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  • MEDLINE/PubMed (NLM)  (740)
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  • 1
    In: Molecular Microbiology, March 2010, Vol.75(6), pp.1389-1401
    Description: Mechanisms of hydrogen peroxide generation in were investigated using a strain lacking scavenging enzymes. Surprisingly, the deletion of many abundant flavoenzymes that are known to autoxidize did not substantially lessen overall HO formation. However, HO production diminished by 25–30% when NadB turnover was eliminated. The flavin‐dependent desaturating dehydrogenase, NadB uses fumarate as an electron acceptor in anaerobic cells. Experiments showed that aerobic NadB turnover depends upon its oxidation by molecular oxygen, with HO as a product. This reaction appears to be mechanistically adventitious. In contrast, most desaturating dehydrogenases are associated with the respiratory chain and deliver electrons to fumarate anaerobically or oxygen aerobically without the formation of toxic by‐products. Presumably, NadB can persist as an HO‐generating enzyme because its flux is limited. The anaerobic respiratory enzyme fumarate reductase uses a flavoprotein subunit that is homologous to NadB and accordingly forms substantial HO upon aeration. This tendency is substantially suppressed by cytochrome oxidase. Thus cytochrome oxidase, which is prevalent among anaerobes, may diminish intracellular HO formation by the anaerobic respiratory chain, whenever these organisms encounter oxygen. These two examples reveal biochemical and physiological arrangements through which evolution has minimized the rate of intracellular oxidant formation.
    Keywords: Hydrogen Peroxide -- Physiological Aspects ; Escherichia Coli -- Physiological Aspects ; Cytochrome Oxidase -- Physiological Aspects;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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  • 2
    Language: English
    In: Physical review letters, 13 May 2016, Vol.116(19), pp.197201
    Description: Using a specially designed Monte Carlo algorithm with directed loops, we investigate the triangular lattice Ising antiferromagnet with coupling beyond the nearest neighbors. We show that the first-order transition from the stripe state to the paramagnet can be split, giving rise to an intermediate nematic phase in which algebraic correlations coexist with a broken symmetry. Furthermore, we demonstrate the emergence of several properties of a more topological nature such as fractional edge excitations in the stripe state, the proliferation of double domain walls in the nematic phase, and the Kasteleyn transition between them. Experimental implications are briefly discussed.
    Keywords: Condensed Matter - Strongly Correlated Electrons ; Condensed Matter - Statistical Mechanics;
    ISSN: 00319007
    E-ISSN: 1079-7114
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  • 3
    In: Circulation, 2012, Vol.126(20), pp.2418-2427
    Description: BACKGROUND—: Carotid intima-media thickening is associated with increased cardiovascular risk in humans. We discovered that intima formation and cell proliferation in response to carotid injury is greater in SJL/J (SJL) in comparison with C3HeB/FeJ (C3H/F) mice. The purpose of this study was to identify candidate genes contributing to intima formation. METHODS AND RESULTS—: We performed microarray and bioinformatic analyses of carotid arteries from C3H/F and SJL mice. Kyoto Encyclopedia of Genes and Genomes analysis showed that the ribosome pathway was significantly up-regulated in C3H/F in comparison with SJL mice. Expression of a ribosomal protein, RpL17, was 〉40-fold higher in C3H/F carotids in comparison with SJL. Aortic vascular smooth muscle cells from C3H/F grew slower in comparison to SJL. To determine the role of RpL17 in vascular smooth muscle cell growth regulation, we analyzed the relationship between RpL17 expression and cell cycle progression. Cultured vascular smooth muscle cells from mice, rats, and humans showed that RpL17 expression inversely correlated with growth as shown by decreased cells in S phase and increased cells in G0/G1. To prove that RpL17 acted as a growth inhibitor in vivo, we used pluronic gel delivery of RpL17 small interfering RNA to C3H/F carotid arteries. This resulted in an 8-fold increase in the number of proliferating cells. Furthermore, following partial carotid ligation in SJL mice, RpL17 expression in the intima and media decreased, but the number of proliferating cells increased. CONCLUSIONS—: RpL17 acts as a vascular smooth muscle cell growth inhibitor (akin to a tumor suppressor) and represents a potential therapeutic target to limit carotid intima-media thickening.
