'Special K' and a loss of cell-to-cell adhesion in proximal tubule-derived epithelial cells: modulation of the adherens junction complex by ketamine

Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention

Relativistic cross sections of mass stripping and tidal disruption of a star by a super-massive rotating black hole

[abbreviated] We consider the problem of tidal disruption of a star by a super-massive Kerr black hole. Using a numerically fast Lagrangian model of the tidally disrupted star we survey the parameter space of the problem and find the regions in the parameter space where the total disruption of the star or a partial mass loss take place as a result of fly-by around the black hole. Our treatment is based on General Relativity, and we consider the range of the black hole masses where the tidal disruption competes with the relativistic effect of direct capture of the star by the black hole. We find that our results can be represented on the plane of specific orbital angular momenta of the star $(j_{\theta}, j_{\phi})$. We calculate the contours of a given mass loss of the star on this plane, referred to as the tidal cross sections, for a given black hole mass $M$, rotational parameter $a$ and inclination of the trajectory of the star with respect to the black hole equatorial plane. It is shown that the tidal cross sections can be approximated as circles symmetric above the axis $j_{\phi}=0$, and shifted with respect to the origin of the coordinates in direction of negative $j_{\theta}$. The radii and shifts of these circles are obtained numerically for the black hole masses in the range $5\cdot 10^{5}M_{\odot}-10^{9}M_{\odot}$ and different values of $a$. It is shown that when $a=0$ the tidal disruption takes place for $M < 5\cdot 10^{7}M_{\odot}$ and when $a\approx 1$ the tidal disruption is possible for $M < 10^{9}M_{\odot}$.Comment: 11 pages, 16 figures, A&A in press, the text is clarified, the title and the abstract shown in text are change

Attention misplaced: the role of diagnostic features in the face-inversion effect

Inversion disproportionately impairs recognition of face stimuli compared to non-face stimuli arguably due to the holistic manner in which faces are processed. A qualification is put forward in which the first point fixated upon is different for upright and inverted faces and this carries some of the face-inversion effect. Three experiments explored this possibility by using fixation crosses to guide attention to the eye or mouth region of the to-be-presented faces in different orientations. Recognition was better when the fixation cross appeared at the eye region than at the mouth region. The face-inversion effect was smaller when the eyes were cued than when the mouth was cued or when there was no cueing. The results suggest that the first facial feature attended to is important for accurate face recognition and this may carry some of the effects of inversion

Unsymmetrical shear loading and its influence on the frictional shakedown of incomplete contacts

Published versio

Stellar Collisions and the Interior Structure of Blue Stragglers

Collisions of main sequence stars occur frequently in dense star clusters. In open and globular clusters, these collisions produce merger remnants that may be observed as blue stragglers. Detailed theoretical models of this process require lengthy hydrodynamic computations in three dimensions. However, a less computationally expensive approach, which we present here, is to approximate the merger process (including shock heating, hydrodynamic mixing, mass ejection, and angular momentum transfer) with simple algorithms based on conservation laws and a basic qualitative understanding of the hydrodynamics. These algorithms have been fine tuned through comparisons with the results of our previous hydrodynamic simulations. We find that the thermodynamic and chemical composition profiles of our simple models agree very well with those from recent SPH (smoothed particle hydrodynamics) calculations of stellar collisions, and the subsequent stellar evolution of our simple models also matches closely that of the more accurate hydrodynamic models. Our algorithms have been implemented in an easy to use software package, which we are making publicly available (see http://vassun.vassar.edu/~lombardi/mmas/). This software could be used in combination with realistic dynamical simulations of star clusters that must take into account stellar collisions.Comment: This revised version has 37 pages, 13 figures, 4 tables; submitted to ApJ; for associated software package, see http://vassun.vassar.edu/~lombardi/mmas/ This revised version presents additional comparisons with SPH results and slightly improved merger recipe

