Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism?

In man, cells accumulate somatic mutations of mitochondrial DNA (mtDNA) as part of normal ageing. Although the overall concentration of mutant mtDNA is low in tissue as a whole, very high numbers of various mtDNA mutations develop in individual cells within the same person, which causes age-associated mitochondrial dysfunction. Some tumours contain high numbers of mtDNA mutations that are not present in healthy tissues from the same individual.

The length of cytochrome c oxidase-negative segments in muscle fibres in patients with mtDNA myopathy.

Heteroplasmic mitochondrial DNA mutations often cause a skeletal myopathy associated with a mosaic distribution of cytochrome c oxidase-deficient muscle fibres. The function of an individual muscle fibre is dependent upon the metabolic activity throughout its length, but little is known about the length of cytochrome c oxidase-deficient segments in human skeletal muscle in patients with mitochondrial disease. We studied cytochrome c oxidase activity by serial section analysis of quadriceps muscle from two patients.

groEL expression in gyrB mutants of Borrelia burgdorferi.

GroEL protein and groEL mRNA transcript were up-regulated in gyrB mutants of Borrelia burgdorferi, a causative agent of Lyme disease. Furthermore, the protein and transcript levels in gyrB mutants were greater than those in experimentally heat-shocked cultures of wild-type B. burgdorferi.

Evaporation of a packet of quantized vorticity.

We study the diffusion of a packet of quantized vorticity initially confined inside a small region. We find that reconnections fragment the packet into a gas of small vortex loops which fly away. The time scale of the process is in order-of-magnitude agreement with recent experiments performed in 3He-B.

Intermediate sanctions for healthcare organizations.

Intermediate sanctions legislation requires that tax-exempt providers take steps to ensure that their senior staff members are compensated at fair-market value. A first-time violation could subject an individual to an excise tax of 25 percent of the compensation amount deemed to be excess benefit. Failure to correct the violation could subject the individual to an excise tax of 200 percent of the excess benefit.

Integration host factor interactions with Neisseria gene sequences: correlation between predicted binding sites and in vitro binding of Neisseria -derived IHF protein.

Putative integration host factor (IHF) binding sites are frequently being identified in Neisseria gene sequences on the basis of similarity to a degenerate Escherichia coli -derived consensus binding sequence. In this report, three different Neisseria genetic systems that contain predicted IHF binding sites were assessed for IHF binding through gel retardation analysis. The results show a positive correlation between the identification of a predicted Neisseria IHF binding site and in vitro binding of Neisseria -derived IHF protein.

Identification of loci critical for replication and compatibility of a Borrelia burgdorferi cp32 plasmid and use of a cp32-based shuttle vector for the expression of fluorescent reporters in the lyme disease spirochaete.

The 32kb circular plasmid (cp32) family of Borrelia burgdorferi has been the subject of intensive investigation because its members encode numerous differentially expressed lipoproteins. As many as nine different cp32s appear to be capable of stable replication within a single spirochaete. Here, we show that a construct (pCE310) containing a 4 kb fragment from the putative maintenance region of a B.

Quantum signature of superfluid turbulence.

Using a numerical simulation backed up by physical arguments, we predict that the pressure spectrum of superfluid turbulence has a k(-2) dependence on the wave number k, which represents a macroscopic quantum signature not to be found in the classical Kolmogorov theory of turbulence.

Ultrafast time-resolved soft x-ray photoelectron spectroscopy of dissociating Br2.

The dissociation of excited state Br2 is probed with the novel technique of ultrafast soft x-ray photoelectron spectroscopy. Excited Br2 molecules are prepared in the dissociative (1)Pi(u) state with 80 fs, 400 nm pulses, and a series of photoelectron spectra are obtained during dissociation with pulses of soft x-ray light (47 nm, 26.4 eV, 250 fs).

Fractal dimension of superfluid turbulence.

Superfluid turbulence consists of a disordered tangle of quantized vortex filaments which interact with each other and with the normal fluid. We develop a kinematic model of normal-fluid turbulence to study superfluid vortex tangles at finite temperatures and show by numerical simulation that the system of filaments has a fractal dimension larger than one. We find that the fractal dimension is directly related to the vortex-line density and is independent of temperature over a wide range.

Transduction by phiBB-1, a bacteriophage of Borrelia burgdorferi.

We previously described a bacteriophage of the Lyme disease agent Borrelia burgdorferi designated phiBB-1. This phage packages the host complement of the 32-kb circular plasmids (cp32s), a group of homologous molecules found throughout the genus Borrelia. To demonstrate the ability of phiBB-1 to package and transduce DNA, a kanamycin resistance cassette was inserted into a cloned fragment of phage DNA, and the resulting construct was transformed into B.

