The EBV-encoded oncoprotein, LMP1, induces an epithelial-to-mesenchymal transition (EMT) via Its CTAR1 domain through integrin-mediated ERK-MAPK signalling

The Epstein⁻Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene can induce profound effects on epithelial growth and differentiation including many of the features of the epithelial-to-mesenchymal transition (EMT). To better characterise these effects, we used the well-defined Madin Darby Canine Kidney (MDCK) epithelial cell model and found that LMP1 expression in these cells induces EMT as defined by characteristic morphological changes accompanied by loss of E-cadherin, desmosomal cadherin and tight junction protein expression. The induction of the EMT phenotype required a functional CTAR1 domain of LMP1 and studies using pharmacological inhibitors revealed contributions from signalling pathways commonly induced by integrin⁻ligand interactions: extracellular signal-regulated kinases/mitogen-activated protein kinases (ERK-MAPK), PI3-Kinase and tyrosine kinases, but not transforming growth factor beta (TGFβ). More detailed analysis implicated the CTAR1-mediated induction of Slug and Twist in LMP1-induced EMT. A key role for β1 integrin signalling in LMP1-mediated ERK-MAPK and focal adhesion kianse (FAK) phosphorylation was observed, and β1 integrin activation was found to enhance LMP1-induced cell viability and survival. These findings support an important role for LMP1 in disease pathogenesis through transcriptional reprogramming that enhances tumour cell survival and leads to a more invasive, metastatic phenotype

Displaying the Heterogeneity of the SN 2002cx-like Subclass of Type Ia Supernovae with Observations of the Pan-STARRS-1 Discovered SN2009ku

SN2009ku, discovered by Pan-STARRS-1, is a Type Ia supernova (SNIa), and a member of the distinct SN2002cx-like class of SNeIa. Its light curves are similar to the prototypical SN2002cx, but are slightly broader and have a later rise to maximum in g. SN2009ku is brighter (~0.6 mag) than other SN2002cx-like objects, peaking at M_V = -18.4 mag - which is still significantly fainter than typical SNeIa. SN2009ku, which had an ejecta velocity of ~2000 kms^-1 at 18 days after maximum brightness is spectroscopically most similar to SN2008ha, which also had extremely low-velocity ejecta. However, SN2008ha had an exceedingly low luminosity, peaking at M_V = -14.2 mag, ~4 mag fainter than SN2009ku. The contrast of high luminosity and low ejecta velocity for SN2009ku is contrary to an emerging trend seen for the SN2002cx class. SN2009ku is a counter-example of a previously held belief that the class was more homogeneous than typical SNeIa, indicating that the class has a diverse progenitor population and/or complicated explosion physics. As the first example of a member of this class of objects from the new generation of transient surveys, SN2009ku is an indication of the potential for these surveys to find rare and interesting objects.Comment: 7 pages, 3 figure

Properties of pattern formation and selection processes in nonequilibrium systems with external fluctuations

We extend the phase field crystal method for nonequilibrium patterning to stochastic systems with external source where transient dynamics is essential. It was shown that at short time scales the system manifests pattern selection processes. These processes are studied by means of the structure function dynamics analysis. Nonequilibrium pattern-forming transitions are analyzed by means of numerical simulations.Comment: 15 poages, 8 figure

The Approach to Ergodicity in Monte Carlo Simulations

The approach to the ergodic limit in Monte Carlo simulations is studied using both analytic and numerical methods. With the help of a stochastic model, a metric is defined that enables the examination of a simulation in both the ergodic and non-ergodic regimes. In the non-ergodic regime, the model implies how the simulation is expected to approach ergodic behavior analytically, and the analytically inferred decay law of the metric allows the monitoring of the onset of ergodic behavior. The metric is related to previously defined measures developed for molecular dynamics simulations, and the metric enables the comparison of the relative efficiencies of different Monte Carlo schemes. Applications to Lennard-Jones 13-particle clusters are shown to match the model for Metropolis, J-walking and parallel tempering based approaches. The relative efficiencies of these three Monte Carlo approaches are compared, and the decay law is shown to be useful in determining needed high temperature parameters in parallel tempering and J-walking studies of atomic clusters.Comment: 17 Pages, 7 Figure

Possible origins of macroscopic left-right asymmetry in organisms

I consider the microscopic mechanisms by which a particular left-right (L/R) asymmetry is generated at the organism level from the microscopic handedness of cytoskeletal molecules. In light of a fundamental symmetry principle, the typical pattern-formation mechanisms of diffusion plus regulation cannot implement the "right-hand rule"; at the microscopic level, the cell's cytoskeleton of chiral filaments seems always to be involved, usually in collective states driven by polymerization forces or molecular motors. It seems particularly easy for handedness to emerge in a shear or rotation in the background of an effectively two-dimensional system, such as the cell membrane or a layer of cells, as this requires no pre-existing axis apart from the layer normal. I detail a scenario involving actin/myosin layers in snails and in C. elegans, and also one about the microtubule layer in plant cells. I also survey the other examples that I am aware of, such as the emergence of handedness such as the emergence of handedness in neurons, in eukaryote cell motility, and in non-flagellated bacteria.Comment: 42 pages, 6 figures, resubmitted to J. Stat. Phys. special issue. Major rewrite, rearranged sections/subsections, new Fig 3 + 6, new physics in Sec 2.4 and 3.4.1, added Sec 5 and subsections of Sec

The institutional shaping of management: in the tracks of English individualism

Globalisation raises important questions about the shaping of economic action by cultural factors. This article explores the formation of what is seen by some as a prime influence on the formation of British management: individualism. Drawing on a range of historical sources, it argues for a comparative approach. In this case, the primary comparison drawn is between England and Scotland. The contention is that there is a systemic approach to authority in Scotland that can be contrasted to a personal approach in England. An examination of the careers of a number of Scottish pioneers of management suggests the roots of this systemic approach in practices of church governance. Ultimately this systemic approach was to take a secondary role to the personal approach engendered by institutions like the universities of Oxford and Cambridge, but it found more success in the different institutional context of the USA. The complexities of dealing with historical evidence are stressed, as is the value of taking a comparative approach. In this case this indicates a need to take religious practice as seriously as religious belief as a source of transferable practice. The article suggests that management should not be seen as a simple response to economic imperatives, but as shaped by the social and cultural context from which it emerges

The influence of probiotic supplementation on selected athletic performance-related blood markers in men

It has been speculated that probiotics can improve athletic performance. Significant increases in haemoglobin concentration and oxygen consumption have also been shown to follow the ingestion of lactic acid bacteria in athletes. The aim of this study was to determine whether the administration of commercially prepared probiotics could influence haemoglobin concentration and other haematological parameters in moderately active males. Fifty healthy, moderately active male volunteers were divided into two groups (Test Group and Control Group). A randomized, double-blind, placebo-controlled, pre-test/post-test, group comparison study was done. The study showed no significant differences (p≥0.05) between the two groups on any of the dependent measurements. There were statistically significant changes (p≤0.05) between pre- and post-test results within the two groups. These changes were within physiological limits. Sodium increased significantly (p=0,001) from 139.29 mmol/L to 140.96 mmol/L in the Control Group. In the Test Group sodium increased significantly (p=0,035) from 139.60 mmol/L to 140.90 mmol/L, and potassium decreased (p=0.010) from 4.67 mmol/L to 4.44 mmol/L. Study results thus indicated that the ingestion of a lactic acid bacteria preparation for 42 days did not increase the haemoglobin concentration in moderately active males.http://www.ajol.info/journal_index.php?jid=153&ab=ajpher