'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

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

Detection of the tau protein in human serum by a sensitive four-electrode electrochemical biosensor

This study presents a novel approach based on a four-electrode electrochemical biosensor for the detection of tau protein – one of the possible markers for the prediction of Alzheimer's disease (AD). The biosensor is based on the formation of stable antibody–antigen complexes on gold microband electrodes covered with a layer of a self-assembled monolayer and protein G. Antibodies were immobilized on the gold electrode surface in an optimal orientation by protein G interaction. Electrochemical impedance spectroscopy was used to analyze impedance change, which revealed a linear response with increasing tau concentrations. The assay is fast (<1 h for incubation and measurement) and very sensitive. The limit of quantification for the full-length 2N4R tau protein is 0.03 pM, a value unaltered when the assay was processed in bovine serum albumin or human serum. This technology could be adapted for the detection of other biomarkers to provide a multiple assay to identify AD progression in a point of care setting

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

Global three-dimensional flow of a neutron superfluid in a spherical shell in a neutron star

We integrate for the first time the hydrodynamic Hall-Vinen-Bekarevich-Khalatnikov equations of motion of a $^{1}S_{0}$-paired neutron superfluid in a rotating spherical shell, using a pseudospectral collocation algorithm coupled with a time-split fractional scheme. Numerical instabilities are smoothed by spectral filtering. Three numerical experiments are conducted, with the following results. (i) When the inner and outer spheres are put into steady differential rotation, the viscous torque exerted on the spheres oscillates quasiperiodically and persistently (after an initial transient). The fractional oscillation amplitude ($\sim 10^{-2}$) increases with the angular shear and decreases with the gap width. (ii) When the outer sphere is accelerated impulsively after an interval of steady differential rotation, the torque increases suddenly, relaxes exponentially, then oscillates persistently as in (i). The relaxation time-scale is determined principally by the angular velocity jump, whereas the oscillation amplitude is determined principally by the gap width. (iii) When the mutual friction force changes suddenly from Hall-Vinen to Gorter-Mellink form, as happens when a rectilinear array of quantized Feynman-Onsager vortices is destabilized by a counterflow to form a reconnecting vortex tangle, the relaxation time-scale is reduced by a factor of $\sim 3$ compared to (ii), and the system reaches a stationary state where the torque oscillates with fractional amplitude $\sim 10^{-3}$ about a constant mean value. Preliminary scalings are computed for observable quantities like angular velocity and acceleration as functions of Reynolds number, angular shear, and gap width. The results are applied to the timing irregularities (e.g., glitches and timing noise) observed in radio pulsars.Comment: 6 figures, 23 pages. Accepted for publication in Astrophysical Journa

Asymmetric supernova in hierarchical multiple star systems and application to J1903+0327

We develop a method to analyze the effect of an asymmetric supernova on hierarchical multiple star systems and we present analytical formulas to calculate orbital parameters for surviving binaries or hierarchical triples and runaway velocities for their dissociating equivalents. The effect of an asymmetric supernova on the orbital parameters of a binary system has been studied to great extent (e.g. Hills 1983; Kalogera 1996; Tauris & Takens 1998), but this effect on higher multiplicity hierarchical systems has not been explored before. With our method, the supernova effect can be computed by reducing the hierarchical multiple to an effective binary by means of recursively replacing the inner binary by an effective star at the center of mass of that binary. We apply our method to a hierarchical triple system similar to the progenitor of PSR J1903+0327 suggested by Portegies Zwart et al. (2011). We confirm their earlier finding that PSR J1903+0327 could have evolved from a hierarchical triple that became unstable and ejected the secondary star of the inner binary. Furthermore, if such as system did evolve via this mechanism the most probable configuration would be a small supernova kick velocity, an inner binary with a large semi-major axis, and the fraction of mass accreted onto the neutron star to the mass lost by the secondary would most likely be between 0.35 and 0.5Comment: 13 pages, 9 figures, accepted for publication in MNRA

Recovery following a marathon: a comparison of cold water immersion, whole body cryotherapy and a placebo control

Purpose: Cryotherapy is an increasingly popular recovery strategy used in an attempt to attenuate the negative impact of strenuous physical activity on subsequent exercise. Therefore, this study aimed to assess the effects of whole body cryotherapy (WBC) and cold water immersion (CWI) on markers of recovery following a marathon. Methods: Thirty-one endurance trained males completed a marathon. Participants were randomly assigned to a CWI, WBC or placebo group. Perceptions of muscle soreness, training stress and markers of muscle function were recorded before the marathon and at 24 and 48 h post exercise. Blood samples were taken at baseline, post intervention and 24 and 48 h post intervention to assess inflammation and muscle damage. Results: WBC had a harmful effect on muscle function compared to CWI post marathon. WBC positively influenced perceptions of training stress compared to CWI. With the exception of C-reactive protein (CRP) at 24 and 48 h, neither cryotherapy intervention positively influenced blood borne markers of inflammation or structural damage compared to placebo. Conclusion: The findings show WBC has a negative impact on muscle function, perceptions of soreness and a number of blood parameters compared to CWI, contradicting the suggestion that WBC may be a superior recovery strategy. Further, cryotherapy is no more effective than a placebo intervention at improving functional recovery or perceptions of training stress following a marathon. These findings lend further evidence to suggest that treatment belief and the placebo effect may be largely responsible for the beneficial effects of cryotherapy on recovery following a marathon

A Derivation of Three-Dimensional Inertial Transformations

The derivation of the transformations between inertial frames made by Mansouri and Sexl is generalised to three dimensions for an arbitrary direction of the velocity. Assuming lenght contraction and time dilation to have their relativistic values, a set of transformations kinematically equivalent to special relativity is obtained. The ``clock hypothesis'' allows the derivation to be extended to accelerated systems. A theory of inertial transformations maintaining an absolute simultaneity is shown to be the only one logically consistent with accelerated movements. Algebraic properties of these transformations are discussed. Keywords: special relativity, synchronization, one-way velocity of light, ether, clock hypothesis.Comment: 16 pages (A5), Latex, one figure, to be published in Found. Phys. Lett. (1997

A combination of cherry juice and cold water immersion does not enhance marathon recovery compared to either treatment in isolation: a randomized placebo-controlled trial

Purpose: Cherry juice (CJ) and cold water immersion (CWI) are both effective recovery strategies following strenuous endurance exercise. However, athletes routinely combine recovery interventions and less is known about the impact of a combined CJ and CWI protocol. Therefore, this study investigated the effects of combining CWI and CJ (a “cocktail” (CT)) on inflammation and muscle damage following a marathon. Methods: A total 39 endurance trained males were randomly assigned to a placebo (PL), CWI, CJ, or CT group before completing a trail marathon run. Muscle damage (creatine kinase (CK)), muscle function (maximal voluntary isometric contraction (MVIC)), and inflammation (interleukin-6 (IL-6); C-reactive protein (CRP)) were measured at baseline, immediately after marathon (only IL-6), 24 h, and 48 h after marathon. Results: There were no statistically significant differences between groups and no group × time interaction effects for any of the dependent variables. Confidence intervals (CI) illustrated that CT had unclear effects on inflammation (IL-6; CRP) and MVIC, but may have increased CK to a greater extent than PL and CJ conditions. Conclusion: There is no evidence of an additive effect of CJ and CWI when the treatments are used in conjunction with each other. On the contrary, combining CJ and CWI may result in slightly increased circulating CK