and its adaptation to natural Q substrates. The results provide answers to fundamental questions regarding various aspects of complex I reaction with Q and help re-defining the old concept that this reaction may involve two Q or inhibitor sites. The re-definition leads to a simplified classification of the plethora of complex I inhibitors while throwing a new light on the evolution of the enzyme function. PMID:26615219

Social grouping: perceptual grouping of objects by cooperative but not competitive relationships in dynamic chase.

PubMed

Yin, Jun; Ding, Xiaowei; Zhou, Jifan; Shui, Rende; Li, Xinyu; Shen, Mowei

2013-10-01

Historically, perceptual grouping is associated with physical principles. This article reports a novel finding that social information-cooperative but not competitive relationships-can drive perceptual grouping of objects in dynamic chase. Particularly, each relationship was constructed with human-generated chasing motions (i.e., two predators and one prey), and its role on perceptual grouping was examined by grouping-induced effect-attentional consequences. The results showed that: (1) Predators can be perceived as a group due to their cooperative relationship, causing attention to automatically spread within grouped predators, thus the response to target appearing on uncued predator is also facilitated; and (2) The attentional effect on competitive predators has no difference from any condition which controls low-level motion patterns, even including the random-motion condition wherein no grouping factor was contained. These findings extend perceptual grouping into the social field, implying that social information gets involved in visual cognition at an early perceptual stage. Copyright © 2013 Elsevier B.V. All rights reserved.

43 CFR 3192.12 - What activities may Tribes or States perform under cooperative agreements?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false What activities may Tribes or States perform under cooperative agreements? 3192.12 Section 3192.12 Public Lands: Interior Regulations Relating... Cooperative Agreements § 3192.12 What activities may Tribes or States perform under cooperative agreements...

43 CFR 3192.12 - What activities may Tribes or States perform under cooperative agreements?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false What activities may Tribes or States perform under cooperative agreements? 3192.12 Section 3192.12 Public Lands: Interior Regulations Relating... Cooperative Agreements § 3192.12 What activities may Tribes or States perform under cooperative agreements...

Evolutionary prisoner's dilemma games on the network with punishment and opportunistic partner switching

NASA Astrophysics Data System (ADS)

Takesue, H.

2018-02-01

Punishment and partner switching are two well-studied mechanisms that support the evolution of cooperation. Observation of human behaviour suggests that the extent to which punishment is adopted depends on the usage of alternative mechanisms, including partner switching. In this study, we investigate the combined effect of punishment and partner switching in evolutionary prisoner's dilemma games conducted on a network. In the model, agents are located on the network and participate in the prisoner's dilemma games with punishment. In addition, they can opportunistically switch interaction partners to improve their payoff. Our Monte Carlo simulation showed that a large frequency of punishers is required to suppress defectors when the frequency of partner switching is low. In contrast, cooperation is the most abundant strategy when the frequency of partner switching is high regardless of the strength of punishment. Interestingly, cooperators become abundant not because they avoid the cost of inflicting punishment and earn a larger average payoff per game but rather because they have more numerous opportunities to be referred to as a role agent by defectors. Our results imply that the fluidity of social relationships has a profound effect on the adopted strategy in maintaining cooperation.

Cheating is evolutionarily assimilated with cooperation in the continuous snowdrift game

PubMed Central

Sasaki, Tatsuya; Okada, Isamu

2015-01-01

It is well known that in contrast to the Prisoner’s Dilemma, the snowdrift game can lead to a stable coexistence of cooperators and cheaters. Recent theoretical evidence on the snowdrift game suggests that gradual evolution for individuals choosing to contribute in continuous degrees can result in the social diversification to a 100% contribution and 0% contribution through so-called evolutionary branching. Until now, however, game-theoretical studies have shed little light on the evolutionary dynamics and consequences of the loss of diversity in strategy. Here, we analyze continuous snowdrift games with quadratic payoff functions in dimorphic populations. Subsequently, conditions are clarified under which gradual evolution can lead a population consisting of those with 100% contribution and those with 0% contribution to merge into one species with an intermediate contribution level. The key finding is that the continuous snowdrift game is more likely to lead to assimilation of different cooperation levels rather than maintenance of diversity. Importantly, this implies that allowing the gradual evolution of cooperative behavior can facilitate social inequity aversion in joint ventures that otherwise could cause conflicts that are based on commonly accepted notions of fairness. PMID:25868940

Cheating is evolutionarily assimilated with cooperation in the continuous snowdrift game.

PubMed

Sasaki, Tatsuya; Okada, Isamu

2015-05-01

It is well known that in contrast to the Prisoner's Dilemma, the snowdrift game can lead to a stable coexistence of cooperators and cheaters. Recent theoretical evidence on the snowdrift game suggests that gradual evolution for individuals choosing to contribute in continuous degrees can result in the social diversification to a 100% contribution and 0% contribution through so-called evolutionary branching. Until now, however, game-theoretical studies have shed little light on the evolutionary dynamics and consequences of the loss of diversity in strategy. Here, we analyze continuous snowdrift games with quadratic payoff functions in dimorphic populations. Subsequently, conditions are clarified under which gradual evolution can lead a population consisting of those with 100% contribution and those with 0% contribution to merge into one species with an intermediate contribution level. The key finding is that the continuous snowdrift game is more likely to lead to assimilation of different cooperation levels rather than maintenance of diversity. Importantly, this implies that allowing the gradual evolution of cooperative behavior can facilitate social inequity aversion in joint ventures that otherwise could cause conflicts that are based on commonly accepted notions of fairness. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A comprehensive performance evaluation on the prediction results of existing cooperative transcription factors identification algorithms.

PubMed

Lai, Fu-Jou; Chang, Hong-Tsun; Huang, Yueh-Min; Wu, Wei-Sheng

2014-01-01

Eukaryotic transcriptional regulation is known to be highly connected through the networks of cooperative transcription factors (TFs). Measuring the cooperativity of TFs is helpful for understanding the biological relevance of these TFs in regulating genes. The recent advances in computational techniques led to various predictions of cooperative TF pairs in yeast. As each algorithm integrated different data resources and was developed based on different rationales, it possessed its own merit and claimed outperforming others. However, the claim was prone to subjectivity because each algorithm compared with only a few other algorithms and only used a small set of performance indices for comparison. This motivated us to propose a series of indices to objectively evaluate the prediction performance of existing algorithms. And based on the proposed performance indices, we conducted a comprehensive performance evaluation. We collected 14 sets of predicted cooperative TF pairs (PCTFPs) in yeast from 14 existing algorithms in the literature. Using the eight performance indices we adopted/proposed, the cooperativity of each PCTFP was measured and a ranking score according to the mean cooperativity of the set was given to each set of PCTFPs under evaluation for each performance index. It was seen that the ranking scores of a set of PCTFPs vary with different performance indices, implying that an algorithm used in predicting cooperative TF pairs is of strength somewhere but may be of weakness elsewhere. We finally made a comprehensive ranking for these 14 sets. The results showed that Wang J's study obtained the best performance evaluation on the prediction of cooperative TF pairs in yeast. In this study, we adopted/proposed eight performance indices to make a comprehensive performance evaluation on the prediction results of 14 existing cooperative TFs identification algorithms. Most importantly, these proposed indices can be easily applied to measure the performance of new algorithms developed in the future, thus expedite progress in this research field.

Colwellia agarivorans sp. nov., an agar-digesting marine bacterium isolated from coastal seawater.

PubMed

Xu, Zhen-Xing; Zhang, Heng-Xi; Han, Ji-Ru; Dunlap, Christopher A; Rooney, Alejandro P; Mu, Da-Shuai; Du, Zong-Jun

2017-06-01

A novel Gram-stain-negative, facultatively anaerobic, yellowish and agar-digesting marine bacterium, designated strain QM50T, was isolated from coastal seawater in an aquaculture site near Qingdao, China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate represented a member of the genus Colwellia and exhibited the highest sequence similarity (97.4 %) to Colwellia aestuarii SMK-10T. Average nucleotide identity (ANI) values based on draft genome sequences between strain QM50T and C. aestuarii KCTC 12480T showed a relatedness of 72.0 % (ANIb) and 85.1 % (ANIm). Cells of strain QM50T were approximately 0.3-0.6×0.8-2.5 µm in size and motile by means of a polar flagellum. Growth occurred in the presence of 1.0-6.0 % (w/v) NaCl (optimum, 2.0-3.0 %), at pH 6.5-8.5 (optimum, pH 7.0) and at 4-37 °C (optimum, 28-30 °C). Strain QM50T was found to contain ubiquinone 8 (Q-8) as the predominant ubiquinone and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH), C16 : 0 and C17 : 1ω8c as the main cellular fatty acids. Phosphatidylethanolamine and phosphatidylglycerol were found to be major polar lipids. The DNA G+C content of strain QM50T was determined to be 35.7 mol%. On the basis of phylogenetic and phenotypic data, strain QM50T represents a novel species of the genus Colwellia, for which the name Colwellia agarivorans sp. nov. is proposed. The type strain is QM50T (=KCTC 52273T=MCCC 1H00143T).

76 FR 53492 - South Carolina Public Service Authority (Also Referred to as Santee Cooper); Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-26

... Carolina Public Service Authority (Also Referred to as Santee Cooper); Combined Licenses for Virgil C... as Santee Cooper), for two Title 10 of the Code of Federal Regulations (10 CFR) part 52 combined... Service Authority (Also Referred to as Santee Cooper) Application for the Virgil C. Summer Nuclear Station...

Games of corruption in preventing the overuse of common-pool resources.

PubMed

Lee, Joung-Hun; Jusup, Marko; Iwasa, Yoh

2017-09-07

Maintaining human cooperation in the context of common-pool resource management is extremely important because otherwise we risk overuse and corruption. To analyse the interplay between economic and ecological factors leading to corruption, we couple the resource dynamics and the evolutionary dynamics of strategic decision making into a powerful analytical framework. The traits of this framework are: (i) an arbitrary number of harvesters share the responsibility to sustainably exploit a specific part of an ecosystem, (ii) harvesters face three strategic choices for exploiting the resource, (iii) a delegated enforcement system is available if called upon, (iv) enforcers are either honest or corrupt, and (v) the resource abundance reflects the choice of harvesting strategies. The resulting dynamical system is bistable; depending on the initial conditions, it evolves either to cooperative (sustainable exploitation) or defecting (overexploitation) equilibria. Using the domain of attraction to cooperative equilibria as an indicator of successful management, we find that the more resilient the resource (as implied by a high growth rate), the more likely the dominance of corruption which, in turn, suppresses the cooperative outcome. A qualitatively similar result arises when slow resource dynamics relative to the dynamics of decision making mask the benefit of cooperation. We discuss the implications of these results in the context of managing common-pool resources. Copyright © 2017 Elsevier Ltd. All rights reserved.

Localization of new, microdissection- generated, anonymous markers and of the genes Pcsk1, Dhfr, Ndub13, and Ccnb1 to rat chromosome region 2q1.

PubMed

Quan, X; Laes, J F; Ravoet, M; Van Vooren, P; Szpirer, J; Szpirer, C

2000-01-01

The centromeric region of rat chromosome 2 (2q1) harbors unidentified quantitative trait loci of genes that control tumor growth or development. To improve the mapping of this chromosome region, we microdissected it and generated 10 new microsatellite markers, which we included in the linkage map and/or radiation hybrid map of 2q1, together with other known markers, including four genes: Pcsk1 (protein convertase 1), Dhfr (dihydrofolate reductase), Ndub13 (NADH ubiquinone oxidoreductase subunit b13), and Ccnb1 (cyclin B1). To generate anchor points between the different maps, the gene Ndub13 and the microsatellite markers D2Ulb25 and D2Mit1 were also localized cytogenetically. The radiation map generated in region 2q1 extends its centromeric end of about 150 cR. Copyright 2000 S. Karger AG, Basel

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

Breton, J.; Berger, G.; Nabedryk, E.

The photoreduction of the secondary quinone acceptor Q{sub B} in reaction centers (RCs) of the photosynthetic bacteria Rhodobacter sphaeroides and Rhodopseudomonas viridis has been investigated by light-induced FTIR difference spectroscopy of RCs reconstituted with several isotopically labeled ubiquinones. The labels used were {sup 18}O on both carbonyls and {sup 13}C either uniformly or selectively at the 1- or the 4-position, i.e., on either one of the two carbonyls. The Q{sub B}{sup {minus}}/Q{sub B} spectra of RCs reconstituted with the isotopically labeled and unlabeled quinones as well as the double differences calculated form these spectra exhibit distinct isotopic shifts for amore » numer of bands attributed to vibrations of Q{sub B} and Q{sub B}{sup {minus}}. The vibrational modes of the quinone in the Q{sub B} site are compared to those of ubiquinone in vitro, leading to band assignments for the C{double_bond}O and C{double_bond}C vibrations of the neutral Q{sub B} and for the C---O and C---C of the semiquinone. The C{double_bond}O frequency of each of the carbonyls of the unlabeled quinone is revealed at 1641 cm{sup {minus}1} for both species. This demonstrates symmetrical and weak hydrogen bonding of the two C{double_bond}O groups to the protein at the Q{sub B} site. In contrast, the C{double_bond}C vibrations are not equivalent for selective labeling at C{sub 1} or at C{sub 4}, although they both contribute to the {approximately}1611-cm{sup {minus}1} band in the Q{sub B}{sup {minus}}/Q{sub B} spectra of the two species. Compared to the vibrations of isolated ubiquinone, the C{double_bond}C mode of Q{sub B} does not involve displacement of the C{sub 4} carbon atom, while the motion of C{sub 1} is not hindered. Further analysis of the spectra suggests that the protein at the binding site imposes a specific constraint on the methoxy and/or the methyl group proximal to the C{sub 4} carbonyl. 49 refs., 5 figs.« less

Role of the PufX protein in photosynthetic growth of Rhodobacter sphaeroides. 2. PufX is required for efficient ubiquinone/ubiquinol exchange between the reaction center QB site and the cytochrome bc1 complex.

PubMed

Barz, W P; Verméglio, A; Francia, F; Venturoli, G; Melandri, B A; Oesterhelt, D

1995-11-21

The PufX membrane protein is essential for photosynthetic growth of Rhodobacter sphaeroides because it is required for multiple-turnover electron transfer under anaerobic conditions [see accompanying article; Barz, W. P., Francia, F., Venturoli, G., Melandri, B. A., Verméglio, A., & Oesterhelt, D. (1995) Biochemistry 34, 15235-15247]. In order to understand the molecular role of PufX, light-induced absorption spectroscopy was performed using a pufX- mutant, a pufX+ strain, and two suppressor mutants. We show that the reaction center (RC) requires PufX for its functionality under different redox conditions than the cytochrome bc1 complex: When the kinetics of flash-induced reduction of cytochrome b561 were monitored in chromatophores, we observed a requirement of PufX for turnover of the cytochrome bc1 complex only at high redox potential (Eh > 140 mV), suggesting a function of PufX in lateral ubiquinol transfer from the RC. In contrast, PufX is required for multiple turnover of the RC only under reducing conditions: When the Q pool was partially oxidized in vivo using oxygen or electron acceptors like dimethyl sulfoxide or trimethylamine N-oxide, the deletion of PufX had no effect on light-driven electron flow through the RC. Flash train experiments under anaerobic in vivo conditions revealed that RC photochemistry does not depend on PufX for the first two flash excitations. Following the third and subsequent flashes, however, efficient charge separation requires PufX, indicating an important role of PufX for fast Q/QH2 exchange at the QB site of the RC. We show that the Q/QH2 exchange rate is reduced approximately 500-fold by the deletion of PufX when the Q pool is nearly completely reduced, demonstrating an essential role of PufX for the access of ubiquinone to the QB site. The fast ubiquinone/ubiquinol exchange is partially restored by suppressor mutations altering the macromolecular antenna structure. These results suggest an indirect role of PufX in structurally organizing a functional photosynthetic apparatus.

Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9.

PubMed

Danhauser, Katharina; Herebian, Diran; Haack, Tobias B; Rodenburg, Richard J; Strom, Tim M; Meitinger, Thomas; Klee, Dirk; Mayatepek, Ertan; Prokisch, Holger; Distelmaier, Felix

2016-03-01

Coenzyme Q10 (CoQ10) has an important role in mitochondrial energy metabolism by way of its functioning as an electron carrier in the respiratory chain. Genetic defects disrupting the endogenous biosynthesis pathway of CoQ10 may lead to severe metabolic disorders with onset in early childhood. Using exome sequencing in a child with fatal neonatal lactic acidosis and encephalopathy, we identified a homozygous loss-of-function variant in COQ9. Functional studies in patient fibroblasts showed that the absence of the COQ9 protein was concomitant with a strong reduction of COQ7, leading to a significant accumulation of the substrate of COQ7, 6-demethoxy ubiquinone10. At the same time, the total amount of CoQ10 was severely reduced, which was reflected in a significant decrease of mitochondrial respiratory chain succinate-cytochrome c oxidoreductase (complex II/III) activity. Lentiviral expression of COQ9 restored all these parameters, confirming the causal role of the variant. Our report on the second COQ9 patient expands the clinical spectrum associated with COQ9 variants, indicating the importance of COQ9 already during prenatal development. Moreover, the rescue of cellular CoQ10 levels and respiratory chain complex activities by CoQ10 supplementation points to the importance of an early diagnosis and immediate treatment.

An Optical Fiber Communication System Based on Coherent Modulation. Part 1.

DTIC Science & Technology

1985-06-01

the’ local oscillator signal. In the receiver the two signals are recombined optically using a single mode fiber coupler or a beam splitter , and the...Fig. 2. Design of practical systems may imply the use of non - ideal laser diodes. In a cooperation with British Telecom Research Labora- tories we...frequency stabilisation *the transmission fiber - *injection locking of semiconductor lasers *the coherent receiver Our next target is complete design

Thalassospira permensis sp. nov., a new terrestrial halotolerant bacterium isolated from a naphthalene-utilizing microbial consortium.

PubMed

Plotnikova, E G; Anan'ina, L N; Krausova, V I; Ariskina, E V; Prisyazhnaya, N V; Lebedev, A T; Demakov, V A; Evtushenko, L I

2011-01-01

A halotolerant bacterium, strain SMB34T, was isolated from a naphthalene-utilizing bacterial consortium obtained from primitive technogeneous soil (Vrkhnekamsk salt deposit, Perm region, Russia) by enrichment procedure. The strain itself was unable to degrade naphthalene and grew at NaCl concentrations up to 11% (w/v). The 16S rRNA-based phylogenetic analysis showed that the strain belongs to the genus Thalassospira. The DNA-DNA hybridization values between SMB34T and the type strains of phylogenetically closest species (T. xiamenensis, T. profundimaris and T. tepidiphila) did not exceed 50%. The novel strain could be distinguished from the above species by the cell motility, MALDI/TOF mass spectra of whole cells and a range of physiological and biochemical characteristics. SMB34T also considerably differs from the recently described species T. xianhensis, with the most striking differences in the DNA G + C content (53.7 +/- 1.0 vs. 61.2 +/- 1.0 mol.%) and predominant ubiquinones (Q-10 vs. Q-9). The data obtained suggest strain SMB34T (=VKM B-2527T = NBRC 106175T), designated as the type strain, represents a novel species, named Thalassospira permensis sp. nov.

Dysfunctional Coq9 protein causes predominant encephalomyopathy associated with CoQ deficiency.

PubMed

García-Corzo, Laura; Luna-Sánchez, Marta; Doerrier, Carolina; García, José A; Guarás, Adela; Acín-Pérez, Rebeca; Bullejos-Peregrín, Javier; López, Ana; Escames, Germaine; Enríquez, José A; Acuña-Castroviejo, Darío; López, Luis C

2013-03-15

Coenzyme Q10 (CoQ(10)) or ubiquinone is a well-known component of the mitochondrial respiratory chain. In humans, CoQ(10) deficiency causes a mitochondrial syndrome with an unexplained variability in the clinical presentations. To try to understand this heterogeneity in the clinical phenotypes, we have generated a Coq9 Knockin (R239X) mouse model. The lack of a functional Coq9 protein in homozygous Coq9 mutant (Coq9(X/X)) mice causes a severe reduction in the Coq7 protein and, as consequence, a widespread CoQ deficiency and accumulation of demethoxyubiquinone. The deficit in CoQ induces a brain-specific impairment of mitochondrial bioenergetics performance, a reduction in respiratory control ratio, ATP levels and ATP/ADP ratio and specific loss of respiratory complex I. These effects lead to neuronal death and demyelinization with severe vacuolization and astrogliosis in the brain of Coq9(X/X) mice that consequently die between 3 and 6 months of age. These results suggest that the instability of mitochondrial complex I in the brain, as a primary event, triggers the development of mitochondrial encephalomyopathy associated with CoQ deficiency.

Identification of Carotenoids and Isoprenoid Quinones from Asaia lannensis and Asaia bogorensis.

PubMed

Antolak, Hubert; Oracz, Joanna; Otlewska, Anna; Żyżelewicz, Dorota; Kręgiel, Dorota

2017-09-25

The aim of the study was to identify and quantitatively assess of carotenoids and isoprenoid quinones biosynthesized by six different strains of acetic acid bacteria, belonging to genus Asaia , that are common beverage-spoiling bacteria in Europe. Bacterial cultures were conducted in a laboratory liquid culture minimal medium with 2% sucrose. Carotenoids and isoprenoid quinones were investigated using UHPLC-DAD-ESI-MS analysis. In general, tested strains of Asaia spp. were able to produce 10 carotenoids and 3 isoprenoid quinones: menaquinone-7, menaquinone-8, and ubiquinone-10. The main identified carotenoids in Asaia lannensis strains were phytofluene, neurosporene, α-carotene, while for Asaia bogorensis , neurosporene, canthaxanthin, and zeaxanthin were noted. What is more, tested Asaia spp. were able to produce myxoxanthophyll, which has so far been identified primarily in cyanobacteria. The results show that A. lannensis are characterized by statistically higher concentrations of produced carotenoids, as well as a greater variety of these compounds. We have noted that carotenoids were not only accumulated by bacterial cells, but also some strains of A. lannensis produced extracellular carotenoids.

Roseomonas wooponensis sp. nov., isolated from wetland freshwater.

PubMed

Lee, Ji Hee; Kim, Mi Sun; Baik, Keun Sik; Kim, Hyang Mi; Lee, Kang Hyun; Seong, Chi Nam

2015-11-01

A non-motile, cocobacilli-shaped and pink-pigmented bacterium, designated strain WW53T, was isolated from wetland freshwater (Woopo wetland, Republic of Korea). Cells were Gram-stain-negative, catalase- and oxidase-positive. The major fatty acids were C18 : 1ω7c/C18 : 1ω6c and C16 : 0.The predominant quinone and polyamine were ubiquinone 10 (Q-10) and spermidine, respectively. The DNA G+C content was 71 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine and an unknown aminolipid. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain WW53T belongs to the family Acetobacteraceae, and is related to the genus Roseomonas. Strain WW53T was most closely related to Roseomonas stagni HS-69T (95.3 % 16S rRNA gene sequence similarity). Results of a polyphasic taxonomy study suggested that the isolate represents a novel species in the genus Roseomonas, for which the name Roseomonas wooponensis sp. nov. is proposed. The type strain is WW53T ( = KCTC 32534T = JCM 19527T).

7 CFR 1484.73 - Are Cooperators penalized for failing to make required contributions?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Are Cooperators penalized for failing to make... Cooperators penalized for failing to make required contributions? A Cooperator's contribution requirement is specified in the Cooperator program allocation letter. If a Cooperator fails to contribute the amount...

7 CFR 1484.73 - Are Cooperators penalized for failing to make required contributions?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Are Cooperators penalized for failing to make... Cooperators penalized for failing to make required contributions? A Cooperator's contribution requirement is specified in the Cooperator program allocation letter. If a Cooperator fails to contribute the amount...

7 CFR 1484.73 - Are Cooperators penalized for failing to make required contributions?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Are Cooperators penalized for failing to make... Cooperators penalized for failing to make required contributions? A Cooperator's contribution requirement is specified in the Cooperator program allocation letter. If a Cooperator fails to contribute the amount...

7 CFR 1484.73 - Are Cooperators penalized for failing to make required contributions?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Are Cooperators penalized for failing to make... § 1484.73 Are Cooperators penalized for failing to make required contributions? A Cooperator's contribution requirement is specified in the Cooperator program allocation letter. If a Cooperator fails to...

7 CFR 1484.73 - Are Cooperators penalized for failing to make required contributions?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Are Cooperators penalized for failing to make... § 1484.73 Are Cooperators penalized for failing to make required contributions? A Cooperator's contribution requirement is specified in the Cooperator program allocation letter. If a Cooperator fails to...

45 CFR 630.620 - Cooperative agreement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Cooperative agreement. 630.620 Section 630.620... agreement. Cooperative agreement means an award of financial assistance that, consistent with 31 U.S.C. 6305... development agreements as defined in 15 U.S.C. 3710a. ...

45 CFR 630.620 - Cooperative agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Cooperative agreement. 630.620 Section 630.620... agreement. Cooperative agreement means an award of financial assistance that, consistent with 31 U.S.C. 6305... development agreements as defined in 15 U.S.C. 3710a. ...

45 CFR 630.620 - Cooperative agreement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Cooperative agreement. 630.620 Section 630.620... agreement. Cooperative agreement means an award of financial assistance that, consistent with 31 U.S.C. 6305... development agreements as defined in 15 U.S.C. 3710a. ...

49 CFR 37.57 - Required cooperation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Required cooperation. 37.57 Section 37.57 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Transportation Facilities § 37.57 Required cooperation. An owner or person in control of an...

Payoff non-linearity sways the effect of mistakes on the evolution of reciprocity.

PubMed

Kurokawa, Shun

2016-09-01

The existence of cooperation is considered to require explanation, and reciprocity is a potential explanatory mechanism. Animals sometimes fail to cooperate even when they attempt to do so, and a reciprocator has an Achilles' heel: it is vulnerable to error (the interaction between two reciprocators can lead to an endless vendetta.). However, the strategy favored by natural selection is determined also by its interaction with other strategies. The relationship between two reciprocators leading to a collapse of cooperation through error does not straightforwardly imply that mistakes make the conditions under which reciprocity evolves stringent. Hence, mistakes may facilitate the evolution of reciprocity. However, it has been shown through the analysis of the interaction between reciprocators and unconditional defectors that the existence of mistakes makes the conditions for reciprocators stable against invasion by an unconditional defector more stringent, which indicates that mistakes discourage the evolution of reciprocity. However, this result is based on the assumption that the effects of cooperation are additive (payoff is linear), while the game played by real animals does not always display this feature. In such cases, the result may be swayed. In this paper, we remove this assumption, reexamining whether mistakes disturb the evolution of reciprocity. Using the analysis of an evolutionarily stable strategy (ESS), we show that when extra fitness costs are present in cases where mutual cooperation is established, mistakes can facilitate the evolution of reciprocity; whereas, when the effect of cooperation is additive, mistakes always disturb the evolution of reciprocity, as has been shown previously. Copyright © 2016. Published by Elsevier Inc.

10 CFR 603.1240 - Cooperative agreement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Cooperative agreement. 603.1240 Section 603.1240 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in this Part § 603.1240 Cooperative agreement. A legal instrument which, consistent with 31 U.S.C...

10 CFR 603.1240 - Cooperative agreement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Cooperative agreement. 603.1240 Section 603.1240 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in this Part § 603.1240 Cooperative agreement. A legal instrument which, consistent with 31 U.S.C...

48 CFR 702.170-5 - Cooperating country national (CCN).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Cooperating country national (CCN). 702.170-5 Section 702.170-5 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT GENERAL DEFINITIONS OF WORDS AND TERMS Definitions 702.170-5 Cooperating country national (CCN...

48 CFR 225.7902 - Defense Trade Cooperation Treaties.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Defense Trade Cooperation Treaties. 225.7902 Section 225.7902 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION EXPORT CONTROL 225.7902 Defense Trade Cooperation Treaties. This...

48 CFR 225.7902 - Defense Trade Cooperation Treaties.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Defense Trade Cooperation Treaties. 225.7902 Section 225.7902 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION EXPORT CONTROL 225.7902 Defense Trade Cooperation Treaties. This...

Delftia rhizosphaerae sp. nov. isolated from the rhizosphere of Cistus ladanifer.

PubMed

Carro, Lorena; Mulas, Rebeca; Pastor-Bueis, Raquel; Blanco, Daniel; Terrón, Arsenio; González-Andrés, Fernando; Peix, Alvaro; Velázquez, Encarna

2017-06-01

A bacterial strain, designated RA6T, was isolated from the rhizosphere of Cistus ladanifer. Phylogenetic analyses based on 16S rRNA gene sequence placed the isolate into the genus Delftia within a cluster encompassing the type strains of Delftia lacustris, Delftia tsuruhatensis, Delftia acidovorans and Delftia litopenaei, which presented greater than 97 % sequence similarity with respect to strain RA6T. DNA-DNA hybridization studies showed average relatedness ranging from of 11 to 18 % between these species of the genus Delftia and strain RA6T. Catalase and oxidase were positive. Casein was hydrolysed but gelatin and starch were not. Ubiquinone 8 was the major respiratory quinone detected in strain RA6T together with low amounts of ubiquinones 7 and 9. The major fatty acids were those from summed feature 3 (C16 : 1ω7c/C16 : 1 ω6c) and C16 : 0. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Phylogenetic, chemotaxonomic and phenotypic analyses showed that strain RA6T should be considered as a representative of a novel species of genus Delftia, for which the name Delftia rhizosphaerae sp. nov. is proposed. The type strain is RA6T (=LMG 29737T= CECT 9171T).

