Cannabinoid receptor interacting protein suppresses agonist-driven CB1 receptor internalization and regulates receptor replenishment in an agonist-biased manner

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown clones to investigate gene dose effects of CRIP1a on CB1R plasma membrane expression. Results indicate that CP55940 or WIN55212-2 (10 nM, 5 min) reduced cell surface CB1R by a dynamin-and clathrin-dependent process, and this was attenuated by CRIP1a over-expression. CP55940-mediated cell surface CB1R loss was followed by a cycloheximide-sensitive recovery of surface receptors (30120 min), suggesting the requirement for new protein synthesis. In contrast, WIN55212-2-mediated cell surface CB(1)Rs recovered only in CRIP1a knockdown cells. Changes in CRIP1a expression levels did not affect a transient rimonabant (10 nM)mediated increase in cell surface CB(1)Rs, which is postulated to be as a result of rimonabant effects on \u27non-agonist-driven\u27 internalization. These studies demonstrate a novel role for CRIP1a in agonist-driven CB1R cell surface regulation postulated to occur by two mechanisms: 1) attenuating internalization that is agonist-mediated, but not that in the absence of exogenous agonists, and 2) biased agonist-dependent trafficking of de novo synthesized receptor to the cell surface

A Catalog of Very Isolated Galaxies from the SDSS Data Release 1

We present a new catalog of isolated galaxies obtained through an automated systematic search. These 2980 isolated galaxies were found in approximately 2099 sq deg of sky in the Sloan Digital Sky Survey Data Release 1 (SDSS DR1) photometry. The selection algorithm, implementing a variation on the criteria developed by Karachentseva in 1973, proved to be very efficient and fast. This catalog will be useful for studies of the general galaxy characteristics. Here we report on our results.Comment: 67 pages, which includes 14 figures. Accepted for publication by A

Fast Large-Tip-Angle Multidimensional and Parallel RF Pulse Design in MRI

Large-tip-angle multidimensional radio-frequency (RF) pulse design is a difficult problem, due to the nonlinear response of magnetization to applied RF at large tip-angles. In parallel excitation, multidimensional RF pulse design is further complicated by the possibility for transmit field patterns to change between subjects, requiring pulses to be designed rapidly while a subject lies in the scanner. To accelerate pulse design, we introduce a fast version of the optimal control method for large-tip-angle parallel excitation. The new method is based on a novel approach to analytically linearizing the Bloch equation about a large-tip-angle RF pulse, which results in an approximate linear model for the perturbations created by adding a small-tip-angle pulse to a large-tip-angle pulse. The linear model can be evaluated rapidly using nonuniform fast Fourier transforms, and we apply it iteratively to produce a sequence of pulse updates that improve excitation accuracy. We achieve drastic reductions in design time and memory requirements compared to conventional optimal control, while producing pulses of similar accuracy. The new method can also compensate for nonidealities such as main field inhomogeneties.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86004/1/Fessler12.pd

Predictors of surgical site skin infection and clinical outcome at caesarean section in the very severely obese : A retrospective cohort study

Introduction The optimal surgical approach for caesarean section is uncertain in women with very severe obesity (body mass index (BMI) >40kg/m2). We aimed to assess maternal and surgical predictors of surgical site skin infection (SSSI) in very severely obese women and to undertake an exploratory evaluation of clinical outcomes in women with a supra-panniculus transverse compared to an infra-panniculus transverse skin incision. Material and methods Using a retrospective cohort design, case-records were reviewed of very severely obese women with a singleton pregnancy delivered by caesarean between August 2011 and December 2015 (n = 453) in two maternity hospitals in Scotland. Logistic regression analysis was used to determine predictors for SSSI. Outcomes were compared between women who had a supra-panniculus transverse compared to infra-panniculus transverse skin incision. Results Lower maternal age was predictive of SSSI, with current smoking status and longer wound open times being marginally significant. Maternal BMI, suture method and material demonstrated univariate associations with SSSI but were not independent predictors. Women with a supra-panniculus transverse skin incision were older (32.9 (4.4), vs. 30.6 (5.7), p = 0.002), had higher BMI (49.2 (7.1), vs. 43.3 (3.3), pPeer reviewe

Additive angle method for fast large-tip-angle RF pulse design in parallel excitation

Current methods for parallel excitation RF pulse design are based on the small-tip-angle approximation, which provides a computationally efficient means of pulse calculation. In general, pulses designed with those methods are inaccurate when scaled to produce large-tip angles, and methods for large-tipangle pulse design are more computationally demanding. This paper introduces a fast iterative method for large-tip-angle parallel pulse design that is formulated as a small number of Bloch equation simulations and fast small-tip-angle pulse designs, the results of which add to produce large-tip-angle pulses. Simulations and a phantom experiment demonstrate that the method is effective in designingmultidimensional large-tip-angle pulses of high excitation accuracy, compared to pulses designed with small-tip-angle methods. Magn Reson Med 59:779–787, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58569/1/21510_ftp.pd

A newly synthetic chromium complex – chromium(phenylalanine)3 improves insulin responsiveness and reduces whole body glucose tolerance

AbstractLow-molecular-weight organic chromium complexes such as chromium picolinate are often used as dietary supplements to improve insulin sensitivity and to correct dyslipidemia. However, toxicity associated with such chromium compounds has compromised their therapeutic value. The aim of this study was to evaluate the impact of a newly synthesized complex of chromium with phenylalanine, Cr(pa)3 on insulin-signaling and glucose tolerance. Cr(pa)3 was synthesized by chelating chromium(III) with d-phenylalanine ligand in aqueous solution. In mouse 3T3-adipocytes, Cr(pa)3 augmented insulin-stimulated glucose-uptake as assessed by a radioactive-glucose uptake assay. At the molecular level, Cr(pa)3 enhanced insulin-stimulated phosphorylation of Akt in a time- and concentration-dependent manner without altering the phosphorylation of insulin receptor. Oral treatment with Cr(pa)3 (150μg/kg/d, for six weeks) in ob/ob(+/+) obese mice significantly alleviated glucose tolerance compared with untreated obese mice. Unlike chromium picolinate, Cr(pa)3 does not cleave DNA under physiological reducing conditions. Collectively, these data suggest that Cr(pa)3 may represent a novel, less-toxic chromium supplement with potential therapeutic value to improve insulin sensitivity and glycemic control in type II diabetes