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Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein's biological functions in dopamine-based neurogenesis. [ABSTRACT FROM AUTHOR]

Background: The self-expandable COMPLETE™ stent (Medtronic) has greater elasticity, allowing it to regain its shape after the compression force reduces, and has higher trackability, thus is easier to maneuver through tortuous vessels, whereas the balloon-expandable SCUBA™ stent (Medtronic) has higher radial stiffness and can afford more accurate placement without geographic miss, which is important in aortoiliac bifurcation lesions. To date, there have been no randomized control trials comparing efficacy and safety between the self-expanding stent and balloon-expandable stent in advanced atherosclerotic iliac artery disease.Methods/design: The purpose of our study is to examine primary patency (efficacy) and incidence of stent fracture and geographic miss (safety) between two different major representative stents, the self-expanding nitinol stent (COMPLETE-SE™) and the balloon-expanding cobalt-chromium stent (SCUBA™), in stenotic or occlusive iliac arterial lesions. This trial is designed as a prospective, randomized, multicenter trial to demonstrate a noninferiority of SCUBA™ stent to COMPLETE-SE™ stent following balloon angioplasty in iliac arterial lesions, and a total of 280 patients will be enrolled. The primary end point of this study is the rate of primary patency in the treated segment at 12 months after intervention as determined by catheter angiography, computed tomography angiography, or duplex ultrasound.Discussion: The SENS-ILIAC trial will give powerful insight into whether the stent choice according to deployment mechanics would impact stent patency, geographic miss, or stent fracture in patients undergoing stent implantation in iliac artery lesions.Trial Registration: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT01834495 ), registration date: May 8, 2012. [ABSTRACT FROM AUTHOR]

series of amphiphilic graft copolymers based on polyaspartamide were synthesized by a successive aminolysis reaction of polysuccinimide using 2-diisopropylaminoethyl (DIP) and laurylamine as a pH sensitive and hydrophobic group, respectively. The pH-dependent self-assembly behavior of the aqueous copolymer solution was investigated. Nano-aggregation occurred at a pH in the vicinity of the pKa of the DIP group, which was induced by a hydrophilic-hydrophobic shift of the DIP group in solution. The mean diameter of the nano-aggregate could be modulated by changing the composition of both pendants. The mean diameter of the nanoparticles increased with increasing solution pH from 6.5 to 8. At pH 8, the mean diameter of the nanoparticles increased rapidly at the temperature above 45 °C, probably due to the change in hydrophilic-hydrophobic balance of the pH-sensitive DIP moiety. The dissolution of paclitaxel (PTX) into this amphiphilic nanoparticle was attempted and the pH-dependent release behavior was examined with the stability study of the particle. The results showed significantly faster release of PTX at pH 6.5, which is a tumoral acidic pH, than in a neutral physiological pH. These thermo- and pH-sensitive polyaspartamide derivatives have potential use as a tumor-targeting delivery. [ABSTRACT FROM AUTHOR]