Effect of hexavalent chromium on electron leakage of respiratory chain in mitochondria isolated from rat liver.

PubMed

Xie, Ying; Zhong, Caigao; Zeng, Ming; Guan, Lan; Luo, Lei

2013-01-01

In the present study, we explored reactive axygen species (ROS) production in mitochondria, the mechanism of hexavalent chromium (Cr(VI)) hepatotoxicity, and the role of protection by GSH. Intact mitochondria were isolated from rat liver tissues and mitochondrial basal respiratory rates of NADH and FADH2 respiratory chains were determined. Mitochondria were treated with Cr(VI), GSH and several complex inhibitors. Mitochondria energized by glutamate/malate were separately or jointly treated with Rotenone (Rot), diphenyleneiodonium (DPI) and antimycinA (Ant), while mitochondria energized by succinate were separately or jointly treated with Rot, DPI ' thenoyltrifluoroacetone (TTFA) and Ant. Cr(VI) concentration-dependently induced ROS production in the NADH and FADH2 respiratory chain in liver mitochondria. Basal respiratory rate of the mitochondrial FADH2 respiratory chain was significantly higher than that of NADH respiratory chain. Hepatic mitochondrial electron leakage induced by Cr(VI) from NADH respiratory chain were mainly from ubiquinone binding sites of complex I and complex III. Treatment with 50µM Cr(VI) enhances forward movement of electrons through FADH2 respiratory chain and leaking through the ubiquinone binding site of complex III. Moreover, the protective effect of GSH on liver mitochondria electron leakage is through removing excess H2O2 and reducing total ROS. Copyright © 2013 S. Karger AG, Basel.

Cohesion-decohesion asymmetry in geckos

NASA Astrophysics Data System (ADS)

Puglisi, G.; Truskinovsky, L.

2013-03-01

Lizards and insects can strongly attach to walls and then detach applying negligible additional forces. We propose a simple mechanical model of this phenomenon which implies active muscle control. We show that the detachment force may depend not only on the properties of the adhesive units, but also on the elastic interaction among these units. By regulating the scale of such cooperative interaction, the organism can actively switch between two modes of adhesion: delocalized (pull off) and localized (peeling).

Asymmetric interaction paired with a super-rational strategy might resolve the tragedy of the commons without requiring recognition or negotiation.

PubMed

He, Jun-Zhou; Wang, Rui-Wu; Jensen, Christopher X J; Li, Yao-Tang

2015-01-14

Avoiding the tragedy of the commons requires that one or more individuals in a group or partnership "volunteer", benefiting the group at a cost to themselves. Recognition and negotiation with social partners can maintain cooperation, but are often not possible. If recognition and negotiation are not always the mechanism by which cooperative partnerships avoid collective tragedies, what might explain the diverse social cooperation observed in nature? Assuming that individuals interact asymmetrically and that both "weak" and "strong" players employ a super-rational strategy, we find that tragedy of the commons can be avoided without requiring either recognition or negotiation. Whereas in the volunteer's dilemma game a rational "strong" player is less likely to volunteer to provide a common good in larger groups, we show that under a wide range of conditions a super-rational "strong" player is more likely to provide a common good. These results imply that the integration of super-rationality and asymmetric interaction might have the potential to resolve the tragedy of the commons. By illuminating the conditions under which players are likely to volunteer, we shed light on the patterns of volunteerism observed in variety of well-studied cooperative social systems, and explore how societies might avert social tragedies.

Asymmetric interaction paired with a super-rational strategy might resolve the tragedy of the commons without requiring recognition or negotiation

PubMed Central

He, Jun-Zhou; Wang, Rui-Wu; Jensen, Christopher X. J.; Li, Yao-Tang

2015-01-01

Avoiding the tragedy of the commons requires that one or more individuals in a group or partnership “volunteer”, benefiting the group at a cost to themselves. Recognition and negotiation with social partners can maintain cooperation, but are often not possible. If recognition and negotiation are not always the mechanism by which cooperative partnerships avoid collective tragedies, what might explain the diverse social cooperation observed in nature? Assuming that individuals interact asymmetrically and that both “weak” and “strong” players employ a super-rational strategy, we find that tragedy of the commons can be avoided without requiring either recognition or negotiation. Whereas in the volunteer's dilemma game a rational “strong” player is less likely to volunteer to provide a common good in larger groups, we show that under a wide range of conditions a super-rational “strong” player is more likely to provide a common good. These results imply that the integration of super-rationality and asymmetric interaction might have the potential to resolve the tragedy of the commons. By illuminating the conditions under which players are likely to volunteer, we shed light on the patterns of volunteerism observed in variety of well-studied cooperative social systems, and explore how societies might avert social tragedies. PMID:25586876

Undermining the rules in home care services for the elderly in Norway: flexibility and cooperation.

PubMed

Wollscheid, Sabine; Eriksen, John; Hallvik, Jørgen

2013-06-01

This study explores the provision of home care services (home nursing and domiciliary help) for the elderly in Norwegian municipalities with purchaser-provider split model. The study draws on the assumption that flexibility in adjusting services to the care receivers' needs, and cooperation between provider and purchasers are indicators of good quality of care. Data were collected through semi-structured telephone interviews with 22 team leaders of provider units in nine municipalities. Data were collected in 2008-2009. The study has been approved by the Norwegian Social Science Data Services. We identified four different ways of organising home care services under a purchaser-provider split model: Provider empowerment, New Public Management, Vague instructions and undermining the rules. High flexibility in providing care and cooperation with the purchaser unit were identified by the team leaders as characteristics for good care. Our findings suggest that the care providers use individual strategies that allow flexibility and cooperation rather than rigidly abiding to the regulations the purchaser-provider split models implies. Ironically, in provider units where the 'rules were undermined', the informants (team leaders of provider units) seemed to be most satisfied with the quality of home care that they delivered. © 2012 Nordic College of Caring Science.

Asymmetric interaction paired with a super-rational strategy might resolve the tragedy of the commons without requiring recognition or negotiation

NASA Astrophysics Data System (ADS)

He, Jun-Zhou; Wang, Rui-Wu; Jensen, Christopher X. J.; Li, Yao-Tang

2015-01-01

Avoiding the tragedy of the commons requires that one or more individuals in a group or partnership ``volunteer'', benefiting the group at a cost to themselves. Recognition and negotiation with social partners can maintain cooperation, but are often not possible. If recognition and negotiation are not always the mechanism by which cooperative partnerships avoid collective tragedies, what might explain the diverse social cooperation observed in nature? Assuming that individuals interact asymmetrically and that both ``weak'' and ``strong'' players employ a super-rational strategy, we find that tragedy of the commons can be avoided without requiring either recognition or negotiation. Whereas in the volunteer's dilemma game a rational ``strong'' player is less likely to volunteer to provide a common good in larger groups, we show that under a wide range of conditions a super-rational ``strong'' player is more likely to provide a common good. These results imply that the integration of super-rationality and asymmetric interaction might have the potential to resolve the tragedy of the commons. By illuminating the conditions under which players are likely to volunteer, we shed light on the patterns of volunteerism observed in variety of well-studied cooperative social systems, and explore how societies might avert social tragedies.

Competition of tolerant strategies in the spatial public goods game

NASA Astrophysics Data System (ADS)

Szolnoki, Attila; Perc, Matjaž

2016-08-01

Tolerance implies enduring trying circumstances with a fair and objective attitude. To determine whether evolutionary advantages might be stemming from diverse levels of tolerance in a population, we study a spatial public goods game, where in addition to cooperators, defectors, and loners, tolerant players are also present. Depending on the number of defectors within a group, a tolerant player can either cooperate in or abstain from a particular instance of the game. We show that the diversity of tolerance can give rise to synergistic effects, wherein players with a different threshold in terms of the tolerated number of defectors in a group compete most effectively against defection and default abstinence. Such synergistic associations can stabilise states of full cooperation where otherwise defection would dominate. We observe complex pattern formation that gives rise to an intricate phase diagram, where invisible yet stable strategy alliances require outmost care lest they are overlooked. Our results highlight the delicate importance of diversity and tolerance for the provisioning of public goods, and they reveal fascinating subtleties of the spatiotemporal dynamics that is due to the competition of subsystem solutions in structured populations.

Technology transfer through a network of standard methods and recommended practices - The case of petrochemicals

NASA Astrophysics Data System (ADS)

Batzias, Dimitris F.; Karvounis, Sotirios

2012-12-01

Technology transfer may take place in parallel with cooperative action between companies participating in the same organizational scheme or using one another as subcontractor (outsourcing). In this case, cooperation should be realized by means of Standard Methods and Recommended Practices (SRPs) to achieve (i) quality of intermediate/final products according to specifications and (ii) industrial process control as required to guarantee such quality with minimum deviation (corresponding to maximum reliability) from preset mean values of representative quality parameters. This work deals with the design of the network of SRPs needed in each case for successful cooperation, implying also the corresponding technology transfer, effectuated through a methodological framework developed in the form of an algorithmic procedure with 20 activity stages and 8 decision nodes. The functionality of this methodology is proved by presenting the path leading from (and relating) a standard test method for toluene, as petrochemical feedstock in the toluene diisocyanate production, to the (6 generations distance upstream) performance evaluation of industrial process control systems (ie., from ASTM D5606 to BS EN 61003-1:2004 in the SRPs network).

42 CFR 476.76 - Cooperation with health care facilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 4 2012-10-01 2012-10-01 false Cooperation with health care facilities. 476.76 Section 476.76 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... § 476.76 Cooperation with health care facilities. Before implementation of review, a QIO must make a...

42 CFR 476.76 - Cooperation with health care facilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Cooperation with health care facilities. 476.76 Section 476.76 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Responsibilities of Quality Improvement Organizations (QIOs) General Provisions § 476.76 Cooperation with health...

43 CFR 3400.4 - Federal/state government cooperation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Federal/state government cooperation. 3400.4 Section 3400.4 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF... Introduction: General § 3400.4 Federal/state government cooperation. (a) In order to implement the requirements...

43 CFR 422.9 - Reclamation law enforcement contracts and cooperative agreements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Reclamation law enforcement contracts and... PROJECTS Program Requirements § 422.9 Reclamation law enforcement contracts and cooperative agreements. (a... Federal laws. (b) Each contract and cooperative agreement authorizing the exercise of Reclamation law...

7 CFR 1415.17 - Cooperative agreements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Cooperative agreements. 1415.17 Section 1415.17... Cooperative agreements. (a) NRCS may enter into cooperative agreements which establish terms and conditions... cooperative agreement with those eligible entities selected for funding. Once a proposal is selected by the...

7 CFR 1415.17 - Cooperative agreements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Cooperative agreements. 1415.17 Section 1415.17... Cooperative agreements. (a) NRCS may enter into cooperative agreements which establish terms and conditions... cooperative agreement with those eligible entities selected for funding. Once a proposal is selected by the...

Dynamics of Uncrystallized Water, Ice, and Hydrated Protein in Partially Crystallized Gelatin-Water Mixtures Studied by Broadband Dielectric Spectroscopy.

PubMed

Sasaki, Kaito; Panagopoulou, Anna; Kita, Rio; Shinyashiki, Naoki; Yagihara, Shin; Kyritsis, Apostolos; Pissis, Polycarpos

2017-01-12

The glass transition of partially crystallized gelatin-water mixtures was investigated using broadband dielectric spectroscopy (BDS) over a wide range of frequencies (10 mHz to 10 MHz), temperatures (113-298 K), and concentrations (10-45 wt %). Three dielectric relaxation processes (processes I, II, and III) were clearly observed. Processes I, II, and III originate from uncrystallized water (UCW) in the hydration shells of gelatin, ice, and hydrated gelatin, respectively. A dynamic crossover, called the Arrhenius to non-Arrhenius transition of UCW, was observed at the glass transition temperature of the relaxation process of hydrated gelatin for all mixtures. The amount of UCW increases with increasing gelatin content. However, above 35 wt % gelatin, the amount of UCW became more dependent on the gelatin concentration. This increase in UCW causes a decrease in the glass transition temperature of the cooperative motion of gelatin and UCW, which appears to result from a change in the aggregation structure of gelatin in the mixture at a gelatin concentration of approximately 35 wt %. The temperature dependence of the relaxation time of process II has nearly the same activation energy as pure ice made by slow crystallization of ice Ih. This implies that process II originates from the dynamics of slowly crystallized ice Ih.

7 CFR 1491.20 - Cooperative agreements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Cooperative agreements. 1491.20 Section 1491.20... Cooperative Agreements and Conservation Easement Deeds § 1491.20 Cooperative agreements. (a) NRCS, on behalf of CCC, shall enter into a cooperative agreement with those entities selected for funding. Once a...

7 CFR 1425.19 - Member cooperatives.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Member cooperatives. 1425.19 Section 1425.19... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COOPERATIVE MARKETING ASSOCIATIONS § 1425.19 Member cooperatives. A CMA may obtain loans or LDP's on behalf of a member cooperative when the member...

7 CFR 1491.20 - Cooperative agreements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Cooperative agreements. 1491.20 Section 1491.20... Cooperative Agreements and Conservation Easement Deeds § 1491.20 Cooperative agreements. (a) NRCS, on behalf of CCC, shall enter into a cooperative agreement with those entities selected for funding. Once a...

Quasiparticle Excitations in the Superconducting State of FeSe Probed by Thermal Hall Conductivity in the Vicinity of the BCS-BEC Crossover

NASA Astrophysics Data System (ADS)

Watashige, Tatsuya; Arsenijević, Stevan; Yamashita, Takuya; Terazawa, Daiki; Onishi, Takafumi; Opherden, Lars; Kasahara, Shigeru; Tokiwa, Yoshifumi; Kasahara, Yuichi; Shibauchi, Takasada; von Löhneysen, Hilbert; Wosnitza, Jochen; Matsuda, Yuji

2017-01-01

There is growing evidence that the superconducting semimetal FeSe (Tc ˜ 8 K) is in the crossover regime between weak-coupling Bardeen-Cooper-Schrieffer (BCS) and strong-coupling Bose-Einstein-condensate (BEC) limits. We report on longitudinal and transverse thermal conductivities, κxx and κxy, respectively, in magnetic fields up to 20 T. The field dependences of κxx and κxy imply that a highly anisotropic small superconducting gap forms at the electron Fermi-surface pocket whereas a more isotropic and larger gap forms at the hole pocket. Below ˜1.0 K, both κxx and κxy exhibit distinct anomalies (kinks) at the upper critical field Hc2 and at a field H* slightly below Hc2. The analysis of the thermal Hall angle (κxy/κxx) indicates a change of the quasiparticle scattering rate at H*. These results provide strong support to the previous suggestion that above H* a distinct field-induced superconducting phase emerges with an unprecedented large spin imbalance.

43 CFR 13.3 - Cooperation in selection of facilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Cooperation in selection of facilities. 13.3 Section 13.3 Public Lands: Interior Office of the Secretary of the Interior VENDING FACILITIES OPERATED BY BLIND PERSONS § 13.3 Cooperation in selection of facilities. Upon request from a State...

Electrochemistry of LB films of mixed MGDG:UQ on ITO.

PubMed

Hoyo, Javier; Guaus, Ester; Torrent-Burgués, Juan; Sanz, Fausto

2015-08-01

The electrochemical behaviour of biomimetic monolayers of monogalactosyldiacylglycerol (MGDG) incorporating ubiquinone-10 (UQ) has been investigated. MGDG is the principal component in the thylakoid membrane and UQ seems a good substitute for plastoquinone-9, involved in photosynthesis chain. The monolayers have been performed using the Langmuir and Langmuir-Blodgett (LB) techniques and the redox behaviour of the LB films, transferred at several surface pressures on a glass covered with indium-tin oxide (ITO), has been characterized by cyclic voltammetry. The cyclic voltammograms show that UQ molecules present two redox processes (I and II) at high UQ content and high surface pressures, and only one redox process (I) at low UQ content and low surface pressures. The apparent rate constants calculated for processes I and II indicate a different kinetic control for the reduction and the oxidation of UQ/UQH2 redox couple, being k(Rapp)(I) = 2.2 · 10(-5) s(-1), k(Rapp)(II) = 5.1 · 10(-14) k(Oapp)(I) = 3.3 · 10(-3) s(-1) and k(Oapp)(II) = 6.1 · 10(-6) s(-1), respectively. The correlation of the redox response with the physical states of the LB films allows determining the positions of the UQ molecules in the biomimetic monolayer, which change with the surface pressure and the UQ content. These positions are known as diving and swimming. Copyright © 2015 Elsevier B.V. All rights reserved.

Green Bank Telescope Detection of HI Clouds in the Fermi Bubble Wind

NASA Astrophysics Data System (ADS)

Lockman, Felix; Di Teodoro, Enrico M.; McClure-Griffiths, Naomi M.

2018-01-01

We used the Robert C. Byrd Green Bank Telescope to map HI 21cm emission in two large regions around the Galactic Center in a search for HI clouds that might be entrained in the nuclear wind that created the Fermi bubbles. In a ~160 square degree region at |b|>4 deg. and |long|<10 deg we detect 106 HI clouds that have large non-circular velocities consistent with their acceleration by the nuclear wind. Rapidly moving clouds are found as far as 1.5 kpc from the center; there are no detectable asymmetries in the cloud populations above and below the Galactic Center. The cloud kinematics is modeled as a population with an outflow velocity of 330 km/s that fills a cone with an opening angle ~140 degrees. The total mass in the clouds is ~10^6 solar masses and we estimate cloud lifetimes to be between 2 and 8 Myr, implying a cold gas mass-loss rate of about 0.1 solar masses per year into the nuclear wind.The Green Bank Telescope is a facility of the National Science Foundation, operated under a cooperative agreement by Associated Universities, Inc.

Reciprocal cooperation in avian mobbing: playing nice pays.

PubMed

Wheatcroft, David J; Price, Trevor D

2008-08-01

Unrelated passerine birds often join together while mobbing, a widespread antipredator behavior during which birds harass a predator. Although previous analyses concluded that mobbing could not have evolved via reciprocity, Krams and colleagues' field experiments show that birds preferentially join mobs with neighbors that have aided them previously, suggesting that these birds utilize reciprocity-based strategies involving individual recognition and recollection of previous interactions with others. This implies a level of sophistication in bird communities greater than had previously been realized.

Candida konsanensis sp. nov., a new yeast species isolated from Jasminum adenophyllum in Thailand with potentially carboxymethyl cellulase-producing capability.

PubMed

Sarawan, Somporn; Mahakhan, Polson; Jindamorakot, Sasitorn; Vichitphan, Kanit; Vichitphan, Sukanda; Sawaengkaew, Jutaporn

2013-08-01

A new yeast species (KKU-FW10) belonging to the Candida genus was isolated from Jasminum adenophyllum in the Plant Genetic Conservation Project under The Royal Initiative of Her Royal Highness Princess Maha Chakri Sirindhorn area, Chulabhorn Dam, Konsan district within Chaiyaphum province in Thailand. The strain was identified via analysis of nucleotide sequences from the D1/D2 domain of 26S ribosomal DNA and based on its morphological, physiological and biochemical characteristics. The sequence obtained from yeast isolate KKU-FW10 was 97 percent identical to that of Candida chanthaburiensis (GenBank accession number AB500861.1), with 506/517 (nucleotides identity/total nucleotides) matching nucleotides, nine substitutions and two gaps being detected. This species belonged to the Candida clade. Regarding morphological characteristics, isolate KKU-FW10 presents cream-colored butyrous colonies, vegetative reproduction through budding and, round cells without filaments or ascospores. The major ubiquinone detected was Q-9. The above results suggest that isolate KKU-FW10 is a new member of the genus Candida, and the name Candida konsanensis is proposed for this yeast. The type strain of the new species is KKU-FW10(T) (= BCC 52588(T), = NBRC 109082(T), = CBS 12666(T)). In addition, this KKU-FW10 could potentially produce 58.24 Units/ml of carboxymethyl cellulase when it was cultured in YP broth containing 1.0 % carboxymethyl cellulose for 24 h.

42 CFR 137.305 - May Self-Governance Tribes act as lead, cooperating, or joint lead agencies for environmental...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false May Self-Governance Tribes act as lead, cooperating, or joint lead agencies for environmental review purposes? 137.305 Section 137.305 Public Health... Tribes act as lead, cooperating, or joint lead agencies for environmental review purposes? Yes, Self...

42 CFR 137.305 - May Self-Governance Tribes act as lead, cooperating, or joint lead agencies for environmental...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false May Self-Governance Tribes act as lead, cooperating, or joint lead agencies for environmental review purposes? 137.305 Section 137.305 Public Health... Tribes act as lead, cooperating, or joint lead agencies for environmental review purposes? Yes, Self...

42 CFR 137.305 - May Self-Governance Tribes act as lead, cooperating, or joint lead agencies for environmental...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false May Self-Governance Tribes act as lead, cooperating, or joint lead agencies for environmental review purposes? 137.305 Section 137.305 Public Health... Tribes act as lead, cooperating, or joint lead agencies for environmental review purposes? Yes, Self...

42 CFR 137.305 - May Self-Governance Tribes act as lead, cooperating, or joint lead agencies for environmental...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false May Self-Governance Tribes act as lead, cooperating, or joint lead agencies for environmental review purposes? 137.305 Section 137.305 Public Health... Tribes act as lead, cooperating, or joint lead agencies for environmental review purposes? Yes, Self...

42 CFR 137.305 - May Self-Governance Tribes act as lead, cooperating, or joint lead agencies for environmental...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false May Self-Governance Tribes act as lead, cooperating, or joint lead agencies for environmental review purposes? 137.305 Section 137.305 Public Health... Tribes act as lead, cooperating, or joint lead agencies for environmental review purposes? Yes, Self...

Pollution control costs of a transboundary river basin: Empirical tests of the fairness and stability of cost allocation mechanisms using game theory.

PubMed

Shi, Guang-Ming; Wang, Jin-Nan; Zhang, Bing; Zhang, Zhe; Zhang, Yong-Liang

2016-07-15

With rapid economic growth, transboundary river basin pollution in China has become a very serious problem. Based on practical experience in other countries, cooperation among regions is an economic way to control the emission of pollutants. This study develops a game theoretic simulation model to analyze the cost effectiveness of reducing water pollutant emissions in four regions of the Jialu River basin while considering the stability and fairness of four cost allocation schemes. Different schemes (the nucleolus, the weak nucleolus, the Shapley value and the Separable Cost Remaining Benefit (SCRB) principle) are used to allocate regionally agreed-upon water pollutant abatement costs. The main results show that the fully cooperative coalition yielded the highest incremental gain for regions willing to cooperate if each region agreed to negotiate by transferring part of the incremental gain obtained from the cooperation to cover the losses of other regions. In addition, these allocation schemes produce different outcomes in terms of their fairness to the players and in terms of their derived stability, as measured by the Shapley-Shubik Power Index and the Propensity to Disrupt. Although the Shapley value and the SCRB principle exhibit superior fairness and stabilization to the other methods, only the SCRB principle may maintains full cooperation among regions over the long term. The results provide clear empirical evidence that regional gain allocation may affect the sustainability of cooperation. Therefore, it is implied that not only the cost-effectiveness but also the long-term sustainability should be considered while formulating and implementing environmental policies. Copyright © 2016 Elsevier Ltd. All rights reserved.

7 CFR 1220.107 - Cooperator organization.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Cooperator organization. 1220.107 Section 1220.107... CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.107 Cooperator organization. The term Cooperator Organization means the American Soybean Association, or any successor organization...

Dynamical phase diagrams of a love capacity constrained prey-predator model

NASA Astrophysics Data System (ADS)

Simin, P. Toranj; Jafari, Gholam Reza; Ausloos, Marcel; Caiafa, Cesar Federico; Caram, Facundo; Sonubi, Adeyemi; Arcagni, Alberto; Stefani, Silvana

2018-02-01

One interesting question in love relationships is: finally, what and when is the end of this love relationship? Using a prey-predator Verhulst-Lotka-Volterra (VLV) model we imply cooperation and competition tendency between people in order to describe a "love dilemma game". We select the most simple but immediately most complex case for studying the set of nonlinear differential equations, i.e. that implying three persons, being at the same time prey and predator. We describe four different scenarios in such a love game containing either a one-way love or a love triangle. Our results show that it is hard to love more than one person simultaneously. Moreover, to love several people simultaneously is an unstable state. We find some condition in which persons tend to have a friendly relationship and love someone in spite of their antagonistic interaction. We demonstrate the dynamics by displaying flow diagrams.

Congestion schemes and Nash equilibrium in complex networks

NASA Astrophysics Data System (ADS)

Almendral, Juan A.; López, Luis; Cholvi, Vicent; Sanjuán, Miguel A. F.

2005-09-01

Whenever a common resource is scarce, a set of rules are needed to share it in a fairly way. However, most control schemes assume that users will behave in a cooperative way, without taking care of guaranteeing that they will not act in a selfish manner. Then, a fundamental issue is to evaluate the impact of cheating. From the point of view of game theory, a Nash equilibrium implies that nobody can take advantage by unilaterally deviating from this stable state, even in the presence of selfish users. In this paper we prove that any efficient Nash equilibrium strongly depends on the number of users, if the control scheme policy does not record their previous behavior. Since this is a common pattern in real situations, this implies that the system would be always out of equilibrium. Consequently, this result proves that, in practice, oblivious control schemes must be improved to cope with selfish users.

Two hydrophobic subunits are essential for the heme b ligation and functional assembly of complex II (succinate-ubiquinone oxidoreductase) from Escherichia coli.

PubMed

Nakamura, K; Yamaki, M; Sarada, M; Nakayama, S; Vibat, C R; Gennis, R B; Nakayashiki, T; Inokuchi, H; Kojima, S; Kita, K

1996-01-05

Complex II (succinate-ubiquinone oxidoreductase) from Escherichia coli is composed of four nonidentical subunits encoded by the sdhCDAB operon. Gene products of sdhC and sdhD are small hydrophobic subunits that anchor the hydrophilic catalytic subunits (flavoprotein and iron-sulfur protein) to the cytoplasmic membrane and are believed to be the components of cytochrome b556 in E. coli complex II. In the present study, to elucidate the role of two hydrophobic subunits in the heme b ligation and functional assembly of complex II, plasmids carrying portions of the sdh gene were constructed and introduced into E. coli MK3, which lacks succinate dehydrogenase and fumarate reductase activities. The expression of polypeptides with molecular masses of about 19 and 17 kDa was observed when sdhC and sdhD were introduced into MK3, respectively, indicating that sdhC encodes the large subunit (cybL) and sdhD the small subunit (cybS) of cytochrome b556. An increase in cytochrome b content was found in the membrane when sdhD was introduced, while the cytochrome b content did not change when sdhC was introduced. However, the cytochrome b expressed by the plasmid carrying sdhD differed from cytochrome b556 in its CO reactivity and red shift of the alpha absorption peak to 557.5 nm at 77 K. Neither hydrophobic subunit was able to bind the catalytic portion to the membrane, and only succinate dehydrogenase activity, not succinate-ubiquinone oxidoreductase activity, was found in the cytoplasmic fractions of the cells. In contrast, significantly higher amounts of cytochrome b556 were expressed in the membrane when sdhC and sdhD genes were both present, and the catalytic portion was found to be localized in the membrane with succinate-ubiquitnone oxidoreductase and succinate oxidase activities. These results strongly suggest that both hydrophobic subunits are required for heme insertion into cytochrome b556 and are essential for the functional assembly of E. coli complex II in the membrane. Accumulation of the catalytic portion in the cytoplasm was found when sdhCDAB was introduced into a heme synthesis mutant, suggesting the importance of heme in the assembly of E. coli complex II.

Arabidopsis ETR1 and ERS1 Differentially Repress the Ethylene Response in Combination with Other Ethylene Receptor Genes1[W

PubMed Central

Liu, Qian; Wen, Chi-Kuang

2012-01-01

The ethylene response is negatively regulated by a family of five ethylene receptor genes in Arabidopsis (Arabidopsis thaliana). The five members of the ethylene receptor family can physically interact and form complexes, which implies that cooperativity for signaling may exist among the receptors. The ethylene receptor gene mutations etr1-1(C65Y)(for ethylene response1-1), ers1-1(I62P) (for ethylene response sensor1-1), and ers1C65Y are dominant, and each confers ethylene insensitivity. In this study, the repression of the ethylene response by these dominant mutant receptor genes was examined in receptor-defective mutants to investigate the functional significance of receptor cooperativity in ethylene signaling. We showed that etr1-1(C65Y), but not ers1-1(I62P), substantially repressed various ethylene responses independent of other receptor genes. In contrast, wild-type receptor genes differentially supported the repression of ethylene responses by ers1-1(I62P); ETR1 and ETHYLENE INSENSITIVE4 (EIN4) supported ers1-1(I62P) functions to a greater extent than did ERS2, ETR2, and ERS1. The lack of both ETR1 and EIN4 almost abolished the repression of ethylene responses by ers1C65Y, which implied that ETR1 and EIN4 have synergistic effects on ers1C65Y functions. Our data indicated that a dominant ethylene-insensitive receptor differentially repressed ethylene responses when coupled with a wild-type ethylene receptor, which supported the hypothesis that the formation of a variety of receptor complexes may facilitate differential receptor signal output, by which ethylene responses can be repressed to different extents. We hypothesize that plants can respond to a broad ethylene concentration range and exhibit tissue-specific ethylene responsiveness with differential cooperation of the multiple ethylene receptors. PMID:22227969

Characteristics of a pink-pigmented bacterium isolated from biofilm in a cooling tower in Tokyo, Japan.

