Compromised cardiovascular function in aged rats corresponds with increased expression and activity of calcium/calmodulin dependent protein kinase IIδ in aortic endothelium

Ageing is the greatest risk factor for cardiovascular disease. Calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) plays a fundamental role in the pathology of heart disease yet a potential role for CaMKIIδ in cardiovascular pathology associated with ageing remains unclear. Taking a combined in vivo and in vitro approach, we have for the first time investigated whether CaMKIIδ expression and CaMKII activity may be altered following age-related cardiovascular deterioration. Both cardiac contractility and aortic blood flow are compromised in aged rats and we have shown that this occurs in parallel with increased inflammation and crucially, autonomous activation of CaMKII. Endothelial cells isolated from young and aged aortae exhibit differences in cell phenotype and physiology. In line with observations in aortic tissue, aged aortic endothelial cells also show increased basal levels of pro-inflammatory markers and oxidative stress with concurrent increased basal activation of CaMKII. These results are the first to demonstrate that elevated CaMKIIδ expression and CaMKII activation occur in parallel with the pathological progression associated with ageing of the heart and vasculature. Specifically, CaMKIIδ expression is significantly increased and activated in the endothelium of aged aorta. As such, CaMKIIδ could serve as an important marker of endothelial dysfunction that accompanies the ageing process and may be an appropriate candidate for investigating targeted therapeutic intervention

A quantitative study of neurochemically-defined populations of inhibitory interneurons in the superficial dorsal horn of the mouse spinal cord

Around a quarter of neurons in laminae I-II of the dorsal horn are inhibitory interneurons. These play an important role in modulating somatosensory information, including that perceived as pain or itch. Previous studies in rat identified four largely non-overlapping neurochemical populations among these cells, defined by expression of galanin, neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS) or parvalbumin. The galanin cells were subsequently shown to coexpress dynorphin. Several recent studies have used genetically-modified mice to investigate the function of different interneuron populations, and it is therefore important to determine whether the same pattern applies in mouse, and to estimate the relative sizes of these populations. We show that the neurochemical organisation of inhibitory interneurons in mouse superficial dorsal horn is similar to that in the rat, although a larger proportion of these neurons (33%) express NPY. Between them, these four populations account for ∼75% of inhibitory cells in laminae I-II. Since ∼25% of inhibitory interneurons in this region belong to a novel calretinin-expressing type, our results suggest that virtually all inhibitory interneurons in superficial dorsal horn can be assigned to one of these five neurochemical populations. Although our main focus was inhibitory neurons, we also identified a population of excitatory dynorphin-expressing cells in laminae I-II that are largely restricted to the medial part of the mid-lumbar dorsal horn, corresponding to glabrous skin territory. These findings are important for interpretation of studies using molecular-genetic techniques to manipulate the functions of interneuron populations to investigate their roles in somatosensory processing

How do patients from South Asian backgrounds experience life on haemodialysis in the UK? : A multicentre qualitative study

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES: End-stage kidney disease disproportionately affects people of South Asian origin. This study aimed to uncover the lived experiences of this group of patients on centre-based haemodialysis (HD), the most prevalent dialysis modality. DESIGN: The study utilised a qualitative focus group methodology. Seven focus groups were conducted across four NHS Trusts in the UK including three in Gujarati and two each in Punjabi and Urdu. This provided an inclusive opportunity for South Asian patients to contribute in their language of origin. A total of 24 patients participated. Focus groups were facilitated by bilingual project workers and data were forward translated and analysed using thematic analysis. RESULTS: Four themes were identified. This included (1) 'treatment imposition', which comprised of the restrictive nature of HD, the effects of treatment and the feeling of being trapped in an endless process. (2) The 'patient-clinician relationship' centred around the impact of a perceived lack of staff time, and inadequacies in the quality of interactions. (3) 'Coping strategies' highlighted the role of cognitive reappraisal, living in the moment and family support networks in facilitating adjustment. (4) 'Pursuit of transplantation' included equating this form of treatment with restoring normality, alongside cultural factors limiting hopefulness for receiving an organ. CONCLUSIONS: In general, the experiences of South Asian patients receiving HD were not unique to this ethnic group. We did find distinct issues in relation to interactions with healthcare professionals, views on access to transplantation and the importance of family support networks. The study provides useful insights which may help enhance culturally tailored renal care.Peer reviewe

