The melanocortin 4 receptor: Oligomer formation, interaction sites and functional significance

This study involves the structural and functional properties of the recombinant melanocortin 4 receptor (MC4R) expressed in the HEK-293 cell line. Using co-immuno-purification approaches, the receptor appears to be an oligomer, which can be crosslinked through disulphide bonds involving a native cysteine residue (84) to give a dimeric species. This position is located near the cytosolic region of transmembrane segment 2 and it is suggested that this is an interacting interface between MC4R monomers. Using co-expression of the native protein and a C84A mutant, it appears that the receptor also forms higher order oligomers via alternative interfaces. Interestingly, disulphide crosslink formation does not occur if the receptor is uncoupled from its G-protein, even though the oligomeric state is preserved. This suggests that the conformational changes, which occur on activation, affect the TM2 interface. The pharmacology of the agonist, NDP-MSH, indicates that the MC4R retains high affinity for the ligand in the absence of the G-protein but occupancy for the ligand is increased. The data can be interpreted to suggest that the G-protein exerts a negative allosteric effect on the receptor. Co-expression of one receptor lacking the ability to signal with another, which cannot bind the agonist, restored ligand-dependent activation of the G-protein to situations in which neither receptor on its own could activate the G-protein. Such transactivation suggests meaningful cross talk between the receptor subunits in the oligomeric complex. These studies demonstrate further unique features of the MC4R

Impact of birth weight and gender on early postnatal hypothalamic energy balance regulatory gene expression in the young lamb

Peer reviewedPreprin

A model to map levelised cost of energy for wave energy projects

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.An economic model has been developed which allows the spatial dependence of wave energy levelised cost of energy (LCOE) to be calculated and mapped in graphical information system (GIS) software. Calculation is performed across a domain of points which define hindcast wave data; these data are obtained from wave propagation models like Simulating WAves Nearshore (SWAN). Time series of metocean data are interpolated across a device power matrix, obtaining energy production at every location. Spatial costs are calculated using Dijkstra's algorithm, to find distances between points from which costs are inferred. These include the export cable and operations, the latter also calculated by statistically estimating weather window waiting time. A case study is presented, considering the Scottish Western Isles and using real data from a device developer. Results indicate that, for the small scale device examined, the lowest LCOE hotspots occur in the Minches. This area is relatively sheltered, showing that performance is device specific and does not always correspond to the areas of highest energy resource. Sensitivity studies are performed, examining the effects of cut-in and cut-out significant wave height on LCOE, and month on installation cost. The results show that the impact of these parameters is highly location-specific.The authors wish to thank Albatern Ltd, the industrial partner of the research project, for their funding and support in sponsoring the lead author. In addition, the Energy Technology Institute (ETI) and Research Councils UK Energy Programme who have funded this research through the IDCORE programme (grant number: EP/J500847/1)

Risk factors of ischemic stroke and subsequent outcome in hemodialysis patients

Background and purpose: End stage renal disease (ESRD) requiring hemodialysis (HD) carries up to a 10-fold greater risk of stroke than normal renal function. Knowledge concerning risk factors and management strategies derived from the general population may not be applicable to those with ESRD. We studied a large ESRD population to identify risk factors and outcomes for stroke. Methods: All adult patients receiving HD for ESRD from 01/01/2007 to 31/12/2012 were extracted from the electronic patient record. Variables associated with stroke were identified by survival analysis; demographic, clinical, imaging and dialysis related variables were assessed and case-fatality determined. Follow-up was until 31/12/2013. Results: 1382 patients were identified (mean age 60.5 years, 58.5% male). The prevalence of AF was 21.2% and 59.4% were incident HD patients. 160 (11.6%) experienced a stroke during 3471 patient-years of follow-up (95% ischemic). Stroke incidence was 41.5/1000 patient-years in prevalent and 50.1/1000 patient-years in incident HD patients. Factors associated with stroke on regression analysis were prior stroke, diabetes and age at starting renal replacement therapy. AF was not significantly associated with stroke and warfarin did not affect stroke risk in warfarin treated patients. Fatality was 18.8% at 7, 26.9% at 28 and 56.3% 365 days after stroke.<p></p> Conclusions: Incidence of stroke is high in patients with ESRD on HD with high case-fatality. Incident HD patients had the highest stroke incidence. Many, but not all, important risk factors commonly associated with stroke in the general population were not associated with stroke in patients receiving HD

Does nurses’ health affect their intention to remain in their current position?

© 2016 The Authors. Journal of Nursing Management Published by John Wiley & Sons Ltd Aim: To investigate and describe nurses’ and midwives’ physical health, rates of symptoms and disease, and to determine if these factors contribute to intention to leave. Background: The nursing and midwifery workforce is ageing yet little is known about their physical health or its relationship to intention to leave. Methods: An online survey of health and work-related assessments was distributed through the New South Wales Nurses and Midwives Association and professional contacts. Results: Nurses and midwives (n = 5041) reported good-very good health overall. With 22.2% intending to leave in the next 12 months, older age, better perceived health and job satisfaction, regional residence and not working shifts predicted no intention to leave while breathing problems predicted intention to leave. Conclusions: Study findings flag the importance of health as an influence on intention to leave. Alongside job satisfaction and shift-working, health presents opportunities for workplace initiatives to maintain nurses in the workforce. Implications for nursing management: Educators, managers and policy makers should heed the significant influence of health for retention of staff and consider what strategies may mitigate health risks for this workforce

High brightness solution-processed OLEDs employing linear, small molecule emitters

Two novel linear oligomers that can be solution-processed to form green organic light-emitting diodes (OLEDs) are reported. Each oligomer has a donor-acceptor structure, incorporating a benzothiadiazole core with bifluorene arms attached at the 4- and 7-positions. Further electron donor behaviour is inferred from a terminal triphenylamine unit in Green 2. The resulting solution-processed OLEDs exhibited excellent performance, with a maximum luminance of 20 388 cd m-2 recorded for Green 2