PubMed

Furuhata, Katsunori; Goto, Keiichi; Kato, Yuko; Saitou, Keiko; Sugiyama, Jun-ichi; Hara, Motonobu; Yoshida, Shin-ichi; Fukuyama, Masafumi

2007-01-01

Strain K-20, a Gram-negative, non-motile, non-spore-forming and strictly aerobic rod, which produces a pale pink pigment, was isolated from biofilm in a cooling tower in Tokyo, Japan. The taxonomic feature of the strain was studied using phenotypic tests and phylogenetic analysis. Phylogenetic analysis of 16S rRNA gene sequences showed that the strain was related to Roseomonas gilardii subsp. rosea, Roseomonas gilardii subsp. gilardii, Roseomonas cervicalis and Roseomonas mucosa at 94.3-94.6 sequence similarities. Growth occurred at 25-40 C and pH 5.0-10.0, optimal at 35 C and pH 7.0. Growth did not occur in the presence of >or=2% NaCl. The API 20NE identification system gave a positive result for urease, L-arabinose, potassium gluconate, adipic acid, malic acid and trisodium citrate (API code number 0201465). The predominant fatty acids of strain K-20 were C18:1Delta11 (50.8%) and C16:1 (17.2%). Cells contained ubiquinone 10 (Q-10) as the major quinone and the G+C content was 72.0 mol%. Based on phenotypic, chemotaxonomic and phylogenetic data, it was assumed that strain K-20 (=JCM 14634) is a novel species of the genus Roseomonas.

7 CFR 650.10 - Adoption of an EIS prepared by a cooperating agency.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Adoption of an EIS prepared by a cooperating agency... for NRCS-Assisted Programs § 650.10 Adoption of an EIS prepared by a cooperating agency. (a) If NRCS adopts an EIS prepared by another Federal or State agency, the RFO is to review the document to insure...

Assessing Water Security in the Amu Darya River Basin, Afghanistan

DTIC Science & Technology

2006-06-16

Television 11/20/04 Turkmenistan, Uzbekistan 3 Turkmenistan and Uzbekistan sign friendship accord. Cooperation Dushanbe Tajik Avesta (WWW...center for bilateral cooperation to support counter- narcotics efforts. Security Dushanbe Avesta WWW 10/8/05 Tajikistan, Uzbekistan -1...Tajikistanis demand compensation for injury from antipersonnel mines on the Tajik-Uzbek border. Cooperation Dushanbe Avesta WWW 116 10/13/05

Variability in group size and the evolution of collective action.

PubMed

Peña, Jorge; Nöldeke, Georg

2016-01-21

Models of the evolution of collective action typically assume that interactions occur in groups of identical size. In contrast, social interactions between animals occur in groups of widely dispersed size. This paper models collective action problems as two-strategy multiplayer games and studies the effect of variability in group size on the evolution of cooperative behavior under the replicator dynamics. The analysis identifies elementary conditions on the payoff structure of the game implying that the evolution of cooperative behavior is promoted or inhibited when the group size experienced by a focal player is more or less variable. Similar but more stringent conditions are applicable when the confounding effect of size-biased sampling, which causes the group-size distribution experienced by a focal player to differ from the statistical distribution of group sizes, is taken into account. Copyright © 2015 Elsevier Ltd. All rights reserved.

Concerted formation of macromolecular Suppressor–mutator transposition complexes

PubMed Central

Raina, Ramesh; Schläppi, Michael; Karunanandaa, Balasulojini; Elhofy, Adam; Fedoroff, Nina

1998-01-01

Transposition of the maize Suppressor–mutator (Spm) transposon requires two element-encoded proteins, TnpA and TnpD. Although there are multiple TnpA binding sites near each element end, binding of TnpA to DNA is not cooperative, and the binding affinity is not markedly affected by the number of binding sites per DNA fragment. However, intermolecular complexes form cooperatively between DNA fragments with three or more TnpA binding sites. TnpD, itself not a sequence-specific DNA-binding protein, binds to TnpA and stabilizes the TnpA–DNA complex. The high redundancy of TnpA binding sites at both element ends and the protein–protein interactions between DNA-bound TnpA complexes and between these and TnpD imply a concerted transition of the element from a linear to a protein crosslinked transposition complex within a very narrow protein concentration range. PMID:9671711

The Alzheimer's Disease Cooperative Study Prevention Instrument Project: Longitudinal Outcome of Behavioral Measures as Predictors of Cognitive Decline

PubMed Central

Banks, Sarah Jane; Raman, Rema; He, Feng; Salmon, David P.; Ferris, Steven; Aisen, Paul; Cummings, Jeffrey

2014-01-01

Background/Methods The Alzheimer's Disease Cooperative Study Prevention Instrument Project is a longitudinal study that recruited 644 cognitively healthy older subjects (aged between 75 and 93 years, 58% women) at baseline and evaluated their cognitive change over 4 years. The study was structured like a clinical trial to anticipate a prevention trial and to determine the performance of novel trial instruments in a longitudinal non-interventional trial framework. Behavioral symptoms were assessed at baseline. Results The existence of participant-reported behavioral symptoms at baseline predicted conversion to Clinical Dementia Rating scale score ≥0.5 over the 4-year period. Conclusions The results imply that early anxiety and depression may be harbingers of future cognitive decline, and that patients exhibiting such symptoms, even in the absence of co-occurring cognitive symptoms, should be closely followed over time. PMID:25685141

Regional cooperation and transportation planning in Alaska : a regional models of cooperation peer exchange summary report.

DOT National Transportation Integrated Search

2017-01-31

This report summarizes the proceedings of a Regional Models of Cooperation Virtual Peer Exchange Workshop held on March 9 10, 2016 for the State of Alaska. Participants discussed the benefits and challenges of cooperation across jurisdictions and...

Hypothalamic digoxin and hemispheric chemical dominance in relation to the pathogenesis of bronchial asthma.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-08-01

The isoprenoid pathway produces three key metabolites--digoxin (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter transport), dolichol (regulator of N-glycosylation of proteins), and ubiquinone (free radical scavenger). The isoprenoid pathway was assessed in patients with bronchial asthma. The pathway was also assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of bronchial asthma. The pathway was upregulated with increase in digoxin synthesis in bronchial asthma. There was an increase in tryptophan catabolites and a reduction in tyrosine catabolites in patients with bronchial asthma. The ubiquinone levels were low and lipid peroxidation increased in these patients. There was increase in dolichol and glycoconjugate levels and reduction in lysosomal stability in these patients. The cholesterol:phospholipid ratio was increased and glycoconjugate levels were reduced in the membranes of these patients. The patterns noticed in bronchial asthma were similar to those in patients with right hemispheric chemical dominance. Bronchial asthma occurs in right hemispheric chemically dominant individuals. Ninety percent of the patients with bronchial asthma were right-handed and left hemispheric dominant by the dichotic listening test. But their biochemical patterns were similar to those obtained in right hemispheric chemical dominance. Hemispheric chemical dominance is a different entity and has no correlation with handedness or the dichotic listening test.

Hypothalamic digoxin, hemispheric chemical dominance, and mesenteric artery occlusion.

PubMed

Kurup, Ravi Kumar; Kurup, Paramesware Achutha

2003-12-01

The role of the isoprenoid pathway in vascular thrombosis, especially mesenteric artery occlusion and its relation to hemispheric dominance, was assessed in this study. The following parameters were measured in patients with mesenteric artery occlusion and individuals with right hemispheric, left hemispheric, and bihemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition. In patients with mesenteric artery occlusion there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, low ubiquinone, and elevated free radical levels. The RBC membrane Na(+)-K+ ATPase activity and serum magnesium were decreased. There was also an increase in tryptophan catabolites and reduction in tyrosine catabolites in the serum. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these patients. The biochemical patterns obtained in mesenteric artery occlusion is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with mesenteric artery occlusion were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Mesenteric artery occlusion occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function. Hemispheric chemical dominance may thus control the risk for developing vascular thrombosis in individuals.

TCDD decreases ATP levels and increases reactive oxygen production through changes in mitochondrial F F{sub 1}-ATP synthase and ubiquinone

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

Shertzer, Howard G.; Genter, Mary Beth; Shen, Dongxiao

2006-12-15

Mitochondria generate ATP and participate in signal transduction and cellular pathology and/or cell death. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) decreases hepatic ATP levels and generates mitochondrial oxidative DNA damage, which is exacerbated by increasing mitochondrial glutathione redox state and by inner membrane hyperpolarization. This study identifies mitochondrial targets of TCDD that initiate and sustain reactive oxygen production and decreased ATP levels. One week after treating mice with TCDD, liver ubiquinone (Q) levels were significantly decreased, while rates of succinoxidase and Q-cytochrome c oxidoreductase activities were increased. However, the expected increase in Q reduction state following TCDD treatment did not occur; instead, Q wasmore » more oxidized. These results could be explained by an ATP synthase defect, a premise supported by the unusual finding that TCDD lowers ATP/O ratios without concomitant changes in respiratory control ratios. Such results suggest either a futile cycle in ATP synthesis, or hydrolysis of newly synthesized ATP prior to release. The TCDD-mediated decrease in Q, concomitant with an increase in respiration, increases complex 3 redox cycling. This acts in concert with glutathione to increase membrane potential and reactive oxygen production. The proposed defect in ATP synthase explains both the greater respiratory rates and the lower tissue ATP levels.« less

Conformational control of cofactors in nature: The effect of methoxy group orientation on the electronic structure of ubisemiquinone

NASA Astrophysics Data System (ADS)

De Almeida, Wagner B.; O'Malley, Patrick J.

2018-03-01

Ubiquinone is the key electron and proton transfer agent in biology. Its mechanism involves the formation of its intermediate one-electron reduced form, the ubisemiquinone radical. This is formed in a protein-bound form which permits the semiquinone to vary its electronic and redox properties. This can be achieved by hydrogen bonding acceptance by one or both oxygen atoms or as we now propose by restricted orientations for the methoxy groups of the headgroup. We show how the orientation of the two methoxy groups of the quinone headgroup affects the electronic structure of the semiquinone form and demonstrate a large dependence of the ubisemiquinone spin density distribution on the orientation each methoxy group takes with respect to the headgroup ring plane. This is shown to significantly modify associated hyperfine couplings which in turn needs to be accounted for in interpreting experimental values in vivo. The study uncovers the key potential role the methoxy group orientation can play in controlling the electronic structure and spin density of ubisemiquinone and provides an electronic-level insight into the variation in electron affinity and redox potential of ubiquinone as a function of the methoxy orientation. Taken together with the already known influence of cofactor conformation on heme and chlorophyll electronic structure, it reveals a more widespread role for cofactor conformational control of electronic structure and associated electron transfer in biology.

Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23.

PubMed

Hirawake, H; Taniwaki, M; Tamura, A; Kojima, S; Kita, K

1997-01-01

Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex in both the tricarboxylic acid cycle and the aerobic respiratory chains of mitochondria in eukaryotic cells and prokaryotic organisms. In this study, the amino acid sequences of the large (cybL) and small (cybS) subunits of cytochrome b in human liver complex II were deduced from cDNAs isolated by homology probing with mixed primers for the polymerase chain reaction. The mature cybL and cybS contain 140 and 103 amino acids, respectively, and show little similarity to the amino acid sequences of the subunits from other species in contrast to the highly conserved features of the flavoprotein (Fp) subunit and iron-sulfur protein (Ip) subunit. From hydrophobicity analysis, both cybL and cybS appear to have three transmembrane segments, indicating their role as membrane-anchors for the enzyme complex. Histidine residues, which are possible heme axial ligands in cytochrome b of complex II, were found in the second transmembrane segment of each subunit. The genes for cybL (SDHC) and cybS (SDHD) were mapped to chromosome 1q21 and 11q23, respectively by fluorescent in situ hybridization (FISH).

Inhibition of the sodium-translocating NADH-ubiquinone oxidoreductase [Na+-NQR] decreases cholera toxin production in Vibrio cholerae O1 at the late exponential growth phase

PubMed Central

Minato, Yusuke; Fassio, Sara R.; Reddekopp, Rylan L.; Häse, Claudia C.

2014-01-01

Two virulence factors produced by Vibrio cholerae, cholera toxin (CT) and toxin-corregulated pilus (TCP), are indispensable for cholera infection. ToxT is the central regulatory protein involved in activation of CT and TCP expression. We previously reported that lack of a respiration-linked sodium-translocating NADH–ubiquinone oxidoreductase (Na+-NQR) significantly increases toxT transcription. In this study, we further characterized this link and found that Na+-NQR affects toxT expression only at the early-log growth phase, whereas lack of Na+-NQR decreases CT production after the mid-log growth phase. Such decreased CT production was independent of toxT and ctxB transcription. Supplementing a respiratory substrate, L-lactate, into the growth media restored CT production in the nqrA-F mutant, suggesting that decreased CT production in the Na+-NQR mutant is dependent on electron transport chain (ETC) activity. This notion was supported by the observations that two chemical inhibitors, a Na+-NQR specific inhibitor 2-n-Heptyl-4-hydroxyquinoline N-oxide (HQNO) and a succinate dehydrogenase (SDH) inhibitor, thenoyltrifluoroacetone (TTFA), strongly inhibited CT production in both classical and El Tor biotype strains of V. cholerae. Accordingly, we propose the main respiratory enzyme of V. cholerae, as a potential drug target to treat cholera because human mitochondria do not contain Na+-NQR orthologs. PMID:24361395

On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm.

PubMed

Pincemail, J; Defraigne, J O; Cheramy-Bien, J P; Dardenne, N; Donneau, A F; Albert, A; Labropoulos, N; Sakalihasan, N

2012-01-01

Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients. Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (≤ 50 or > 50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased. The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression.

Anti-cancer analogues ME-143 and ME-344 exert toxicity by directly inhibiting mitochondrial NADH: ubiquinone oxidoreductase (Complex I).

PubMed

Lim, Sze Chern; Carey, Kirstyn T; McKenzie, Matthew

2015-01-01

Isoflavonoids have been shown to inhibit tumor proliferation and metastasis by activating cell death pathways. As such, they have been widely studied as potential therapies for cancer prevention. The second generation synthetic isoflavan analogues ME-143 and ME-344 also exhibit anti-cancer effects, however their specific molecular targets have not been completely defined. To identify these targets, we examined the effects of ME-143 and ME-344 on cellular metabolism and found that they are potent inhibitors of mitochondrial oxidative phosphorylation (OXPHOS) complex I (NADH: ubiquinone oxidoreductase) activity. In isolated HEK293T mitochondria, ME-143 and ME-344 reduced complex I activity to 14.3% and 28.6% of control values respectively. In addition to the inhibition of complex I, ME-344 also significantly inhibited mitochondrial complex III (ubiquinol: ferricytochrome-c oxidoreductase) activity by 10.8%. This inhibition of complex I activity (and to a lesser extent complex III activity) was associated with a reduction in mitochondrial oxygen consumption. In permeabilized HEK293T cells, ME-143 and ME-344 significantly reduced the maximum ADP-stimulated respiration rate to 62.3% and 70.0% of control levels respectively in the presence of complex I-linked substrates. Conversely, complex II-linked respiration was unaffected by either drug. We also observed that the inhibition of complex I-linked respiration caused the dissipation of the mitochondrial membrane potential (ΔΨm). Blue native (BN-PAGE) analysis revealed that prolonged loss of ΔΨm results in the destabilization of the native OXPHOS complexes. In particular, treatment of 143B osteosarcoma, HeLa and HEK293T human embryonic kidney cells with ME-344 for 4 h resulted in reduced steady-state levels of mature complex I. Degradation of the complex I subunit NDUFA9, as well as the complex IV (ferrocytochrome c: oxygen oxidoreductase) subunit COXIV, was also evident. The identification of OXPHOS complex I as a target of ME-143 and ME-344 advances our understanding of how these drugs induce cell death by disrupting mitochondrial metabolism, and will direct future work to maximize the anti-cancer capacity of these and other isoflavone-based compounds.

Secondary coenzyme Q10 deficiency and oxidative stress in cultured fibroblasts from patients with riboflavin responsive multiple Acyl-CoA dehydrogenation deficiency.

PubMed

Cornelius, Nanna; Byron, Colleen; Hargreaves, Iain; Guerra, Paula Fernandez; Furdek, Andrea K; Land, John; Radford, Weston W; Frerman, Frank; Corydon, Thomas J; Gregersen, Niels; Olsen, Rikke K J

2013-10-01

Coenzyme Q10 (CoQ10) is essential for the energy production of the cells and as an electron transporter in the mitochondrial respiratory chain. CoQ10 links the mitochondrial fatty acid β-oxidation to the respiratory chain by accepting electrons from electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). Recently, it was shown that a group of patients with the riboflavin responsive form of multiple acyl-CoA dehydrogenation deficiency (RR-MADD) carrying inherited amino acid variations in ETF-QO also had secondary CoQ10 deficiency with beneficial effects of CoQ10 treatment, thus adding RR-MADD to an increasing number of diseases involving secondary CoQ10 deficiency. In this study, we show that moderately decreased CoQ10 levels in fibroblasts from six unrelated RR-MADD patients were associated with increased levels of mitochondrial reactive oxygen species (ROS). Treatment with CoQ10, but not with riboflavin, could normalize the CoQ10 level and decrease the level of ROS in the patient cells. Additionally, riboflavin-depleted control fibroblasts showed moderate CoQ10 deficiency, but not increased mitochondrial ROS, indicating that variant ETF-QO proteins and not CoQ10 deficiency are the causes of mitochondrial ROS production in the patient cells. Accordingly, the corresponding variant Rhodobacter sphaeroides ETF-QO proteins, when overexpressed in vitro, bind a CoQ10 pseudosubstrate, Q10Br, less tightly than the wild-type ETF-QO protein, suggesting that molecular oxygen can get access to the electrons in the misfolded ETF-QO protein, thereby generating superoxide and oxidative stress, which can be reversed by CoQ10 treatment.

75 FR 4422 - Notice Pursuant to The National Cooperative Research and Production Act of 1993-Cooperative...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to The National Cooperative Research and Production Act of 1993--Cooperative Research Group on Clean Diesel V Notice is hereby given that, on December 10, 2009, pursuant to Section [[Page 4423

7 CFR 1491.20 - Cooperative agreements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Cooperative agreements. 1491.20 Section 1491.20... OF AGRICULTURE EXPORT PROGRAMS FARM AND RANCH LANDS PROTECTION PROGRAM Cooperative Agreements and Conservation Easement Deeds § 1491.20 Cooperative agreements. (a) NRCS, on behalf of the CCC, will enter into a...

Albibacter methylovorans gen. nov., sp. nov., a novel aerobic, facultatively autotrophic and methylotrophic bacterium that utilizes dichloromethane.

PubMed

Doronina, N V; Trotsenko, Y A; Tourova, T P; Kuznetsov, B B; Leisinger, T

2001-05-01

A novel genus, Albibacter, with one species, Albibacter methylovorans sp. nov., is proposed for a facultatively chemolithotrophic and methylotrophic bacterium (strain DM10T) with the ribulose bisphosphate (RuBP) pathway of C1 assimilation. The bacterium is a Gram-negative, aerobic, asporogenous, nonmotile, colourless rod that multiplies by binary fission. The organism utilizes dichloromethane, methanol, methylamine, formate and CO2/H2, as well as a variety of polycarbon compounds, as carbon and energy sources. It is neutrophilic and mesophilic. The major cellular fatty acids are straight-chain unsaturated C18:1, saturated C16:0 and cyclopropane C19:0 acids. The main ubiquinone is Q-10. The dominant phospholipids are phosphatidyl ethanolamine, phosphatidyl glycerol, phosphatidyl choline and cardiolipin. The DNA G+C content is 66.7 mol%. Strain DM10T has a very low degree of DNA-DNA hybridization (4-7%) with the type species of the genera Paracoccus, Xanthobacter, Blastobacter, Angulomicrobium, Ancylobacter and Ralstonia of RuBP pathway methylobacteria. Another approach, involving comparative 16S rDNA analysis, has shown that the novel isolate represents a separate branch within the alpha-2 subgroup of the Proteobacteria. The type species of the new genus is Albibacter methylovorans sp. nov.; the type strain is DM10T (= VKM B-2236T = DSM 13819T).

Agaricicola taiwanensis gen. nov., sp. nov., an alphaproteobacterium isolated from the edible mushroom Agaricus blazei.

PubMed

Chu, Jiunn-Nan; Arun, A B; Chen, Wen-Ming; Chou, Jui-Hsing; Shen, Fo-Ting; Rekha, P D; Kämpfer, P; Young, Li-Sen; Lin, Shih-Yao; Young, Chiu-Chung

2010-09-01

A Gram-negative, beige-pigmented, aerobic, motile, club-shaped bacterium, designated strain CC-SBABM117(T), was isolated from the stipe of the edible mushroom Agaricus blazei Murrill. 16S rRNA gene sequence analysis demonstrated that the strain shared <93 % similarity with the type strains of species in the genera Pannonibacter, Methylopila, Nesiotobacter and Stappia. The organism was unable to produce acid from carbohydrates, but utilized a number of organic acids and amino acids. Ubiquinone 10 (Q-10) was the major respiratory quinone and C(18 : 1) ω 7c, C(19 : 0) cyclo ω 8c, C(16 : 0) and C(18 : 0) were the predominant fatty acids. The predominant polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content of strain CC-SBABM117(T) was 62.7 mol%. On the basis of 16S rRNA gene sequence analysis and chemotaxonomic and physiological data, strain CC-SBABM117(T) is considered to represent a novel species of a new genus, for which the name Agaricicola taiwanensis gen. nov., sp. nov. is proposed. The type strain of Agaricicola taiwanensis is CC-SBABM117(T) (=BCRC 17964(T) =CCM 7684(T)).

Methylopila capsulata gen. nov., sp. nov., a novel non-pigmented aerobic facultatively methylotrophic bacterium.

PubMed

Doronina, N V; Trotsenko, Y A; Krausova, V I; Boulygina, E S; Tourova, T P

1998-10-01

A new genus, Methylopila, and one new species are described for a group of seven strains of facultatively methylotrophic bacteria with the serine pathway of C1 assimilation. These bacteria are aerobic, Gram-negative, non-spore--forming, motile, colourless rods that multiply by binary fission. Their DNA base content ranges from 66 to 70 mol % G + C. Their cellular fatty acid profile consists primarily of C18:1 omega 7 cis-vaccenic and C19:0 cyclopropane acids. The major hydroxy acid is 3-OH C14:0. The main ubiquinone is Q-10. The dominant cellular phospholipids are phosphatidylethanolamine and phosphatidylcholine. The new isolates have a low level of DNA-DNA homology (5-10%) with the type strains of the serine pathway methylobacteria belonging to the genera Methylobacterium, Aminobacter, Hyphomicrobium and Methylorhabdus. Another approach, involving 16S rRNA gene sequence analysis of strain IM1T, has shown that the new isolates represent a separate branch within the alpha-2 subclass of the Proteobacteria. The type species of the new genus is Methylopila capsulata sp. nov., with the type strain IM1T (= VKM B-1606T).

Beyond promiscuity: mate-choice commitments in social breeding

PubMed Central

Boomsma, Jacobus J.

2013-01-01

Obligate eusociality with distinct caste phenotypes has evolved from strictly monogamous sub-social ancestors in ants, some bees, some wasps and some termites. This implies that no lineage reached the most advanced form of social breeding, unless helpers at the nest gained indirect fitness values via siblings that were identical to direct fitness via offspring. The complete lack of re-mating promiscuity equalizes sex-specific variances in reproductive success. Later, evolutionary developments towards multiple queen-mating retained lifetime commitment between sexual partners, but reduced male variance in reproductive success relative to female's, similar to the most advanced vertebrate cooperative breeders. Here, I (i) discuss some of the unique and highly peculiar mating system adaptations of eusocial insects; (ii) address ambiguities that remained after earlier reviews and extend the monogamy logic to the evolution of soldier castes; (iii) evaluate the evidence for indirect fitness benefits driving the dynamics of (in)vertebrate cooperative breeding, while emphasizing the fundamental differences between obligate eusociality and cooperative breeding; (iv) infer that lifetime commitment is a major driver towards higher levels of organization in bodies, colonies and mutualisms. I argue that evolutionary informative definitions of social systems that separate direct and indirect fitness benefits facilitate transparency when testing inclusive fitness theory. PMID:23339241

Labor-Management Cooperation: The American Experience.

ERIC Educational Resources Information Center

Siegel, Irving H.; Weinberg, Edgar

This book examines the wide range of opportunities, the attendant problems, and the potential benefits of labor-management cooperation. Cooperative arrangements are considered at different economic levels, and 65 cases are discussed. The first of 10 chapters sets up a conceptual framework for the review of American experience in cooperation.…

49 CFR 383.72 - Implied consent to alcohol testing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Implied consent to alcohol testing. 383.72 Section 383.72 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER... consent to alcohol testing. Any person who holds a CDL is considered to have consented to such testing as...

Presentation of a Swedish study program concerning recruitment, selection and training of student air traffic controllers: The MRU project phase 1

NASA Technical Reports Server (NTRS)

Haglund, Rune

1994-01-01

The Director of the ANS Department has set up an objective for the efficiency of screening and training procedures for air traffic controller students which implies that all students admitted 'shall be considered to have the qualification for - and be given the means of - completing the training'. As a consequence, a study project has been established. It is run by the ANS Department with members from the Swedish CAA, in close cooperation with Uppsala University.

Classical synchronization indicates persistent entanglement in isolated quantum systems

PubMed Central

Witthaut, Dirk; Wimberger, Sandro; Burioni, Raffaella; Timme, Marc

2017-01-01

Synchronization and entanglement constitute fundamental collective phenomena in multi-unit classical and quantum systems, respectively, both equally implying coordinated system states. Here, we present a direct link for a class of isolated quantum many-body systems, demonstrating that synchronization emerges as an intrinsic system feature. Intriguingly, quantum coherence and entanglement arise persistently through the same transition as synchronization. This direct link between classical and quantum cooperative phenomena may further our understanding of strongly correlated quantum systems and can be readily observed in state-of-the-art experiments, for example, with ultracold atoms. PMID:28401881

Socially Extended Cognition and Shared Intentionality

PubMed Central

Lyre, Holger

2018-01-01

The paper looks at the intersection of extended cognition and social cognition. The central claim is that the mechanisms of shared intentionality can equally be considered as coupling mechanisms of cognitive extension into the social domain. This claim will be demonstrated by investigating a detailed example of cooperative action, and it will be argued that such cases imply that socially extended cognition is not only about cognitive vehicles, but that content must additionally be taken into account. It is finally outlined how social content externalism can in principle be grounded in socially extended cognition. PMID:29892254

Classical synchronization indicates persistent entanglement in isolated quantum systems.

PubMed

Witthaut, Dirk; Wimberger, Sandro; Burioni, Raffaella; Timme, Marc

2017-04-12

Synchronization and entanglement constitute fundamental collective phenomena in multi-unit classical and quantum systems, respectively, both equally implying coordinated system states. Here, we present a direct link for a class of isolated quantum many-body systems, demonstrating that synchronization emerges as an intrinsic system feature. Intriguingly, quantum coherence and entanglement arise persistently through the same transition as synchronization. This direct link between classical and quantum cooperative phenomena may further our understanding of strongly correlated quantum systems and can be readily observed in state-of-the-art experiments, for example, with ultracold atoms.

Coastal watershed management across an international border in the Tijuana River watershed

NASA Astrophysics Data System (ADS)

Fernandez, Linda

2005-05-01

The paper develops and applies a game theoretic model of upstream and downstream countries to examine cooperative and noncooperative strategies of a common watershed. The application to the Tijuana River watershed shared by the United States and Mexico provides quantification of the strategies for internalizing water quality externalities to upstream and downstream originating from sedimentation. Results show that different transfer payments, such as the Chander/Tulkens cost sharing rule and the Shapley value, imply the size of the existing transfer from downstream to upstream could increase the amount currently allocated.

7 CFR 1484.34 - Must Cooperators adhere to specific standards of ethical conduct?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Must Cooperators adhere to specific standards of ethical conduct? 1484.34 Section 1484.34 Agriculture Regulations of the Department of Agriculture... Cooperators adhere to specific standards of ethical conduct? (a) A Cooperator shall conduct its business in...

7 CFR 1484.57 - Will FAS make advance payments to a Cooperator?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Will FAS make advance payments to a Cooperator? 1484... DEVELOP FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Contributions and Reimbursements § 1484.57 Will FAS make advance payments to a Cooperator? (a) Policy. In general, FAS operates the Cooperator program on a...

7 CFR 1484.57 - Will FAS make advance payments to a Cooperator?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Will FAS make advance payments to a Cooperator? 1484... DEVELOP FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Contributions and Reimbursements § 1484.57 Will FAS make advance payments to a Cooperator? (a) Policy. In general, FAS operates the Cooperator program on a...

