start of the infusion and at hourly intervals. Blood spots and urine AT 7867 filter papers were air-dried and stored at room temperature until analysis. Glucose and paracetamol-glucuronic acid were extracted from blood spot and urine filter papers, respectively, derivatised, and measured by GC-MS, essentially as described previously. The fractional isotopomer distribution according to GC-MS was corrected for fractional distribution due to the natural abundance of 13C by multiple linear regression to obtain the excess mole fraction of mass isotopomers M0-M6 due to incorporation of infused labeled carbohydrates. From isotope dilution and infusion rates, the flux rates of the following metabolic pathways could be calculated: 1) de novo synthesis of G6P, 2) glucokinase, 3) glucose-6phosphatase, 4) glycogenolysis, and 5) glycogen synthesis. The method of calculation was performed as described before. Mouse CIA model The experiment was essentially performed as described previously. At day 0 mice were immunized at the base of the tail with 100 mg bovine type II collagen in Complete Freund’s Adjuvant enriched with 2 mg/ml Mycobacterium tuberculosis H37RA. At day 21 mice were boosted by an i.p. injection of 100 mg bovine type II collagen dissolved in saline. After disease onset, mice with an arthritis score ranging from 0.25 to 1.25 were divided into matched groups. Animals were orally treated once daily with vehicle or compound for 21 to 23 days. The clinical severity of arthritis was graded and scored as described. To assess the effects of treatments, the area under the curve of arthritis score was used. One day after the final treatment animals were sacrificed and the knee and ankle joints were imaged using a Faxitron X-ray, Modl MX-20 digital imaging system and analysed 16699066 using Specimen. The bone destruction was scored on a scale of 05 as described previously. The cumulative scores of 2 joints were used as radiological scores. From H&H-stained sections, articular cartilage destruction and inflammatory infiltrate in the right knee joint were scored on a scale of 03. The whole study was carried out in a blinded fashion. Statistical analysis was performed using one-way ANOVA. Micro array on muscle tissue mRNA from mice Two and a half hours after the final treatment animals were sacrificed and samples were collected from the thigh muscle. Samples were stored immediately at 280uC and send to Covance for RNA extraction and subsequent analysis of gene expression on the Mouse Genome 430A 2.0 array. For statistical analysis, the. CEL files obtained after hybridization were analyzed with the R and the BioConductor software package as described previously. Normalization was done using gcrma. Building of the experimental design and calculation of the ratios was done with the limma package. Differentially expressed probe sets were selected on basis Supporting Information Org 214007-0, a SGRM with Improved TI It has been shown that axonal transport of mitochondria ensures proper neuronal function. Aberrant mitochondrial trafficking has been linked to a number of neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Lou Gehrig’s disease. Although several signals have been found to modulate mitochondrial trafficking in neurons, the precise roles of these signals have not been fully characterized. Previously, we identified 15647369 serotonin as an extracellular signal that can promote axonal mitochondrial movement in culture