    Keywords: Medicine ; Anatomy & Physiology;
    ISSN: 0009-7322
    E-ISSN: 15244539
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  • 4
    In: Nature, 2013, Vol.497(7451), p.624
    Description: Recent exon-sequencing studies of human tumours have revealed that subunits of BAF (mammalian SWI/SNF) complexes are mutated in more than 20% of all human malignancies, but the mechanisms involved in tumour suppression are unclear. BAF chromatin-remodelling complexes are polymorphic assemblies that use energy provided by ATP hydrolysis to regulate transcription through the control of chromatin structure and the placement of Polycomb repressive complex 2 (PRC2) across the genome. Several proteins dedicated to this multisubunit complex, including BRG1 (also known as SMARCA4) and BAF250a (also known as ARID1A), are mutated at frequencies similar to those of recognized tumour suppressors. In particular, the core ATPase BRG1 is mutated in 5-10% of childhood medulloblastomas and more than 15% of Burkitt's lymphomas. Here we show a previously unknown function of BAF complexes in decatenating newly replicated sister chromatids, a requirement for proper chromosome segregation during mitosis. We find that deletion of Brg1 in mouse cells, as well as the expression of BRG1 point mutants identified in human tumours, leads to anaphase bridge formation (in which sister chromatids are linked by catenated strands of DNA) and a G2/M-phase block characteristic of the decatenation checkpoint. Endogenous BAF complexes interact directly with endogenous topoisomerase IIα (TOP2A) through BAF250a and are required for the binding of TOP2A to approximately 12,000 sites across the genome. Our results demonstrate that TOP2A chromatin binding is dependent on the ATPase activity of BRG1, which is compromised in oncogenic BRG1 mutants. These studies indicate that the ability of TOP2A to prevent DNA entanglement at mitosis requires BAF complexes and suggest that this activity contributes to the role of BAF subunits as tumour suppressors.
    Keywords: Antigens, Neoplasm -- Metabolism ; DNA Helicases -- Metabolism ; DNA Topoisomerases, Type II -- Metabolism ; DNA, Catenated -- Chemistry ; DNA-Binding Proteins -- Metabolism ; Nuclear Proteins -- Metabolism ; Transcription Factors -- Metabolism;
    ISSN: 0028-0836
    E-ISSN: 14764687
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  • 5
    In: Molecular Microbiology, July 2016, Vol.101(1), pp.62-77
    Description: When sulfur compounds are scarce or difficult to process, adapts by inducing the high‐level expression of sulfur‐compound importers. If cystine then becomes available, the cystine is rapidly overimported and reduced, leading to a burgeoning pool of intracellular cysteine. Most of the excess cysteine is exported, but some is adventitiously degraded, with the consequent release of sulfide. Sulfide is a potent ligand of copper and heme moieties, raising the prospect that it interferes with enzymes. We observed that when cystine was provided and sulfide levels rose, became strictly dependent upon cytochrome oxidase for continued respiration. Inspection revealed that low‐micromolar levels of sulfide inhibited the proton‐pumping cytochrome oxidase that is regarded as the primary respiratory oxidase. In the absence of the back‐up cytochrome oxidase, growth failed. Exogenous sulfide elicited the same effect. The potency of sulfide was enhanced when oxygen concentrations were low. Natural oxic‐anoxic interfaces are often sulfidic, including the intestinal environment where dwells. We propose that the sulfide resistance of the cytochrome oxidase is a key trait that permits respiration in such habitats. Toxic levels of intracellular sulfide arise either from the degradation of excess cysteine or from an influx of hydrogen sulfide itself. Sulfide inhibits the primary respiratory cytochrome oxidase, and continued respiration depends upon the presence of the secondary cytochrome oxidase. This scenario is likely common to sulfidic environments, such as the mammalian gut.