7 CFR 1484.57 - Will FAS make advance payments to a Cooperator?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Will FAS make advance payments to a Cooperator? 1484... FOR AGRICULTURAL COMMODITIES Contributions and Reimbursements § 1484.57 Will FAS make advance payments to a Cooperator? (a) Policy. In general, FAS operates the Cooperator program on a reimbursable basis...

7 CFR 1484.57 - Will FAS make advance payments to a Cooperator?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Will FAS make advance payments to a Cooperator? 1484... FOR AGRICULTURAL COMMODITIES Contributions and Reimbursements § 1484.57 Will FAS make advance payments to a Cooperator? (a) Policy. In general, FAS operates the Cooperator program on a reimbursable basis...

7 CFR 1484.57 - Will FAS make advance payments to a Cooperator?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Will FAS make advance payments to a Cooperator? 1484... FOR AGRICULTURAL COMMODITIES Contributions and Reimbursements § 1484.57 Will FAS make advance payments to a Cooperator? (a) Policy. In general, FAS operates the Cooperator program on a reimbursable basis...

Eliciting Survey Cooperation: Incentives, Self-Interest, and Norms of Cooperation

ERIC Educational Resources Information Center

Kropf, Martha E.; Blair, Johnny

2005-01-01

Given the weaker ties to community as noted by scholars such as Robert Putnam, survey researchers should not be surprised by a decline in survey participation over the past 10 years. This research analyzes the use of incentives coupled with introductory themes emphasizing cooperation and helpfulness--cooperative norms in American society--to…

7 CFR 621.10 - Description.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE WATER RESOURCES RIVER BASIN INVESTIGATIONS AND SURVEYS USDA Cooperative Studies § 621.10 Description. Cooperative river basin studies provide USDA planning assistance to Federal, State, and local... the requesting agencies and citizen groups that are consistent with USDA authorities and...

7 CFR 621.10 - Description.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE WATER RESOURCES RIVER BASIN INVESTIGATIONS AND SURVEYS USDA Cooperative Studies § 621.10 Description. Cooperative river basin studies provide USDA planning assistance to Federal, State, and local... the requesting agencies and citizen groups that are consistent with USDA authorities and...

Cooperative Learning in Rural and Small Schools. Rural/Small Schools Network Information Exchange: Number 10, Spring 1991.

ERIC Educational Resources Information Center

Regional Laboratory for Educational Improvement of the Northeast & Islands, Andover, MA.

This packet includes reprints of journal articles and other resources pertaining to cooperative learning strategies in small, rural schools. The four sections of the packet cover introduction to cooperative learning, examples of how team strategies and cooperative learning can be used, issues such as program evaluation and public relations, and…

49 CFR 383.72 - Implied consent to alcohol testing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false Implied consent to alcohol testing. 383.72 Section 383.72 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER... consent to alcohol testing. Any person who holds a CLP or CDL or is required to hold a CLP or CDL is...

Low-intensity laser irradiation at 660 nm stimulates transcription of genes involved in the electron transport chain.

PubMed

Masha, Roland T; Houreld, Nicolette N; Abrahamse, Heidi

2013-02-01

Low-intensity laser irradiation (LILI) has been shown to stimulate cellular functions leading to increased adenosine triphosphate (ATP) synthesis. This study was undertaken to evaluate the effect of LILI on genes involved in the mitochondrial electron transport chain (ETC, complexes I-IV) and oxidative phosphorylation (ATP synthase). Four human skin fibroblast cell models were used in this study: normal non-irradiated cells were used as controls while wounded, diabetic wounded, and ischemic cells were irradiated. Cells were irradiated with a 660 nm diode laser with a fluence of 5 J/cm(2) and gene expression determined by quantitative real-time reverse transcription (RT) polymerase chain reaction (PCR). LILI upregulated cytochrome c oxidase subunit VIb polypeptide 2 (COX6B2), cytochrome c oxidase subunit VIc (COX6C), and pyrophosphatase (inorganic) 1 (PPA1) in diabetic wounded cells; COX6C, ATP synthase, H+transporting, mitochondrial Fo complex, subunit B1 (ATP5F1), nicotinamide adenine dinucleotide (NADH) dehydrogenase (ubiquinone) 1 alpha subcomplex, 11 (NDUFA11), and NADH dehydrogenase (ubiquinone) Fe-S protein 7 (NDUFS7) in wounded cells; and ATPase, H+/K+ exchanging, beta polypeptide (ATP4B), and ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C2 (subunit 9) (ATP5G2) in ischemic cells. LILI at 660 nm stimulates the upregulation of genes coding for subunits of enzymes involved in complexes I and IV and ATP synthase.

Identification of the Catalytic Ubiquinone-binding Site of Vibrio cholerae Sodium-dependent NADH Dehydrogenase

PubMed Central

Tuz, Karina; Li, Chen; Fang, Xuan; Raba, Daniel A.; Liang, Pingdong; Minh, David D. L.; Juárez, Oscar

2017-01-01

The sodium-dependent NADH dehydrogenase (Na+-NQR) is a key component of the respiratory chain of diverse prokaryotic species, including pathogenic bacteria. Na+-NQR uses the energy released by electron transfer between NADH and ubiquinone (UQ) to pump sodium, producing a gradient that sustains many essential homeostatic processes as well as virulence factor secretion and the elimination of drugs. The location of the UQ binding site has been controversial, with two main hypotheses that suggest that this site could be located in the cytosolic subunit A or in the membrane-bound subunit B. In this work, we performed alanine scanning mutagenesis of aromatic residues located in transmembrane helices II, IV, and V of subunit B, near glycine residues 140 and 141. These two critical glycine residues form part of the structures that regulate the site's accessibility. Our results indicate that the elimination of phenylalanine residue 211 or 213 abolishes the UQ-dependent activity, produces a leak of electrons to oxygen, and completely blocks the binding of UQ and the inhibitor HQNO. Molecular docking calculations predict that UQ interacts with phenylalanine 211 and pinpoints the location of the binding site in the interface of subunits B and D. The mutagenesis and structural analysis allow us to propose a novel UQ-binding motif, which is completely different compared with the sites of other respiratory photosynthetic complexes. These results are essential to understanding the electron transfer pathways and mechanism of Na+-NQR catalysis. PMID:28053088

Origin and Evolution of the Sodium -Pumping NADH: Ubiquinone Oxidoreductase

PubMed Central

Reyes-Prieto, Adrian; Barquera, Blanca; Juárez, Oscar

2014-01-01

The sodium -pumping NADH: ubiquinone oxidoreductase (Na+-NQR) is the main ion pump and the primary entry site for electrons into the respiratory chain of many different types of pathogenic bacteria. This enzymatic complex creates a transmembrane gradient of sodium that is used by the cell to sustain ionic homeostasis, nutrient transport, ATP synthesis, flagellum rotation and other essential processes. Comparative genomics data demonstrate that the nqr operon, which encodes all Na+-NQR subunits, is found in a large variety of bacterial lineages with different habitats and metabolic strategies. Here we studied the distribution, origin and evolution of this enzymatic complex. The molecular phylogenetic analyses and the organizations of the nqr operon indicate that Na+-NQR evolved within the Chlorobi/Bacteroidetes group, after the duplication and subsequent neofunctionalization of the operon that encodes the homolog RNF complex. Subsequently, the nqr operon dispersed through multiple horizontal transfer events to other bacterial lineages such as Chlamydiae, Planctomyces and α, β, γ and δ -proteobacteria. Considering the biochemical properties of the Na+-NQR complex and its physiological role in different bacteria, we propose a detailed scenario to explain the molecular mechanisms that gave rise to its novel redox- dependent sodium -pumping activity. Our model postulates that the evolution of the Na+-NQR complex involved a functional divergence from its RNF homolog, following the duplication of the rnf operon, the loss of the rnfB gene and the recruitment of the reductase subunit of an aromatic monooxygenase. PMID:24809444

Real-time Monitoring of Intermediates Reveals the Reaction Pathway in the Thiol-Disulfide Exchange between Disulfide Bond Formation Protein A (DsbA) and B (DsbB) on a Membrane-immobilized Quartz Crystal Microbalance (QCM) System*

PubMed Central

Yazawa, Kenjiro; Furusawa, Hiroyuki; Okahata, Yoshio

2013-01-01

Disulfide bond formation protein B (DsbBS-S,S-S) is an inner membrane protein in Escherichia coli that has two disulfide bonds (S-S, S-S) that play a role in oxidization of a pair of cysteine residues (SH, SH) in disulfide bond formation protein A (DsbASH,SH). The oxidized DsbAS-S, with one disulfide bond (S-S), can oxidize proteins with SH groups for maturation of a folding preprotein. Here, we have described the transient kinetics of the oxidation reaction between DsbASH,SH and DsbBS-S,S-S. We immobilized DsbBS-S,S-S embedded in lipid bilayers on the surface of a 27-MHz quartz crystal microbalance (QCM) device to detect both formation and degradation of the reaction intermediate (DsbA-DsbB), formed via intermolecular disulfide bonds, as a mass change in real time. The obtained kinetic parameters (intermediate formation, reverse, and oxidation rate constants (kf, kr, and kcat, respectively) indicated that the two pairs of cysteine residues in DsbBS-S,S-S were more important for the stability of the DsbA-DsbB intermediate than ubiquinone, an electron acceptor for DsbBS-S,S-S. Our data suggested that the reaction pathway of almost all DsbASH,SH oxidation processes would proceed through this stable intermediate, avoiding the requirement for ubiquinone. PMID:24145032

The Mitochondria-targeted ubiquinone MitoQ decreases ethanol-dependent micro and macro hepatosteatosis

PubMed Central

Chacko, Balu K; Srivastava, Anup; Johnson, Michelle; Benavides, Gloria A.; Chang, Mi Jung; Ye, Yaozu; Jhala, Nirag; Murphy, Michael P; Kalyanaraman, Balaraman; Darley-Usmar, Victor M.

2011-01-01

Chronic alcohol-induced liver disease results in inflammation, steatosis and increased oxidative and nitrosative damage to the mitochondrion. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate the steatosis associated with alcoholic liver disease. To test this we investigated the effects of mitochondria-targeted ubiquinone, MitoQ, (5 & 25 mg/kg/d for 4 weeks) in male Sprague-Dawley rats consuming ethanol using the Lieber-DeCarli diet with pair-fed controls. Hepatic steatosis, 3-nitrotyosine (3-NT), 4-hydroxynonenal (4-HNE), hypoxia inducible factor α (HIF1α) and the activity of the mitochondrial respiratory chain complexes were assessed. As reported previously, ethanol consumption resulted in hepatocyte ballooning, increased lipid accumulation in the form of micro and macrovesicular steatosis and induction of CYP2E1. MitoQ had a minor on the ethanol-dependent decrease in mitochondrial respiratory chain proteins and their activities, it did however decrease hepatic steatosis in ethanol consuming animals and prevented the ethanol-induced formation of 3-NT and 4-HNE. Interestingly, MitoQ completely blocks the increase in HIF1α in all ethanol-fed groups which has previously been demonstrated in cell culture models and shown to be essential in ethanol-dependent hepatosteatosis. These results demonstrate the antioxidant capacity of MitoQ in alleviating alcohol associated mitochondrial ROS and several downstream effects of ROS/RNS production such as inhibiting protein nitration and protein aldehyde formation and specifically ROS-dependant HIF1α stabilization. PMID:21520201

Developmental and hormone-induced changes of mitochondrial electron transport chain enzyme activities during the last instar larval development of maize stem borer, Chilo partellus (Lepidoptera: Crambidae).

PubMed

VenkatRao, V; Chaitanya, R K; Naresh Kumar, D; Bramhaiah, M; Dutta-Gupta, A

2016-12-01

The energy demand for structural remodelling in holometabolous insects is met by cellular mitochondria. Developmental and hormone-induced changes in the mitochondrial respiratory activity during insect metamorphosis are not well documented. The present study investigates activities of enzymes of mitochondrial electron transport chain (ETC) namely, NADH:ubiquinone oxidoreductase or complex I, Succinate: ubiquinone oxidoreductase or complex II, Ubiquinol:ferricytochrome c oxidoreductase or complex III, cytochrome c oxidase or complex IV and F 1 F 0 ATPase (ATPase), during Chilo partellus development. Further, the effect of juvenile hormone (JH) analog, methoprene, and brain and corpora-allata-corpora-cardiaca (CC-CA) homogenates that represent neurohormones, on the ETC enzyme activities was monitored. The enzymatic activities increased from penultimate to last larval stage and thereafter declined during pupal development with an exception of ATPase which showed high enzyme activity during last larval and pupal stages compared to the penultimate stage. JH analog, methoprene differentially modulated ETC enzyme activities. It stimulated complex I and IV enzyme activities, but did not alter the activities of complex II, III and ATPase. On the other hand, brain homogenate declined the ATPase activity while the injected CC-CA homogenate stimulated complex I and IV enzyme activities. Cumulatively, the present study is the first to show that mitochondrial ETC enzyme system is under hormone control, particularly of JH and neurohormones during insect development. Copyright © 2015 Elsevier Inc. All rights reserved.

Succinate modulation of H2O2 release at NADH:ubiquinone oxidoreductase (Complex I) in brain mitochondria

PubMed Central

Zoccarato, Franco; Cavallini, Lucia; Bortolami, Silvia; Alexandre, Adolfo

2007-01-01

Complex I (NADH:ubiquinone oxidoreductase) is responsible for most of the mitochondrial H2O2 release, both during the oxidation of NAD-linked substrates and during succinate oxidation. The much faster succinate-dependent H2O2 production is ascribed to Complex I, being rotenone-sensitive. In the present paper, we report high-affinity succinate-supported H2O2 generation in the absence as well as in the presence of GM (glutamate/malate) (1 or 2 mM of each). In brain mitochondria, their only effect was to increase from 0.35 to 0.5 or to 0.65 mM the succinate concentration evoking the semi-maximal H2O2 release. GM are still oxidized in the presence of succinate, as indicated by the oxygen-consumption rates, which are intermediate between those of GM and of succinate alone when all substrates are present together. This effect is removed by rotenone, showing that it is not due to inhibition of succinate influx. Moreover, α-oxoglutarate production from GM, a measure of the activity of Complex I, is decreased, but not stopped, by succinate. It is concluded that succinate-induced H2O2 production occurs under conditions of regular downward electron flow in Complex I. Succinate concentration appears to modulate the rate of H2O2 release, probably by controlling the hydroquinone/quinone ratio. PMID:17477844

A SWOT Analysis of the Various Backup Scenarios Used in Electronic Medical Record Systems.

PubMed

Seo, Hwa Jeong; Kim, Hye Hyeon; Kim, Ju Han

2011-09-01

Electronic medical records (EMRs) are increasingly being used by health care services. Currently, if an EMR shutdown occurs, even for a moment, patient safety and care can be seriously impacted. Our goal was to determine the methodology needed to develop an effective and reliable EMR backup system. Our "independent backup system by medical organizations" paradigm implies that individual medical organizations develop their own EMR backup systems within their organizations. A "personal independent backup system" is defined as an individual privately managing his/her own medical records, whereas in a "central backup system by the government" the government controls all the data. A "central backup system by private enterprises" implies that individual companies retain control over their own data. A "cooperative backup system among medical organizations" refers to a networked system established through mutual agreement. The "backup system based on mutual trust between an individual and an organization" means that the medical information backup system at the organizational level is established through mutual trust. Through the use of SWOT analysis it can be shown that cooperative backup among medical organizations is possible to be established through a network composed of various medical agencies and that it can be managed systematically. An owner of medical information only grants data access to the specific person who gave the authorization for backup based on the mutual trust between an individual and an organization. By employing SWOT analysis, we concluded that a linkage among medical organizations or between an individual and an organization can provide an efficient backup system.

A SWOT Analysis of the Various Backup Scenarios Used in Electronic Medical Record Systems

PubMed Central

Seo, Hwa Jeong; Kim, Hye Hyeon

2011-01-01

Objectives Electronic medical records (EMRs) are increasingly being used by health care services. Currently, if an EMR shutdown occurs, even for a moment, patient safety and care can be seriously impacted. Our goal was to determine the methodology needed to develop an effective and reliable EMR backup system. Methods Our "independent backup system by medical organizations" paradigm implies that individual medical organizations develop their own EMR backup systems within their organizations. A "personal independent backup system" is defined as an individual privately managing his/her own medical records, whereas in a "central backup system by the government" the government controls all the data. A "central backup system by private enterprises" implies that individual companies retain control over their own data. A "cooperative backup system among medical organizations" refers to a networked system established through mutual agreement. The "backup system based on mutual trust between an individual and an organization" means that the medical information backup system at the organizational level is established through mutual trust. Results Through the use of SWOT analysis it can be shown that cooperative backup among medical organizations is possible to be established through a network composed of various medical agencies and that it can be managed systematically. An owner of medical information only grants data access to the specific person who gave the authorization for backup based on the mutual trust between an individual and an organization. Conclusions By employing SWOT analysis, we concluded that a linkage among medical organizations or between an individual and an organization can provide an efficient backup system. PMID:22084811

30 CFR 745.10 - Information collection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR FEDERAL LANDS PROGRAM STATE-FEDERAL COOPERATIVE AGREEMENTS § 745.10 Information collection. (a) In accordance... Federal lands under certain conditions. States that desire to enter into cooperative agreements to do so...

30 CFR 745.10 - Information collection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR FEDERAL LANDS PROGRAM STATE-FEDERAL COOPERATIVE AGREEMENTS § 745.10 Information collection. (a) In accordance... Federal lands under certain conditions. States that desire to enter into cooperative agreements to do so...

50 CFR 401.9 - Payments to cooperators.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A ANADROMOUS FISHERIES... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Payments to cooperators. 401.9 Section 401.9 Wildlife and Fisheries JOINT REGULATIONS (UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF...

Water-soluble Coenzyme Q10 formulation (Q-ter) promotes outer hair cell survival in a guinea pig model of noise induced hearing loss (NIHL).

PubMed

Fetoni, Anna Rita; Piacentini, Roberto; Fiorita, Antonella; Paludetti, Gaetano; Troiani, Diana

2009-02-27

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS) also in noise induced hearing loss (NIHL) and anti-oxidants and free-radicals scavengers have been shown to attenuate the damage. Coenzyme Q(10) (CoQ(10)) or ubiquinone has a bioenergetic role as a component of the mithocondrial respiratory chain, it inhibits mitochondrial lipid peroxidation, inducing ATP production and it is involved in ROS removal and prevention of oxidative stress-induced apoptosis. However the therapeutic application of CoQ(10) is limited by the lack of solubility and poor bio- availability, therefore it is a challenge to improve its water solubility in order to ameliorate the efficacy in tissues and fluids. This study was conducted in a model of acoustic trauma in the guinea pig where the effectiveness of CoQ(10) was compared with a soluble formulation of CoQ(10) (multicomposite CoQ(10) Terclatrate, Q-ter) given intraperitoneally 1 h before and once daily for 3 days after pure tone noise exposure (6 kHz for 1 h at 120 dB SPL). Functional and morphological studies were carried out by measuring auditory brainstem responses, scanning electron microscopy for hair cell loss count, active caspase 3 staining and terminal deoxynucleotidyl transferase-mediated dUTP labelling assay in order to identify initial signs of apoptosis. Treatments decreased active caspase 3 expression and the number of apoptotic cells, but animals injected with Q-ter showed a greater degree of activity in preventing apoptosis and thus in improving hearing. These data confirm that solubility of Coenzyme Q(10) improves the ability of CoQ(10) in preventing oxidative injuries that result from mitochondrial dysfunction.

Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis123

PubMed Central

Thompson-Paul, Angela M; Bazzano, Lydia A

2013-01-01

Background: Coenzyme Q10 (CoQ10; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ10 on CHF with inconclusive results. Objective: The objective of this meta-analysis was to evaluate the impact of CoQ10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. Design: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ10 supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. Results: Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and −0.30 (95% CI: −0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ10/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. Conclusions: Pooled analyses of available randomized controlled trials suggest that CoQ10 may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed. PMID:23221577

Hepatitis B virus core protein allosteric modulators can distort and disrupt intact capsids.

PubMed

Schlicksup, Christopher John; Wang, Joseph Che-Yen; Francis, Samson; Venkatakrishnan, Balasubramanian; Turner, William W; VanNieuwenhze, Michael; Zlotnick, Adam

2018-01-29

Defining mechanisms of direct-acting antivirals facilitates drug development and our understanding of virus function. Heteroaryldihydropyrimidines (HAPs) inappropriately activate assembly of hepatitis B virus (HBV) core protein (Cp), suppressing formation of virions. We examined a fluorophore-labeled HAP, HAP-TAMRA. HAP-TAMRA induced Cp assembly and also bound pre-assembled capsids. Kinetic and spectroscopic studies imply that HAP-binding sites are usually not available but are bound cooperatively. Using cryo-EM, we observed that HAP-TAMRA asymmetrically deformed capsids, creating a heterogeneous array of sharp angles, flat regions, and outright breaks. To achieve high resolution reconstruction (<4 Å), we introduced a disulfide crosslink that rescued particle symmetry. We deduced that HAP-TAMRA caused quasi-sixfold vertices to become flatter and fivefold more angular. This transition led to asymmetric faceting. That a disordered crosslink could rescue symmetry implies that capsids have tensegrity properties. Capsid distortion and disruption is a new mechanism by which molecules like the HAPs can block HBV infection. © 2017, Schlicksup et al.

Hepatitis B virus core protein allosteric modulators can distort and disrupt intact capsids

PubMed Central

Schlicksup, Christopher John; Wang, Joseph Che-Yen; Francis, Samson; Venkatakrishnan, Balasubramanian; Turner, William W; VanNieuwenhze, Michael

2018-01-01

Defining mechanisms of direct-acting antivirals facilitates drug development and our understanding of virus function. Heteroaryldihydropyrimidines (HAPs) inappropriately activate assembly of hepatitis B virus (HBV) core protein (Cp), suppressing formation of virions. We examined a fluorophore-labeled HAP, HAP-TAMRA. HAP-TAMRA induced Cp assembly and also bound pre-assembled capsids. Kinetic and spectroscopic studies imply that HAP-binding sites are usually not available but are bound cooperatively. Using cryo-EM, we observed that HAP-TAMRA asymmetrically deformed capsids, creating a heterogeneous array of sharp angles, flat regions, and outright breaks. To achieve high resolution reconstruction (<4 Å), we introduced a disulfide crosslink that rescued particle symmetry. We deduced that HAP-TAMRA caused quasi-sixfold vertices to become flatter and fivefold more angular. This transition led to asymmetric faceting. That a disordered crosslink could rescue symmetry implies that capsids have tensegrity properties. Capsid distortion and disruption is a new mechanism by which molecules like the HAPs can block HBV infection. PMID:29377794

A Comparative Study of Cooperative Education and Work-Integrated Learning in Germany, South Africa, and Namibia

ERIC Educational Resources Information Center

Reinhard, Karin; Pogrzeba, Anna; Townsend, Rosemary; Pop, Carver Albertus

2016-01-01

The Baden-Wuerttemberg Cooperative State University was the first higher education institution in Germany to combine on-the-job training and academic studies. The study model integrates theory and practice, both being components of cooperative education. The success of this university is based on its cooperation with over 10,000 companies.…

75 FR 39226 - Combined Notice of Filings No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-08

...: ER10-1573-000. Applicants: Wolverine Power Supply Cooperative, Inc. Description: Wolverine Power Supply... Power Supply Cooperative, Inc. Description: Wolverine Power Supply Cooperative, Inc. submits tariff...-038; ER01-2641-018. Applicants: Tenaska Power Services Co., High Desert Power Project, LLC...

Standardized Curriculum for Business Cooperative Education.

ERIC Educational Resources Information Center

Mississippi State Dept. of Education, Jackson. Office of Vocational, Technical and Adult Education.

Standardized curricula are provided for two courses for the secondary vocational education program in Mississippi: business cooperative education I and II. The 10 units in business cooperative education I are as follows: orientation; keyboarding and skill building; leadership development; personnel development; human relations; business…

44 CFR 208.23 - Allowable costs under Preparedness Cooperative Agreements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Allowable costs under Preparedness Cooperative Agreements. 208.23 Section 208.23 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE NATIONAL URBAN SEARCH AND...

Sustainable Odds

NASA Astrophysics Data System (ADS)

Smith, L. A.

2016-12-01

While probability forecasting has many philosophical and mathematical attractions, it is something of a dishonest nonsense if acting on such forecasts is expected to lead to rapid ruin. Model-based probabilities, when interpreted as actionable, are shown to lead to the rapid ruin of a cooperative entity offering odds interpreting the probability forecasts at face value. Arguably, these odds would not be considered "fair", but inasmuch as some definitions of "fair odds" include this case, this presentation will focus on "sustainable odds": Odds which are not expected to lead to the rapid ruin of the cooperative under the assumption that those placing bets have no information beyond that available to the forecast system. It is argued that sustainable odds will not correspond to probabilities outside the Perfect Model Scenario, that the "implied probabilities" determined from sustainable odds will always sum to more than one, and that the excess of this sum over one reflects the skill of the forecast system, being a quantitative measure of structural model error.

Different selection pressures give rise to distinct ethnic phenomena : a functionalist framework with illustrations from the Peruvian Altiplano.

PubMed

Moya, Cristina; Boyd, Robert

2015-03-01

Many accounts of ethnic phenomena imply that processes such as stereotyping, essentialism, ethnocentrism, and intergroup hostility stem from a unitary adaptation for reasoning about groups. This is partly justified by the phenomena's co-occurrence in correlational studies. Here we argue that these behaviors are better modeled as functionally independent adaptations that arose in response to different selection pressures throughout human evolution. As such, different mechanisms may be triggered by different group boundaries within a single society. We illustrate this functionalist framework using ethnographic work from the Quechua-Aymara language boundary in the Peruvian Altiplano. We show that different group boundaries motivate different ethnic phenomena. For example, people have strong stereotypes about socioeconomic categories, which are not cooperative units, whereas they hold fewer stereotypes about communities, which are the primary focus of cooperative activity. We also show that, despite the cross-cultural importance of ethnolinguistic boundaries, the Quechua-Aymara linguistic distinction does not strongly motivate any of these intergroup processes.

Different Selection Pressures Give Rise to Distinct Ethnic Phenomena

PubMed Central

Moya, Cristina; Boyd, Robert

2015-01-01

Many accounts of ethnic phenomena imply that processes such as stereotyping, essentialism, ethnocentrism, and intergroup hostility stem from a unitary adaptation for reasoning about groups. This is partly justified by the phenomena’s co-occurrence in correlational studies. Here we argue that these behaviors are better modeled as functionally independent adaptations that arose in response to different selection pressures throughout human evolution. As such, different mechanisms may be triggered by different group boundaries within a single society. We illustrate this functionalist framework using ethnographic work from the Quechua-Aymara language boundary in the Peruvian Altiplano. We show that different group boundaries motivate different ethnic phenomena. For example, people have strong stereotypes about socioeconomic categories, which are not cooperative units, whereas they hold fewer stereotypes about communities, which are the primary focus of cooperative activity. We also show that, despite the cross-cultural importance of ethnolinguistic boundaries, the Quechua-Aymara linguistic distinction does not strongly motivate any of these intergroup processes. PMID:25731969

Oxytocin promotes altruistic punishment.

PubMed

Aydogan, Gökhan; Furtner, Nadja C; Kern, Bianca; Jobst, Andrea; Müller, Norbert; Kocher, Martin G

2017-11-01

The role of neuromodulators in the enforcement of cooperation is still not well understood. Here, we provide evidence that intranasal applied oxytocin, an important hormone for modulating social behavior, enhances the inclination to sanction free-riders in a social dilemma situation. Contrary to the notion of oxytocin being a pro-social hormone, we found that participants treated with oxytocin exhibited an amplification of self-reported negative social emotions such as anger towards free-riders, ultimately resulting in higher magnitude and frequency of punishment of free-riders compared to placebo. Furthermore, we found initial evidence that oxytocin contributes to the positive effects of a punishment institution by rendering cooperation preferable in the oxytocin condition for even the most selfish players when punishment was available. Together, these findings imply that the neural circuits underlying altruistic punishment are partly targeted by the oxytonergic system and highlight the importance of neuromodulators in group cohesion and norm enforcement within social groups. © The Author (2017). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Valuing the commons: An international study on the recreational benefits of the Baltic Sea.

PubMed

Czajkowski, Mikołaj; Ahtiainen, Heini; Artell, Janne; Budziński, Wiktor; Hasler, Berit; Hasselström, Linus; Meyerhoff, Jürgen; Nõmmann, Tea; Semeniene, Daiva; Söderqvist, Tore; Tuhkanen, Heidi; Lankia, Tuija; Vanags, Alf; Zandersen, Marianne; Żylicz, Tomasz; Hanley, Nick

2015-06-01

The Baltic Sea provides benefits to all of the nine nations along its coastline, with some 85 million people living within the catchment area. Achieving improvements in water quality requires international cooperation. The likelihood of effective cooperation is known to depend on the distribution across countries of the benefits and costs of actions needed to improve water quality. In this paper, we estimate the benefits associated with recreational use of the Baltic Sea in current environmental conditions using a travel cost approach, based on data from a large, standardized survey of households in each of the 9 Baltic Sea states. Both the probability of engaging in recreation (participation) and the number of visits people make are modeled. A large variation in the number of trips and the extent of participation is found, along with large differences in current annual economic benefits from Baltic Sea recreation. The total annual recreation benefits are close to 15 billion EUR. Under a water quality improvement scenario, the proportional increases in benefits range from 7 to 18% of the current annual benefits across countries. Depending on how the costs of actions are distributed, this could imply difficulties in achieving more international cooperation to achieve such improvements. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dynamics of Complex Systems Built as Coupled Physical, Communication and Decision Layers

PubMed Central

Kühnlenz, Florian; Nardelli, Pedro H. J.

