Human Tubular Epithelial Cells and T-cell Alloreactivity

__Abstract__ Kidney transplantation is the treatment of choice for patients with end-stage renal disease. The first successful transplantation was performed in 1954 and acceptable renal allograft survival was achieved after introduction of azathioporine in combination with high dose of corticosteroids in the mid sixties of the 20th century. Introduction of the immunosuppressant calcineurin inhibitor (CNI) cyclosporin A and later on tacrolimus significantly improved the outcome of kidney graft survival. Tacrolimus compared to cyclosporin diminished the acute rejection rate by 31% during the first year after transplantation, and this percentage was even more reduced using anti-CD25 mAb as induction treatment [5]. This success have shifted the problem of transplantation from short term graft survival to how to improve the long term graft survival. The 5-year allograft survival rate in the Netherlands is 83% for deceased donor kidneys and 92% for living donor kidney transplants (Nederlandse Transplantatie Stichting, 12th August 2013). In contrast, the overall European 5-year graft survival is 77% and the USA 5-year graft survival is even worse, representing only 71% graft survival

Ammonia Concentrations and Emissions in Livestock Production Facilities: Guidelines and Limits in the USA and UK

There is much information about the concentrations and emissions of ammonia in livestock production facilities in Europe and North America; examples of best and worst practice have been identified in terms of building design and environmental management. Numerically, cattle are the largest source of ammonia emissions, while the ammonia concentration in swine and poultry buildings is much higher than in cattle sheds. In this paper, we review the grounds for concern over ammonia and question whether current guidelines and limits are sufficient to protect farmers, livestock and the environment. Firstly, epidemiological studies of worker health have shown that swine, and to a lesser extent, poultry workers experience occupational respiratory disease in which chronic ammonia exposure may play a part: current occupational exposure limits for ammonia are probably too high and should be revised downwards. Secondly, the scientific evidence that ammonia exposure affects animal health and performance is less convincing - though this is contrary to the empirical wisdom of veterinarians and farmers - and the guidelines are correspondingly unclear. A new guideline is provided from preference studies that show that pigs and chickens avoid ammonia concentrations above 10 ppm. Overall, only tentative guidelines for ammonia concentration can be proposed on the grounds of animal health, performance and welfare. Finally, as a result of international protocols, e.g. the UNECE convention on the long-range transport of air pollutants, individual countries are now expected to limit their ammonia emissions at a national level. This intention has not (yet) been translated into a specific limit on emission for individual farms. In the USA, but not UK, guidelines have also been suggested for ammonia concentration at the property line of animal feeding facilities

Drinking in social groups. Does 'groupdrink' provide safety in numbers when deciding about risk?

AimsTo investigate the impact of alcohol consumption on risk decisions taken both individually and while part of a four- to six-person ad-hoc group.DesignA 2 (alcohol: consuming versus not consuming alcohol) x 2 (decision: individual, group) mixed-model design; decision was a repeated measure. The dependent variable was risk preference, measured using choice dilemmas.SettingOpportunity sampling in campus bars and a music event at a campus-based university in the United Kingdom.ParticipantsA total of 101 individuals were recruited from groups of four to six people who either were or were not consuming alcohol.MeasurementsParticipants privately opted for a level of risk in response to a choice dilemma and then, as a group, responded to a second choice dilemma. The choice dilemmas asked participants the level of accident risk at which they would recommend someone could drive while intoxicated.FindingsFive three-level multi-level models were specified in the software program HLM 7. Decisions made in groups were less risky than those made individually (B = -0.73, P < 0.001). Individual alcohol consumers opted for higher risk than non-consumers (B = 1.27, P = 0.025). A significant alcohol?×?decision interaction (B = -2.79, P = 0.001) showed that individual consumers privately opted for higher risk than non-consumers, whereas risk judgements made in groups of either consumers or non-consumers were lower. Decisions made by groups of consumers were less risky than those made by groups of non-consumers (B = 1.23, P < 0.001).ConclusionsModerate alcohol consumption appears to produce a propensity among individuals towards increased risk-taking in deciding to drive while intoxicated, which can be mitigated by group monitoring processes within small (four- to six-person) groups

Higher levels of CO2 during late incubation alter the hatch time of chicken embryos

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The lethal response to Cdk1 inhibition depends on sister chromatid alignment errors generated by KIF4 and isoform 1 of PRC1

Cyclin-dependent kinase 1 (Cdk1) is absolutely essential for cell division. Complete ablation of Cdk1 precludes the entry of G2 phase cells into mitosis, and is early embryonic lethal in mice. Dampening Cdk1 activation, by reducing gene expression or upon treatment with cell-permeable Cdk1 inhibitors, is also detrimental for proliferating cells, but has been associated with defects in mitotic progression, and the formation of aneuploid daughter cells. Here, we used a large-scale RNAi screen to identify the human genes that critically determine the cellular toxicity of Cdk1 inhibition. We show that Cdk1 inhibition leads to fatal sister chromatid alignment errors and mitotic arrest in the spindle checkpoint. These problems start early in mitosis and are alleviated by depletion of isoform 1 of PRC1 (PRC1-1), by gene ablation of its binding partner KIF4, or by abrogation of KIF4 motor activity. Our results show that, normally, Cdk1 activity must rise above the level required for mitotic entry. This prevents KIF4-dependent PRC1-1 translocation to astral microtubule tips and safeguards proper chromosome congression. We conclude that cell death in response to Cdk1 inhibitors directly relates to chromosome alignment defects generated by insufficient repression of PRC1-1 and KIF4 during prometaphase

Tolerance of Atmospheric Ammonia by Laboratory Mice

A novel preference chamber with four inter-connected compartments was designed and built to test the tolerance of atmospheric ammonia by laboratory mice. The preference chamber incorporated a novel tracking system using an infra-red sensor at each end of each tunnel, which monitored all journeys through the tunnels and their direction. An experiment was successfully undertaken with four batches, each of four mice. Each batch was housed in the chamber for 4 days and given the choice between ammonia concentrations of nominally 0, 25, 50 and 100 ppm after initial familiarization. The results showed that there were two motivations acting on mouse behavior. The mice made extensive use of the whole chamber once they had been trained to use the tunnels, at least 2000 movements between compartments for each group over 48 h. The mice clearly preferred to be in the upper two compartments of the top tier of the chamber rather than in the lower compartments. The mice did not exhibit a clear preference for or aversion to ammonia, which implies that their short- term tolerance of ammonia at potentially noxious concentrations may not be in their long-term interest