Sound emission due to superfluid vortex reconnections.

By performing numerical simulations based on the Gross-Pitaevskii equation, we make direct quantitative measurements of the sound energy released due to superfluid vortex reconnections. We show that the energy radiated expressed in terms of the loss of vortex line length is a simple function of the reconnection angle. In addition, we study the temporal and spatial distribution of the radiation and show that energy is emitted in the form of a sound pulse with a wavelength of a few healing lengths.

Kelvin waves cascade in superfluid turbulence.

We study numerically the interaction of four initial superfluid vortex rings in the absence of any dissipation or friction. We find evidence for a cascade of Kelvin waves generated by individual vortex reconnection events which transfers energy to higher and higher wave numbers k. After the vortex reconnections occur, the energy spectrum scales as k(-1) and the curvature spectrum becomes flat.

Renal multigated spectral Doppler imaging before and after captopril challenge.

Rationale And Objectives: A new method of measurement, simultaneous multigated spectral Doppler imaging (MSDI), was used to quantify the hemodynamic changes in kidneys after administration of captopril.

Methods: Forty kidneys in 22 hypertensive patients were included in the study. All underwent MSDI and scintigraphy before and after administration of captopril.

Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age.

Human tissues acquire somatic mitochondrial DNA (mtDNA) mutations with age. Very high levels of specific mtDNA mutations accumulate within individual cells, causing a defect of mitochondrial oxidative metabolism. This is a fundamental property of nondividing tissues, but it is not known how it comes about.

Random genetic drift determines the level of mutant mtDNA in human primary oocytes.

We measured the proportion of mutant mtDNA (mutation load) in 82 primary oocytes from a woman who harbored the A3243G mtDNA mutation. The frequency distribution of mutation load indicates that random drift is the principal mechanism that determines the level of mutant mtDNA within individual oocytes.

Bacteriophages of spirochetes.

Historically, a number of bacteriophage-like particles have been observed in association with members of the bacterial order Spirochetales, the spirochetes. In the last decade, several spirochete bacteriophages have been isolated and characterized at the molecular level. We have recently characterized a bacteriophage of the Lyme disease agent, Borrelia burgdorferi, which we have designated phiBB-1.

The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both?

The mammalian mitochondrial genome (mtDNA) is a small double-stranded DNA molecule that is exclusively transmitted down the maternal line. Pathogenic mtDNA mutations are usually heteroplasmic, with a mixture of mutant and wild-type mtDNA within the same organism. A woman harbouring one of these mutations transmits a variable amount of mutant mtDNA to each offspring.

Characterization of Borrelia burgdorferi BlyA and BlyB proteins: a prophage-encoded holin-like system.

The conserved cp32 plasmid family of Borrelia burgdorferi was recently shown to be packaged into a bacteriophage particle (C. H. Eggers and D.

Triple vortex ring structure in superfluid helium II.

Superfluids such as helium II consist of two interpenetrating fluids: the normal fluid and the superfluid. The helium II vortex ring has generally been considered merely as a superfluid object, neglecting any associated motion of the normal fluid. We report a three-dimensional calculation of the coupled motion of the normal-fluid and superfluid components, which shows that the helium II vortex ring consists of a superfluid vortex ring accompanied by two coaxial normal-fluid vortex rings of opposite polarity.

Borrelia burgdorferi periplasmic flagella have both skeletal and motility functions.

Bacterial shape usually is dictated by the peptidoglycan layer of the cell wall. In this paper, we show that the morphology of the Lyme disease spirochete Borrelia burgdorferi is the result of a complex interaction between the cell cylinder and the internal periplasmic flagella. B.

Disruption of the Borrelia burgdorferi gac gene, encoding the naturally synthesized GyrA C-terminal domain.

The C-terminal domain of the A subunit of DNA gyrase, which we term Gac, is naturally synthesized in Borrelia burgdorferi as an abundant DNA-binding protein. Full-length GyrA, which includes the C-terminal domain, is also synthesized by the spirochete and functions as a subunit of DNA gyrase. We have disrupted synthesis of Gac as an independent protein and demonstrated that it is not essential for growth in a coumarin-resistant background.

Molecular evidence for a new bacteriophage of Borrelia burgdorferi.

We have recovered a DNase-protected, chloroform-resistant molecule of DNA from the cell-free supernatant of a Borrelia burgdorferi culture. The DNA is a 32-kb double-stranded linear molecule that is derived from the 32-kb circular plasmids (cp32s) of the B. burgdorferi genome.