2016-01-01

This paper proposes a simple model to capture the complexity of multilayer systems where their constituent layers affect, and are affected by, each other. The physical layer is a circuit composed by a power source and resistors in parallel. Every individual agent aims at maximizing its own delivered power by adding, removing or keeping the resistors it has; the delivered power is in turn a non-linear function that depends on the other agents’ behavior, its own internal state, its global state perception, the information received from its neighbors via the communication network and a randomized selfishness. We develop an agent-based simulation to analyze the effects of number of agents (system size), communication network topology, communication errors and the minimum power gain that triggers a behavioral change on the system dynamic. Our results show that a wave-like behavior at macro-level (caused by individual changes in the decision layer) can only emerge for a specific system size. The ratio between cooperators and defectors depends on the minimum gain assumed—lower minimal gains lead to less cooperation, and vice-versa. Different communication network topologies imply different levels of power utilization and fairness at the physical layer, and a certain level of error in the communication layer induces more cooperation. PMID:26730590

38 CFR 21.7576 - Entitlement charges.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Correspondence training; (3) Cooperative training; or (4) Apprenticeship or other on-job training. (Authority: 10... for those pursuing flight training, correspondence training, cooperative training, apprenticeship or... cooperative training, VA will make a charge against entitlement of .8 of a month for each month in which the...

Sphingomonas frigidaeris sp. nov., isolated from an air conditioning system.

PubMed

Lee, Yunho; Jeon, Che Ok

2017-10-01

A strictly aerobic Gram-stain-negative bacterium, designated strain KER25-10 T , was isolated from a laboratory air conditioning system in South Korea. Cells were yellow-pigmented, non-motile rods showing catalase- and oxidase-positive reactions. The strain grew at pH 4.0-9.0 (optimum, pH 6.0-7.0) and 10-40 °C (optimum, 30 °C) and in the presence of 0-3 % (w/v) NaCl (optimum, 0 %). The G+C content of the genomic DNA was 65.1 mol%. Strain KER25-10 T contained ubiquinone-10 (Q-10) as the predominant isoprenoid quinone and C16 : 0, C17 : 1ω6c, summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c) and summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c) as the major fatty acids. The major polar lipids were sphingoglycolipid, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine. Only spermidine was detected as the polyamine. Phylogenetic analysis based on 16S rRNA sequences indicated that strain KER25-10 T formed a distinct phylogenetic lineage within the genus Sphingomonas of the family Sphingomonadaceae and the strain was most closely related to Sphingomonas kyeonggiense THG-DT81 T with a 96.8 % 16S rRNA gene sequence similarity. On the basis of phenotypic, chemotaxonomic and molecular features, strain KER25-10 T clearly represents a novel species of the genus Sphingomonas, for which the name Sphingomonas frigidaeris sp. nov. is proposed. The type strain is KER25-10 T (=KACC 19285 T =JCM 32053 T ).

Coenzyme Q10 protects ischemic myocardium in an open-chest swine model.

PubMed

Atar, D; Mortensen, S A; Flachs, H; Herzog, W R

1993-01-01

Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion, may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this study was to test the hypothesis that pretreatment with coenzyme Q10 (ubiquinone), believed to act as a free radical scavenger, reduces myocardial stunning in a porcine model. Twelve swine were randomized to receive either oral supplementation with coenzyme Q10 or placebo for 20 days. A normothermic open-chest model was used with short occlusion (8 min) of the distal left descending coronary artery followed by reperfusion. Regional contractile function was measured with epicardial Doppler crystals in ischemic and nonischemic segments by measuring thickening fraction of the left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility until return to baseline. Coenzyme Q10 concentrations were measured in blood and homogenized myocardial tissue by high performance liquid chromatography. Plasma levels of reduced coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations, however, did not show any changes (mean 0.79 micrograms/mg dry weight versus 0.74 micrograms/mg). Stunning time was significantly reduced in coenzyme Q10 pretreated animals (13.7 +/- 7.7 min versus 32.8 +/- 3.1 min, P < 0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated by a humoral rather than intracellular mechanism.

44 CFR 360.5 - General provisions for State Cooperative Agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false General provisions for State Cooperative Agreement. 360.5 Section 360.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS STATE ASSISTANCE PROGRAMS FOR TRAINING AND EDUCATION...

44 CFR 360.5 - General provisions for State Cooperative Agreement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false General provisions for State Cooperative Agreement. 360.5 Section 360.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS STATE ASSISTANCE PROGRAMS FOR TRAINING AND EDUCATION...

75 FR 44757 - Notice of Funding Availability (NOFA) Inviting Applications for the Rural Microentrepreneur...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-29

... DEPARTMENT OF AGRICULTURE Rural Business-Cooperative Service Notice of Funding Availability (NOFA) Inviting Applications for the Rural Microentrepreneur Assistance Program AGENCY: Rural Business-Cooperative.... Canales, Administrator, Rural Business-Cooperative Service. [FR Doc. 2010-18639 Filed 7-28-10; 8:45 am...

International Library Cooperation. Essen Symposium (10th, Essen, West Germany, October 19-22, 1987).

ERIC Educational Resources Information Center

Helal, Ahmed H., Ed.; Weiss, Joachim W., Ed.

The proceedings of this symposium contain the texts of 21 presentations: (1) "The Alexandriana Library: A New Opportunity in International Library Cooperation" (Stuart Ede); (2) "Conservation, Culture and Curriculum" (Brendan Loughridge); (3) "European Library Cooperation: An EC (European Community) Standpoint"…

Continuity in health care: lessons from supply chain management.

PubMed

Meijboom, Bert R; Bakx, Saskia J W G C; Westert, Gert P

2010-01-01

In health care, multidisciplinary collaboration is both indispensable and complicated. We discuss organizational problems that occur in situations where multiple health care providers are required to cooperate for patients with complex needs. Four problem categories, labelled as communication, patient safety, waiting times and integration are distinguished. Then we develop a supply chain perspective on these problems in the sense of discussing remedies according to supply chain management (SCM) literature. This perspective implies a business focus on inter-organizational conditions and requirements necessary for delivering health care and cure across organizational borders. We conclude by presenting some strategic and policy recommendations.

INSTITUTIONS AND BEHAVIOR: EXPERIMENTAL EVIDENCE ON THE EFFECTS OF DEMOCRACY

PubMed Central

Bó, Pedro Dal; Foster, Andrew; Putterman, Louis

2013-01-01

A novel experiment is used to show that the effect of a policy on the level of cooperation is greater when it is chosen democratically by the subjects than when it is exogenously imposed. In contrast to the previous literature, our experimental design allows us to control for selection effects (e.g. those who choose the policy may be affected differently by it). Our finding implies that democratic institutions may affect behavior directly in addition to having effects through the choice of policies. Our findings have implications for the generalizability of the results of randomized policy interventions. PMID:25076785

A Practice of Rescue Robot Contest in Junior High Schools

NASA Astrophysics Data System (ADS)

Kawada, Kazuo; Nagamatsu, Masayasu; Yamamoto, Toru

The rescue robot contest for junior high school students was created to give students an opportunity to design a robot to rescue the victims under large scale disasters. The activity was not only intended as an humanitarian project but also aiming at students to : (1) take the role of victims and imagining the situation from his or her perspective, (2) enhance thinking skills, creativity through the problem solving processes and, (3) work cooperatively in groups. From results of questionnaire for the participated students, important factors for further implementation as curriculum of technology education are implied.

42 CFR 455.21 - Cooperation with State Medicaid fraud control units.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Cooperation with State Medicaid fraud control units. 455.21 Section 455.21 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Agency Fraud...

42 CFR 476.90 - Lack of cooperation by a provider or practitioner.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 4 2012-10-01 2012-10-01 false Lack of cooperation by a provider or practitioner. 476.90 Section 476.90 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS UTILIZATION AND QUALITY CONTROL REVIEW...

42 CFR 476.90 - Lack of cooperation by a provider or practitioner.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Lack of cooperation by a provider or practitioner. 476.90 Section 476.90 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS QUALITY IMPROVEMENT ORGANIZATION REVIEW...

42 CFR 476.90 - Lack of cooperation by a provider or practitioner.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 4 2013-10-01 2013-10-01 false Lack of cooperation by a provider or practitioner. 476.90 Section 476.90 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS UTILIZATION AND QUALITY CONTROL REVIEW...

50 CFR 15.26 - Approval of cooperative breeding programs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 1 2014-10-01 2014-10-01 false Approval of cooperative breeding programs. 15.26 Section 15.26 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE... program requested for the exotic bird species, including: (i) A breeding protocol, including a genetic...

50 CFR 15.26 - Approval of cooperative breeding programs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 1 2013-10-01 2013-10-01 false Approval of cooperative breeding programs. 15.26 Section 15.26 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE... program requested for the exotic bird species, including: (i) A breeding protocol, including a genetic...

50 CFR 15.26 - Approval of cooperative breeding programs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 1 2012-10-01 2012-10-01 false Approval of cooperative breeding programs. 15.26 Section 15.26 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE... program requested for the exotic bird species, including: (i) A breeding protocol, including a genetic...

50 CFR 81.6 - Project Agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Project Agreement. 81.6 Section 81.6... SPECIES OF FISH, WILDLIFE, AND PLANTS-COOPERATION WITH THE STATES § 81.6 Project Agreement. (a) Subsequent to the establishment of a Cooperative Agreement pursuant to § 81.3, the Secretary may further agree...

50 CFR 81.6 - Project Agreement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Project Agreement. 81.6 Section 81.6... SPECIES OF FISH, WILDLIFE, AND PLANTS-COOPERATION WITH THE STATES § 81.6 Project Agreement. (a) Subsequent to the establishment of a Cooperative Agreement pursuant to § 81.3, the Secretary may further agree...

50 CFR 70.3 - State cooperation in national fish hatchery area management.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false State cooperation in national fish hatchery area management. 70.3 Section 70.3 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) MANAGEMENT OF FISHERIES CONSERVATION AREAS NATIONAL FISH HATCHERIES...

50 CFR 70.3 - State cooperation in national fish hatchery area management.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false State cooperation in national fish hatchery area management. 70.3 Section 70.3 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) MANAGEMENT OF FISHERIES CONSERVATION AREAS NATIONAL FISH HATCHERIES...

50 CFR 70.3 - State cooperation in national fish hatchery area management.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false State cooperation in national fish hatchery area management. 70.3 Section 70.3 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) MANAGEMENT OF FISHERIES CONSERVATION AREAS NATIONAL FISH HATCHERIES...

50 CFR 70.3 - State cooperation in national fish hatchery area management.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false State cooperation in national fish hatchery area management. 70.3 Section 70.3 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) MANAGEMENT OF FISHERIES CONSERVATION AREAS NATIONAL FISH HATCHERIES...

50 CFR 70.3 - State cooperation in national fish hatchery area management.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false State cooperation in national fish hatchery area management. 70.3 Section 70.3 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) MANAGEMENT OF FISHERIES CONSERVATION AREAS NATIONAL FISH HATCHERIES...

48 CFR 352.222-70 - Contractor cooperation in equal employment opportunity investigations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Contractor cooperation in... Regulations System HEALTH AND HUMAN SERVICES CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES... Agency management, Agency EEO officials, the Equal Employment Opportunity Commission (EEOC), or a court...

48 CFR 352.222-70 - Contractor cooperation in equal employment opportunity investigations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Contractor cooperation in... Regulations System HEALTH AND HUMAN SERVICES CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES... Agency management, Agency EEO officials, the Equal Employment Opportunity Commission (EEOC), or a court...

48 CFR 352.222-70 - Contractor cooperation in equal employment opportunity investigations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Contractor cooperation in... Regulations System HEALTH AND HUMAN SERVICES CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES... Agency management, Agency EEO officials, the Equal Employment Opportunity Commission (EEOC), or a court...

48 CFR 352.222-70 - Contractor cooperation in equal employment opportunity investigations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Contractor cooperation in... Regulations System HEALTH AND HUMAN SERVICES CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES... Agency management, Agency EEO officials, the Equal Employment Opportunity Commission (EEOC), or a court...

48 CFR 352.222-70 - Contractor cooperation in equal employment opportunity investigations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Contractor cooperation in... Regulations System HEALTH AND HUMAN SERVICES CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES... Agency management, Agency EEO officials, the Equal Employment Opportunity Commission (EEOC), or a court...

International Cooperation. The Next Generation. Report of the DSMC 1990 - 1991 Military Research Fellows

DTIC Science & Technology

1991-09-01

Maintaining Goal Congruence International Cooperation-the Next Generation ENDNOTES 1. Wolfgang Flume and David Swa, "British Aerospace-Leading...Program Management Questionnaire Report. Michael G. Krause , DSMC internal document, May 1989- 10. Bonn Seminar on Armaments cooperation, proceedings, w...Appendix K 154 International Cooperation-the Next Generation Dudney, Robert S., "The Electronics Industry Flume, Wolfgang , "Electronics for the Ger- Is

U.S.-Russian Civilian Nuclear Cooperation Agreement: Issues for Congress

DTIC Science & Technology

2010-07-09

for nuclear cooperation in 1973 to allow for cooperation in controlled thermonuclear fusion, fast breeder reactors , and fundamental research. The...that a 123 agreement is needed to implement this action plan—for example, full scale technical cooperation on fast reactors and demonstration of...superpowers convened a Joint Coordinating Committee for Civilian Reactor Safety starting in 1988.10 After the fall of the Soviet Union and prior to July

Practices of Cooperating Teachers Contributing to a High Quality Field Experience

ERIC Educational Resources Information Center

Lafferty, Karen Elizabeth

2015-01-01

This mixed methods study framed in cognitive apprenticeship theory involved cooperating and preservice teachers from 10 university-based credentialing programs in California. It examined the connection between cooperating teacher practices and preservice teachers' perceptions of a high quality field experience. Survey responses from 146…

Estimating implied rates of discount in healthcare decision-making.

PubMed

West, R R; McNabb, R; Thompson, A G H; Sheldon, T A; Grimley Evans, J

2003-01-01

To consider whether implied rates of discounting from the perspectives of individual and society differ, and whether implied rates of discounting in health differ from those implied in choices involving finance or "goods". The study comprised first a review of economics, health economics and social science literature and then an empirical estimate of implied rates of discounting in four fields: personal financial, personal health, public financial and public health, in representative samples of the public and of healthcare professionals. Samples were drawn in the former county and health authority district of South Glamorgan, Wales. The public sample was a representative random sample of men and women, aged over 18 years and drawn from electoral registers. The health professional sample was drawn at random with the cooperation of professional leads to include doctors, nurses, professions allied to medicine, public health, planners and administrators. The literature review revealed few empirical studies in representative samples of the population, few direct comparisons of public with private decision-making and few direct comparisons of health with financial discounting. Implied rates of discounting varied widely and studies suggested that discount rates are higher the smaller the value of the outcome and the shorter the period considered. The relationship between implied discount rates and personal attributes was mixed, possibly reflecting the limited nature of the samples. Although there were few direct comparisons, some studies found that individuals apply different rates of discount to social compared with private comparisons and health compared with financial. The present study also found a wide range of implied discount rates, with little systematic effect of age, gender, educational level or long-term illness. There was evidence, in both samples, that people chose a lower rate of discount in comparisons made on behalf of society than in comparisons made for themselves. Both public and health professional samples tended to choose lower discount rates in health-related comparisons than in finance-related comparisons. It was also suggested that implied rates of discount, derived from responses to hypothetical questions, can be influenced by detail of question framing. The study suggested that both the lay public and healthcare professionals consider that the discount rate appropriate for public decisions is lower than that for private decisions. This finding suggests that lay people as well as healthcare professionals, used to making decisions on behalf of others, recognise that society is not simply an aggregate of individuals. It also implies a general appreciation that society is more stable and has a more predictable future than does the individual. There is fairly general support for this view in the theoretical literature and limited support in the few previous direct comparisons. Further research is indicated, possibly involving more in-depth interviewing and drawing inference on real, rather than hypothetical choices.

Synergistic cosolubilization of omega-3 fatty acid esters and CoQ10 in dilutable microemulsions.

PubMed

Deutch-Kolevzon, Rivka; Aserin, Abraham; Garti, Nissim

2011-10-01

Water-dilutable microemulsions were prepared and loaded with two types of omega-3 fatty acid esters (omega-3 ethyl esters, OEE; and omega-3 triacylglycerides, OTG), each separately and together with ubiquinone (CoQ(10)). The microemulsions showed high and synergistic loading capabilities. The linear fatty acid ester (OEE) solubilization capacity was greater than that of the bulky and robust OTG. The location of the guest molecules within the microemulsions at any dilution point were determined by electrical conductivity, viscosity, DSC, SAXS, cryo-TEM, SD-NMR, and DLS. We found that OEE molecules pack well within the surfactant tails to form reverse micelles that gradually, upon water dilution, invert into bicontinuous phase and finally into O/W droplets. The CoQ(10) increases the stabilization and solubilization of the omega-3 fatty acid esters because it functions as a kosmotropic agent in the micellar system. The hydrophobic and bulky OTG molecule strongly interferes with the tail packing and spaces them significantly - mainly in the low and medium range water dilutions. When added to the micellar system, CoQ(10) forms some reverse hexagonal mesophases. The inversion into direct micelles is more difficult in comparison to the OEE system and requires additional water dilution. The OTG with or without CoQ(10) destabilizes the structures and decreases the solubilization capacity since it acts as a chaotropic agent to the micellar system and as a kosmotropic agent to hexagonal packing. These results explain the differences in the behavior of these molecules with vehicles that solubilize them in aqueous phases. Temperature disorders the bicontinuous structures and reduces the supersaturation of the system containing OEE with CoQ(10); as a result CoQ(10) crystallization is retarded. Copyright © 2011. Published by Elsevier Ireland Ltd.

A Conserved START Domain Coenzyme Q-binding Polypeptide is Required for Efficient Q Biosynthesis, Respiratory Electron Transport, and Antioxidant Function in Saccharomyces cerevisiae

PubMed Central

Morvaridi, Susan; Saiki, Ryoichi; Johnson, Jarrett S.; Liau, Wei-Siang; Hirano, Kathleen; Kawashima, Tadashi; Ji, Ziming; Loo, Joseph A.; Shepherd, Jennifer N.; Clarke, Catherine F.

2014-01-01

Coenzyme Qn (ubiquinone or Qn) is a redox active lipid composed of a fully substituted benzoquinone ring and a polyisoprenoid tail of n isoprene units. Saccharomyces cerevisiae coq1-coq9 mutants have defects in Q biosynthesis, lack Q6, are respiratory defective, and sensitive to stress imposed by polyunsaturated fatty acids. The hallmark phenotype of the Q-less yeast coq mutants is that respiration in isolated mitochondria can be rescued by the addition of Q2, a soluble Q analog. Yeast coq10 mutants share each of these phenotypes, with the surprising exception that they continue to produce Q6. Structure determination of the Caulobacter crescentus Coq10 homolog (CC1736) revealed a steroidogenic acute regulatory protein-related lipid transfer (START) domain, a hydrophobic tunnel known to bind specific lipids in other START domain family members. Here we show that purified CC1736 binds Q2, Q3, Q10, or demethoxy-Q3 in an equimolar ratio, but fails to bind 3-farnesyl-4-hydroxybenzoic acid, a farnesylated analog of an early Q-intermediate. Over-expression of C. crescentus CC1736 or COQ8 restores respiratory electron transport and antioxidant function of Q6 in the yeast coq10 null mutant. Studies with stable isotope ring precursors of Q reveal that early Q-biosynthetic intermediates accumulate in the coq10 mutant and de novo Q-biosynthesis is less efficient than in the wild-type yeast or rescued coq10 mutant. The results suggest that the Coq10 polypeptide:Q (protein:ligand) complex may serve essential functions in facilitating de novo Q biosynthesis and in delivering newly synthesized Q to one or more complexes of the respiratory electron transport chain. PMID:23270816

[Investigation of metabolites of Triptergium wilfordii on liver toxicity by LC-MS].

PubMed

Zhao, Xiao-mei; Liu, Xin-ying; Xu, Chang; Ye, Tao; Jin, Cheng; Zhao, Kui-jun; Ma, Zhi-jie; Xiao, Xiao-he

2015-10-01

In this paper, biomarkers of liver toxicity of Triptergium wilfordii based on metabolomics was screened, and mechanism of liver toxicity was explored to provide a reference for the clinical diagnosis for liver toxicity of Triptergium wilfordii. MS method was carried on the analysis to metabolic fingerprint spectrum between treatment group and control group. The potential biomarkers were compared and screened using the multivariate statistical methods. As well, metabolic pathway would be detailed description. Combined with PCA and OPLS-DA pattern recognition analysis, 20 metabolites were selected which showed large differences between model group and blank group (VIP > 1.0). Seven possible endogenous biomarkers were analyzed and identified. They were 6-phosphate glucosamine, lysophospholipid, tryptophan, guanidine acetic acid, 3-indole propionic acid, cortisone, and ubiquinone. The level changes of above metabolites indicated that the metabolism pathways of amino acid, glucose, phospholipid and hormone were disordered. It is speculated that liver damage of T. wilfordii may be associated with the abnormal energy metabolism in citric acid cycle, amino acid metabolism in urea cycle, and glucose metabolism. It will be helpful to further research liver toxicity ingredients of Triptergium wilfordii.

An investigation of the effects of MitoQ on human peripheral mononuclear cells.

PubMed

Marthandan, Shiva; Murphy, Michael P; Billett, Ellen; Barnett, Yvonne

2011-03-01

MitoQ is a ubiquinone derivative targeted to mitochondria which is known to have both antioxidant and anti-apoptotic properties within mammalian cells. Previous research has suggested that the age-related increase in oxidative DNA damage in T lymphocytes might contribute to their functional decline with age. This paper describes the impact of mitoQ on unchallenged or oxidatively challenged ex vivo human peripheral blood mononuclear cells from healthy 25-30 or 55-60 year old volunteers. When cells were challenged with hydrogen peroxide (H(2)O(2)), following mitoQ treatment (0.1-1.0 μM), the ratio of reduced to oxidized forms of glutathione increased, the levels of oxidative DNA damage decreased and there was an increase in the mitochondrial membrane potential. Low levels of mitoQ (0.1 or 0.25 μM) had no impact on endogenous DNA damage, whilst higher levels (0.5 and 1.0 μM) of mitoQ significantly reduced endogenous levels of DNA damage. The results of this investigation suggest that mitoQ may have anti-immunosenescent potential.

Sphingomonas psychrolutea sp. nov., a psychrotolerant bacterium isolated from glacier ice.

PubMed

Liu, Qing; Liu, Hong-Can; Zhang, Jian-Li; Zhou, Yu-Guang; Xin, Yu-Hua

2015-09-01

A Gram-stain-negative, rod-shaped, orange bacterium (strain MDB1-A(T)) was isolated from ice samples collected from Midui glacier in Tibet, south-west China. Cells were aerobic and psychrotolerant (growth occurred at 0-25 °C). Phylogenetic analysis based on 16S rRNA gene sequences showed that it was a member of the genus Sphingomonas, with its closest relative being Sphingomonas glacialis C16y(T) (98.9% similarity). Q-10 was the predominant ubiquinone. C17 : 1ω6c and summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c) were the major cellular fatty acids. The predominant polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and sphingoglycolipid. The polyamines detected were sym-homospermidine, spermidine and spermine. The G+C content of the genomic DNA was 63.6%. Based on data from this polyphasic analysis, strain MDB1-A(T) represents a novel species of the genus Sphingomonas, for which the name Sphingomonas psychrolutea sp. nov. is proposed. The type strain is MDB1-A(T) ( = CGMCC 1.10106(T) = NBRC 109639(T)).

Spatial self-organization favors heterotypic cooperation over cheating.

PubMed

Momeni, Babak; Waite, Adam James; Shou, Wenying

2013-11-12

Heterotypic cooperation-two populations exchanging distinct benefits that are costly to produce-is widespread. Cheaters, exploiting benefits while evading contribution, can undermine cooperation. Two mechanisms can stabilize heterotypic cooperation. In 'partner choice', cooperators recognize and choose cooperating over cheating partners; in 'partner fidelity feedback', fitness-feedback from repeated interactions ensures that aiding your partner helps yourself. How might a spatial environment, which facilitates repeated interactions, promote fitness-feedback? We examined this process through mathematical models and engineered Saccharomyces cerevisiae strains incapable of recognition. Here, cooperators and their heterotypic cooperative partners (partners) exchanged distinct essential metabolites. Cheaters exploited partner-produced metabolites without reciprocating, and were competitively superior to cooperators. Despite initially random spatial distributions, cooperators gained more partner neighbors than cheaters did. The less a cheater contributed, the more it was excluded and disfavored. This self-organization, driven by asymmetric fitness effects of cooperators and cheaters on partners during cell growth into open space, achieves assortment. DOI: http://dx.doi.org/10.7554/eLife.00960.001.

Anti-cancer analogues ME-143 and ME-344 exert toxicity by directly inhibiting mitochondrial NADH: ubiquinone oxidoreductase (Complex I)

PubMed Central

Lim, Sze Chern; Carey, Kirstyn T; McKenzie, Matthew

2015-01-01

Isoflavonoids have been shown to inhibit tumor proliferation and metastasis by activating cell death pathways. As such, they have been widely studied as potential therapies for cancer prevention. The second generation synthetic isoflavan analogues ME-143 and ME-344 also exhibit anti-cancer effects, however their specific molecular targets have not been completely defined. To identify these targets, we examined the effects of ME-143 and ME-344 on cellular metabolism and found that they are potent inhibitors of mitochondrial oxidative phosphorylation (OXPHOS) complex I (NADH: ubiquinone oxidoreductase) activity. In isolated HEK293T mitochondria, ME-143 and ME-344 reduced complex I activity to 14.3% and 28.6% of control values respectively. In addition to the inhibition of complex I, ME-344 also significantly inhibited mitochondrial complex III (ubiquinol: ferricytochrome-c oxidoreductase) activity by 10.8%. This inhibition of complex I activity (and to a lesser extent complex III activity) was associated with a reduction in mitochondrial oxygen consumption. In permeabilized HEK293T cells, ME-143 and ME-344 significantly reduced the maximum ADP-stimulated respiration rate to 62.3% and 70.0% of control levels respectively in the presence of complex I-linked substrates. Conversely, complex II-linked respiration was unaffected by either drug. We also observed that the inhibition of complex I-linked respiration caused the dissipation of the mitochondrial membrane potential (ΔΨm). Blue native (BN-PAGE) analysis revealed that prolonged loss of ΔΨm results in the destabilization of the native OXPHOS complexes. In particular, treatment of 143B osteosarcoma, HeLa and HEK293T human embryonic kidney cells with ME-344 for 4 h resulted in reduced steady-state levels of mature complex I. Degradation of the complex I subunit NDUFA9, as well as the complex IV (ferrocytochrome c: oxygen oxidoreductase) subunit COXIV, was also evident. The identification of OXPHOS complex I as a target of ME-143 and ME-344 advances our understanding of how these drugs induce cell death by disrupting mitochondrial metabolism, and will direct future work to maximize the anti-cancer capacity of these and other isoflavone-based compounds. PMID:25973307

42 CFR 455.21 - Cooperation with State Medicaid fraud control units.

Code of Federal Regulations, 2014 CFR

2014-10-01

... subchapter. In using this information, the unit must protect the privacy rights of beneficiaries; and (3) On... 42 Public Health 4 2014-10-01 2014-10-01 false Cooperation with State Medicaid fraud control units. 455.21 Section 455.21 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND...

43 CFR 46.230 - Role of cooperating agencies in the NEPA process.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Role of cooperating agencies in the NEPA... IMPLEMENTATION OF THE NATIONAL ENVIRONMENTAL POLICY ACT OF 1969 Initiating the NEPA Process § 46.230 Role of...; (b) Arrange for the collection and/or assembly of necessary resource, environmental, social, economic...

49 CFR 26.109 - What are the rules governing information, confidentiality, cooperation, and intimidation or...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false What are the rules governing information, confidentiality, cooperation, and intimidation or retaliation? 26.109 Section 26.109 Transportation Office of the Secretary of Transportation PARTICIPATION BY DISADVANTAGED BUSINESS ENTERPRISES IN DEPARTMENT OF TRANSPORTATION FINANCIAL ASSISTANCE PROGRAMS...

50 CFR 260.73 - Disposition of fees for inspections made under cooperative agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Disposition of fees for inspections made... CERTIFICATION Inspection and Certification of Establishments and Fishery Products for Human Consumption Fees and Charges § 260.73 Disposition of fees for inspections made under cooperative agreement. Fees for inspection...

50 CFR 260.72 - Fees for inspection service performed under cooperative agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Fees for inspection service performed... CERTIFICATION Inspection and Certification of Establishments and Fishery Products for Human Consumption Fees and Charges § 260.72 Fees for inspection service performed under cooperative agreement. The fees to be charged...

46 CFR 385.51 - Criteria: Projects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 8 2014-10-01 2014-10-01 false Criteria: Projects. 385.51 Section 385.51 Shipping... COOPERATIVE AGREEMENTS REGULATIONS Criteria for Award § 385.51 Criteria: Projects. The criteria to be used by MarAd in evaluating all projects prior to award of a grant or cooperative agreement are as follows: (a...