Coral reef species assemblages are associated with ambient soundscapes

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Inter-Research for personal use, not for redistribution. The definitive version was published in Marine Ecology Progress Series 533 (2015): 93-107, doi:10.3354/meps11382.Coral reefs provide a wide array of ecosystem services and harbor some of the highest levels of biodiversity on the planet, but many reefs are in decline worldwide. Tracking changes is necessary for effective resource management. Biological sounds have been suggested as a means to quantify ecosystem health and biodiversity, but this requires an understanding of natural bioacoustic variability and relationships to the taxa present. This investigation sought to characterize spatial and temporal variation in biological sound production within and among reefs that varied in their benthic and fish diversity. Multiple acoustic recorders were deployed for intensive 24-hour periods and longer term (~4-month) duty-cycled deployments on three reefs that varied in coral cover and fish density. Short-term results suggest that while there were statistically significant acoustic differences among recorders on a given reef, these differences were relatively small, indicating that a single sensor may be suitable for acoustic characterization of reefs. Analyses of sounds recorded over ~4 months indicated that the strength of diel trends in a low frequency fish band (100-1000 Hz) was correlated with coral cover and fish density but the strength of high-frequency snapping-shrimp (2-20 kHz) trends was not, suggesting that low-frequency recordings may be better indicators of the species assemblages present. Power spectra varied within reefs over the deployment periods, underscoring the need for long-duration recordings to characterize these trends. These findings suggest that, in spite of considerable spatial and temporal variability within reef soundscapes, diel trends in low-frequency sound production correlate with reef species assemblages.This research was funded by the Mitsubishi Corporation Foundation for the Americas and WHOI’s Access to the Sea program

Yes, The Government Should Tax Soft Drinks: Findings from a Citizens’ Jury in Australia

Taxation has been suggested as a possible preventive strategy to address the serious public health concern of childhood obesity. Understanding the public’s viewpoint on the potential role of taxation is vital to inform policy decisions if they are to be acceptable to the wider community. A Citizens’ Jury is a deliberative method for engaging the public in decision making and can assist in setting policy agendas. A Citizens’ Jury was conducted in Brisbane, Australia in May 2013 to answer the question: Is taxation on food and drinks an acceptable strategy to the public in order to reduce rates of childhood obesity? Citizens were randomly selected from the electoral roll and invited to participate. Thirteen members were purposively sampled from those expressing interest to broadly reflect the diversity of the Australian public. Over two days, participants were presented with evidence on the topic by experts, were able to question witnesses and deliberate on the evidence. The jurors unanimously supported taxation on sugar-sweetened drinks but generally did not support taxation on processed meats, snack foods and foods eaten/ purchased outside the home. They also supported taxation on snack foods on the condition that traffic light labelling was also introduced. Though they were not specifically asked to deliberate strategies outside of taxation, the jurors strongly recommended more nutritional information on all food packaging using the traffic light and teaspoon labelling systems for sugar, salt and fat content. The Citizens’ Jury suggests that the general public may support taxation on sugar-sweetened drinks to reduce rates of obesity in children. Regulatory reforms of taxation on sugar-sweetened drinks and improved labelling of nutritional information on product packaging were strongly supported by all members of the jury. These reforms should be considered by governments to prevent childhood obesity and the future burden on society from the consequences of obesity

Association between protein-bound uremic toxins and asymptomatic cardiac dysfunction in patients with chronic kidney disease

Although the relationship between protein-bound uremic toxins (PBUTs) and cardiac structure and cardiac mortality in chronic kidney disease (CKD) has been studied in the past, the association between cardiac dysfunction and PBUTs has not yet been studied. We therefore evaluated the association between impaired peak cardiac performance and the serum free and total concentrations of potentially cardiotoxic PBUTs. In a cross-sectional study of 56 male CKD patients (stages 2⁻5 (pre-dialysis)) who were asymptomatic with no known cardiac diseases or diabetes we measured peak cardiac power (CPOmax), aerobic exercise capacity (VO2max), and echocardiographic parameters of cardiac morphology and evaluated their association with PBUTs. The serum total and free concentrations of indoxyl sulfate (IXS), p-cresyl sulfate (PCS), p-cresyl glucuronide, indole acetic acid, and hippuric acid showed significant negative correlation with CPOmax and VO2max. IXS and PCS were independently associated with CPOmax and VO2max even after controlling for eGFR. No correlation between left ventricular mass index (LVMI) and PBUTs was seen. The present study for the first time has demonstrated the association between subclinical cardiac dysfunction in CKD and serum levels of a panel of PBUTs. Further studies are required to evaluate the mechanism of cardiotoxicity of the individual uremic toxins

Reflect and Redefine: Deans’ Perspectives on the Positioning of IS within the Business School

