Expression profiling and Ingenuity biological function analyses of interleukin-6- versus nerve growth factor-stimulated PC12 cells

The major goal of the study was to compare the genetic programs utilized by the neuropoietic cytokine Interleukin-6 (IL-6) and the neurotrophin (NT) Nerve Growth Factor (NGF) for neuronal differentiation

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Suppression by cyclosporin A of interleukin 1β-induced expression of group II phospholipase A(2) in rat renal mesangial cells

1. We investigated whether cyclosporin A, a potent immunosuppressive drug, affects group II phospholipase A(2) (PLA(2); EC 3.1.1.4) induction in rat renal mesangial cells. 2. Previously we showed that the expression of group II PLA(2) in rat renal mesangial cells is triggered by exposure of the cells to inflammatory cytokines such as interleukin 1β (IL-1β) or tumour necrosis factor α and agents that elevate cellular levels of cyclic AMP. Treatment of mesangial cells with IL-1β for 24 h induced PLA(2) activity secreted into cell culture supernatants by about 16 fold. Incubation of mesangial cells with cyclosporin A inhibited IL-1β-induced PLA(2) section in a dose-dependent fashion, with an IC(50) value of 4.3 μM. Cyclosporin A did not directly inhibit enzymatic activity of PLA(2). 3. Immunoprecipitation of radioactively labelled PLA(2) protein from mesangial cell supernatants revealed that the inhibition of PLA(2) activity is due to a suppression of PLA(2) protein levels. This effect was preceded by a reduction of PLA(2) mRNA steady state levels, as demonstrated by Northern blot analyses of total cellular RNA isolated from stimulated mesangial cells. 4. In order to evaluate whether cyclosporin A would affect the transcriptional activity of the PLA(2) gene, we performed nuclear run on transcription experiments and provided evidence that the transcription rate of the PLA(2) gene is reduced by cyclosporin A. 5. Previously we found that the nuclear transcription factor κB (NFκB) is an essential component of the IL-1β-dependent upregulation of PLA(2) gene transcription. By electrophoretic mobility shift analysis, we demonstrated that cyclosporin A diminishes the formation of NFκB DNA-binding complexes, thus suggesting that this transcription factor is a target for cyclosporin A-mediated repression of PLA(2) gene transcription. 6. The data presented in this study strongly suggest that the cellular mechanism involved in the IL1β - dependent transcriptional upregulation of the PLA(2) gene in mesangial cells is a target for the action of cyclosporin A