46 CFR 385.51 - Criteria: Projects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 8 2013-10-01 2013-10-01 false Criteria: Projects. 385.51 Section 385.51 Shipping... COOPERATIVE AGREEMENTS REGULATIONS Criteria for Award § 385.51 Criteria: Projects. The criteria to be used by MarAd in evaluating all projects prior to award of a grant or cooperative agreement are as follows: (a...

46 CFR 385.51 - Criteria: Projects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 8 2011-10-01 2011-10-01 false Criteria: Projects. 385.51 Section 385.51 Shipping... COOPERATIVE AGREEMENTS REGULATIONS Criteria for Award § 385.51 Criteria: Projects. The criteria to be used by MarAd in evaluating all projects prior to award of a grant or cooperative agreement are as follows: (a...

Teachers' Reflections on Cooperative Learning: Issues of Implementation

ERIC Educational Resources Information Center

Gillies, Robyn M.; Boyle, Michael

2010-01-01

Cooperative learning (CL) is a well documented pedagogical practice that promotes academic achievement and socialization, yet many teachers struggle with implementing it in their classes. This study reports on the perceptions of 10, middle-year teachers who implemented cooperative learning in a unit of work across two school terms. Data from the…

7 CFR 1484.70 - Must Cooperators report to FAS?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Must Cooperators report to FAS? 1484.70 Section 1484... AGRICULTURAL COMMODITIES Reporting, Evaluation, and Compliance § 1484.70 Must Cooperators report to FAS? (a... contribution report is available on the FAS home page (http://www.fas.usda.gov/mos/programs/fnotice.html) on...

7 CFR 1484.70 - Must Cooperators report to FAS?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Must Cooperators report to FAS? 1484.70 Section 1484... AGRICULTURAL COMMODITIES Reporting, Evaluation, and Compliance § 1484.70 Must Cooperators report to FAS? (a... contribution report is available on the FAS home page (http://www.fas.usda.gov/mos/programs/fnotice.html) on...

7 CFR 1484.34 - Must Cooperators adhere to specific standards of ethical conduct?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Must Cooperators adhere to specific standards of ethical conduct? 1484.34 Section 1484.34 Agriculture Regulations of the Department of Agriculture... specific standards of ethical conduct? (a) A Cooperator shall conduct its business in accordance with the...

7 CFR 1484.34 - Must Cooperators adhere to specific standards of ethical conduct?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Must Cooperators adhere to specific standards of ethical conduct? 1484.34 Section 1484.34 Agriculture Regulations of the Department of Agriculture... specific standards of ethical conduct? (a) A Cooperator shall conduct its business in accordance with the...

7 CFR 1484.34 - Must Cooperators adhere to specific standards of ethical conduct?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Must Cooperators adhere to specific standards of ethical conduct? 1484.34 Section 1484.34 Agriculture Regulations of the Department of Agriculture... specific standards of ethical conduct? (a) A Cooperator shall conduct its business in accordance with the...

Psychological "gel" to bind individuals' goal pursuit: gratitude facilitates goal contagion.

PubMed

Jia, Lile; Tong, Eddie M W; Lee, Li Neng

2014-08-01

Past research demonstrates that gratitude affects individuals' self-regulation of behavior primarily through engendering a prosocial tendency. Based on theories proposing that gratitude plays an unique role in fostering communal relationship (e.g., Algoe, 2012), we propose that gratitude can have an incidental effect in facilitating goal contagion: automatically inferring and adopting the goal implied by a social other's behavior. This hypothesis is supported in 3 studies. In Study 1, after being exposed to the behaviors of a social target that implied either a cooperative or a competitive goal, individuals adopted the respective goal and behaved accordingly in a Resource Dilemma Task. This occurred, however, only when they were feeling gratitude and not when they were feeling joy or a neutral mood. In Study 2, after being exposed to a social target's behavior that implied the goal to make money, people feeling gratitude, as compared to those feeling pride or a neutral mood, strove for a future opportunity to earn money. Study 3 further demonstrated that individuals' goal striving behavior was mediated by a heightened level of goal activation. Finally, it was found that gratitude facilitated goal contagion only when the social target was a member of participants' own social group. Through this mechanism, gratitude, thus, seems to bind one's self-regulation with those of social others. Theoretical and practical implications of this new perspective are discussed.

Initiation of Electron Transport Chain Activity in the Embryonic Heart Coincides with the Activation of Mitochondrial Complex 1 and the Formation of Supercomplexes

PubMed Central

Beutner, Gisela; Eliseev, Roman A.; Porter, George A.

2014-01-01

Mitochondria provide energy in form of ATP in eukaryotic cells. However, it is not known when, during embryonic cardiac development, mitochondria become able to fulfill this function. To assess this, we measured mitochondrial oxygen consumption and the activity of the complexes (Cx) 1 and 2 of the electron transport chain (ETC) and used immunoprecipitation to follow the generation of mitochondrial supercomplexes. We show that in the heart of mouse embryos at embryonic day (E) 9.5, mitochondrial ETC activity and oxidative phosphorylation (OXPHOS) are not coupled, even though the complexes are present. We show that Cx-1 of the ETC is able to accept electrons from the Krebs cycle, but enzyme assays that specifically measure electron flow to ubiquinone or Cx-3 show no activity at this early embryonic stage. At E11.5, mitochondria appear functionally more mature; ETC activity and OXPHOS are coupled and respond to ETC inhibitors. In addition, the assembly of highly efficient respiratory supercomplexes containing Cx-1, -3, and -4, ubiquinone, and cytochrome c begins at E11.5, the exact time when Cx-1 becomes functional activated. At E13.5, ETC activity and OXPHOS of embryonic heart mitochondria are indistinguishable from adult mitochondria. In summary, our data suggest that between E9.5 and E11.5 dramatic changes occur in the mitochondria of the embryonic heart, which result in an increase in OXPHOS due to the activation of complex 1 and the formation of supercomplexes. PMID:25427064

Salicylic Acid-Dependent Plant Stress Signaling via Mitochondrial Succinate Dehydrogenase1[OPEN

PubMed Central

Thatcher, Louise F.

2017-01-01

Mitochondria are known for their role in ATP production and generation of reactive oxygen species, but little is known about the mechanism of their early involvement in plant stress signaling. The role of mitochondrial succinate dehydrogenase (SDH) in salicylic acid (SA) signaling was analyzed using two mutants: disrupted in stress response1 (dsr1), which is a point mutation in SDH1 identified in a loss of SA signaling screen, and a knockdown mutant (sdhaf2) for SDH assembly factor 2 that is required for FAD insertion into SDH1. Both mutants showed strongly decreased SA-inducible stress promoter responses and low SDH maximum capacity compared to wild type, while dsr1 also showed low succinate affinity, low catalytic efficiency, and increased resistance to SDH competitive inhibitors. The SA-induced promoter responses could be partially rescued in sdhaf2, but not in dsr1, by supplementing the plant growth media with succinate. Kinetic characterization showed that low concentrations of either SA or ubiquinone binding site inhibitors increased SDH activity and induced mitochondrial H2O2 production. Both dsr1 and sdhaf2 showed lower rates of SA-dependent H2O2 production in vitro in line with their low SA-dependent stress signaling responses in vivo. This provides quantitative and kinetic evidence that SA acts at or near the ubiquinone binding site of SDH to stimulate activity and contributes to plant stress signaling by increased rates of mitochondrial H2O2 production, leading to part of the SA-dependent transcriptional response in plant cells. PMID:28209841

Exceptional longevity and exceptionally high metabolic rates in anthropoid primates are linked to a major modification of the ubiquinone reduction site of cytochrome b.

PubMed

Rottenberg, Hagai

2014-10-01

The maximal lifespan of Anthropoid primates (monkeys, apes and humans) exceed the lifespan of most other mammals of equal body mass. Unexpectedly, their exceptional longevity is associated with exceptionally high metabolic rates, in apparent contradiction to the Free Radical Theory of Aging. It was therefore suggested that in anthropoid primates (and several other taxa of mammals and birds) the mitochondrial electron transport complexes evolved to modify the relationship between basal electron transport and superoxide generation to allow for the evolution of exceptional longevity. Cytochrome b, the core protein of the bc1 complex is a major source of superoxide. The amino-acid sequence of cytochrome b evolved much faster in anthropoid than in prosimian primates, and most other mammals, resulting in a large change in the amino-acids composition of the protein. As a result of these changes cytochrome b in anthropoid primates is significantly less hydrophobic and contains more polar residues than other primates and most other mammals. Most of these changes are clustered around the reduction site of uboiquinone. In particular a key positively charged residue, arginine 313, that interacts with propionate D of heme bH, and thus raises its redox potential, is substituted in anthropoid primates with the neutral residue glutamine, most likely resulting in a lower redox potential of heme bH and faster reduction of ubiquinone at high proton motive force. It is suggested that these changes contribute to the observed increased rates of basal metabolism and reduce the rates of superoxide production, thus allowing for increased lifespan.

RNA silencing of mitochondrial m-Nfs1 reduces Fe-S enzyme activity both in mitochondria and cytosol of mammalian cells.

PubMed

Fosset, Cédric; Chauveau, Marie-Jeanne; Guillon, Blanche; Canal, Frédéric; Drapier, Jean-Claude; Bouton, Cécile

2006-09-01

In prokaryotes and yeast, the general mechanism of biogenesis of iron-sulfur (Fe-S) clusters involves activities of several proteins among which IscS and Nfs1p provide, through cysteine desulfuration, elemental sulfide for Fe-S core formation. Although these proteins have been well characterized, the role of their mammalian homolog in Fe-S cluster biogenesis has never been evaluated. We report here the first functional study that implicates the putative cysteine desulfurase m-Nfs1 in the biogenesis of both mitochondrial and cytosolic mammalian Fe-S proteins. Depletion of m-Nfs1 in cultured fibroblasts through small interfering RNA-based gene silencing significantly inhibited the activities of mitochondrial NADH-ubiquinone oxidoreductase (complex I) and succinate-ubiquinone oxidoreductase (complex II) of the respiratory chain, as well as aconitase of the Krebs cycle, with no alteration in their protein levels. Activity of cytosolic xanthine oxidase, which holds a [2Fe-2S] cluster, was also specifically reduced, and iron-regulatory protein-1 was converted from its [4Fe-4S] aconitase form to its apo- or RNA-binding form. Reduction of Fe-S enzyme activities occurred earlier and more markedly in the cytosol than in mitochondria, suggesting that there is a mechanism that primarily dedicates m-Nfs1 to the biogenesis of mitochondrial Fe-S clusters in order to maintain cell survival. Finally, depletion of m-Nfs1, which conferred on apo-IRP-1 a high affinity for ferritin mRNA, was associated with the down-regulation of the iron storage protein ferritin.

Perturbation of the quinone-binding site of complex II alters the electronic properties of the proximal [3Fe-4S] iron-sulfur cluster.

PubMed

Ruprecht, Jonathan; Iwata, So; Rothery, Richard A; Weiner, Joel H; Maklashina, Elena; Cecchini, Gary

2011-04-08

Succinate-ubiquinone oxidoreductase (SQR) and menaquinol-fumarate oxidoreductase (QFR) from Escherichia coli are members of the complex II family of enzymes. SQR and QFR catalyze similar reactions with quinones; however, SQR preferentially reacts with higher potential ubiquinones, and QFR preferentially reacts with lower potential naphthoquinones. Both enzymes have a single functional quinone-binding site proximal to a [3Fe-4S] iron-sulfur cluster. A difference between SQR and QFR is that the redox potential of the [3Fe-4S] cluster in SQR is 140 mV higher than that found in QFR. This may reflect the character of the different quinones with which the two enzymes preferentially react. To investigate how the environment around the [3Fe-4S] cluster affects its redox properties and catalysis with quinones, a conserved amino acid proximal to the cluster was mutated in both enzymes. It was found that substitution of SdhB His-207 by threonine (as found in QFR) resulted in a 70-mV lowering of the redox potential of the cluster as measured by EPR. The converse substitution in QFR raised the redox potential of the cluster. X-ray structural analysis suggests that placing a charged residue near the [3Fe-4S] cluster is a primary reason for the alteration in redox potential with the hydrogen bonding environment having a lesser effect. Steady state enzyme kinetic characterization of the mutant enzymes shows that the redox properties of the [3Fe-4S] cluster have only a minor effect on catalysis.

Initiation of electron transport chain activity in the embryonic heart coincides with the activation of mitochondrial complex 1 and the formation of supercomplexes.

PubMed

Beutner, Gisela; Eliseev, Roman A; Porter, George A

2014-01-01

Mitochondria provide energy in form of ATP in eukaryotic cells. However, it is not known when, during embryonic cardiac development, mitochondria become able to fulfill this function. To assess this, we measured mitochondrial oxygen consumption and the activity of the complexes (Cx) 1 and 2 of the electron transport chain (ETC) and used immunoprecipitation to follow the generation of mitochondrial supercomplexes. We show that in the heart of mouse embryos at embryonic day (E) 9.5, mitochondrial ETC activity and oxidative phosphorylation (OXPHOS) are not coupled, even though the complexes are present. We show that Cx-1 of the ETC is able to accept electrons from the Krebs cycle, but enzyme assays that specifically measure electron flow to ubiquinone or Cx-3 show no activity at this early embryonic stage. At E11.5, mitochondria appear functionally more mature; ETC activity and OXPHOS are coupled and respond to ETC inhibitors. In addition, the assembly of highly efficient respiratory supercomplexes containing Cx-1, -3, and -4, ubiquinone, and cytochrome c begins at E11.5, the exact time when Cx-1 becomes functional activated. At E13.5, ETC activity and OXPHOS of embryonic heart mitochondria are indistinguishable from adult mitochondria. In summary, our data suggest that between E9.5 and E11.5 dramatic changes occur in the mitochondria of the embryonic heart, which result in an increase in OXPHOS due to the activation of complex 1 and the formation of supercomplexes.

Archive of digital Chirp subbottom profile data collected during USGS cruises 10CCT01, 10CCT02, and 10CCT03, Mississippi and Alabama Gulf Islands, March and April 2010

USGS Publications Warehouse

Forde, Arnell S.; Dadisman, Shawn V.; Flocks, James G.; Wiese, Dana S.; DeWitt, Nancy T.; Pfeiffer, William R.; Kelso, Kyle W.; Thompson, Phillip R.

2011-01-01

This Digital Versatile Disc (DVD) publication was prepared by an agency of the United States Government. Although these data have been processed successfully on a computer system at the U.S. Geological Survey, no warranty expressed or implied is made regarding the display or utility of the data on any other system, nor shall the act of distribution imply any such warranty. The U.S. Geological Survey shall not be held liable for improper or incorrect use of the data described and (or) contained herein. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof.

Ratio of entropy to enthalpy in thermal transitions in biological tissues.

PubMed

Jacques, Steven L

2006-01-01

Thermal transitions in biological tissues that have been reported in the literature are summarized in terms of the apparent molar entropy (DeltaS) and molar enthalpy (DeltaH) involved in the transition. A plot of DeltaS versus DeltaH for all the data yields a straight line, consistent with the definition of free energy, DeltaG=DeltaH+TDeltaS. Various bonds may be involved in cooperative bond breakage during thermal transitions; however, for the sake of description, the equivalent number of cooperative hydrogen bonds can be cited. Most of the tissue data behave as if 10 to 20 hydrogen bonds are cooperatively broken during coagulation, with one transition, the expression of heat shock protein, involving 90 cooperative hydrogen bonds. The data are consistent with DeltaS=a+bDeltaH, where a=-327.5 J(mol K) and b=31.47 x 10(-4) K(-1). If each additional hydrogen bond adds 19 x 10(3) Jmol to DeltaH, then each additional bond adds 59.8 J(mol K) to DeltaS. Hence, the dynamics of irreversible thermal transitions can be described in terms of one free parameter, the apparent number of cooperative hydrogen bonds broken during the transition.

Effect of temperature on rates of alternative and cytochrome pathway respiration and their relationship with the redox poise of the quinone pool.

PubMed

Atkin, Owen K; Zhang, Qisen; Wiskich, Joe T

2002-01-01

We investigated the effect of short-term changes in temperature on alternative (Alt) and cytochrome (Cyt) pathway respiration, both in intact tissues and isolated mitochondria of 14-d-old cotyledons of soybean (Glycine max L. cv Stevens). We also established the extent to which temperature alters the interaction between the oxidizing pathways and the level of ubiquinone (UQ) reduction (UQ(r)/UQ(t)). No difference was found between the temperature coefficient of respiration (Q(10); proportional change per 10 degrees C) of Alt and Cyt pathway respiration in cotyledon slices (Q(10) = 1.92 and 1.86, respectively). In isolated mitochondria, the Q(10) of the fully activated Alt pathway (Q(10) = 2.24-2.61) was always equal to, or higher than, that of Cyt c oxidase (COX) alone (Q(10) = 2.08) and the complete Cyt pathway (Q(10) = 2.40-2.55). This was true regardless of substrate or whether ADP was present. There was little difference in the Q(10) of the Cyt pathway with or without ADP; however, the Q(10) of COX was substantially lower in the presence of an uncoupler (Q(10) = 1.61) than its absence (Q(10) = 2.08). The kinetics of Alt and Cyt pathway activity in relation to UQ(r)/UQ(t) were not affected by temperature. For a given UQ(r)/UQ(t) value, the proportion of maximum flux taking place was similar at all temperatures for both pathways (+/-ADP). However, the Q(10) of the Alt and the Cyt pathways (+ADP) increased with increasing UQ(r)/UQ(t). We conclude that the Alt pathway is not less temperature sensitive than the Cyt pathway or COX per se and that changes in the degree of control exerted by individual steps in the respiratory apparatus could result in changes in the Q(10) of mitochondrial O(2) uptake.

Pro-oxidant mitochondrial matrix-targeted ubiquinone MitoQ10 acts as anti-oxidant at retarded electron transport or proton pumping within Complex I.

PubMed

Plecitá-Hlavatá, Lydie; Jezek, Jan; Jezek, Petr

2009-01-01

Oxidative stress of mitochondrial origin, i.e. elevated mitochondrial superoxide production, belongs to major factors determining aging and oxidative-stress-related diseases. Antioxidants, such as the mitochondria-targeted coenzyme Q, MitoQ(10), may prevent or cure these pathological conditions. To elucidate pro- and anti-oxidant action of MitoQ(10), we studied its effects on HepG2 cell respiration, mitochondrial network morphology, and rates of superoxide release (above that neutralized by superoxide dismutase) to the mitochondrial matrix (J(m)). MitoSOX Red fluorescence confocal microscopy monitoring of J(m) rates showed pro-oxidant effects of 3.5-fold increased J(m) with MitoQ(10). MitoQ(10) induced fission of the mitochondrial network which was recovered after 24h. In rotenone-inhibited HepG2 cells (i.e., already under oxidative stress) MitoQ(10) sharply decreased rotenone-induced J(m), but not together with the Complex II inhibitor thenoyltrifluoroacetone. Respiration of HepG2 cells and isolated rat liver mitochondria with MitoQ(10) increased independently of rotenone. The increase was prevented by thenoyltrifluoroacetone. These results suggest that MitoQ(10) accepts electrons prior to the rotenone-bound Q-site, and the Complex II reverse mode oxidizes MitoQ(10)H(2) to regenerate MitoQ(10). Consequently, MitoQ(10) has a pro-oxidant role in intact cells, whereas it serves as an antioxidant when Complex I-derived superoxide generation is already elevated due to electron flow retardation. Moreover, unlike mitochondrial uncoupling, MitoQ(10) exerted its antioxidant role when Complex I proton pumping was retarded by a hydrophobic amiloride, 5-(N-ethyl-N-isopropyl) amiloride. Consequently, MitoQ(10) may be useful in the treatment of diseases originating from impairment of respiratory chain Complex I due to oxidatively damaged mitochondrial DNA, when its targeted delivery to pathogenic tissues is ensured.

Identifying Faults Associated with the 2001 Avoca Induced(?) Seismicity Sequence of Western New York State Using Potential Field Wavelets.

NASA Astrophysics Data System (ADS)

Horowitz, F. G.; Ebinger, C.; Jordan, T. E.

2017-12-01

Results from recent DOE and USGS sponsored projects in the (intraplate) northeastern portions of the US and southeastern portions of Canada have identified locations of steeply dipping structures - many previously unknown - from a Poisson wavelet multiscale edge ('worm') analysis of gravity and magnetic fields. The Avoca sequence of induced(?) seismicity in western New York state occurred during January and February of 2001. The Avoca earthquake sequence is associated with industrial hydraulic fracturing activity "related to a proposed natural gas storage facility near Avoca to be constructed by solution mining" (Kim, 2001). The main Avoca event was a felt Mb = 3.2 earthquake on Feb. 3, 2001 recorded by the Lamont Cooperative Seismic Network. Earlier, smaller events were located by the Canadian Geological Survey's seismic network north of the Canadian border - implying that the event locations might be biased because they occurred off the southern edge of the array. Some of these events were also felt locally, according to local newspaper reports. By plotting the location of the seismic events and that of the injection well - reported via it's API number - we find a strong correlation with structures detected via our potential field worms. The injection occurred near a NE-SW striking structure that was not activated. All but one of the earthquakes occurred about 5 km north of the injection well on or nearby to an E-W striking structure that appears to intersect the NE-SW structure. The final, small (MN=2.2) earthquake was located on a different complex structure about 10 km north of the other events. We suggest that potential field methods such as ours might be appropriate to locating structures of concern for induced seismic activity in association with industrial activity. Reference: Kim, W.-Y. (2001). The Lamont cooperative seismic network and the national seismic system: Earthquake hazard studies in the northeastern United States. Tech. Rep. 98-01, Lamont Cooperative Seismic Network, Lamont-Doherty Earth Observatory of Columbia University, Palisades, NY.

Phenylobacterium kunshanense sp. nov., isolated from the sludge of a pesticide manufacturing factory.

PubMed

Chu, Cuiwei; Yuan, Cansheng; Liu, Xin; Yao, Li; Zhu, Jianchun; He, Jian; Kwon, Soon-Wo; Huang, Xing

2015-02-01

A novel aerobic, Gram-stain-negative, motile bacterium, designated strain BUT-10(T), was isolated from the sludge of a pesticide manufacturing factory in Kunshan, China. Cells were rod-shaped (0.4-0.45×0.9-1.4 µm) and colonies were white, circular with entire edges and had a smooth surface. The strain grew at 25-37 °C, at pH 6.0-8.0 and with 0-0.5 % NaCl. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain BUT-10(T) was a member of the genus Phenylobacterium, and showed highest sequence similarities to Phenylobacterium muchangponense A8(T) (97.49 %), Phenylobacterium immobile DSM 1986(T) (97.14 %) and Phenylobacterium lituiforme FaiI3(T) (96.34 %). Major fatty acids (>5 %) were summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0 and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). The major isoprenoid quinone was ubiquinone-10. The DNA G+C content was 71.85 mol%. Strain BUT-10(T) showed low DNA-DNA relatedness with P. muchangponense A8(T) (15.7±2.9 %) and P. immobile DSM 1986(T) (12.8±1.1 %). On the basis of the phenotypic, phylogenetic and genotypic data, strain BUT-10(T) is considered to represent a novel species of the genus Phenylobacterium, for which the name Phenylobacterium kunshanense sp. nov. is proposed. The type strain is BUT-10(T) ( = CCTCC AB 2013085(T) = KCTC 42014(T)). © 2015 IUMS.

Surface activity of lipid extract surfactant in relation to film area compression and collapse.

PubMed

Schürch, S; Schürch, D; Curstedt, T; Robertson, B

1994-08-01

The physical properties of modified porcine surfactant (Curosurf), isolated from minced lungs by extraction with chloroform-methanol and further purified by liquid-gel chromatography, were investigated with the captive bubble technique. Bubble size, and thus the surface tension of an insoluble film at the bubble surface, is altered by changing the pressure within the closed bubble chamber. The film surface tension and area are determined from the shape (height and diameter) of the bubble. Adsorption of fresh Curosurf is characterized by stepwise decreases in surface tension, which can easily be observed by sudden quick movements of the bubble apex. These "adsorption clicks" imply a cooperative movement of large collective units of molecules, approximately 10(14) (corresponding to approximately 120 ng of phospholipid) or approximately 10(18) molecules/m2, into the interface during adsorption. Films formed in this manner are already highly enriched in dipalmitoyl phosphatidylcholine, as seen by the extremely low compressibility, close to that of dipalmitoyl phosphatidylcholine. Near-zero minimum tensions are obtained, even at phospholipid concentrations as low as 50 micrograms/ml. During dynamic cycling (20-50 cycles/min), low minimum surface tensions, good film stability, low compressibility, and maximum surface tensions between 30 and 40 mN/m are possible only if the films are not overcompressed near zero surface tension; i.e., the overall film area compression should not substantially exceed 30%.

Spatial self-organization favors heterotypic cooperation over cheating

PubMed Central

Momeni, Babak; Waite, Adam James; Shou, Wenying

2013-01-01

Heterotypic cooperation—two populations exchanging distinct benefits that are costly to produce—is widespread. Cheaters, exploiting benefits while evading contribution, can undermine cooperation. Two mechanisms can stabilize heterotypic cooperation. In ‘partner choice’, cooperators recognize and choose cooperating over cheating partners; in ‘partner fidelity feedback’, fitness-feedback from repeated interactions ensures that aiding your partner helps yourself. How might a spatial environment, which facilitates repeated interactions, promote fitness-feedback? We examined this process through mathematical models and engineered Saccharomyces cerevisiae strains incapable of recognition. Here, cooperators and their heterotypic cooperative partners (partners) exchanged distinct essential metabolites. Cheaters exploited partner-produced metabolites without reciprocating, and were competitively superior to cooperators. Despite initially random spatial distributions, cooperators gained more partner neighbors than cheaters did. The less a cheater contributed, the more it was excluded and disfavored. This self-organization, driven by asymmetric fitness effects of cooperators and cheaters on partners during cell growth into open space, achieves assortment. DOI: http://dx.doi.org/10.7554/eLife.00960.001 PMID:24220506

Was monogamy a key step on the hominin road? Reevaluating the monogamy hypothesis in the evolution of cooperative breeding.

PubMed

Kramer, Karen L; Russell, Andrew F

2015-01-01

Because human mothers routinely rely on others to help raise their young, humans have been characterized as cooperative breeders.(1-9) Several large-scale phylogenetic analyses have presented compelling evidence that monogamy preceded the evolution of cooperative breeding in a wide variety of nonhuman animals.(10-14) These studies have suggested that monogamy provides a general rule (the monogamy hypothesis) for explaining evolutionary transitions to cooperative breeding.(15) Given the prevalence of cooperative breeding in contemporary human societies, we evaluate whether this suggests a monogamous hominin past. © 2015 Wiley Periodicals, Inc.

7 CFR 1484.70 - Must Cooperators report to FAS?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Must Cooperators report to FAS? 1484.70 Section 1484... COMMODITIES Reporting, Evaluation, and Compliance § 1484.70 Must Cooperators report to FAS? (a) End-of-year... is available on the FAS home page (http://www.fas.usda.gov/mos/programs/fnotice.html) on the Internet...

7 CFR 1484.54 - What expenditures may FAS reimburse under the Cooperator program?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false What expenditures may FAS reimburse under the... may FAS reimburse under the Cooperator program? (a) A Cooperator may seek reimbursement for an... source. (b) Subject to paragraph (a) of this section, FAS will reimburse, in whole or in part, the cost...

7 CFR 1484.70 - Must Cooperators report to FAS?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Must Cooperators report to FAS? 1484.70 Section 1484... COMMODITIES Reporting, Evaluation, and Compliance § 1484.70 Must Cooperators report to FAS? (a) End-of-year... is available on the FAS home page (http://www.fas.usda.gov/mos/programs/fnotice.html) on the Internet...

7 CFR 1484.54 - What expenditures may FAS reimburse under the Cooperator program?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false What expenditures may FAS reimburse under the... may FAS reimburse under the Cooperator program? (a) A Cooperator may seek reimbursement for an... source. (b) Subject to paragraph (a) of this section, FAS will reimburse, in whole or in part, the cost...

7 CFR 1484.54 - What expenditures may FAS reimburse under the Cooperator program?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false What expenditures may FAS reimburse under the... may FAS reimburse under the Cooperator program? (a) A Cooperator may seek reimbursement for an... source. (b) Subject to paragraph (a) of this section, FAS will reimburse, in whole or in part, the cost...

7 CFR 1484.70 - Must Cooperators report to FAS?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Must Cooperators report to FAS? 1484.70 Section 1484... COMMODITIES Reporting, Evaluation, and Compliance § 1484.70 Must Cooperators report to FAS? (a) End-of-year... is available on the FAS home page (http://www.fas.usda.gov/mos/programs/fnotice.html) on the Internet...

PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation.

