To study cross-presentation, the LyUV-treated LCMV-infected HEK cells (5×105 cells/well) were prepared for the assay as described previously 7. Where indicated, inhibitors were added to the APC 45 min before adding the ADC and maintained during the incubation periods. In certain experiments, RNase treatment of ADC was performed. ADC were lysed and treated with 10 μg/mL of RNase for 20 min at RT followed by two washing steps before UVB treatment. BMN 673 solubility dmso To test for cross-priming, B6 mice were injected i.p. with HEK293 (negative control) or LCMV-infected

HEK cells (7×106) treated as LyUV. After 7 days, splenocytes were obtained and stained with 0.5–1 μg of PE-labeled tetramers 36 as described previously 37. Alternatively, epitope-specific CTL were expanded in vitro before performing ICS assays as described previously 7. For ex vivo antigen presentation, peritoneal cells were collected 8 h later using PBS (10 mL). Positive selection for CD11c+ from peritoneal exudates was carried out with a mouse CD11c+ immunomagnetic selection kit from EasySep® (Vancouver, MG 132 BC, Canada). CD11c+ and CD11c− cells were coincubated

with peptide-specific CTL at a ratio of 3:1 for 3 h in the presence of BFA (10 μg/mL) and ICS was performed as described above. Statistics were performed using the paired, two-tailed t-tests science and differences in results between treatment conditions were deemed significant when p<0.05. The authors thank Dr. Groettrup, Dr. van den Broek, Dr. Zinkernagel, Dr. Rock and the NIH tetramer facility for providing reagents, and grants from NSERC to S. B., CIHR to A. L., and LG Fellowship to A. A. Conflict of interest: The authors declare no financial or commercial conflict of interest. "
“Although notable progress has been made in the therapeutic management of patients with chronic kidney

disease in both conservative and renal replacement treatments (dialysis and transplantation), the occurrence of medication-related problems (lack of efficacy, adverse drug reactions) still represents a key clinical issue. Recent evidence suggests that adverse drug reactions are major causes of death and hospital admission in Europe and the United States. The reasons for these conditions are represented by environmental/non-genetic and genetic factors responsible for the great inter-patient variability in drugs metabolism, disposition and therapeutic targets. Over the years several genetic settings have been linked, using pharmacogenetic approaches, to the effects and toxicity of many agents used in clinical nephrology. However, these strategies, analysing single gene or candidate pathways, do not represent the gold standard, being the overall pharmacological effects of medications and not typically monogenic traits.