Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus

Merkel cell polyomavirus (MCV) has been recently described as the cause for most human Merkel cell carcinomas. MCV is similar to simian virus 40 (SV40) and encodes a nuclear large T (LT) oncoprotein that is usually mutated to eliminate viral replication among tumor-derived MCV. We identified the hVam6p cytoplasmic protein involved in lysosomal processing as a novel interactor with MCV LT but not SV40 LT. hVam6p binds through its clathrin heavy chain homology domain to a unique region of MCV LT adjacent to the retinoblastoma binding site. MCV LT translocates hVam6p to the nucleus, sequestering it from involvement in lysosomal trafficking. A naturally occurring, tumor-derived mutant LT (MCV350) lacking a nuclear localization signal binds hVam6p but fails to inhibit hVam6p-induced lysosomal clustering. MCV has evolved a novel mechanism to target hVam6p that may contribute to viral uncoating or egress through lysosomal processing during virus replication

Understanding the core density profile in TCV H-mode plasmas

Results from a database analysis of H-mode electron density profiles on the Tokamak \`a Configuration Variable (TCV) in stationary conditions show that the logarithmic electron density gradient increases with collisionality. By contrast, usual observations of H-modes showed that the electron density profiles tend to flatten with increasing collisionality. In this work it is reinforced that the role of collisionality alone, depending on the parameter regime, can be rather weak and in these, dominantly electron heated TCV cases, the electron density gradient is tailored by the underlying turbulence regime, which is mostly determined by the ratio of the electron to ion temperature and that of their gradients. Additionally, mostly in ohmic plasmas, the Ware-pinch can significantly contribute to the density peaking. Qualitative agreement between the predicted density peaking by quasi-linear gyrokinetic simulations and the experimental results is found. Quantitative comparison would necessitate ion temperature measurements, which are lacking in the considered experimental dataset. However, the simulation results show that it is the combination of several effects that influences the density peaking in TCV H-mode plasmas.Comment: 23 pages, 12 figure

Spherical collapse of dark energy with an arbitrary sound speed

We consider a generic type of dark energy fluid, characterised by a constant equation of state parameter w and sound speed c_s, and investigate the impact of dark energy clustering on cosmic structure formation using the spherical collapse model. Along the way, we also discuss in detail the evolution of dark energy perturbations in the linear regime. We find that the introduction of a finite sound speed into the picture necessarily induces a scale-dependence in the dark energy clustering, which in turn affects the dynamics of the spherical collapse in a scale-dependent way. As with other, more conventional fluids, we can define a Jeans scale for the dark energy clustering, and hence a Jeans mass M_J for the dark matter which feels the effect of dark energy clustering via gravitational interactions. For bound objects (halos) with masses M >> M_J, the effect of dark energy clustering is maximal. For those with M << M_J, the dark energy component is effectively homogeneous, and its role in the formation of these structures is reduced to its effects on the Hubble expansion rate. To compute quantitatively the virial density and the linearly extrapolated threshold density, we use a quasi-linear approach which is expected to be valid up to around the Jeans mass. We find an interesting dependence of these quantities on the halo mass M, given some w and c_s. The dependence is the strongest for masses lying in the vicinity of M ~ M_J. Observing this M-dependence will be a tell-tale sign that dark energy is dynamic, and a great leap towards pinning down its clustering properties.Comment: 25 pages, 6 figures, matches version published in JCA

Functional recovery is considered the most important target: a survey of dedicated professionals

Background: The aim of this study was to survey the relative importance of postoperative recovery targets and perioperative care items, as perceived by a large group of international dedicated professionals. Methods: A questionnaire with eight postoperative recovery targets and 13 perioperative care items was mailed to participants of the first international Enhanced Recovery After Surgery (ERAS) congress and to authors of papers with a clear relevance to ERAS in abdominal surgery. The responders were divided into categories according to profession and region. Results: The recovery targets ‘To be completely free of nausea’, ‘To be independently mobile’ and ‘To be able to eat and drink as soon as possible’ received the highest score irrespective of the responder's profession or region of origin. Equally, the care items ‘Optimizing fluid balance’, ‘Preoperative counselling’ and ‘Promoting early and scheduled mobilisation’ received the highest score across all groups. Conclusions: Functional recovery, as in tolerance of food without nausea and regained mobility, was considered the most important target of recovery. There was a consistent uniformity in the way international dedicated professionals scored the relative importance of recovery targets and care items. The relative rating of the perioperative care items was not dependent on the strength of evidence supporting the items

Ohmic energy confinement saturation and core toroidal rotation reversal in Alcator C-Mod plasmas

Ohmic energy confinement saturation is found to be closely related to core toroidal rotation reversals in Alcator C-Mod tokamak plasmas. Rotation reversals occur at a critical density, depending on the plasma current and toroidal magnetic field, which coincides with the density separating the linear Ohmic confinement regime from the saturated Ohmic confinement regime. The rotation is directed co-current at low density and abruptly changes direction to counter-current when the energy confinement saturates as the density is increased. Since there is a bifurcation in the direction of the rotation at this critical density, toroidal rotation reversal is a very sensitive indicator in the determination of the regime change. The reversal and confinement saturation results can be unified, since these processes occur in a particular range of the collisionality.United States. Dept. of Energy (Contract DE-FC02-99ER54512

