Changes in specific metabolic pathways are essential steps in the early apoptotic process in the liver

the immunosuppressant Cyclosporine A (CsA), we used multinuclear NMR spectroscopy and molecular studies to characterize metabolic pathways in mice liver during anti-Fas-induced apoptosis. An upregulation of specific metabolic pathways of glucose was the earliest indicator of the effect of Fas on the liver. CsA prevented apoptosis and energy failure at late stages, while the reversal of Fas-induced metabolic upregulation at early stages preceded the protective effect of EGF on programmed cell death. These phenomena provide useful hints for the understanding of early mechanisms controlling apoptotic cell death

Magnetohydrodynamics dynamical relaxation of coronal magnetic fields. II. 2D magnetic X-points

We provide a valid magnetohydrostatic equilibrium from the collapse of a 2D X-point in the presence of a finite plasma pressure, in which the current density is not simply concentrated in an infinitesimally thin, one-dimensional current sheet, as found in force-free solutions. In particular, we wish to determine if a finite pressure current sheet will still involve a singular current, and if so, what is the nature of the singularity. We use a full MHD code, with the resistivity set to zero, so that reconnection is not allowed, to run a series of experiments in which an X-point is perturbed and then is allowed to relax towards an equilibrium, via real, viscous damping forces. Changes to the magnitude of the perturbation and the initial plasma pressure are investigated systematically. The final state found in our experiments is a "quasi-static" equilibrium where the viscous relaxation has completely ended, but the peak current density at the null increases very slowly following an asymptotic regime towards an infinite time singularity. Using a high grid resolution allows us to resolve the current structures in this state both in width and length. In comparison with the well known pressureless studies, the system does not evolve towards a thin current sheet, but concentrates the current at the null and the separatrices. The growth rate of the singularity is found to be tD, with 0 < D < 1. This rate depends directly on the initial plasma pressure, and decreases as the pressure is increased. At the end of our study, we present an analytical description of the system in a quasi-static non-singular equilibrium at a given time, in which a finite thick current layer has formed at the null

Continental weathering and recovery from ocean nutrient stress during the Early Triassic Biotic Crisis

Following the latest Permian extinction ∼252 million years ago, normal marine and terrestrial ecosystems did not recover for another 5-9 million years. The driver(s) for the Early Triassic biotic crisis, marked by high atmospheric CO2 concentration, extreme ocean warming, and marine anoxia, remains unclear. Here we constrain the timing of authigenic K-bearing mineral formation extracted from supergene weathering profiles of NW-Pangea by Argon geochronology, to demonstrate that an accelerated hydrological cycle causing intense chemical alteration of the continents occurred between ∼254 and 248 Ma, and continued throughout the Triassic period. We show that enhanced ocean nutrient supply from this intense continental weathering did not trigger increased ocean productivity during the Early Triassic biotic crisis, due to strong thermal ocean stratification off NW Pangea. Nitrogen isotope constraints suggest, instead, that full recovery from ocean nutrient stress, despite some brief amelioration ∼1.5 million years after the latest Permian extinction, did not commence until climate cooling revitalized the global upwelling systems and ocean mixing ∼10 million years after the mass extinction

Locating current sheets in the solar corona

Current sheets are essential for energy dissipation in the solar corona, in particular by enabling magnetic reconnection. Unfortunately, sufficiently thin current sheets cannot be resolved observationally and the theory of their formation is an unresolved issue as well. We consider two predictors of coronal current concentrations, both based on geometrical or even topological properties of a force free coronal magnetic field. First, there are separatrices related to magnetic nulls. Through separatrices the magnetic connectivity changes discontinuously. Coronal magnetic nulls are, however, very rare. At second, inspired by the concept of generalized magnetic reconnection without nulls, quasi-separatrix layers (QSL) were suggested. Through QSL the magnetic connectivity changes continuously, though strongly. The strength of the connectivity change can be quantified by measuring the squashing of the flux tubes which connect the magnetically conjugated photospheres. We verify the QSL and separatrix concepts by comparing the sites of magnetic nulls and enhanced squashing with the location of current concentrations in the corona. Due to the known difficulties of their direct observation we simulated the coronal current sheets by numerically calculating the response of the corona to energy input from the photosphere heating a simultaneously observed EUV Bright Point. We did not find coronal current sheets not at the separatrices but at several QSL locations. The reason is that although the geometrical properties of force free extrapolated magnetic fields can indeed, hint at possible current concentrations, a necessary condition for current sheet formation is the local energy input into the corona

Regression toward the mean – a detection method for unknown population mean based on Mee and Chua's algorithm

<p>Abstract</p> <p>Background</p> <p>Regression to the mean (RTM) occurs in situations of repeated measurements when extreme values are followed by measurements in the same subjects that are closer to the mean of the basic population. In uncontrolled studies such changes are likely to be interpreted as a real treatment effect.</p> <p>Methods</p> <p>Several statistical approaches have been developed to analyse such situations, including the algorithm of Mee and Chua which assumes a known population mean <it>μ</it>. We extend this approach to a situation where <it>μ </it>is unknown and suggest to vary it systematically over a range of reasonable values. Using differential calculus we provide formulas to estimate the range of <it>μ </it>where treatment effects are likely to occur when RTM is present.</p> <p>Results</p> <p>We successfully applied our method to three real world examples denoting situations when (a) no treatment effect can be confirmed regardless which <it>μ </it>is true, (b) when a treatment effect must be assumed independent from the true <it>μ </it>and (c) in the appraisal of results of uncontrolled studies.</p> <p>Conclusion</p> <p>Our method can be used to separate the wheat from the chaff in situations, when one has to interpret the results of uncontrolled studies. In meta-analysis, health-technology reports or systematic reviews this approach may be helpful to clarify the evidence given from uncontrolled observational studies.</p

[2,4-13C]β-hydroxybutyrate Metabolism in Astrocytes and C6 Glioblastoma Cells

This study was undertaken to determine if the ketogenic diet could be useful for glioblastoma patients. The hypothesis tested was whether glioblastoma cells can metabolize ketone bodies. Cerebellar astrocytes and C6 glioblastoma cells were incubated in glutamine and serum free medium containing [2,4-13C]β-hydroxybutyrate (BHB) with and without glucose. Furthermore, C6 cells were incubated with [1-13C]glucose in the presence and absence of BHB. Cell extracts were analyzed by mass spectrometry and media by 1H magnetic resonance spectroscopy and HPLC. Using [2,4-13C]BHB and [1-13C]glucose it could be shown that C6 cells, in analogy to astrocytes, had efficient mitochondrial activity, evidenced by 13C labeling of glutamate, glutamine and aspartate. However, in the presence of glucose, astrocytes were able to produce and release glutamine, whereas this was not accomplished by the C6 cells, suggesting lack of anaplerosis in the latter. We hypothesize that glioblastoma cells kill neurons by not supplying the necessary glutamine, and by releasing glutamate