'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

Stress analysis of V-notches with and without cracks, with application to foreign object damage

Published versio

Out-Of-Focus Holography at the Green Bank Telescope

We describe phase-retrieval holography measurements of the 100-m diameter Green Bank Telescope using astronomical sources and an astronomical receiver operating at a wavelength of 7 mm. We use the technique with parameterization of the aperture in terms of Zernike polynomials and employing a large defocus, as described by Nikolic, Hills & Richer (2006). Individual measurements take around 25 minutes and from the resulting beam maps (which have peak signal to noise ratios of 200:1) we show that it is possible to produce low-resolution maps of the wavefront errors with accuracy around a hundredth of a wavelength. Using such measurements over a wide range of elevations, we have calculated a model for the wavefront-errors due to the uncompensated gravitational deformation of the telescope. This model produces a significant improvement at low elevations, where these errors are expected to be the largest; after applying the model, the aperture efficiency is largely independent of elevation. We have also demonstrated that the technique can be used to measure and largely correct for thermal deformations of the antenna, which often exceed the uncompensated gravitational deformations during daytime observing. We conclude that the aberrations induced by gravity and thermal effects are large-scale and the technique used here is particularly suitable for measuring such deformations in large millimetre wave radio telescopes.Comment: 10 pages, 7 figures (accepted by Astronomy & Astrophysics

IUPHAR-DB: An Expert-Curated, Peer-Reviewed Database of Receptors and Ion Channels

The International Union of Basic and Clinical Pharmacology database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 non-sensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of about a third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. Individual gene pages provide a comprehensive description of the genes and their functions, with information on protein structure, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). The phenotypes resulting from altered gene expression (e.g. in genetically altered animals) and genetic mutations are described. Links are provided to bioinformatics resources such as NCBI RefSeq, OMIM, PubChem, human, rat and mouse genome databases. Recent developments include the addition of ligand-centered pages summarising information about unique ligand molecules in IUPHAR-DB. IUPHAR-DB represents a novel approach to biocuration because most data are provided through manual curation of published literature by a network of over 60 expert subcommittees coordinated by NC-IUPHAR. Data are referenced to the primary literature and linked to PubMed. The data are checked to ensure accuracy and consistency by the curators, added to the production server using custom-built submission tools and peer-reviewed by NC-IUPHAR, before being transferred to the public database. Data are reviewed and updated regularly (at least biennially). Other website features include comprehensive database search tools, online and downloadable gene lists and links to recent publications of interest to the field, such as reports on receptor-ligand pairings. The database is freely available at "http://www.iuphar-db.org":http://www.iuphar-db.org. Curators can be reached at curators [at] iuphar-db.org. We thank British Pharmacological Society, UNESCO (through the ICSU Grants Programme), Incyte, GlaxoSmithKline, Novartis, Servier and Wyeth for their support

The influence function for self-equilibrating forces on a semi-infinite wedge

Published versio

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

The Reliability of Neuromuscular and Perceptual Measures Used to Profile Recovery, and the Time-Course of such Responses following Academy Rugby League Match-Play.

In professional academy rugby league (RL) players, this two-part study examined; A) the within- and between-day reliability of isometric mid-thigh pulls (IMTP), countermovement jumps (CMJ), and a wellness questionnaire (n = 11), and B) profiled the responses with acceptable reliability (no between-trial differences and between-day coefficient of variation (CV) ≤10% and intraclass correlation coefficient (ICC) ≥0.8) for 120 h (baseline: -3, +24, +48, +72, +96, +120 h) following RL match-play (n = 10). In part A, force at 200, and 250 ms, and peak force (PF) demonstrated acceptable within- (CV%: 3.67-8.41%, ICC: 0.89-0.93) and between-day (CV%: 4.34-8.62%, ICC: 0.87-0.92) reliability for IMTP. Most CMJ variables demonstrated acceptable within-day reliability (CV%: 3.03-7.34%, ICC: 0.82-0.98), but only six (i.e., flight-time, PF, peak power (PP), relative PP, velocity at take-off (VTO), jump-height (JH)) showed acceptable between-day reliability (CV%: 2.56-6.79%, ICC: 0.83-0.91). Only total wellness demonstrated acceptable between-day reliability (CV%: 7.05%, ICC: 0.90) from the questionnaire. In part B, reductions of 4.75% and 9.23% (vs. baseline; 2.54 m∙s-1; 0.33 m) occurred at +24 h for CMJ VTO, and JH, respectively. Acceptable reliability was observed in some, but not all, variables and the magnitude and time-course of post-match responses were test and variable specific. Practitioners should therefore be mindful of the influence that the choice of recovery monitoring tool may have upon the practical interpretation of the data

Rethinking professional practice: the logic of competition and the crisis of identity in housing practice

The relationship between professionalism, education and housing practice has become increasingly strained following the introduction of austerity measures and welfare reforms across a range of countries. Focusing on the development of UK housing practice, this article considers how notions of professionalism are being reshaped within the context of welfare retrenchment and how emerging tensions have both affected the identity of housing professionals and impacted on the delivery of training and education programmes. The article analyses the changing knowledge and skills valued in contemporary housing practice and considers how the sector has responded to the challenges of austerity. The central argument is that a dominant logic of competition has culminated in a crisis of identity for the sector. Although the focus of the article is on UK housing practice, the processes identified have a wider relevance for the analysis of housing and welfare delivery in developed economies

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

Pleasure and pedagogy: the consumption of DVD add-ons among Irish teenagers

This article addresses the issue of young people and media use in the digital age, more specifically the interconnection between new media pleasures and pedagogy as they relate to the consumption of DVD add-ons. Arguing against the view of new media as having predominantly detrimental effects on young people, the authors claim that new media can enable young people to develop media literacy skills and are of the view that media literacy strategies must be based on an understanding and legitimating of young people's use patterns and pleasures. The discussion is based on a pilot research project on the use patterns and pleasures of use with a sample of Irish teenagers. They found that DVDs were used predominantly in the home context, and that, while there was variability in use between the groups, overall they developed critical literacy skills and competences which were interwoven into their social life and projects of identity construction. The authors suggest that these findings could be used to develop DVDs and their add-on features as a learning resource in the more formal educational setting and they go on to outline the potential teaching benefits of their use across a range of pedagogical areas