Structured models of cell migration incorporating molecular binding processes

The dynamic interplay between collective cell movement and the various molecules involved in the accompanying cell signalling mechanisms plays a crucial role in many biological processes including normal tissue development and pathological scenarios such as wound healing and cancer. Information about the various structures embedded within these processes allows a detailed exploration of the binding of molecular species to cell-surface receptors within the evolving cell population. In this paper we establish a general spatio-temporal-structural framework that enables the description of molecular binding to cell membranes coupled with the cell population dynamics. We first provide a general theoretical description for this approach and then illustrate it with two examples arising from cancer invasion

Neutrino cosmology and Planck

Relic neutrinos play an important role in the evolution of the Universe, modifying some of the cosmological observables. We summarize the main aspects of cosmological neutrinos and describe how the precision of present cosmological data can be used to learn about neutrino properties. In particular, we discuss how cosmology provides information on the absolute scale of neutrino masses, complementary to beta decay and neutrinoless double-beta decay experiments. We explain why the combination of Planck temperature data with measurements of the baryon acoustic oscillation angular scale provides a strong bound on the sum of neutrino masses, 0.23 eV at the 95% confidence level, while the lensing potential spectrum and the cluster mass function measured by Planck are compatible with larger values. We also review the constraints from current data on other neutrino properties. Finally, we describe the very good perspectives from future cosmological measurements, which are expected to be sensitive to neutrino masses close the minimum values guaranteed by flavour oscillations

Feasibility study for a correlation electron cyclotron emission turbulence diagnostic based on nonlinear gyrokinetic simulations

This paper describes the use of nonlinear gyrokinetic simulations to assess the feasibility of a new correlation electron cyclotron emission (CECE) diagnostic that has been proposed for the Alcator C-Mod tokamak (Marmar et al 2009 Nucl. Fusion 49 104014). This work is based on a series of simulations performed with the GYRO code (Candy and Waltz 2003 J. Comput. Phys. 186 545). The simulations are used to predict ranges of fluctuation level, peak poloidal wavenumber and radial correlation length of electron temperature fluctuations in the core of the plasma. The impact of antenna pattern and poloidal viewing location on measurable turbulence characteristics is addressed using synthetic diagnostics. An upper limit on the CECE sample volume size is determined. The modeling results show that a CECE diagnostic capable of measuring transport-relevant, long-wavelength (k[subscript θ]ρ[subscript s] < 0.5) electron temperature fluctuations is feasible at Alcator C-Mod.United States. Dept. of Energy (DE-FC02-C99ER54512-CMOD

Non-local heat transport, rotation reversals and up/down impurity density asymmetries in Alcator C-Mod ohmic L-mode plasmas

Several seemingly unrelated effects in Alcator C-Mod ohmic L-mode plasmas are shown to be closely connected: non-local heat transport, core toroidal rotation reversals, energy confinement saturation and up/down impurity density asymmetries. These phenomena all abruptly transform at a critical value of the collisionality. At low densities in the linear ohmic confinement regime, with collisionality ν[subscript *] ≤ 0.35 (evaluated inside of the q = 3/2 surface), heat transport exhibits non-local behaviour, core toroidal rotation is directed co-current, edge impurity density profiles are up/down symmetric and a turbulent feature in core density fluctuations with k[subscript θ] up to 15 cm[superscript −1] (k[subscript θ]ρ[subscript s] ~ 1) is present. At high density/collisionality with saturated ohmic confinement, electron thermal transport is diffusive, core rotation is in the counter-current direction, edge impurity density profiles are up/down asymmetric and the high k[subscript θ] turbulent feature is absent. The rotation reversal stagnation point (just inside of the q = 3/2 surface) coincides with the non-local electron temperature profile inversion radius. All of these observations suggest a possible unification in a model with trapped electron mode prevalence at low collisionality and ion temperature gradient mode domination at high collisionality.United States. Dept. of Energy (Contract DE-FC02-99ER54512)United States. Dept. of Energy. Office of Fusion Energy Sciences (Postdoctoral Research Program

Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

The mechanisms of Pb(II) toxicity have been studied in human red blood cells using confocal microscopy, immunolabeling, fluorescence-activated cell sorting and atomic force microscopy. The process follows a sequence of events, starting with calcium entry, followed by potassium release, morphological change, generation of ceramide, lipid flip-flop and finally cell lysis. Clotrimazole blocks potassium channels and the whole process is inhibited. Immunolabeling reveals the generation of ceramide-enriched domains linked to a cell morphological change, while the use of a neutral sphingomyelinase inhibitor greatly delays the process after the morphological change, and lipid flip-flop is significantly reduced. These facts point to three major checkpoints in the process: first the upstream exchange of calcium and potassium, then ceramide domain formation, and finally the downstream scramblase activation necessary for cell lysis. In addition, partial non-cytotoxic cholesterol depletion of red blood cells accelerates the process as the morphological change occurs faster. Cholesterol could have a role in modulating the properties of the ceramide-enriched domains. This work is relevant in the context of cell death, heavy metal toxicity and sphingolipid signaling.AGA was a predoctoral student supported by the Basque Government and later by the University of the Basque Country (UPV/EHU). This work was also supported in part by grants from the Spanish Government (FEDER/MINECO BFU 2015-66306-P to F.M.G. and A.A.) and the Basque Government (IT849-13 to F.M.G. and IT838-13 to A.A.), and by the Swiss National Science Foundation