Escape from apoptosis after prolonged serum deprivation is associated with the regulation of the mitochondrial death pathway by Bcl-x(l)

Bcl-x(l) and Bax play important roles in the regulation of apoptosis. This study investigated the involvement of the mitochondrial death pathway and the role of Bcl-x(l) and Bax in the escape from apoptosis after prolonged serum deprivation in Madin-Darby canine kidney (MDCK) cells. Low level apoptosis and basal activity of the mitochondrial death pathway were detectable in normal cell growth. In serum deprivation, mitosis was partially suppressed, and the mitochondrial activity was stimulated. The level of apoptosis continuously rose over 48 h. This rise was concomitant with the increasing presence of cytochrome c in cytosol. However, both apoptosis and cytosolic cytochrome c fell dramatically at 72 h. Elevation of whole cell Bcl-x(l) and redistribution of Bcl-x(l) protein from cytosol to the membrane at 48 h and 72 h was observed. Redistribution of Bax protein from the membrane to cytosol occurred at 24 h, and remained steady to 72 h. Bax/Bcl-x(l) coimmunoprecipitation by anti-Bax antibody showed reduced Bax/Bcl-x(l) interaction at the membrane at 72 h, but not at 24 or 48 h. These results suggest that apoptosis upon serum withdrawal results from the leakage of cytochrome c to cytosol. Amelioration of the leakage of cytochrome c and apoptosis requires not only the increase of Bcl-x(l)/Bax ratio, but also the release of Bcl-x(l) from Bax at the membrane.

Loss of chromosomal integrity in human mammary epithelial cells subsequent to escape from senescence

The genomic changes that foster cancer can be either genetic or epigenetic in nature. Early studies focused on genetic changes and how mutational events contribute to changes in gene expression. These point mutations, deletions and amplifications are known to activate oncogenes and inactivate tumor suppressor genes. More recently, multiple epigenetic changes that can have a profound effect on carcinogenesis have been identified. These epigenetic events, such as the methylation of promoter sequences in genes, are under active investigation. In this review we will describe a methylation event that occurs during the propagation of human mammary epithelial cells (HMEC) in culture and detail the accompanying genetic alterations that have been observed.

On ion escape from Venus

This doctoral thesis is about the solar wind influence on the atmosphere of the planet Venus. A numerical plasma simulation model was developed for the interaction between Venus and the solar wind to study the erosion of charged particles from the Venus upper atmosphere. The developed model is a hybrid simulation where ions are treated as particles and electrons are modelled as a fluid. The simulation was used to study the solar wind induced ion escape from Venus as observed by the European Space Agency's Venus Express and NASA's Pioneer Venus Orbiter spacecraft. Especially, observations made by the ASPERA-4 particle instrument onboard Venus Express were studied. The thesis consists of an introductory part and four peer-reviewed articles published in scientific journals. In the introduction Venus is presented as one of the terrestrial planets in the Solar System and the main findings of the work are discussed within the wider context of planetary physics. Venus is the closest neighbouring planet to the Earth and the most earthlike planet in its size and mass orbiting the Sun. Whereas the atmosphere of the Earth consists mainly of nitrogen and oxygen, Venus has a hot carbon dioxide atmosphere, which is dominated by the greenhouse effect. Venus has all of its water in the atmosphere, which is only a fraction of the Earth's total water supply. Since planets developed presumably in similar conditions in the young Solar System, why Venus and Earth became so different in many respects? One important feature of Venus is that the planet does not have an intrinsic magnetic field. This makes it possible for the solar wind, a continuous stream of charged particles from the Sun, to flow close to Venus and to pick up ions from the planet's upper atmosphere. The strong intrinsic magnetic field of the Earth dominates the terrestrial magnetosphere and deflects the solar wind flow far away from the atmosphere. The region around Venus where the planet's atmosphere interacts with the solar wind is called the plasma environment or the induced magnetosphere. Main findings of the work include new knowledge about the movement of escaping planetary ions in the Venusian induced magnetosphere. Further, the developed simulation model was used to study how the solar wind conditions affect the ion escape from Venus. Especially, the global three-dimensional structure of the Venusian particle and magnetic environment was studied. The results help to interpret spacecraft observations around the planet. Finally, several remaining questions were identified, which could potentially improve our knowledge of the Venus ion escape and guide the future development of planetary plasma simulations.

