'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

Presentation patterns of invasive cancer of the cervix: results from Parirenyatwa Oncology and Radiotherapy Centre, Harare, Zimbabwe 1998-2010

A research paper on cancer of the cervix in Zimbabwe.Cancer of the uterine cervix is the second most common cancer among women worldwide with a high incidence in Sub-Saharan Africa.1 In developing countries such as Zimbabwe invasive cancer of the cervix (CaCx) is the most common cancer in females and also the leading cause of cancer related deaths in women.2 The American Cancer Society3 estimated that 12.710 million new cases of invasive CaCx were going to be diagnosed in 2011 and about 4.290 million women were going to die with invasive CaCx. The same author reported that there is a significant decrease in incidence and mortality rate of invasive CaCx in developed countries over the past three decades as compared to the developing countries. This was attributed to available options of disease prevention with the possibility of early diagnosis of the disease due to effective screening and accessibility to effective treatment procedures in developed countries. To this end it has been noted that women living in developed countries have a 208% greater chance of being successfully treated when compared with women in less developed countries

Prospects for the rapid detection of mealiness in apples by nondestructive NMR relaxometry

The potential of nuclear magnetic resonance (NMR) relaxometry for quantitative evaluation of apple mealiness has been investigated. The degree of "mealiness" was defined by several mechanical techniques, including penetration, compression and shear rupture as well as by the BRIX (soluble solids) and juiciness levels. These data were correlated with both magnetic resonance imaging (MRI) and NMR water proton transverse relaxation time measurements on a fruit-by-fruit basis. It was found that increasing mealiness caused a systematic increase in the transverse relaxation rate. The potential for rapid, on-line NMR/MRI detection of apple mealiness is discussed

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

Dissipative dynamics of superfluid vortices at non-zero temperatures

We consider the evolution and dissipation of vortex rings in a condensate at non-zero temperature, in the context of the classical field approximation, based on the defocusing nonlinear Schr\"odinger equation. The temperature in such a system is fully determined by the total number density and the number density of the condensate. A vortex ring is introduced into a condensate in a state of thermal equilibrium, and interacts with non-condensed particles. These interactions lead to a gradual decrease in the vortex line density, until the vortex ring completely disappears. We show that the square of the vortex line length changes linearly with time, and obtain the corresponding universal decay law. We relate this to mutual friction coefficients in the fundamental equation of vortex motion in superfluids.Comment: 4 pages, 3 figure

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

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

Dust and gas in luminous infrared galaxies - results from SCUBA observations

We present new data taken at 850 $\mu$m with SCUBA at the JCMT for a sample of 19 luminous infrared galaxies. Fourteen galaxies were detected. We have used these data, together with fluxes at 25, 60 and 100 $\mu$m from IRAS, to model the dust emission. We find that the emission from most galaxies can be described by an optically thin, single temperature dust model with an exponent of the dust extinction coefficient ($k_\lambda \propto \lambda^{-\beta}$) of $\beta \simeq 1.5 - 2$. A lower $\beta\simeq 1$ is required to model the dust emission from two of the galaxies, Arp 220 and NGC 4418. We discuss various possibilities for this difference and conclude that the most likely is a high dust opacity. In addition, we compare the molecular gas mass derived from the dust emission, $M_{dust}$, with the molecular gas mass derived from the CO emission, $M_{CO}$, and find that $M_{CO}$ is on average a factor 3 higher than $M_{dust}$.Comment: 10 pages, 6 figures, latex, with MN-macros, accepted by MNRAS - revised version (changed flux values for some galaxies

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