A new model of a tidally disrupted star

A new semi-analytical model of a star evolving in a tidal field is proposed. The model is a generalization of the so-called 'affine' stellar model. In our model the star is composed of elliptical shells with different parameters and different orientations, depending on time and on the radial Lagrangian coordinate of the shell. The evolution equations of this model are derived from the virial relations under certain assumptions, and the integrals of motion are identified. It is shown that the evolution equations can be deduced from a variational principle. The evolution equations are solved numerically and compared quantitatively with the results of 3D numerical computations of the tidal interaction of a star with a supermassive black hole. The comparison shows very good agreement between the main ``integral'' characteristics describing the tidal interaction event in our model and in the 3D computations. Our model is effectively a one-dimensional Lagrangian model from the point of view of numerical computations, and therefore it can be evolved numerically $10^{2}-10^{3}$ times faster than the 3D approach allows. This makes our model well suited for intensive calculations covering the whole parameter space of the problem.Comment: This version is accepted for publication in ApJ. Stylistic and grammatical changes, new Appendix adde

An explanation for metallicity effects on X-ray Binary properties

We show that irradiation induced stellar winds can explain two important metallicity effects in X-ray binaries - the higher numbers and the softer spectra of the X-ray binaries in metal rich globular clusters compared to the metal poor ones. As has been previously noted by Iben, Tutukov and Fedorova, the winds should be stronger at lower metallicity due to less efficient line cooling. This will speed up the evolution of the LMXBs in metal poor clusters, hence reducing their numbers. These winds can also provide extra material near the accreting object which may create an intrinsic absorber to harden the X-ray spectra of the metal poor cluster systems relative to the metal rich ones, as suggested by observations. We outline some additional observational predictions of the model.Comment: 6 pages, no figures, accepted to Ap

Another Non-segregated Blue Straggler Population in a Globular Cluster: the Case of NGC 2419

We have used a combination of ACS-HST high-resolution and wide-field SUBARU data in order to study the Blue Straggler Star (BSS) population over the entire extension of the remote Galactic globular cluster NGC 2419. The BSS population presented here is among the largest ever observed in any stellar system, with more than 230 BSS in the brightest portion of the sequence. The radial distribution of the selected BSS is essentially the same as that of the other cluster stars. In this sense the BSS radial distribution is similar to that of omega Centauri and unlike that of all Galactic globular clusters studied to date, which have highly centrally segregated distributions and, in most cases, a pronounced upturn in the external regions. As in the case of omega Centauri, this evidence indicates that NGC 2419 is not yet relaxed even in the central regions. This observational fact is in agreement with estimated half-mass relaxation time, which is of the order of the cluster age.Comment: in press in the Ap

Adaptive Lévy processes and area-restricted search in human foraging

A considerable amount of research has claimed that animals’ foraging behaviors display movement lengths with power-law distributed tails, characteristic of Lévy flights and Lévy walks. Though these claims have recently come into question, the proposal that many animals forage using Lévy processes nonetheless remains. A Lévy process does not consider when or where resources are encountered, and samples movement lengths independently of past experience. However, Lévy processes too have come into question based on the observation that in patchy resource environments resource-sensitive foraging strategies, like area-restricted search, perform better than Lévy flights yet can still generate heavy-tailed distributions of movement lengths. To investigate these questions further, we tracked humans as they searched for hidden resources in an open-field virtual environment, with either patchy or dispersed resource distributions. Supporting previous research, for both conditions logarithmic binning methods were consistent with Lévy flights and rank-frequency methods–comparing alternative distributions using maximum likelihood methods–showed the strongest support for bounded power-law distributions (truncated Lévy flights). However, goodness-of-fit tests found that even bounded power-law distributions only accurately characterized movement behavior for 4 (out of 32) participants. Moreover, paths in the patchy environment (but not the dispersed environment) showed a transition to intensive search following resource encounters, characteristic of area-restricted search. Transferring paths between environments revealed that paths generated in the patchy environment were adapted to that environment. Our results suggest that though power-law distributions do not accurately reflect human search, Lévy processes may still describe movement in dispersed environments, but not in patchy environments–where search was area-restricted. Furthermore, our results indicate that search strategies cannot be inferred without knowing how organisms respond to resources–as both patched and dispersed conditions led to similar Lévy-like movement distributions