'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

Blue Straggler Stars: The Spectacular Population in M80

Using HST-WFPC2 observations in two ultraviolet (UV) filters (F225W and F336W) of the central region of the high density Galactic Globular cluster (GGC) M80 we have identified 305 Blue Straggler Stars (BSS) which represents the largest and most concentrated population of BSS ever observed in a GGC. We also identify the largest, clean sample of evolved BSS yet found. The high stellar density alone cannot explain the BSS, and we suggest that in M80 we are witnessing a transient dynamical state, during which stellar interactions are delaying the core-collapse process leading to an exceptionally large population of collisional-BSS.Comment: 15 pages, 5 figures, Astrophysical Journal Letters, in pres

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

The surprising external upturn of the Blue Straggler radial distribution in M55

By combining high-resolution HST and wide-field ground based observations, in ultraviolet and optical bands, we study the Blue Straggler Star (BSS) population of the low density galactic globular cluster M55 (NGC 6809) over its entire radial extent. The BSS projected radial distribution is found to be bimodal, with a central peak, a broad minimum at intermediate radii, and an upturn at large radii. Similar bimodal distributions have been found in other globular clusters (M3, 47 Tucanae, NGC 6752, M5), but the external upturn in M55 is the largest found to date. This might indicate a large fraction of primordial binaries in the outer regions of M55, which seems somehow in contrast with the relatively low (\sim 10%) binary fraction recently measured in the core of this cluster.Comment: in press on Ap

Molecular systematics of Malpighiaceae: evidence from plastid rbcL and matK sequences

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141234/1/ajb21847.pd

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

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

Discovery of Extended Blue Horizontal Branches in Two Metal-Rich Globular Clusters

We have used WFPC2 to construct B, V color-magnitude diagrams of four metal-rich globular clusters, NGC 104 (47 Tuc), NGC 5927, NGC 6388, and NGC 6441. All four clusters have well populated red horizontal branches (RHB), as expected for their metallicity. However, NGC 6388 and 6441 also exhibit a prominent blue HB (BHB) extension, including stars reaching as faint in V as the turnoff luminosity. This discovery demonstrates directly for the first time that a major population of hot HB stars can exist in old, metal-rich systems. This may have important implications for the interpretation of the integrated spectra of elliptical galaxies. The cause of the phenomenon remains uncertain. We examine the possibility that NGC 6388 and 6441 are older than the other clusters, but a simple difference in age may not be sufficient to produce the observed distributions along the HB. The high central densities in NGC 6388 and 6441 suggest that the existence of the blue HB (BHB) tails might be caused by stellar interactions in the dense cores of these clusters, which we calculate to have two of the highest collision rates among globular clusters in the Galaxy. Tidal collisions might act in various ways to enhance loss of envelope mass, and therefore populate the blue side of the HB. However, the relative frequency of tidal collisions does not seem large enough (compared to that of the clusters with pure RHBs) to account for such a drastic difference in HB morphology. While a combination of an age difference and dynamical interactions may help, prima facie the lack of a radial gradient in the BHB/RHB star ratio seems to argue against dynamical effects playing a role.Comment: LaTeX, includes one Postscript figure. To appear in ApJ

Globular Clusters and X-ray Point Sources in Centaurus A (NGC 5128)

We detect 353 X-ray point sources, mostly low-mass X-ray binaries (LMXBs), in four Chandra observations of Centaurus A (NGC 5128), the nearest giant early-type galaxy, and correlate this point source population with the largest available ensemble of confirmed and likely globular clusters associated with this galaxy. Of the X-ray sources, 31 are coincident with 30 globular clusters that are confirmed members of the galaxy by radial velocity measurement (2 X-ray sources match one globular cluster within our search radius), while 1 X-ray source coincides with a globular cluster resolved by HST images. Another 36 X-ray point sources match probable, but spectroscopically unconfirmed, globular cluster candidates. The color distribution of globular clusters and cluster candidates in Cen A is bimodal, and the probability that a red, metal rich GC candidate contains an LMXB is at least 1.7 times that of a blue, metal poor one. If we consider only spectroscopically confirmed GCs, this ratio increases to ~3. We find that LMXBs appear preferentially in more luminous (massive) GCs. These two effects are independent, and the latter is likely a consequence of enhanced dynamical encounter rates in more massive clusters which have on average denser cores. The X-ray luminosity functions of the LMXBs found in GCs and of those that are unmatched with GCs reveal similar underlying populations, though there is some indication that fewer X-ray faint LMXBs are found in globular clusters than X-ray bright ones. Our results agree with previous observations of the connection of GCs and LMXBs in early-type galaxies and extend previous work on Centaurus A.Comment: 34 pages, 10 figures, 2 tables, Accepted for Publication in The Astrophysical Journa

A Primer on Eulerian Computational Fluid Dynamics for Astrophysics

We present a pedagogical review of some of the methods employed in Eulerian computational fluid dynamics (CFD). Fluid mechanics is governed by the Euler equations, which are conservation laws for mass, momentum, and energy. The standard approach to Eulerian CFD is to divide space into finite volumes or cells and store the cell-averaged values of conserved hydro quantities. The integral Euler equations are then solved by computing the flux of the mass, momentum, and energy across cell boundaries. We review both first-order and second-order flux assignment schemes. All linear schemes are either dispersive or diffusive. The nonlinear, second-order accurate total variation diminishing (TVD) approach provides high resolution capturing of shocks and prevents unphysical oscillations. We review the relaxing TVD scheme, a simple and robust method to solve systems of conservation laws like the Euler equations. A 3-D relaxing TVD code is applied to the Sedov-Taylor blast wave test. The propagation of the blast wave is accurately captured and the shock front is sharply resolved. We apply a 3-D self-gravitating hydro code to simulating the formation of blue straggler stars through stellar mergers and present some numerical results. A sample 3-D relaxing TVD code is provided in the appendix.Comment: 23 pages, 12 figures; includes sample 3-D hydro code and new section on stellar mergers; accepted by PAS