    Keywords: Sulfur Compounds ; Cytochromes ; Heme ; Respiration ; Enzymes ; Copper ; Hydrogen Sulfide ; Habitat ; Sulfide ; Oxygen ; Digestive Tract ; Cysteine ; Intestine ; Cytochrome Bd ; Escherichia Coli ; Cell Biology;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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  • 6
    Language: English
    In: Physical review letters, 02 November 2012, Vol.109(18), pp.187202
    Description: Using extensive classical and quantum Monte Carlo simulations, we investigate the ground-state phase diagram of the fully frustrated transverse field Ising model on the square lattice. We show that pure columnar order develops in the low-field phase above a surprisingly large length scale, below which an effective U(1) symmetry is present. The same conclusion applies to the quantum dimer model with purely kinetic energy, to which the model reduces in the zero-field limit, as well as to the stacked classical version of the model. By contrast, the 2D classical version of the model is shown to develop plaquette order. Semiclassical arguments show that the transition from plaquette to columnar order is a consequence of quantum fluctuations.
    Keywords: Condensed Matter - Strongly Correlated Electrons;
    ISSN: 00319007
    E-ISSN: 1079-7114
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  • 7
    Language: English
    In: Journal of Neuroscience Methods, 30 April 2012, Vol.206(1), pp.15-22
    Description: ► We described the multichannel preamplifier for neuronal recordings in small animals. ► The device may be used in any kinds of tasks including swimming in Morris water maze. ► Reusable headstage can adopt both chronically implanted and movable wire electrodes. ► For the first time multichannel recordings of neuronal activity were made in swimming mice. The design of a miniature multichannel preamplifier for extracellular recordings of single unit activity in freely moving and swimming small animals is presented. The advantages of this design include perfect protection of the critical components and electric contacts from water. Thus, neuronal activity and EEG may be recorded differentially in any kinds of behavioral tasks including swimming in Morris water maze. Recordings are stable even if an animal is diving and swimming under the water surface. The reusable dismountable base can adopt different types of chronically implanted fine wire electrodes and movable arrays. Electrodes may be implanted to any desired depth. The assembly weight is less than 240 mg. Thus, the construction is light enough even for mice. This work is the first successful attempt for multichannel recording of neuronal activity in mice performing spatial task in Morris water maze.
    Keywords: Multichannel Preamplifier ; Reusable Base ; Microdrive ; Fine Wire Electrodes ; Single Unit Activity ; Freely Moving Animals ; Swimming Mice and Rats ; Water Maze ; Medicine ; Anatomy & Physiology
    ISSN: 0165-0270
    E-ISSN: 1872-678X
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  • 8
    Language: English
    In: Journal of bacteriology, December 2015, Vol.197(23), pp.3629-44
    Description: When cystine is added to Escherichia coli, the bacterium becomes remarkably sensitive to hydrogen peroxide. This effect is due to enlarged intracellular pools of cysteine, which can drive Fenton chemistry. Genetic analysis linked the sensitivity to YdjN, a secondary transporter that along with the FliY-YecSC ABC system is responsible for cystine uptake. FliY-YecSC has a nanomolar Km and is essential for import of trace cystine, whereas YdjN has a micromolar Km and is the predominant importer when cystine is more abundant. Oddly, both systems are strongly induced by the CysB response to sulfur scarcity. The FliY-YecSC system can import a variety of biomolecules, including diaminopimelate; it is therefore vulnerable to competitive inhibition, presumably warranting YdjN induction under low-sulfur conditions. But the consequence is that if micromolar cystine then becomes available, the abundant YdjN massively overimports it, at 〉30 times the total sulfur demand of the cell. The imported cystine is rapidly reduced to cysteine in a