PubMed

Inagaki, Yuichiro; Hayakawa, Fumihiko; Hirano, Daiki; Kojima, Yuki; Morishita, Takanobu; Yasuda, Takahiko; Naoe, Tomoki; Kiyoi, Hitoshi

2016-06-24

Plasma cell differentiation is initiated by antigen stimulation of the B cell receptor (BCR) and is regulated by BLIMP1. Prior to the stimulation of BCR, BLIMP1 is suppressed by PAX5, which is a key transcriptional repressor that maintains B cell identity. The upregulation of BLIMP1 and subsequent suppression of PAX5 by BLIMP1 are observed after the BCR stimulation. These events are considered to trigger plasma cell differentiation; however, the mechanisms responsible currently remain unclear. We herein demonstrated that the BCR signaling component, SYK, caused PAX5 tyrosine phosphorylation in vitro and in cells. Transcriptional repression on the BLIMP1 promoter by PAX5 was attenuated by this phosphorylation. The BCR stimulation induced the phosphorylation of SYK, tyrosine phosphorylation of PAX5, and up-regulation of BLIMP1 mRNA expression in B cells. The tyrosine phosphorylation of PAX5 co-operatively functioned with PAX5 serine phosphorylation by ERK1/2, which was our previous findings, to cancel the PAX5-dependent repression of BLIMP1. This co-operation may be a trigger for plasma cell differentiation. These results imply that PAX5 phosphorylation by a BCR signal is the initial event in plasma cell differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

Different gain/loss sensitivity and social adaptation ability in gifted adolescents during a public goods game.

PubMed

Chung, Dongil; Yun, Kyongsik; Kim, Jin Ho; Jang, Bosun; Jeong, Jaeseung

2011-02-16

Gifted adolescents are considered to have high IQs with advanced mathematical and logical performances, but are often thought to suffer from social isolation or emotional mal-adaptation to the social group. The underlying mechanisms that cause stereotypic portrayals of gifted adolescents are not well known. We aimed to investigate behavioral performance of gifted adolescents during social decision-making tasks to assess their affective and social/non-social cognitive abilities. We examined cooperation behaviors of 22 gifted and 26 average adolescents during an iterative binary public goods (PG) game, a multi-player social interaction game, and analyzed strategic decision processes that include cooperation and free-riding. We found that the gifted adolescents were more cooperative than average adolescents. Particularly, comparing the strategies for the PG game between the two groups, gifted adolescents were less sensitive to loss, yet were more sensitive to gain. Additionally, the behavioral characteristics of average adolescents, such as low trust of the group and herding behavior, were not found in gifted adolescents. These results imply that gifted adolescents have a high cognitive ability but a low ability to process affective information or to adapt in social groups compared with average adolescents. We conclude that gain/loss sensitivity and the ability to adapt in social groups develop to different degrees in average and gifted adolescents.

Hospital-physician relations: overcoming barriers to cooperation.

PubMed

Orr, S R; Siegal, J T

1986-01-01

In the September-October 1986 issue of Physician Executive, we discussed the application of strategic business units (SBUs) to health care. SBUs are those corporate entities that market similar products to one or more target populations with similar characteristics. Examples of SBUs in health care are obstetrics, cardiology, orthopedics, etc. When the services within each SBU are linked together, they might resemble a vertically integrated health care system. In the case of obstetrics, a woman may have contact with physicians, a hospital, home care nurses, house-cleaning services, birthing teachers, and maternity clothing boutiques. Each of these are products/services within the SBU of obstetrics. Strategy development by SBU implies an external focus on the marketplace in terms of the specific mission of the SBU (clinical specialty). It also implies responding to the needs of consumers for whom the historical and present divisiveness between hospitals and physicians is immaterial and irrelevant. In this article, we will focus on ways to stabilize the relationship between hospitals and physicians within an SBU context in order to compete more successfully as a team in today's health care environment.

Roseomonas arcticisoli sp. nov., isolated from Arctic tundra soil.

PubMed

Kim, Myong Chol; Rim, Songguk; Pak, Sehong; Ren, Lvzhi; Zhang, Yumin; Chang, Xulu; Li, Xuhuan; Fang, Chengxiang; Zheng, Congyi; Peng, Fang

2016-10-01

A pale pink, Gram-reaction-negative, non-motile, aerobic bacterium, designated MC 3624T, was isolated from a tundra soil near Ny-Ålesund, Svalbard Archipelago, Norway (78° N). Growth occurred at 10-37 °C (optimum 25-30 °C) and at pH 6.0-9.0 (optimum pH 8.0). The predominant fatty acids were C16 : 0 (17.7 %), C18 : 1ω7c 11-methyl (13.4 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) (10.1 %) and summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c) (38.3 %). The major respiratory quinone was ubiquinone-10, and the main polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and an unidentified aminolipids. The DNA G+C content was 68.9 mol%. Carotenoids of the spirilloxanthin series were produced. The nearest neighbour to the novel strain was Roseomonas wooponensis WW53T (94.36 % 16S rRNA gene sequence similarity). On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain MC 3624T represents a novel species of the genus Roseomonas, for which the name Roseomonas arcticisoli sp. nov. is proposed. The type strain is MC 3624T (=CCTCC AB 2014278T=LMG 28637T).

Electrochemical measurement of lateral diffusion coefficients of ubiquinones and plastoquinones of various isoprenoid chain lengths incorporated in model bilayers.

PubMed Central

Marchal, D; Boireau, W; Laval, J M; Moiroux, J; Bourdillon, C

1998-01-01

The long-range diffusion coefficients of isoprenoid quinones in a model of lipid bilayer were determined by a method avoiding fluorescent probe labeling of the molecules. The quinone electron carriers were incorporated in supported dimyristoylphosphatidylcholine layers at physiological molar fractions (<3 mol%). The elaborate bilayer template contained a built-in gold electrode at which the redox molecules solubilized in the bilayer were reduced or oxidized. The lateral diffusion coefficient of a natural quinone like UQ10 or PQ9 was 2.0 +/- 0.4 x 10(-8) cm2 s(-1) at 30 degrees C, two to three times smaller than the diffusion coefficient of a lipid analog in the same artificial bilayer. The lateral mobilities of the oxidized or reduced forms could be determined separately and were found to be identical in the 4-13 pH range. For a series of isoprenoid quinones, UQ2 or PQ2 to UQ10, the diffusion coefficient exhibited a marked dependence on the length of the isoprenoid chain. The data fit very well the quantitative behavior predicted by a continuum fluid model in which the isoprenoid chains are taken as rigid particles moving in the less viscous part of the bilayer and rubbing against the more viscous layers of lipid heads. The present study supports the concept of a homogeneous pool of quinone located in the less viscous region of the bilayer. PMID:9545054

Individual Characteristics vs. Experience: An Experimental Study on Cooperation in Prisoner's Dilemma

PubMed Central

Barreda-Tarrazona, Iván; Jaramillo-Gutiérrez, Ainhoa; Pavan, Marina; Sabater-Grande, Gerardo

2017-01-01

Cooperative behavior is often assumed to depend on individuals' characteristics, such as altruism and reasoning ability. Evidence is mixed about what the precise impact of these characteristics is, as the subjects of study are generally randomly paired, generating a heterogeneous mix of the two characteristics. In this study we ex-ante create four different groups of subjects by factoring their higher or lower than the median scores in both altruism and reasoning ability. Then we use these groups in order to analyze the joint effect of the two characteristics on the individual choice of cooperating and on successful paired cooperation. Subjects belonging to each group play first 10 one-shot prisoner's dilemma (PD) games with ten random partners and then three consecutive 10-round repeated PD games with three random partners. In all games, we elicit players' beliefs regarding cooperation using an incentive compatible method. Individuals with high altruism are more optimistic about the cooperative behavior of the other player in the one-shot game. They also show higher individual cooperation and paired cooperation rates in the first repetitions of this game. Contrary to the one-shot PD games where high reasoning ability reduces the probability of playing cooperatively, the sign of the relationship is inverted in the first repeated PD game, showing that high reasoning ability individuals better adjust their behavior to the characteristics of the game they are playing. In this sense, the joint effect of reasoning ability and altruism is not linear, with reasoning ability counteracting the cooperative effect of altruism in the one-shot game and reinforcing it in the first repeated game. However, experience playing the repeated PD games takes over the two individual characteristics in explaining individual and paired cooperation. Thus, in a (PD) setting, altruism and reasoning ability significantly affect behavior in single encounters, while in repeated interactions individual and paired cooperation reach similarly high levels independently of these individual characteristics. PMID:28473787

Proceedings of the DRG Seminar on The Defence of Small Ships against Missile Attacks (30th) Held in Ottawa, Canada on 12-14 September 1990. Volume 1 (Actes de 30ieme Seminaire sur la Defense de Petits Navires Contre les Attaques de Missiles)

DTIC Science & Technology

1991-04-12

LONG TERM 14. Abstract: The paper gives an overview of US Navy programme and objectives of anti-ship missile defence. Both evolutionary near term ...Integration of ESM with radar and IR sensors has Impli- cations with respect to ESM performance in terms of bearing accuracy, sensitivity and robustness in...defence budgets. The Terms of Reference of the Defence Research Group call for exchange of information, and the development of co-operative research

Intragenic inversion of mtDNA: a new type of pathogenic mutation in a patient with mitochondrial myopathy.

PubMed Central

Musumeci, O; Andreu, A L; Shanske, S; Bresolin, N; Comi, G P; Rothstein, R; Schon, E A; DiMauro, S

2000-01-01

We report an unusual molecular defect in the mitochondrially encoded ND1 subunit of NADH ubiquinone oxidoreductase (complex I) in a patient with mitochondrial myopathy and isolated complex I deficiency. The mutation is an inversion of seven nucleotides within the ND1 gene, which maintains the reading frame. The inversion, which alters three highly conserved amino acids in the polypeptide, was heteroplasmic in the patient's muscle but was not detectable in blood. This is the first report of a pathogenic inversion mutation in human mtDNA. PMID:10775530

A qualitative study of participants' views on re-consent in a longitudinal biobank.

PubMed

Dixon-Woods, Mary; Kocman, David; Brewster, Liz; Willars, Janet; Laurie, Graeme; Tarrant, Carolyn

2017-03-23

Biomedical research increasingly relies on long-term studies involving use and re-use of biological samples and data stored in large repositories or "biobanks" over lengthy periods, often raising questions about whether and when a re-consenting process should be activated. We sought to investigate the views on re-consent of participants in a longitudinal biobank. We conducted a qualitative study involving interviews with 24 people who were participating in a longitudinal biobank. Their views were elicited using a semi-structured interview schedule and scenarios based on a hypothetical biobank. Data analysis was based on the constant comparative method. What participants identified as requiring new consent was not a straightforward matter predictable by algorithms about the scope of the consent, but instead was contingent. They assessed whether proposed new research implied a fundamental alteration in the underlying character of the biobank and whether specific projects were within the scope of the original consent. What mattered most to them was that the cooperative bargain into which they had entered was maintained in good faith. They saw re-consent as one important safeguard in this bargain. In determining what required re-consent, they deployed two logics. First, they used a logic of boundaries, where they sought to detect any possible rupture with their existing framework of cooperation. Second, they used a logic of risk, where they assessed proposed research for any potential threats for them personally or the research endeavour. When they judged that a need for re-consent had been activated, participants saw the process as way of re-actualising and renewing the cooperative bargain. Participants' perceptions of research as a process of mutual co-operation between volunteer and researcher were fundamental to their views on consent. Consenting arrangements for biobanks should respect the cooperative values that are important to participants, recognise the two logics used by research volunteers, and avoid rigidity. Agility may be favoured by tiered consent combined with strong oversight mechanisms; this approach requires evaluation.

Research on International Space Station - Building a Partnership for the Future

NASA Technical Reports Server (NTRS)

Gindl, Heinz; Scheimann, Jens; Shirakawa, Masaki; Suvorov, Vadim; Uri, John J.

2004-01-01

As its name implies, the International Space Station is a platform where the research programs of 16 partner nations are conducted. While each partner pursues its own research priorities, cooperation and coordination of the various national and agency research programs occurs at multiple levels, from strategic through tactical planning to experiment operations. Since 2000, a significant number of experiments have been carried out in the Russian ISS utilization program, which consists of the Russian national program of fundamental and applied research in 11 research areas and international cooperative programs and contract activities. The US research program began with simple payloads in 2000 and was significantly expanded with the addition of the US Laboratory module Destiny in 2001, and its outfitting with seven research racks to date. The Canadian Space Agency (CSA), the European Space Agency (ESA) and the Japan Aerospace Exploration Agency (JAXA) have made use of international cooperative arrangements with both the US and Russia to implement a variety of investigations in diverse research areas, and in the case of ESA included the flights of crewmembers to ISS as part of Soyuz Science Missions. In the future, ESA and JAXA will add their own research modules, Columbus and Kibo, respectively, to expand research capabilities both inside and outside ISS. In the aftermath of the Columbia accident and the temporary grounding of the Space Shuttle fleet, all ISS logistics have relied on Russian Progress and Sopz vehicles. The Russian national program has continued as before the Shuttle accident, as have international cooperative programs and contract activities, both during long-duration expeditions and visiting taxi missions. In several instances, Russian international cooperative activities with JAXA and ESA have also involved the use of US facilities and crewmembers in successful truly multilateral efforts. The US research program was rapidly refocused after the Shuttle accident to rely on greatly reduced upmass, and for the first time in the ISS program, US research hardware was launched on Progress vehicles and returned with crews on Soyuz spacecraft. It is hoped that these small but significant steps in international cooperation will lead to even greater endeavors once the remaining research modules are added to ISS.

The Effects of 10 Communication Modes on the Behavior of Teams During Co-Operative Problem-Solving

ERIC Educational Resources Information Center

Ochsman, Richard B.; Chapanis, Alphonse

1974-01-01

Sixty teams of two college students each solved credible "real world" problems co-operatively. Conversations were carried on in one of 10 modes of communication: (1) typewriting only, (2) handwriting only, (3) handwriting and typewriting, (4) typewriting and video, (5) handwriting and video, (6) voice only, (7) voice and typewriting, (8) voice and…

Going Boldly Into the Future: A Series of Case Studies of Co-Operative Research Centres and Their Relationships with the VET Sector.

ERIC Educational Resources Information Center

Ferrier, Fran; Trood, Clifford; Whittingham, Karen

This document presents case studies of 10 cooperative research centers (CRCs) across Australia and their relationships with the vocational education and training (VET) sector. The CRCs profiled in the case studies are as follows: Co-operative Research Centre for Sustainable Rice Production; Cast Alloy and Solidification Technology Co-operative…

75 FR 65657 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-Alliance for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-26

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--Alliance for Water Stewardship Notice is hereby given that, on September 10, 2010, pursuant to Section 6(a) of the National Cooperative Research and Production Act of 1993, 15 U.S.C. 4301 et...

78 FR 67399 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-PXI System...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--PXI System Alliance, Inc. Notice is hereby given that, on October 10, 2013, pursuant to Section 6(a) of the National Cooperative Research and Production Act of 1993, 15 U.S.C. 4301 et...

Children's Sympathy, Guilt, and Moral Reasoning in Helping, Cooperation, and Sharing: A 6-Year Longitudinal Study

ERIC Educational Resources Information Center

Malti, Tina; Ongley, Sophia F.; Peplak, Joanna; Chaparro, Maria P.; Buchmann, Marlis; Zuffianò, Antonio; Cui, Lixian

2016-01-01

This study examined the role of sympathy, guilt, and moral reasoning in helping, cooperation, and sharing in a 6-year, three-wave longitudinal study involving 175 children (M[subscript age] 6.10, 9.18, and 12.18 years). Primary caregivers reported on children's helping and cooperation; sharing was assessed behaviorally. Child sympathy was assessed…

Functional cooperation between GATA factors and cJUN on the star promoter in MA-10 Leydig cells.

PubMed

Martin, Luc J; Bergeron, Francis; Viger, Robert S; Tremblay, Jacques J

2012-01-01

Steroid hormone biosynthesis requires the steroidogenic acute regulatory protein (STAR). STAR is part of a protein complex that transports cholesterol through the mitochondrial membrane where steroidogenesis begins. Several transcription factors participate to direct the proper spatiotemporal and hormonal regulation of the Star gene in Leydig cells. Mechanistically, this is believed to involve the functional interplay between many of these factors. Here we report a novel transcriptional cooperation between GATA factors and cJUN on the mouse Star and human STAR promoters in MA-10 Leydig cells. This cooperation was observed with different GATA members (GATA1, 4, and 6), whereas only cJUN could cooperate with GATA factors. GATA/cJUN transcriptional cooperation on the Star promoter is mediated via closely juxtaposed GATA and AP-1 binding motifs. Mutation of all functional GATA and cJUN elements abolished GATA/cJUN cooperation, which is in agreement with previous data reporting a direct interaction between GATA4 and cJUN in a heterologous system. These data add valuable new insights that further define the molecular mechanisms that govern Star transcription in steroidogenic cells of the testis.

A network of web multimedia medical information servers for a medical school and university hospital.

PubMed

Denier, P; Le Beux, P; Delamarre, D; Fresnel, A; Cleret, M; Courtin, C; Seka, L P; Pouliquen, B; Cleran, L; Riou, C; Burgun, A; Jarno, P; Leduff, F; Lesaux, H; Duvauferrier, R

1997-08-01

Modern medicine requires a rapid access to information including clinical data from medical records, bibliographic databases, knowledge bases and nomenclature databases. This is especially true for University Hospitals and Medical Schools for training as well as for fundamental and clinical research for diagnosis and therapeutic purposes. This implies the development of local, national and international cooperation which can be enhanced via the use and access to computer networks such as Internet. The development of professional cooperative networks goes with the development of the telecommunication and computer networks and our project is to make these new tools and technologies accessible to the medical students both during the teaching time in Medical School and during the training periods at the University Hospital. We have developed a local area network which communicates between the School of Medicine and the Hospital which takes advantage of the new Web client-server technology both internally (Intranet) and externally by access to the National Research Network (RENATER in France) connected to the Internet network. The address of our public web server is http:(/)/www.med.univ-rennesl.fr.

Dual origin of relapses in retinoic-acid resistant acute promyelocytic leukemia.

PubMed

Lehmann-Che, Jacqueline; Bally, Cécile; Letouzé, Eric; Berthier, Caroline; Yuan, Hao; Jollivet, Florence; Ades, Lionel; Cassinat, Bruno; Hirsch, Pierre; Pigneux, Arnaud; Mozziconacci, Marie-Joelle; Kogan, Scott; Fenaux, Pierre; de Thé, Hugues

2018-05-24

Retinoic acid (RA) and arsenic target the t(15;17)(q24;q21) PML/RARA driver of acute promyelocytic leukemia (APL), their combination now curing over 95% patients. We report exome sequencing of 64 matched samples collected from patients at initial diagnosis, during remission, and following relapse after historical combined RA-chemotherapy treatments. A first subgroup presents a high incidence of additional oncogenic mutations disrupting key epigenetic or transcriptional regulators (primarily WT1) or activating MAPK signaling at diagnosis. Relapses retain these cooperating oncogenes and exhibit additional oncogenic alterations and/or mutations impeding therapy response (RARA, NT5C2). The second group primarily exhibits FLT3 activation at diagnosis, which is lost upon relapse together with most other passenger mutations, implying that these relapses derive from ancestral pre-leukemic PML/RARA-expressing cells that survived RA/chemotherapy. Accordingly, clonogenic activity of PML/RARA-immortalized progenitors ex vivo is only transiently affected by RA, but selectively abrogated by arsenic. Our studies stress the role of cooperating oncogenes in direct relapses and suggest that targeting pre-leukemic cells by arsenic contributes to its clinical efficacy.

Testosterone is associated with cooperation during intergroup competition by enhancing parochial altruism

PubMed Central

Reimers, Luise; Diekhof, Esther K.

2015-01-01

The steroid hormone testosterone is widely associated with negative behavioral effects, such as aggression or dominance. However, recent studies applying economic exchange tasks revealed conflicting results. While some point to a prosocial effect of testosterone by increasing altruistic behavior, others report that testosterone promotes antisocial tendencies. Taking into account additional factors such as parochial altruism (i.e., ingroup favoritism and outgroup hostility) might help to explain this contradiction. First evidence for a link between testosterone and parochial altruism comes from recently reported data of male soccer fans playing the ultimatum game. In this study high levels of endogenous testosterone predicted increased altruistic punishment during outgroup interactions and at the same time heightened ingroup generosity. Here, we report findings of another experimental task, the prisoner's dilemma, applied in the same context to examine the role of testosterone on parochial tendencies in terms of cooperation. In this task, 50 male soccer fans were asked to decide whether or not they wanted to cooperate with partners marked as either fans of the subject's own favorite team (ingroup) or fans of other teams (outgroups). Our results show that high testosterone levels were associated with increased ingroup cooperation during intergroup competition. In addition, subjects displaying a high degree of parochialism during intergroup competition had significantly higher levels of testosterone than subjects who did not differentiate much between the different groups. In sum, the present data demonstrate that the behavioral effects of testosterone are not limited to aggressive and selfish tendencies but may imply prosocial aspects depending on the context. By this means, our results support the previously reported findings on testosterone-dependent intergroup bias and indicate that this social hormone might be an important factor driving parochial altruism. PMID:26124701

Testosterone is associated with cooperation during intergroup competition by enhancing parochial altruism.

PubMed

Reimers, Luise; Diekhof, Esther K

2015-01-01

The steroid hormone testosterone is widely associated with negative behavioral effects, such as aggression or dominance. However, recent studies applying economic exchange tasks revealed conflicting results. While some point to a prosocial effect of testosterone by increasing altruistic behavior, others report that testosterone promotes antisocial tendencies. Taking into account additional factors such as parochial altruism (i.e., ingroup favoritism and outgroup hostility) might help to explain this contradiction. First evidence for a link between testosterone and parochial altruism comes from recently reported data of male soccer fans playing the ultimatum game. In this study high levels of endogenous testosterone predicted increased altruistic punishment during outgroup interactions and at the same time heightened ingroup generosity. Here, we report findings of another experimental task, the prisoner's dilemma, applied in the same context to examine the role of testosterone on parochial tendencies in terms of cooperation. In this task, 50 male soccer fans were asked to decide whether or not they wanted to cooperate with partners marked as either fans of the subject's own favorite team (ingroup) or fans of other teams (outgroups). Our results show that high testosterone levels were associated with increased ingroup cooperation during intergroup competition. In addition, subjects displaying a high degree of parochialism during intergroup competition had significantly higher levels of testosterone than subjects who did not differentiate much between the different groups. In sum, the present data demonstrate that the behavioral effects of testosterone are not limited to aggressive and selfish tendencies but may imply prosocial aspects depending on the context. By this means, our results support the previously reported findings on testosterone-dependent intergroup bias and indicate that this social hormone might be an important factor driving parochial altruism.

Involvement of a Broccoli COQ5 Methyltransferase in the Production of Volatile Selenium Compounds[C][OA

PubMed Central

Zhou, Xin; Yuan, Youxi; Yang, Yong; Rutzke, Michael; Thannhauser, Theodore W.; Kochian, Leon V.; Li, Li

2009-01-01

Selenium (Se) is an essential micronutrient for animals and humans but becomes toxic at high dosage. Biologically based Se volatilization, which converts Se into volatile compounds, provides an important means for cleanup of Se-polluted environments. To identify novel genes whose products are involved in Se volatilization from plants, a broccoli (Brassica oleracea var italica) cDNA encoding COQ5 methyltransferase (BoCOQ5-2) in the ubiquinone biosynthetic pathway was isolated. Its function was authenticated by complementing a yeast coq5 mutant and by detecting increased cellular ubiquinone levels in the BoCOQ5-2-transformed bacteria. BoCOQ5-2 was found to promote Se volatilization in both bacteria and transgenic Arabidopsis (Arabidopsis thaliana) plants. Bacteria expressing BoCOQ5-2 produced an over 160-fold increase in volatile Se compounds when they were exposed to selenate. Consequently, the BoCOQ5-2-transformed bacteria had dramatically enhanced tolerance to selenate and a reduced level of Se accumulation. Transgenic Arabidopsis expressing BoCOQ5-2 volatilized three times more Se than the vector-only control plants when treated with selenite and exhibited an increased tolerance to Se. In addition, the BoCOQ5-2 transgenic plants suppressed the generation of reactive oxygen species induced by selenite. BoCOQ5-2 represents, to our knowledge, the first plant enzyme that is not known to be directly involved in sulfur/Se metabolism yet was found to mediate Se volatilization. This discovery opens up new prospects regarding our understanding of the complete metabolism of Se and may lead to ways to modify Se-accumulator plants with increased efficiency for phytoremediation of Se-contaminated environments. PMID:19656903

Hypothalamic digoxin, hemispheric chemical dominance and sarcoidosis.

PubMed

Ravi Kumar, A; Kurup, Parameswara Achutha

2004-06-01

The isoprenoid pathway produces three key metabolites: endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins) and ubiquinone (free radical scavenger). The role of the isoprenoid pathway in the pathogenesis of sarcoidosis in relation to hemispheric dominance was studied. The isoprenoid pathway-related cascade was assessed in patients with systemic sarcoidosis with pulmonary involvement. The pathway was also assessed in patients with right hemispheric, left hemispheric and bihemispheric dominance for comparison to find out the role of hemispheric dominance in the pathogenesis of sarcoidosis. In patients with sarcoidosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in the cholesterol:phospholipid ratio and a reduction in the glycoconjugate level of red blood cell (RBC) membrane in this group of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. In individuals with left hemispheric dominance the patterns were reversed. Endogenous digoxin, by activating the calcineurin signal transduction pathway of T cells, can contribute to immune activation in sarcoidosis. An altered glycoconjugate metabolism can lead to the generation of endogenous self-glycoprotein antigens in the lung as well as other tissues. Increased free radical generation can also lead to immune activation. The role of a dysfunctional isoprenoid pathway and endogenous digoxin in the pathogenesis of sarcoidosis in relation to right hemispheric chemical dominance is discussed. All the patients with sarcoidosis were right-handed/left hemispheric dominant according to the dichotic listening test, but their biochemical patterns were suggestive of right hemispheric chemical dominance. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test.

Hypothalamic digoxin, hemispheric chemical dominance, and peptic ulcer disease.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-10-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin-like factor (EDLF) (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter transport), ubiquinone (free radical scavenger), and dolichol (regulator of glycoconjugate metabolism). The pathway was assessed in peptic ulcer and acid peptic disease and its relation to hemispheric dominance studied. The activity of HMG CoA reductase, serum levels of EDLF, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in acid peptic disease, right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals. All the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. The pathway was upregulated with increased EDLF synthesis in peptic ulcer disease (PUD). There was increase in tryptophan catabolites and reduction in tyrosine catabolites in these patients. The ubiquinone levels were low and free radical production increased. Dolichol and glycoconjugate levels were increased and lysosomal stability reduced in patients with acid peptic disease (APD). There was increase in cholesterol:phospholipid ratio with decreased glyco conjugate levels in membranes of patients with PUD. Acid peptic disease represents an elevated EDLF state which can modulate gastric acid secretion and the structure of the gastric mucous barrier. It can also lead to persistence of Helicobacter pylori infection. The biochemical pattern obtained in peptic ulcer disease is similar to those obtained in left-handed/right hemispheric chemically dominant individuals. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listen ing test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Peptic ulcer disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Hypothalamic digoxin and hemispheric chemical dominance: relation to alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-08-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin (modulate tryptophan/tyrosine transport), dolichol (important in N -glycosylation of proteins), and ubiquinone (free radical scavenger). It was considered pertinent to assess the pathway in alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration. Since endogenous digoxin can regulate neurotransmitter transport, the pathway was also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. In the patient group there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites as reduced endogenous morphine synthesis from tyrosine. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. The same patterns were obtained in individuals with right hemispheric chemical dominance. Alcoholic cirrhosis, alcoholic addiction, and acquired hepatocerebral degeneration are associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to NMDA excitotoxicity and altered connective tissue/lipid metabolism important in its pathogenesis. Endogenous morphine deficiency plays a role in alcoholic addiction. Alcoholic cirrhosis, addiction, and acquired hepato -cerebral degeneration occur in right hemispheric chemically dominant individuals. Ninety percent of the patients with alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration were right-handed and left hemispheric dominant by the dichotic listening test. However, their biochemical patterns were similar to those obtained in right hemispheric chemical dominance. Hemispheric chemical dominance is a different entity and has no correlation with handedness or the dichotic listening test.

The UbiK protein is an accessory factor necessary for bacterial ubiquinone (UQ) biosynthesis and forms a complex with the UQ biogenesis factor UbiJ.

