'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

First Evidence of Circumstellar Disks around Blue Straggler Stars

We present an analysis of optical HST/STIS and HST/FOS spectroscopy of 6 blue stragglers found in the globular clusters M3, NGC6752 and NGC6397. These stars are a subsample of a set of ~50 blue stragglers and stars above the main sequence turn-off in four globular clusters which will be presented in an forthcoming paper. All but the 6 stars presented here can be well fitted with non-LTE model atmospheres. The 6 misfits, on the other hand, possess Balmer jumps which are too large for the effective temperatures implied by their Paschen continua. We find that our data for these stars are consistent with models only if we account for extra absorption of stellar Balmer photons by an ionized circumstellar disk. Column densities of HI and CaII are derived as are the the disks' thicknesses. This is the first time that a circumstellar disk is detected around blue stragglers. The presence of magnetically-locked disks attached to the stars has been suggested as a mechanism to lose the large angular momentum imparted by the collision event at the birth of these stars. The disks implied by our study might not be massive enough to constitute such an angular momentum sink, but they could be the leftovers of once larger disks.Comment: Accepted by ApJ Letters 10 pages, 2 figure

The Evolution of Blue Stragglers Formed Via Stellar Collisions

We have used the results of recent smoothed particle hydrodynamic simulations of colliding stars to create models appropriate for input into a stellar evolution code. In evolving these models, we find that little or no surface convection occurs, precluding angular momentum loss via a magnetically-driven stellar wind as a viable mechanism for slowing rapidly rotating blue stragglers which have been formed by collisions. Angular momentum transfer to either a circumstellar disk (possibly collisional ejecta) or a nearby companion are plausible mechanisms for explaining the observed low rotation velocities of blue stragglers. Under the assumption that the blue stragglers seen in NGC 6397 and 47 Tuc have been created solely by collisions, we find that the majority of these blue stragglers cannot have been highly mixed by convection or meridional circulation currents at anytime during their evolution. Also, on the basis of the agreement between the predictions of our non-rotating models and the observed blue straggler distribution, the evolution of blue stragglers is apparently not dominated by the effects of rotation.Comment: 36 pages, including 1 table and 7 postscript figures (LaTeX2e). Also avaliable at http://astrowww.phys.uvic.ca/~ouellet/ . Accepted for publication in A

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

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

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

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

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

Benefits of GLP-1 Analogue and Insulin Combination in a Nurse Practitioner Supported Service

Benefits of GLP-1 Analogue and Insulin Combinations in a Nurse Practitioner Supported Service (#117) Giuliana Murfet , Michelle Woods , Jenna Hills 1. Diabetes Centre, Tasmanian Health Organisation-North West, Burnie, TAS, Australia 2. Royal Hobart Hospital Diabetes Centre, Tasmanian Health Organisation - South, Hobart, Tasmania, Australia 3. School of Health Sciences, University of Tasmania, Hobart, Tasmania, Australia Aim: To describe outcomes of a GLP-1 analogue and insulin combination service supported by nurse practitioners/credentialled diabetes educators Background: NICE guidelines place use of GLP-1 analogues as third-line addition to oral therapy in obese patients where weight loss would benefit comorbidities. In 2012 the TGA approved their use as an adjunct to insulin Glargine; but this is not reimbursed by PBS. Ceasing GLP-1 analogues to commence insulin therapy can have a major impact on people with type 2 diabetes in terms of excess weight gain that may impact other co-morbidities. Methodology: Tasmanian has State-wide Drug and Therapeutics Committee approval to support 100 patients on combination GLP-1 analogue and insulin. Patients not able to reach target HbA1c on OHAs and GLP-1 analogue alone are listed onto the SDTC list for supported insulin combination treatment. The NP/CDE supports the success of this combination by coordination, initiating GLP-1 analogue, decreasing insulin titration and cessation of OHA’s, reviewing how the person is coping and his perspective into interpretation/ narrative of living with a chronic condition. NP/CDE assessment includes information about the client’s perceptions/reactions to health and illness, their knowledge, self help activities and alternative treatment modalities. Results: Approximately 70% of patients had a sustained reduction of HbA1c over 12 months greater than 1% (28% ≥2%). Weight loss was seen in 70% of cases (ranging 1.3 - 14kg); weight maintenance or up to 1.5kg gain in others. Pre-intervention mean HbA1c was 9.7% (range 7.7-12.9%), post mean 7.7% (range 6.5 – 9.2%). Review of data shows that additional benefits realised by patients are the reduction of hypoglycaemic risk and events. Further, other benefits seen were contextual and reflective to complexity of each case. Notably patients living with multiple morbidities had a diminished progression in other morbidities; such as; resolved chronic bilateral cellulitis. Conclusion: Use of GLP-1s in combination with insulin therapy may have a place in supporting metabolic profiles. This approach can be supported by NPs/CDEs

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

Binge-watching: Video-on-demand, quality TV and mainstreaming fandom

This article explores the concept of the binge as viewing protocol associated with fan practices, industry practice and linked to ‘cult’ and ‘quality’ serialised content. Viewing binge-watching as an intersection of discourses of industry, audience and text, the concept is analysed here as shaped by a range of issues that dominate the contemporary media landscape. In this, factors like technological developments, fan discourses and practices being adopted as ‘mainstream’ media practice, changes in the discursive construction of ‘television’ and an emerging Video-on-Demand industry contribute to the construction of binge-watching as deliberate, self-scheduled alternative to ‘watching TV’