glutathione-dependent process. This action avoids the hazard of disulfide stress, but it precludes feedback inhibition of YdjN by cystine. We conjecture that YdjN possesses no cysteine allosteric site because the isostructural amino acid serine might inappropriately bind in its place. Instead, the cell partially resolves the overaccumulation of cysteine by immediately excreting it, completing a futile import/reduction/export cycle that consumes a large amount of cellular energy. These unique, wasteful, and dangerous features of cystine metabolism are reproduced by other bacteria. We propose to rename ydjN as tcyP and fliY-yecSC as tcyJLN. In general, intracellular metabolite pools are kept at steady, nontoxic levels by a sophisticated combination of transcriptional and allosteric controls. Surprisingly, in E. coli allosteric control is utterly absent from the primary importer of cystine. This flaw allows massive overimport of cystine, which causes acute vulnerability to oxidative stress and is remedied only by wasteful cysteine efflux. The lack of import control may be rationalized by the unusual properties of cysteine itself. This phenomenon justifies the existence of countervailing cysteine export systems, whose purpose is otherwise hard to understand. It also highlights an unexpected link between sulfur metabolism and oxidative damage. Although this investigation focused upon E. coli, experiments confirmed that similar phenomena occur in other species.
    Keywords: Biological Transport ; Cystine -- Metabolism ; Escherichia Coli -- Metabolism
    ISSN: 00219193
    E-ISSN: 1098-5530
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  • 9
    Language: English
    In: Journal of Physics: Condensed Matter, 2011, Vol.23(4), p.045701 (6pp)
    Description: Several experimental and theoretical studies indicate the existence of a critical point separating the underdoped and overdoped regions of the high- T c cuprates phase diagram. There are at least two distinct proposals on the critical concentration and its physical origin. The first one is associated with the pseudogap formation for p 〈 p * , with p * 0.2. The other relies on the Hall effect measurements and suggests that the critical point and the quantum phase transition (QPT) take place at optimal doping, p opt 0.16. Here we have performed a precise density of states calculation and found that there are two QPTs and the corresponding critical concentrations associated with the change of the Fermi surface topology upon doping.
    Keywords: Phases ; Phase Transformations ; Cuprates ; Mathematical Analysis ; Doping ; Mathematical Analysis ; Doping ; Phase Diagrams ; Copper Oxide ; Condensed Matter ; Phase Diagrams ; Phase Transformations ; Optimization ; Critical Point ; Condensed Matter Physics (General) (So) ; General and Nonclassified (Ep) ; General and Nonclassified (Ed) ; General and Nonclassified (EC) ; Physical Metallurgy (CD);
    ISSN: 0953-8984
    E-ISSN: 1361-648X
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  • 10
    Language: English
    In: Physical review letters, 08 June 2012, Vol.108(23), pp.236401
    Description: We report electronic transport measurements on high quality floating zone grown Na(x)CoO2 and Na0.41CoO2·0.6H2O single crystals. We find an in-plane electronic scattering minimum near 11 K and a clear charge ordering at approximately 50 K. The electronic and magnetic properties in hydrated and nonhydrated Na0.41CoO2 samples are similar at higher temperature, but evolve in markedly different ways below ∼50  K, where a strong ferromagnetic tendency is observed in the hydrated sample. Model calculations show the relationship of this tendency to the structure of the Fermi surface. The results, particularly the clear differences between the hydrated and nonhydrated material show a substantially enhanced ferromagnetic tendency upon hydration. Implications for superconductivity are discussed.
    Keywords: Classical And Quantum Mechanics, General Physics ; Fermi Level ; Hydration ; Magnetic Properties ; Monocrystals ; Scattering ; Superconductivity ; Transport ; Physics;
    ISSN: 00319007
    E-ISSN: 1079-7114
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