'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

Identification of premature infant states in relation to introducing oral feeding

Background Recognizing oral readiness signs in infants is vital when planning the introduction of oral feeding. However, with premature infants, this can be difficult to gauge accurately because of immature development. Methods Twenty three staff from a level 2 neonatal unit participated. A questionnaire elicited knowledge about oral readiness and other factors related to oral feeding with premature infants. Participant knowledge of the written Als (1986) infant state descriptors was completed. A comparison was made of the skills in identification of the various infant states on video without and with written descriptors (Als, 1986). Correlations investigated if years of experience and grade had any relation to accurate infant state identification. Results There was wide variation in the type of training about premature infant feeding participants had received. Participants (65%) recognized the importance of oral readiness signs in relation to feeding development. A Wilcoxon signed ranks test revealed no significant differences in ability to identify infant states without and with the written Als (1986) descriptors when observing infant video materials. When not using the written descriptors, there was a strong negative correlation between grade and the identification of the [Active sleep] state, (p < 0.01), and a strong positive correlation between grade and the identification of the [Drowsy] state, (p < 0.05). There were no strong correlations between grade and years working when using the written descriptors. Conclusion Oral readiness signs are important when introducing oral feeding with premature infants. However, accurate identification of oral readiness remains challenging

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

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

Interferometric Observations of the Nuclear Region of Arp220 at Submillimeter Wavelengths

We report the first submillimeter interferometric observations of an ultraluminous infrared galaxy. We observed Arp220 in the CO J=3-2 line and 342GHz continuum with the single baseline CSO-JCMT interferometer consisting of the Caltech Submillimeter Observatory (CSO) and the James Clerk Maxwell Telescope (JCMT). Models were fit to the measured visibilities to constrain the structure of the source. The morphologies of the CO J=3-2 line and 342GHz continuum emission are similar to those seen in published maps at 230 and 110GHz. We clearly detect a binary source separated by about 1 arcsec in the east-west direction in the 342GHz continuum. The CO J=3-2 visibility amplitudes, however, indicate a more complicated structure, with evidence for a compact binary at some velocities and rather more extended structure at others. Less than 30% of the total CO J=3-2 emission is detected by the interferometer, which implies the presence of significant quantities of extended gas. We also obtained single-dish CO J=2-1, CO J=3-2 and HCN J=4-3 spectra. The HCN J=4-3 spectrum, unlike the CO spectra, is dominated by a single redshifted peak. The HCN J=4-3/CO J=3-2, HCN J=4-3/HCN J=1-0 and CO J=3-2/2-1 line ratios are larger in the redshifted (eastern) source, which suggests that the two sources may have different physical conditions. This result might be explained by the presence of an intense starburst that has begun to deplete or disperse the densest gas in the western source, while the eastern source harbors undispersed high density gas.Comment: 17 pages, 9 figures, 4 Tables. accepted by Ap

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

Alternative approaches to the legal, institutional and financial aspects of developing an inter-island electrical transmission cable system

This study (I) delineates three comprehensive alternative scenarios for the development, financing, construction, ownership, regulation and operation of an inter-island electric energy transmission cable systemDepartment of Planning and Economic Development, State of Hawai

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