PubMed

Loiseau, Laurent; Fyfe, Cameron; Aussel, Laurent; Hajj Chehade, Mahmoud; Hernández, Sara B; Faivre, Bruno; Hamdane, Djemel; Mellot-Draznieks, Caroline; Rascalou, Bérengère; Pelosi, Ludovic; Velours, Christophe; Cornu, David; Lombard, Murielle; Casadesús, Josep; Pierrel, Fabien; Fontecave, Marc; Barras, Frédéric

2017-07-14

Ubiquinone (UQ), also referred to as coenzyme Q, is a widespread lipophilic molecule in both prokaryotes and eukaryotes in which it primarily acts as an electron carrier. Eleven proteins are known to participate in UQ biosynthesis in Escherichia coli , and we recently demonstrated that UQ biosynthesis requires additional, nonenzymatic factors, some of which are still unknown. Here, we report on the identification of a bacterial gene, yqiC , which is required for efficient UQ biosynthesis, and which we have renamed ubiK Using several methods, we demonstrated that the UbiK protein forms a complex with the C-terminal part of UbiJ, another UQ biogenesis factor we previously identified. We found that both proteins are likely to contribute to global UQ biosynthesis rather than to a specific biosynthetic step, because both ubiK and ubiJ mutants accumulated octaprenylphenol, an early intermediate of the UQ biosynthetic pathway. Interestingly, we found that both proteins are dispensable for UQ biosynthesis under anaerobiosis, even though they were expressed in the absence of oxygen. We also provide evidence that the UbiK-UbiJ complex interacts with palmitoleic acid, a major lipid in E. coli Last, in Salmonella enterica , ubiK was required for proliferation in macrophages and virulence in mice. We conclude that although the role of the UbiK-UbiJ complex remains unknown, our results support the hypothesis that UbiK is an accessory factor of Ubi enzymes and facilitates UQ biosynthesis by acting as an assembly factor, a targeting factor, or both. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Two solanesyl diphosphate synthases with different subcellular localizations and their respective physiological roles in Oryza sativa

PubMed Central

Ohara, Kazuaki; Sasaki, Kanako; Yazaki, Kazufumi

2010-01-01

Long chain prenyl diphosphates are crucial biosynthetic precursors of ubiquinone (UQ) in many organisms, ranging from bacteria to humans, as well as precursors of plastoquinone in photosynthetic organisms. The cloning and characterization of two solanesyl diphosphate synthase genes, OsSPS1 and OsSPS2, in Oryza sativa is reported here. OsSPS1 was highly expressed in root tissue whereas OsSPS2 was found to be high in both leaves and roots. Enzymatic characterization using recombinant proteins showed that both OsSPS1 and OsSPS2 could produce solanesyl diphosphates as their final product, while OsSPS1 showed stronger activity than OsSPS2. However, an important biological difference was observed between the two genes: OsSPS1 complemented the yeast coq1 disruptant, which does not form UQ, whereas OsSPS2 only very weakly complemented the growth defect of the coq1 mutant. HPLC analyses showed that both OsSPS1 and OsSPS2 yeast transformants produced UQ9 instead of UQ6, which is the native yeast UQ. According to the complementation study, the UQ9 levels in OsSPS2 transformants were much lower than that of OsSPS1. Green fluorescent protein fusion analyses showed that OsSPS1 localized to mitochondria, while OsSPS2 localized to plastids. This suggests that OsSPS1 is involved in the supply of solanesyl diphosphate for ubiquinone-9 biosynthesis in mitochondria, whereas OsSPS2 is involved in providing solanesyl diphosphate for plastoquinone-9 formation. These findings indicate that O. sativa has a different mechanism for the supply of isoprenoid precursors in UQ biosynthesis from Arabidopsis thaliana, in which SPS1 provides a prenyl moiety for UQ9 at the endoplasmic reticulum. PMID:20421194

Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1 lead to impaired citrate export required for lipid, dolichol, ubiquinone and sterol synthesis.

PubMed

Majd, Homa; King, Martin S; Smith, Anthony C; Kunji, Edmund R S

2018-01-01

Missense mutations of the human mitochondrial citrate carrier, encoded by the SLC25A1 gene, lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development, often resulting in early death. Here, we have measured the effect of all twelve known pathogenic mutations on the transport activity. The results show that nine mutations abolish transport of citrate completely, whereas the other three reduce the transport rate by >70%, indicating that impaired citrate transport is the most likely primary cause of the disease. Some mutations may be detrimental to the structure of the carrier, whereas others may impair key functional elements, such as the substrate binding site and the salt bridge network on the matrix side of the carrier. To understand the consequences of impaired citrate transport on metabolism, the substrate specificity was also determined, showing that the human citrate carrier predominantly transports citrate, isocitrate, cis-aconitate, phosphoenolpyruvate and malate. Although D-2- and L-2 hydroxyglutaric aciduria is a metabolic hallmark of the disease, it is unlikely that the citrate carrier plays a significant role in the removal of hydroxyglutarate from the cytosol for oxidation to oxoglutarate in the mitochondrial matrix. In contrast, computer simulations of central metabolism predict that the export of citrate from the mitochondrion cannot be fully compensated by other pathways, restricting the cytosolic production of acetyl-CoA that is required for the synthesis of lipids, sterols, dolichols and ubiquinone, which in turn explains the severe disease phenotypes. Copyright © 2017. Published by Elsevier B.V.

Two solanesyl diphosphate synthases with different subcellular localizations and their respective physiological roles in Oryza sativa.

PubMed

Ohara, Kazuaki; Sasaki, Kanako; Yazaki, Kazufumi

2010-06-01

Long chain prenyl diphosphates are crucial biosynthetic precursors of ubiquinone (UQ) in many organisms, ranging from bacteria to humans, as well as precursors of plastoquinone in photosynthetic organisms. The cloning and characterization of two solanesyl diphosphate synthase genes, OsSPS1 and OsSPS2, in Oryza sativa is reported here. OsSPS1 was highly expressed in root tissue whereas OsSPS2 was found to be high in both leaves and roots. Enzymatic characterization using recombinant proteins showed that both OsSPS1 and OsSPS2 could produce solanesyl diphosphates as their final product, while OsSPS1 showed stronger activity than OsSPS2. However, an important biological difference was observed between the two genes: OsSPS1 complemented the yeast coq1 disruptant, which does not form UQ, whereas OsSPS2 only very weakly complemented the growth defect of the coq1 mutant. HPLC analyses showed that both OsSPS1 and OsSPS2 yeast transformants produced UQ9 instead of UQ6, which is the native yeast UQ. According to the complementation study, the UQ9 levels in OsSPS2 transformants were much lower than that of OsSPS1. Green fluorescent protein fusion analyses showed that OsSPS1 localized to mitochondria, while OsSPS2 localized to plastids. This suggests that OsSPS1 is involved in the supply of solanesyl diphosphate for ubiquinone-9 biosynthesis in mitochondria, whereas OsSPS2 is involved in providing solanesyl diphosphate for plastoquinone-9 formation. These findings indicate that O. sativa has a different mechanism for the supply of isoprenoid precursors in UQ biosynthesis from Arabidopsis thaliana, in which SPS1 provides a prenyl moiety for UQ9 at the endoplasmic reticulum.

Analysis of a Range of Catabolic Mutants Provides Evidence That Phytanoyl-Coenzyme A Does Not Act as a Substrate of the Electron-Transfer Flavoprotein/Electron-Transfer Flavoprotein:Ubiquinone Oxidoreductase Complex in Arabidopsis during Dark-Induced Senescence1[W][OA

PubMed Central

Araújo, Wagner L.; Ishizaki, Kimitsune; Nunes-Nesi, Adriano; Tohge, Takayuki; Larson, Tony R.; Krahnert, Ina; Balbo, Ilse; Witt, Sandra; Dörmann, Peter; Graham, Ian A.; Leaver, Christopher J.; Fernie, Alisdair R.

2011-01-01

The process of dark-induced senescence in plants is not fully understood, however, the functional involvement of an electron-transfer flavoprotein/electron-transfer flavoprotein:ubiquinone oxidoreductase (ETF/ETFQO), has been demonstrated. Recent studies have revealed that the enzymes isovaleryl-coenzyme A (CoA) dehydrogenase and 2-hydroxyglutarate dehydrogenase act as important electron donors to this complex. In addition both enzymes play a role in the breakdown of cellular carbon storage reserves with isovaleryl-CoA dehydrogenase being involved in degradation of the branched-chain amino acids, phytol, and lysine while 2-hydroxyglutarate dehydrogenase is exclusively involved in lysine degradation. Given that the chlorophyll breakdown intermediate phytanoyl-CoA accumulates dramatically both in knockout mutants of the ETF/ETFQO complex and of isovaleryl-CoA dehydrogenase following growth in extended dark periods we have investigated the direct importance of chlorophyll breakdown for the supply of carbon and electrons during this process. For this purpose we isolated three independent Arabidopsis (Arabidopsis thaliana) knockout mutants of phytanoyl-CoA 2-hydroxylase and grew them under the same extended darkness regime as previously used. Despite the fact that these mutants accumulated phytanoyl-CoA and also 2-hydroxyglutarate they exhibited no morphological changes in comparison to the other mutants previously characterized. These results are consistent with a single entry point of phytol breakdown into the ETF/ETFQO system and furthermore suggest that phytol is not primarily metabolized by this pathway. Furthermore analysis of isovaleryl-CoA dehydrogenase/2-hydroxyglutarate dehydrogenase double mutants generated here suggest that these two enzymes essentially account for the entire electron input via the ETF complex. PMID:21788362

Electron spin relaxation enhancement measurements of interspin distances in human, porcine, and Rhodobacter electron transfer flavoprotein ubiquinone oxidoreductase (ETF QO)

NASA Astrophysics Data System (ADS)

Fielding, Alistair J.; Usselman, Robert J.; Watmough, Nicholas; Simkovic, Martin; Frerman, Frank E.; Eaton, Gareth R.; Eaton, Sandra S.

2008-02-01

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a membrane-bound electron transfer protein that links primary flavoprotein dehydrogenases with the main respiratory chain. Human, porcine, and Rhodobacter sphaeroides ETF-QO each contain a single [4Fe-4S] 2+,1+ cluster and one equivalent of FAD, which are diamagnetic in the isolated enzyme and become paramagnetic on reduction with the enzymatic electron donor or with dithionite. The anionic flavin semiquinone can be reduced further to diamagnetic hydroquinone. The redox potentials for the three redox couples are so similar that it is not possible to poise the proteins in a state where both the [4Fe-4S] + cluster and the flavoquinone are fully in the paramagnetic form. Inversion recovery was used to measure the electron spin-lattice relaxation rates for the [4Fe-4S] + between 8 and 18 K and for semiquinone between 25 and 65 K. At higher temperatures the spin-lattice relaxation rates for the [4Fe-4S] + were calculated from the temperature-dependent contributions to the continuous wave linewidths. Although mixtures of the redox states are present, it was possible to analyze the enhancement of the electron spin relaxation of the FAD semiquinone signal due to dipolar interaction with the more rapidly relaxing [4Fe-4S] + and obtain point-dipole interspin distances of 18.6 ± 1 Å for the three proteins. The point-dipole distances are within experimental uncertainty of the value calculated based on the crystal structure of porcine ETF-QO when spin delocalization is taken into account. The results demonstrate that electron spin relaxation enhancement can be used to measure distances in redox poised proteins even when several redox states are present.

Electron Spin Relaxation Enhancement Measurements of Interspin Distances in Human, Porcine, and Rhodobacter Electron Transfer Flavoprotein-ubiquinone Oxidoreductase (ETF-QO)

PubMed Central

Fielding, Alistair J.; Usselman, Robert J.; Watmough, Nicholas; Simkovic, Martin; Frerman, Frank E.; Eaton, Gareth R.; Eaton, Sandra S.

2008-01-01

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a membrane-bound electron transfer protein that links primary flavoprotein dehydrogenases with the main respiratory chain. Human, porcine, and Rhodobacter sphaeroides ETF-QO each contain a single [4Fe-4S]2+,1+ cluster and one equivalent of FAD, which are diamagnetic in the isolated enzyme and become paramagnetic on reduction with the enzymatic electron donor or with dithionite. The anionic flavin semiquinone can be reduced further to diamagnetic hydroquinone. The redox potentials for the three redox couples are so similar that it is not possible to poise the proteins in a state where both the [4Fe-4S]+ cluster and the flavoquinone are fully in the paramagnetic form. Inversion recovery was used to measure the electron spin-lattice relaxation rates for the [4Fe-4S]+ between 8 and 18 K and for semiquinone between 25 and 65 K. At higher temperatures the spin-lattice relaxation rates for the [4Fe-4S]+ were calculated from the temperature-dependent contributions to the continuous wave linewidths. Although mixtures of the redox states are present, it was possible to analyze the enhancement of the electron spin relaxation of the FAD semiquinone signal due to dipolar interaction with the more rapidly relaxing [4Fe-4S]+ and obtain point dipole interspin distances of 18.6 ± 1 Å for the three proteins. The point-dipole distances are within experimental uncertainty of the value calculated based on the crystal structure of porcine ETF-QO when spin delocalization is taken into account. The results demonstrate that electron spin relaxation enhancement can be used to measure distances in redox poised proteins even when several redox states are present. PMID:18037314

Electron spin relaxation enhancement measurements of interspin distances in human, porcine, and Rhodobacter electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO).

PubMed

Fielding, Alistair J; Usselman, Robert J; Watmough, Nicholas; Simkovic, Martin; Frerman, Frank E; Eaton, Gareth R; Eaton, Sandra S

2008-02-01

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a membrane-bound electron transfer protein that links primary flavoprotein dehydrogenases with the main respiratory chain. Human, porcine, and Rhodobacter sphaeroides ETF-QO each contain a single [4Fe-4S](2+,1+) cluster and one equivalent of FAD, which are diamagnetic in the isolated enzyme and become paramagnetic on reduction with the enzymatic electron donor or with dithionite. The anionic flavin semiquinone can be reduced further to diamagnetic hydroquinone. The redox potentials for the three redox couples are so similar that it is not possible to poise the proteins in a state where both the [4Fe-4S](+) cluster and the flavoquinone are fully in the paramagnetic form. Inversion recovery was used to measure the electron spin-lattice relaxation rates for the [4Fe-4S](+) between 8 and 18K and for semiquinone between 25 and 65K. At higher temperatures the spin-lattice relaxation rates for the [4Fe-4S](+) were calculated from the temperature-dependent contributions to the continuous wave linewidths. Although mixtures of the redox states are present, it was possible to analyze the enhancement of the electron spin relaxation of the FAD semiquinone signal due to dipolar interaction with the more rapidly relaxing [4Fe-4S](+) and obtain point-dipole interspin distances of 18.6+/-1A for the three proteins. The point-dipole distances are within experimental uncertainty of the value calculated based on the crystal structure of porcine ETF-QO when spin delocalization is taken into account. The results demonstrate that electron spin relaxation enhancement can be used to measure distances in redox poised proteins even when several redox states are present.

Comparative Genomic Analysis of Phylogenetically Closely Related Hydrogenobaculum sp. Isolates from Yellowstone National Park

PubMed Central

Romano, Christine; D'Imperio, Seth; Woyke, Tanja; Mavromatis, Konstantinos; Lasken, Roger; Shock, Everett L.

2013-01-01

We describe the complete genome sequences of four closely related Hydrogenobaculum sp. isolates (≥99.7% 16S rRNA gene identity) that were isolated from the outflow channel of Dragon Spring (DS), Norris Geyser Basin, in Yellowstone National Park (YNP), WY. The genomes range in size from 1,552,607 to 1,552,931 bp, contain 1,667 to 1,676 predicted genes, and are highly syntenic. There are subtle differences among the DS isolates, which as a group are different from Hydrogenobaculum sp. strain Y04AAS1 that was previously isolated from a geographically distinct YNP geothermal feature. Genes unique to the DS genomes encode arsenite [As(III)] oxidation, NADH-ubiquinone-plastoquinone (complex I), NADH-ubiquinone oxidoreductase chain, a DNA photolyase, and elements of a type II secretion system. Functions unique to strain Y04AAS1 include thiosulfate metabolism, nitrate respiration, and mercury resistance determinants. DS genomes contain seven CRISPR loci that are almost identical but are different from the single CRISPR locus in strain Y04AAS1. Other differences between the DS and Y04AAS1 genomes include average nucleotide identity (94.764%) and percentage conserved DNA (80.552%). Approximately half of the genes unique to Y04AAS1 are predicted to have been acquired via horizontal gene transfer. Fragment recruitment analysis and marker gene searches demonstrated that the DS metagenome was more similar to the DS genomes than to the Y04AAS1 genome, but that the DS community is likely comprised of a continuum of Hydrogenobaculum genotypes that span from the DS genomes described here to an Y04AAS1-like organism, which appears to represent a distinct ecotype relative to the DS genomes characterized. PMID:23435891

Prevention of gentamicin-induced apoptosis with the mitochondria-targeted antioxidant mitoquinone.

PubMed

Ojano-Dirain, Carolyn P; Antonelli, Patrick J

2012-11-01

Antioxidants have been shown to protect against aminoglycoside-induced hearing loss. Mitoquinone (MitoQ) is a mitochondria-targeted derivative of the antioxidant ubiquinone. MitoQ is attached to a lipophilic triphenylphosphonium (TPP) cation, which enables its accumulation inside the mitochondria several hundred-fold over the untargeted antioxidant. The goals of this study were to determine if MitoQ attenuates gentamicin-induced activation of caspase-3/7 activity as a marker of apoptosis and to determine if MitoQ impacts aminoglycoside antimicrobial efficacy. Prospective and controlled. Antibiotic efficacy and minimum inhibitory concentrations (MICs) of gentamicin against three strains each of Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa were evaluated with and without MitoQ using broth dilution methods. Apoptosis was assessed by caspase-3/7 activity in untreated HEI-OC1 cells and cells exposed to 2 mM gentamicin for 24 hours, with and without a 24-hour preincubation with 0.5 μM each of MitoQ, idebenone (an untargeted ubiquinone), or decylTPP (positive control). Gentamicin MICs for P aeruginosa and H influenzae were not affected by MitoQ at pharmacological levels. MICs for S aureus were enhanced by MitoQ. Cell viability was significantly lower in the gentamicin-treated cells. A significant increase in caspase-3/7 activity was observed in cells treated with gentamicin or with idebenone + gentamicin (P = .005). Preincubation with MitoQ decreased the gentamicin-induced apoptosis of HEI-OC1 cells to a greater extent compared to idebenone (P = .002). MitoQ attenuates gentamicin-induced apoptosis in HEI-OC1 cells and does not compromise gentamicin antibiotic efficacy. MitoQ holds promise as a means of preventing aminoglycoside ototoxicity. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

A mitochondrial-targeted ubiquinone modulates muscle lipid profile and improves mitochondrial respiration in obesogenic diet-fed rats.

PubMed

Coudray, Charles; Fouret, Gilles; Lambert, Karen; Ferreri, Carla; Rieusset, Jennifer; Blachnio-Zabielska, Agnieszka; Lecomte, Jérôme; Ebabe Elle, Raymond; Badia, Eric; Murphy, Michael P; Feillet-Coudray, Christine

2016-04-14

The prevalence of the metabolic syndrome components including abdominal obesity, dyslipidaemia and insulin resistance is increasing in both developed and developing countries. It is generally accepted that the development of these features is preceded by, or accompanied with, impaired mitochondrial function. The present study was designed to analyse the effects of a mitochondrial-targeted lipophilic ubiquinone (MitoQ) on muscle lipid profile modulation and mitochondrial function in obesogenic diet-fed rats. For this purpose, twenty-four young male Sprague-Dawley rats were divided into three groups and fed one of the following diets: (1) control, (2) high fat (HF) and (3) HF+MitoQ. After 8 weeks, mitochondrial function markers and lipid metabolism/profile modifications in skeletal muscle were measured. The HF diet was effective at inducing the major features of the metabolic syndrome--namely, obesity, hepatic enlargement and glucose intolerance. MitoQ intake prevented the increase in rat body weight, attenuated the increase in adipose tissue and liver weights and partially reversed glucose intolerance. At the muscle level, the HF diet induced moderate TAG accumulation associated with important modifications in the muscle phospholipid classes and in the fatty acid composition of total muscle lipid. These lipid modifications were accompanied with decrease in mitochondrial respiration. MitoQ intake corrected the lipid alterations and restored mitochondrial respiration. These results indicate that MitoQ protected obesogenic diet-fed rats from some features of the metabolic syndrome through its effects on muscle lipid metabolism and mitochondrial activity. These findings suggest that MitoQ is a promising candidate for future human trials in the metabolic syndrome prevention.

Mitochondria-targeted ubiquinone (MitoQ) decreases ethanol-dependent micro and macro hepatosteatosis.

PubMed

Chacko, Balu K; Srivastava, Anup; Johnson, Michelle S; Benavides, Gloria A; Chang, Mi Jung; Ye, Yaozu; Jhala, Nirag; Murphy, Michael P; Kalyanaraman, Balaraman; Darley-Usmar, Victor M

2011-07-01

Chronic alcohol-induced liver disease results in inflammation, steatosis, and increased oxidative and nitrosative damage to the mitochondrion. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate the steatosis associated with alcoholic liver disease. To test this we investigated the effects of mitochondria-targeted ubiquinone (MitoQ) (5 and 25 mg/kg/day for 4 weeks) in male Sprague-Dawley rats consuming ethanol using the Lieber-DeCarli diet with pair-fed controls. Hepatic steatosis, 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), hypoxia inducible factor α (HIF1α), and the activity of the mitochondrial respiratory chain complexes were assessed. As reported previously, ethanol consumption resulted in hepatocyte ballooning, increased lipid accumulation in the form of micro and macrovesicular steatosis, and induction of cytochrome P450 2E1 (CYP2E1). MitoQ had a minor effect on the ethanol-dependent decrease in mitochondrial respiratory chain proteins and their activities; however, it did decrease hepatic steatosis in ethanol-consuming animals and prevented the ethanol-induced formation of 3-NT and 4-HNE. Interestingly, MitoQ completely blocked the increase in HIF1α in all ethanol-fed groups, which has previously been demonstrated in cell culture models and shown to be essential in ethanol-dependent hepatosteatosis. These results demonstrate the antioxidant capacity of MitoQ in alleviating alcohol-associated mitochondrial reactive oxygen species (ROS) and several downstream effects of ROS/RNS (reactive nitrogen species) production such as inhibiting protein nitration and protein aldehyde formation and specifically ROS-dependent HIF1α stabilization. Copyright © 2011 American Association for the Study of Liver Diseases.

NADH:ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits.

PubMed Central

Fearnley, I M; Finel, M; Skehel, J M; Walker, J E

1991-01-01

The 39 kDa and 42 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria are nuclear-coded components of the hydrophobic protein fraction of the enzyme. Their amino acid sequences have been deduced from the sequences of overlapping cDNA clones. These clones were amplified from total bovine heart cDNA by means of the polymerase chain reaction, with the use of complex mixtures of oligonucleotide primers based upon fragments of protein sequence determined at the N-terminals of the proteins and at internal sites. The protein sequences of the 39 kDa and 42 kDa subunits are 345 and 320 amino acid residues long respectively, and their calculated molecular masses are 39,115 Da and 36,693 Da. Both proteins are predominantly hydrophilic, but each contains one or two hydrophobic segments that could possibly be folded into transmembrane alpha-helices. The bovine 39 kDa protein sequence is related to that of a 40 kDa subunit from complex I from Neurospora crassa mitochondria; otherwise, it is not related significantly to any known sequence, including redox proteins and two polypeptides involved in import of proteins into mitochondria, known as the mitochondrial processing peptidase and the processing-enhancing protein. Therefore the functions of the 39 kDa and 42 kDa subunits of complex I are unknown. The mitochondrial gene product, ND4, a hydrophobic component of complex I with an apparent molecular mass of about 39 kDa, has been identified in preparations of the enzyme. This subunit stains faintly with Coomassie Blue dye, and in many gel systems it is not resolved from the nuclearcoded 36 kDa subunit. Images Fig. 1. PMID:1832859

Using Hyperfine Electron Paramagnetic Resonance Spectroscopy to Define the Proton-Coupled Electron Transfer Reaction at Fe-S Cluster N2 in Respiratory Complex I.

PubMed

Le Breton, Nolwenn; Wright, John J; Jones, Andrew J Y; Salvadori, Enrico; Bridges, Hannah R; Hirst, Judy; Roessler, Maxie M

2017-11-15

Energy-transducing respiratory complex I (NADH:ubiquinone oxidoreductase) is one of the largest and most complicated enzymes in mammalian cells. Here, we used hyperfine electron paramagnetic resonance (EPR) spectroscopic methods, combined with site-directed mutagenesis, to determine the mechanism of a single proton-coupled electron transfer reaction at one of eight iron-sulfur clusters in complex I, [4Fe-4S] cluster N2. N2 is the terminal cluster of the enzyme's intramolecular electron-transfer chain and the electron donor to ubiquinone. Because of its position and pH-dependent reduction potential, N2 has long been considered a candidate for the elusive "energy-coupling" site in complex I at which energy generated by the redox reaction is used to initiate proton translocation. Here, we used hyperfine sublevel correlation (HYSCORE) spectroscopy, including relaxation-filtered hyperfine and single-matched resonance transfer (SMART) HYSCORE, to detect two weakly coupled exchangeable protons near N2. We assign the larger coupling with A( 1 H) = [-3.0, -3.0, 8.7] MHz to the exchangeable proton of a conserved histidine and conclude that the histidine is hydrogen-bonded to N2, tuning its reduction potential. The histidine protonation state responds to the cluster oxidation state, but the two are not coupled sufficiently strongly to catalyze a stoichiometric and efficient energy transduction reaction. We thus exclude cluster N2, despite its proton-coupled electron transfer chemistry, as the energy-coupling site in complex I. Our work demonstrates the capability of pulse EPR methods for providing detailed information on the properties of individual protons in even the most challenging of energy-converting enzymes.

Biochemical studies of membrane bound Plasmodium falciparum mitochondrial L-malate:quinone oxidoreductase, a potential drug target.

PubMed

Hartuti, Endah Dwi; Inaoka, Daniel Ken; Komatsuya, Keisuke; Miyazaki, Yukiko; Miller, Russell J; Xinying, Wang; Sadikin, Mohamad; Prabandari, Erwahyuni Endang; Waluyo, Danang; Kuroda, Marie; Amalia, Eri; Matsuo, Yuichi; Nugroho, Nuki B; Saimoto, Hiroyuki; Pramisandi, Amila; Watanabe, Yoh-Ichi; Mori, Mihoko; Shiomi, Kazuro; Balogun, Emmanuel Oluwadare; Shiba, Tomoo; Harada, Shigeharu; Nozaki, Tomoyoshi; Kita, Kiyoshi

2018-03-01

Plasmodium falciparum is an apicomplexan parasite that causes the most severe malaria in humans. Due to a lack of effective vaccines and emerging of drug resistance parasites, development of drugs with novel mechanisms of action and few side effects are imperative. To this end, ideal drug targets are those essential to parasite viability as well as absent in their mammalian hosts. The mitochondrial electron transport chain (ETC) of P. falciparum is one source of such potential targets because enzymes, such as L-malate:quinone oxidoreductase (PfMQO), in this pathway are absent humans. PfMQO catalyzes the oxidation of L-malate to oxaloacetate and the simultaneous reduction of ubiquinone to ubiquinol. It is a membrane protein, involved in three pathways (ETC, the tricarboxylic acid cycle and the fumarate cycle) and has been shown to be essential for parasite survival, at least, in the intra-erythrocytic asexual stage. These findings indicate that PfMQO would be a valuable drug target for development of antimalarial with novel mechanism of action. Up to this point in time, difficulty in producing active recombinant mitochondrial MQO has hampered biochemical characterization and targeted drug discovery with MQO. Here we report for the first time recombinant PfMQO overexpressed in bacterial membrane and the first biochemical study. Furthermore, about 113 compounds, consisting of ubiquinone binding site inhibitors and antiparasitic agents, were screened resulting in the discovery of ferulenol as a potent PfMQO inhibitor. Finally, ferulenol was shown to inhibit parasite growth and showed strong synergism in combination with atovaquone, a well-described anti-malarial and bc 1 complex inhibitor. Copyright © 2017 Elsevier B.V. All rights reserved.

Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ 10).

PubMed

Horvath, Rita

2012-07-01

Riboflavin and ubiquinone (Coenzyme Q(10), CoQ(10)) deficiencies are heterogeneous groups of autosomal recessive conditions affecting both children and adults. Riboflavin (vitamin B(2))-derived cofactors are essential for the function of numerous dehydrogenases. Genetic defects of the riboflavin transport have been detected in Brown-Vialetto-Van Laere and Fazio-Londe syndromes (C20orf54), and haploinsufficiency of GPR172B has been proposed in one patient to cause persistent riboflavin deficiency. Mutations in the electron tranferring fravoprotein genes (ETFA/ETFB) and its dehydrogenase (ETFDH) are causative for multiple acyl-CoA dehydrogenase deficiency. Mutations in ACAD9, encoding the acyl-CoA dehydrogenase 9 protein were recently reported in mitochondrial disease with respiratory chain complex I deficiency. All these conditions may respond to riboflavin therapy. CoQ(10) is a lipid-soluble component of the cell membranes, where it functions as a mobile electron and proton carrier, but also participates in other cellular processes as a potent antioxidant, and by influencing pyrimidine metabolism. The increasing number of molecular defects in enzymes of the CoQ(10) biosynthetic pathways (PDSS1, PDSS2, COQ2, COQ6, COQ9, CABC1/ADCK3) underlies the importance of these conditions. The clinical heterogeneity may reflect blocks at different levels in the complex biosynthetic pathway. Despite the identification of several primary CoQ(10) deficiency genes, the number of reported patients is still low, and no true genotype-phenotype correlations are known which makes the genetic diagnosis still difficult. Additionally to primary CoQ(10) deficiencies, where the mutation impairs a protein directly involved in CoQ(10) biosynthesis, we can differentiate secondary deficiencies. CoQ(10) supplementation may be beneficial in both primary and secondary deficiencies and therefore the early recognition of these diseases is of utmost importance.

15 CFR 10.9 - Publication of a standard.

Code of Federal Regulations, 2010 CFR

2010-01-01

... standard. A voluntary standard by itself has no mandatory or legally binding effect. Any person may choose to use or not to use such a standard. Appropriate reference in contracts, codes, advertising... establish, but no product may be advertised or represented in any manner which would imply or tend to imply...