Derangements of liver tissue bioenergetics in Concanavalin A-induced hepatitis

BACKGROUND: A novel in vitro system was employed to investigate liver tissue respiration (mitochondrial O(2) consumption) in mice treated with concanavalin A (Con A). This study aimed to investigate hepatocyte bioenergetics in this well-studied hepatitis model. METHODS: C57Bl/6 and C57Bl/6 IFN-γ(−/−) mice were injected intravenously with 12 mg ConA/kg. Liver specimens were collected at various timepoints after injection and analyzed for cellular respiration and caspase activation. Serum was analyzed for interferon-gamma (IFN-γ) and aminotransferases. Fluorescence activated cell sorting analysis was used to determine the phenotype of infiltrating cells, and light and electron microscopy were used to monitor morphological changes. Phosphorescence analyzer that measured dissolved O(2) as function of time was used to evaluate respiration. RESULTS: In sealed vials, O(2) concentrations in solutions containing liver specimen and glucose declined linearly with time, confirming zero-order kinetics of hepatocyte respiration. O(2) consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Enhanced liver respiration (by ≈68%, p<0.02) was noted 3 hr after ConA treatment, and occurred in conjunction with limited cellular infiltrations around the blood vessels. Diminished respiration (by ≈30%, p=0.005) was noted 12 hr after ConA treatment, and occurred in conjunction with deranged mitochondria, areas of necrosis, and prominent infiltrations with immune cells, most significantly, CD3(+)NKT(+) cells. Increases in intracellular caspase activity and serum IFN-γ and aminotransferase levels were noted 3 hr after ConA treatment and progressed with time. The above-noted changes were less pronounced in C57Bl/6 IFN-γ(−/−) mice treated with ConA. CONCLUSIONS: Based on these results, liver tissue bioenergetics is increased 3 hr after ConA exposure. This effect is driven by the pathogenesis of the disease, in which IFN-γ and other cytokines contribute to. Subsequent declines in liver bioenergetics appear to be a result of necrosis and active caspases targeting the mitochondria within hepatocytes

A lifetime’s adventure in extracellular K+ regulation: the Scottish connection

In a career that has spanned 45 years and shows no signs of slowing down, Dr Bruce Ransom has devoted considerable time and energy to studying regulation of interstitial K+. When Bruce commenced his studies in 1969 virtually nothing was known of the functions of glial cells, but Bruce’s research contributed to the physiological assignation of function to mammalian astrocytes, namely interstitial K+ buffering. The experiments that I describe in this review concern the response of the membrane potential (Em) of in vivo cat cortical astrocytes to changes in [K+]o, an experimental manoeuvre that was achieved in two different ways. The first involved recording the Em of an astrocyte while the initial aCSF was switched to one with different K+, whereas in the second series of experiments the cortex was stimulated and the response of the astrocyte Em to the K+ released from neighbouring neurons was recorded. The astrocytes responded in a qualitatively predictable manner, but quantitatively the changes were not as predicted by the Nernst equation. Elevations in interstitial K+ are not sustained and K+ returns to baseline rapidly due to the buffering capacity of astrocytes, a phenomenon studied by Bruce, and his son Chris, published 27 years after Bruce’s initial publications. Thus, a lifetime spent investigating K+ buffering has seen enormous advances in glial research, from the time cells were identified as ‘presumed’ glial cells or ‘silent cells’, to the present day, where glial cells are recognised as contributing to every important physiological brain function

Fragments of the earliest land plants

The earliest fossil evidence for land plants comes from microscopic dispersed spores. These microfossils are abundant and widely distributed in sediments, and the earliest generally accepted reports are from rocks of mid-Ordovician age (Llanvirn, 475 million years ago). Although distribution, morphology and ultrastructure of the spores indicate that they are derived from terrestrial plants, possibly early relatives of the bryophytes, this interpretation remains controversial as there is little in the way of direct evidence for the parent plants. An additional complicating factor is that there is a significant hiatus between the appearance of the first dispersed spores and fossils of relatively complete land plants (megafossils): spores predate the earliest megafossils (Late Silurian, 425 million year ago) by some 50 million years. Here we report the description of spore-containing plant fragments from Ordovician rocks of Oman. These fossils provide direct evidence for the nature of the spore-producing plants. They confirm that the earliest spores developed in large numbers within sporangia, providing strong evidence that they are the fossilized remains of bona fide land plants. Furthermore, analysis of spore wall ultrastructure supports liverwort affinities

Causality and the AdS Dirichlet problem

The (planar) AdS Dirichlet problem has previously been shown to exhibit superluminal hydrodynamic sound modes. This problem is defined by bulk gravitational dynamics with Dirichlet boundary conditions imposed on a rigid timelike cut-off surface. We undertake a careful examination of this set-up and argue that, in most cases, the propagation of information between points on the Dirichlet hypersurface is nevertheless causal with respect to the induced light cones. In particular, the high-frequency dynamics is causal in this sense. There are however two exceptions and both involve boundary gravitons whose propagation is not constrained by the Einstein equations. These occur in i) AdS$_3$, where the boundary gravitons generally do not respect the induced light cones on the boundary, and ii) Rindler space, where they are related to the infinite speed of sound in incompressible fluids. We discuss implications for the fluid/gravity correspondence with rigid Dirichlet boundaries and for the black hole membrane paradigm.Comment: 29 pages, 5 figures. v2: added refs. v3: minor clarification

On The Stability Of Non-Supersymmetric AdS Vacua

We consider two infinite families of Non-Supersymmetric $AdS_4$ vacua, called Type 2) and Type 3) vacua, that arise in massive IIA supergravity with flux. We show that both families are perturbatively stable. We then examine non-perturbative decays of these vacua to other supersymmetric and non-supersymmetric $AdS_4$ vacua mediated by instantons in the thin wall approximation. We find that many decays are ruled out since the tension of the interpolating domain wall is too big compared to the energy difference in AdS units. In fact, within our approximations no decays of Type 2) vacua are allowed, although some decays are only marginally forbidden. This can be understood in terms of a "pairing symmetry" in the landscape which relate Type 2) vacua with supersymmetric ones of the same energy.Comment: 50 pages, Minor changes in section 2.2.

Current knowledge of external sulfate attack

This paper offers an update of the current understanding of sulfate attack, with emphasis on the sulfates present in an external water source percolating through, and potentially reacting with, the cement matrix. The paper considers the explanations put forward to explain sulfate attack, both from a chemical and microstructural perspective. Similarly, this paper reviews work on the physical damage caused by the precipitation of sulfate salts in porous materials. With the increased use of binary and ternary blends, this paper also considers the impact of binder composition on sulfate resistance, and similarly reviews how the nature of the sulfate species can affect the nature and extent of any deterioration. This then leads on to the important consideration of differences between field- and lab-based studies; reviewing the effect of various experimental parameters on sulfate resistance. This latter topic is of great importance to anyone who wishes to carry out such experiments

Cytomegalovirus Infection of the Cervix Detected By Cytology and Histology: A Report of Five Cases

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72846/1/j.1365-2303.1993.tb00094.x.pd