Atmospheric reaction systems as null-models to identify structural traces of evolution in metabolism

The metabolism is the motor behind the biological complexity of an organism. One problem of characterizing its large-scale structure is that it is hard to know what to compare it to. All chemical reaction systems are shaped by the same physics that gives molecules their stability and affinity to react. These fundamental factors cannot be captured by standard null-models based on randomization. The unique property of organismal metabolism is that it is controlled, to some extent, by an enzymatic machinery that is subject to evolution. In this paper, we explore the possibility that reaction systems of planetary atmospheres can serve as a null-model against which we can define metabolic structure and trace the influence of evolution. We find that the two types of data can be distinguished by their respective degree distributions. This is especially clear when looking at the degree distribution of the reaction network (of reaction connected to each other if they involve the same molecular species). For the Earth's atmospheric network and the human metabolic network, we look into more detail for an underlying explanation of this deviation. However, we cannot pinpoint a single cause of the difference, rather there are several concurrent factors. By examining quantities relating to the modular-functional organization of the metabolism, we confirm that metabolic networks have a more complex modular organization than the atmospheric networks, but not much more. We interpret the more variegated modular arrangement of metabolism as a trace of evolved functionality. On the other hand, it is quite remarkable how similar the structures of these two types of networks are, which emphasizes that the constraints from the chemical properties of the molecules has a larger influence in shaping the reaction system than does natural selection.     

Light-induced changes of photosystem II activity in dark-grown Scots pine seedlings

Both chlorophyll a and b and polypeptides of the photosynthetic apparatus are found in gymnosperm seedlings. germinated and grown in absolute darkness. The photosystem II (PSII) activity is, however, limited, probably due to an inactive oxygen evolving system. In the present study dark-grown seedlings of Scots pine ( Pinus sylvestris L.) were transferred to light and changes in antenna size and the activation process of PSII were investigated using fluorescence measurements and quantitative western blotting. It was found that the activation process is rapid, requires very little light and that strong light inhibits the process. It takes place without any changes in the primary reactions of PSII. Furthermore, all polypeptides except the major light-harvesting chlorophyll a/b -binding protein complex of PSII (LHCII) were present in dark-grown seedlings in amounts comparable to the light treated control. The dark-grown seedlings had the same LHCII polypeptide composition as light treated seedlings, and the LHCII present seemed to be fully connected to the reaction centre. The results indicate that activation of PSII in dark-grown conifer seedlings resembles the photoactivation process of angiosperms. This implies that the fundamental processes in the assembly of the photosystem II complex is the same in all plants, but that the regulation differs between different taxa.     

Lupus Nephritis: Enigmas,Conflicting Models and an Emerging Concept

Autoantibodies to components of chromatin, which include double-stranded DNA (dsDNA), histones and nucleosomes, are central in the pathogenesis of lupus nephritis. How anti-chromatin autoantibodies exert their nephritogenic activity, however, is controversial. One model assumes that autoantibodies initiate inflammation when they cross-react with intrinsic glomerular structures such as components of membranes, matrices or exposed nonchromatin ligands released from cells. Another model suggests glomerular deposition of autoantibodies in complex with chromatin, thereby inducing classic immune complex–mediated tissue damage. Recent data suggest acquired error of renal chromatin degradation due to the loss of renal DNaseI enzyme activity is an important contributing factor to the development of lupus nephritis in lupus-prone (NZBxNZW)F1 mice and in patients with lupus nephritis. Down-regulation of DNaseI expression results in reduced chromatin fragmentation and in deposition of extracellular chromatin–IgG complexes in glomerular basement membranes in individuals who produce IgG anti-chromatin autoantibodies. The main focus of the present review is to discuss whether exposed chromatin fragments in glomeruli are targeted by potentially nephritogenic anti-dsDNA autoantibodies or if the nephritogenic activity of these autoantibodies is explained by cross-reaction with intrinsic glomerular constituents or if both models coexist in diseased kidneys. In addition, the role of silencing of the renal DNaseI gene and the biological consequences of reduced chromatin fragmentation in nephritic kidneys are discussed.     

DNA-damage, cell-cycle arrest and apoptosis induced in BEAS-2B cells by 2-hydroxyethyl methacrylate (HEMA)

The methacrylate monomer 2-hydroxyethyl methacrylate (HEMA) is commonly used in resin-based dental restorative materials. These materials are cured in situ and HEMA and other monomers have been identified in ambient air during dental surgery. In vitro studies have demonstrated a toxic potential of methacrylates, and concerns have been raised regarding possible health effects due to inhalation. In this study we have investigated the mechanisms of HEMA-induced toxicity in the human lung epithelial cell line BEAS-2B. Depletion of cellular glutathione (GSH) and an increased level of reactive oxygen species (ROS) were seen after 2h of exposure, but the levels were restored to control levels after 12h. After 24h, inhibited cell proliferation and apoptotic cell death were found. The results of the Comet assay and the observed phosphorylation of DNA-damage-associated signalling proteins including Chk2, H2AX, and p53 suggest that the toxicity of HEMA is mediated by DNA damage. Further, the antioxidant trolox did not counteract the HEMA-induced cell-cycle arrest, which indicates that the DNA damage is of non-oxidative origin.     

Fast spatiotemporal smoothing of calcium measurements in dendritic trees

We discuss methods for fast spatiotemporal smoothing of calcium signals in dendritic trees, given single-trial, spatially localized imaging data obtained via multi-photon microscopy. By analyzing the dynamics of calcium binding to probe molecules and the effects of the imaging procedure, we show that calcium concentration can be estimated up to an affine transformation, i.e., an additive and multiplicative constant. To obtain a full spatiotemporal estimate, we model calcium dynamics within the cell using a functional approach. The evolution of calcium concentration is represented through a smaller set of hidden variables that incorporate fast transients due to backpropagating action potentials (bAPs), or other forms of stimulation. Because of the resulting state space structure, inference can be done in linear time using forward-backward maximum-a-posteriori methods. Non-negativity constraints on the calcium concentration can also be incorporated using a log-barrier method that does not affect the computational scaling. Moreover, by exploiting the neuronal tree structure we show that the cost of the algorithm is also linear in the size of the dendritic tree, making the approach applicable to arbitrarily large trees. We apply this algorithm to data obtained from hippocampal CA1 pyramidal cells with experimentally evoked bAPs, some of which were paired with excitatory postsynaptic potentials (EPSPs). The algorithm recovers the timing of the bAPs and provides an estimate of the induced calcium transient throughout the tree. The proposed methods could be used to further understand the interplay between bAPs and EPSPs in synaptic strength modification. More generally, this approach allows us to infer the concentration on intracellular calcium across the dendritic tree from noisy observations at a discrete set of points in space.