Narrow escape: how ionizing photons escape from disc galaxies

In this paper we calculate the escape fraction (f(esc)) of ionizing photons from starburst galaxies. Using 2D axisymmetric hydrodynamic simulations, we study superbubbles created by overlapping supernovae in OB associations. We calculate the escape fraction of ionizing photons from the centre of the disc along different angles through the superbubble and the gas disc. After convolving with the luminosity function of OB associations, we show that the ionizing photons escape within a cone of similar to 40 degrees, consistent with observations of nearby galaxies. The evolution of the escape fraction with time shows that it falls initially as cold gas is accumulated in a dense shell. After the shell crosses a few scaleheights and fragments, the escape fraction through the polar regions rises again. The angle-averaged escape fraction cannot exceed similar to1 - cos (1 rad)] = 0.5 from geometrical considerations (using the emission cone opening angle). We calculate the dependence of the time-and angle-averaged escape fraction on the mid-plane disc gas density (in the range n(0) = 0.15-50 cm(-3)) and the disc scaleheight (between z(0) = 10 and 600 pc). We find that the escape fraction is related to the disc parameters (the mid-plane disc density and scaleheight) roughly so that f(esc)(alpha)n(0)(2)z(0)(3) (with alpha approximate to 2.2) is a constant. For discs with a given warm neutral medium temperature, massive discs have lower escape fraction than low-mass galaxies. For Milky Way ISM parameters, we find f(esc) similar to 5 per cent, and it increases to approximate to 10 per cent for a galaxy 10 times less massive. We discuss the possible effects of clumpiness of the ISM on the estimate of the escape fraction and the implications of our results for the reionization of the Universe.

Cosmic-ray acceleration and escape from supernova remnants

Galactic cosmic-ray (CR) acceleration to the knee in the spectrum at a few PeV is only possible if the magnetic field ahead of a supernova remnant (SNR) shock is strongly amplified by CRs escaping the SNR. A model formulated in terms of the electric charge carried by escaping CRs predicts the maximum CR energy and the energy spectrum of CRs released into the surrounding medium. We find that historical SNRs such as Cas A, Tycho and Kepler may be expanding too slowly to accelerate CRs to the knee at the present time.

Extracting statistically dominant modes of a steel truss bridge from vehicle-induced vibrations

This study is intended to investigate the validity of the stability diagram (SD) aided multivariate autoregressive (MAR) analysis for identifying modal parameters of a real truss bridge. The MAR models are adopted to fit the time series of the dynamic accelerations recorded from a number of observation points on the bridge; then the modal parameters are extracted from the MAR model coefficient matrix. The SD is adopted to determine statistically dominant modes. In plotting the SD, a number of stability criteria are further adopted for filtering out those modes with unstable modal parameters. By the present method, the first five modal frequencies and mode shapes are identified with very high precision, while the damping ratios are identified with high precision for the 1st mode but with poorer precision for higher modes. Moreover, the ability of the SD in selecting structural modes without getting involved in any model-order optimization problem is highlighted through a comparison study.

Very short delays prior to escape from potential predators may function efficiently as adaptive risk-assessment periods

Periods between predator detection and an escape response (escape delays) by prey upon attack by a predator often arise because animals trade-off the benefits such a delay gives for assessing risk accurately with the costs of not escaping as quickly as possible. We tested whether freezing behaviour (complete immobility in a previously foraging bird) observed in chaffinches before escaping from an approaching potential threat functions as a period of risk-assessment, and whether information on predator identity is gained even when time available is very short. We flew either a model of a sparrowhawk (predator) or a woodpigeon (no threat) at single chaffinches. Escape delays were significantly shorter with the hawk, except when a model first appeared close to the chaffinch. Chaffinches were significantly more vigilant when they resumed feeding after exposure to the sparrowhawk compared to the woodpigeon showing that they were able to distinguish between threats, and this applied even when time available for assessment was short (an average of 0.29 s). Our results show freezing in chaffinches functions as an effective economic risk assessment period, and that threat information is gained even when very short periods of time are available during an attack.