Over the 12 years since the glory days of the dot com and Y2K phenomena at the turn of the last century, IS departments at many colleges and schools of business have suffered significant declines in student enrolments, elimination from core curricula, reduced faculty numbers, and overall a weakened strategic positioning within the business school. Recent AACSB faculty hiring and salary reports indicate that “CIS” is the only discipline which has seen an overall decline in faculty hiring over the past 10 years, in contrast with significant growth in all other disciplines. Many IS departments have been merged with other disciplines, or closed entirely. In contrast, however, a number of IS departments have continued to enjoy significant growth and success. This panel of five current/recent business school deans and members of the IS community will offer their perspectives on the strategic positioning of IS within the business school, and share their recommendations on what IS departments need to do to strengthen their positioning within the business school across the domains of teaching, research and relationships with the broader academic and business communities

An injectable bone marrow-like scaffold enhances T cell immunity after hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for multiple disorders, but deficiency and dysregulation of T cells limit its utility. Here we report a biomaterial-based scaffold that mimics features of T cell lymphopoiesis in the bone marrow. The bone marrow cryogel (BMC) releases bone morphogenetic protein-2 to recruit stromal cells and presents the Notch ligand Delta-like ligand-4 to facilitate T cell lineage specification of mouse and human hematopoietic progenitor cells. BMCs subcutaneously injected in mice at the time of HSCT enhanced T cell progenitor seeding of the thymus, T cell neogenesis and diversification of the T cell receptor repertoire. Peripheral T cell reconstitution increased ~6-fold in mouse HSCT and ~2-fold in human xenogeneic HSCT. Furthermore, BMCs promoted donor CD4+ regulatory T cell generation and improved survival after allogeneic HSCT. In comparison to adoptive transfer of T cell progenitors, BMCs increased donor chimerism, T cell generation and antigen-specific T cell responses to vaccination. BMCs may provide an off-the-shelf approach for enhancing T cell regeneration and mitigating graft-versus-host disease in HSCT

A novel AhR ligand, 2AI, protects the retina from environmental stress.

Various retinal degenerative diseases including dry and neovascular age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy are associated with the degeneration of the retinal pigmented epithelial (RPE) layer of the retina. This consequently results in the death of rod and cone photoreceptors that they support, structurally and functionally leading to legal or complete blindness. Therefore, developing therapeutic strategies to preserve cellular homeostasis in the RPE would be a favorable asset in the clinic. The aryl hydrocarbon receptor (AhR) is a conserved, environmental ligand-dependent, per ARNT-sim (PAS) domain containing bHLH transcription factor that mediates adaptive response to stress via its downstream transcriptional targets. Using in silico, in vitro and in vivo assays, we identified 2,2'-aminophenyl indole (2AI) as a potent synthetic ligand of AhR that protects RPE cells in vitro from lipid peroxidation cytotoxicity mediated by 4-hydroxynonenal (4HNE) as well as the retina in vivo from light-damage. Additionally, metabolic characterization of this molecule by LC-MS suggests that 2AI alters the lipid metabolism of RPE cells, enhancing the intracellular levels of palmitoleic acid. Finally, we show that, as a downstream effector of 2AI-mediated AhR activation, palmitoleic acid protects RPE cells from 4HNE-mediated stress, and light mediated retinal degeneration in mice

A Rubbish Idea: The material dump, and casting trash talk in a new light

Inspired by the trash-art creations of artists such as Tim Noble and Sue Webster, this creative article-assemblage was gathered together over several months by the UNNC Litter Lovers collective. The aleatoric article attempts to provocatively explore alternative ways of thinking about (or with) trash, modern life and recycling. The article is formed by found, chanced upon, and recycled fragments of used cultural material, at times united by original-organic discussions and catalytic ideas, but ultimately demands the intellectual light of the reader to cast the concepts into relief. The collective utilises form and content to generate new ways of seeing and thinking about waste and rubbish, and like the actual trash heaps and trash-art that inspired this work, they attempt to show how matter itself and (used) material is not inert and passive but rather vibrant, expressive and alive: boasting productive powers and forces capable of bringing about unforeseen reactions and new forms of synthesis. The article is designed to ignite new processes within, between, across and ‘below’ the chaotically assembled fragments. The piece is in part motivated by a drive to ethically recycle in an inspiring and creative way, and be part of new things emerging out of the old. This alternative intellectual happening is also in part designed to help people ‘clean’ their collective conscience and learn to 'love rubbish.' We hope that this is in part achieved by de-centering the human, and foregrounding a polysemous concept of the material dump that forces readers to reinterrogate everyday (non-thought) notions of waste, nature, (human) resources, thought and art.Additional co-author: the UNNC Litter Lovers (a creative academic collective