108 research outputs found
Metastability in Josephson transmission lines
Thermal activation and macroscopic quantum tunneling in current-biased
discrete Josephson transmission lines are studied theoretically. The degrees of
freedom under consideration are the phases across the junctions which are
coupled to each other via the inductances of the system. The resistively
shunted junctions that we investigate constitute a system of N interacting
degrees of freedom with an overdamped dynamics. We calculate the decay rate
within exponential accuracy as a function of temperature and current. Slightly
below the critical current, the decay from the metastable state occurs via a
unique ("rigid") saddlepoint solution of the Euclidean action describing the
simultaneous decay of the phases in all the junctions. When the current is
reduced, a crossover to a regime takes place, where the decay occurs via an
"elastic" saddlepoint solution and the phases across the junctions leave the
metastable state one after another. This leads to an increased decay rate
compared with the rigid case both in the thermal and the quantum regime. The
rigid-to-elastic crossover can be sharp or smooth analogous to first- or
second- order phase transitions, respectively. The various regimes are
summarized in a current-temperature decay diagram.Comment: 11 pages, RevTeX, 3 PS-figures, revised versio
Functional Dissection of the Proton Pumping Modules of Mitochondrial Complex I
A catalytically active subcomplex of respiratory chain complex I lacks 14 of its 42 subunits yet retains half of its proton-pumping capacity, indicating that its membrane arm has two pump modules
Crossovers in the thermal decay of metastable states in discrete systems
The thermal decay of linear chains from a metastable state is investigated. A
crossover from rigid to elastic decay occurs when the number of particles, the
single particle energy barrier or the coupling strength between the particles
is varied. In the rigid regime, the single particle energy barrier is small
compared to the coupling strength and the decay occurs via a uniform
saddlepoint solution, with all degrees of freedom decaying instantly.
Increasing the barrier one enters the elastic regime, where the decay is due to
bent saddlepoint configurations using the elasticity of the chain to lower
their activation energy. Close to the rigid-to-elastic crossover, nucleation
occurs at the boundaries of the system. However, in large systems, a second
crossover from boundary to bulk nucleation can be found within the elastic
regime, when the single particle energy barrier is further increased. We
compute the decay rate in the rigid and in the elastic regimes within the
Gaussian approximation. Around the rigid-to-elastic crossover, the calculations
are performed beyond the steepest descent approximation. In this region, the
prefactor exhibits a scaling property. The theoretical results are discussed in
the context of discrete Josephson transmission lines and pancake vortex stacks
that are pinned by columnar defects.Comment: 13 pages, RevTeX, 7 PS-figure
Phase diagram of localization in a magnetic field
The phase diagram of localization is numerically calculated for a
three-dimensional disordered system in the presence of a magnetic field using
the Peierls substitution. The mobility edge trajectory shifts in the
energy-disorder space when increasing the field. In the band center, localized
states near the phase boundary become delocalized. The obtained field
dependence of the critical disorder is in agreement with a power law behavior
expected from scaling theory. Close to the tail of the band the magnetic field
causes localization of extended states.Comment: 4 pages, RevTeX, 3 PS-figures (4 extra references are included, minor
additions), to appear in Phys. Rev. B as a Brief Repor
Global gene disruption in human cells to assign genes to phenotypes
Insertional mutagenesis in a haploid background can disrupt gene function[superscript 1]. We extend our earlier work by using a retroviral gene-trap vector to generate insertions in >98% of the genes expressed in a human cancer cell line that is haploid for all but one of its chromosomes. We apply phenotypic interrogation via tag sequencing (PhITSeq) to examine millions of mutant alleles through selection and parallel sequencing. Analysis of pools of cells, rather than individual clones[superscript 1] enables rapid assessment of the spectrum of genes involved in the phenotypes under study. This facilitates comparative screens as illustrated here for the family of cytolethal distending toxins (CDTs). CDTs are virulence factors secreted by a variety of pathogenic Gram-negative bacteria responsible for tissue damage at distinct anatomical sites[superscript 2]. We identify 743 mutations distributed over 12 human genes important for intoxication by four different CDTs. Although related CDTs may share host factors, they also exploit unique host factors to yield a profile characteristic for each CDT
Reduction of Hydrophilic Ubiquinones by the Flavin in Mitochondrial NADH:Ubiquinone Oxidoreductase (Complex I) and Production of Reactive Oxygen Species†
ABSTRACT: NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria is a complicated, energy-transducing, membrane-bound enzyme that contains 45 different subunits, a non-covalently bound flavin mononucleotide, and eight iron-sulfur clusters. The mechanisms of NADH oxidation and intramolecular electron transfer by complex I are gradually being defined, but the mechanism linking ubiquinone reduction to proton translocation remains unknown. Studies of ubiquinone reduction by isolated complex I are problematic because the extremely hydrophobic natural substrate, ubiquinone-10, must be substituted with a relatively hydrophilic analogue (such as ubiquinone-1). Hydrophilic ubiquinones are reduced by an additional, non-energy-transducing pathway (which is insensitive to inhibitors such as rotenone and piericidin A). Here, we show that inhibitor-insensitive ubiquinone reduction occurs by a ping-pong type mechanism, catalyzed by the flavin mononucleotide cofactor in the active site for NADH oxidation. Moreover, semiquinones produced at the flavin site initiate redox cycling reactions with molecular oxygen, producing superoxide radicals and hydrogen peroxide. The ubiquinone reactant is regenerated, so the NADH:Q reaction becomes superstoichiometric. Idebenone, an artificial ubiquinone showing promise in the treatment of Friedreich’s Ataxia, reacts at the flavin site. The factors which determine the balance of reactivity between the two sites of ubiquinone reduction (the energy-transducing site and the flavi
Transport of Anthocyanins and other Flavonoids by the Arabidopsis ATP-Binding Cassette Transporter AtABCC2
Flavonoids have important developmental, physiological, and ecological roles in plants and are primarily stored in the large central vacuole. Here we show that both an ATP-binding cassette (ABC) transporter(s) and an H+-antiporter(s) are involved in the uptake of cyanidin 3-O-glucoside (C3G) by Arabidopsis vacuolar membrane-enriched vesicles. We also demonstrate that vesicles isolated from yeast expressing the ABC protein AtABCC2 are capable of MgATP-dependent uptake of C3G and other anthocyanins. The uptake of C3G by AtABCC2 depended on the co-transport of glutathione (GSH). C3G was not altered during transport and a GSH conjugate was not formed. Vesicles from yeast expressing AtABCC2 also transported flavone and flavonol glucosides. We performed ligand docking studies to a homology model of AtABCC2 and probed the putative binding sites of C3G and GSH through site-directed mutagenesis and functional studies. These studies identified residues important for substrate recognition and transport activity in AtABCC2, and suggest that C3G and GSH bind closely, mutually enhancing each other’s binding. In conclusion, we suggest that AtABCC2 along with possibly other ABCC proteins are involved in the vacuolar transport of anthocyanins and other flavonoids in the vegetative tissue of Arabidopsis
Mössbauer Spectroscopy on Respiratory Complex I: The Iron–Sulfur Cluster Ensemble in the NADH-Reduced Enzyme Is Partially Oxidized
Tuning Reactivity and Electronic Properties through Ligand Reorganization within a Cerium Heterobimetallic Framework
Differential expression analysis of the broiler tracheal proteins responsible for the immune response and muscle contraction induced by high concentration of ammonia using iTRAQ-coupled 2D LC-MS/MS
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