Shah R

References (6)

Title : CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced obesity and glucose intolerance - Brown_2010_J.Lipid.Res_51_3306
Author(s) : Brown JM , Betters JL , Lord C , Ma Y , Han X , Yang K , Alger HM , Melchior J , Sawyer J , Shah R , Wilson MD , Liu X , Graham MJ , Lee R , Crooke R , Shulman GI , Xue B , Shi H , Yu L
Ref : J Lipid Res , 51 :3306 , 2010
Abstract : Mutations of Comparative Gene Identification-58 (CGI-58) in humans cause triglyceride (TG) accumulation in multiple tissues. Mice genetically lacking CGI-58 die shortly after birth due to a skin barrier defect. To study the role of CGI-58 in integrated lipid and energy metabolism, we utilized antisense oligonucleotides (ASOs) to inhibit CGI-58 expression in adult mice. Treatment with two distinct CGI-58-targeting ASOs resulted in approximately 80-95% knockdown of CGI-58 protein expression in both liver and white adipose tissue. In chow-fed mice, ASO-mediated depletion of CGI-58 did not alter weight gain, plasma TG, or plasma glucose, yet raised hepatic TG levels approximately 4-fold. When challenged with a high-fat diet (HFD), CGI-58 ASO-treated mice were protected against diet-induced obesity, but their hepatic contents of TG, diacylglycerols, and ceramides were all elevated, and intriguingly, their hepatic phosphatidylglycerol content was increased by 10-fold. These hepatic lipid alterations were associated with significant decreases in hepatic TG hydrolase activity, hepatic lipoprotein-TG secretion, and plasma concentrations of ketones, nonesterified fatty acids, and insulin. Additionally, HFD-fed CGI-58 ASO-treated mice were more glucose tolerant and insulin sensitive. Collectively, this work demonstrates that CGI-58 plays a critical role in limiting hepatic steatosis and maintaining hepatic glycerophospholipid homeostasis and has unmasked an unexpected role for CGI-58 in promoting HFD-induced obesity and insulin resistance.
ESTHER : Brown_2010_J.Lipid.Res_51_3306
PubMedSearch : Brown_2010_J.Lipid.Res_51_3306
PubMedID: 20802159
Gene_locus related to this paper: human-ABHD5 , mouse-abhd5

Title : An albumin-butyrylcholinesterase for cocaine toxicity and addiction: catalytic and pharmacokinetic properties - Gao_2008_Chem.Biol.Interact_175_83
Author(s) : Gao Y , Lafleur D , Shah R , Zhao Q , Singh M , Brimijoin S
Ref : Chemico-Biological Interactions , 175 :83 , 2008
Abstract : Butyrylcholinesterase (BChE, EC 3.1.1.8) is important in human cocaine metabolism despite its limited ability to hydrolyze this drug. Efforts to improve the catalytic efficiency of this enzyme have led to a quadruple mutant cocaine hydrolase, "CocH", that in animal models of addiction appears promising for treatment of overdose and relapse. We incorporated the CocH mutations into a BChE-albumin fusion protein, "Albu-CocH", and evaluated the pharmacokinetics of the enzyme after i.v. injection in rats. As assessed from the time course of cocaine hydrolyzing activity in plasma, Albu-CocH redistributed into extracellular fluid (16% of estimated total body water) with a t(1/2) of 0.66h and it underwent elimination with a t(1/2) of 8h. These results indicate that the enzyme has ample stability for short-term applications and may be suitable for longer-term treatment as well. Present data also confirm the markedly enhanced power of Albu-CocH for cocaine hydrolysis and they support the view that Albu-CocH might prove valuable in treating phenomena associated with cocaine abuse.
ESTHER : Gao_2008_Chem.Biol.Interact_175_83
PubMedSearch : Gao_2008_Chem.Biol.Interact_175_83
PubMedID: 18514640

Title : A cocaine hydrolase engineered from human butyrylcholinesterase selectively blocks cocaine toxicity and reinstatement of drug seeking in rats - Brimijoin_2008_Neuropsychopharmacology_33_2715
Author(s) : Brimijoin S , Gao Y , Anker JJ , Gliddon LA , Lafleur D , Shah R , Zhao Q , Singh M , Carroll ME
Ref : Neuropsychopharmacology , 33 :2715 , 2008
Abstract : Successive rational mutations of human butyrylcholinesterase (BChE) followed by fusion to human serum albumin have yielded an efficient hydrolase that offers realistic options for therapy of cocaine overdose and abuse. This albumin-BChE prevented seizures in rats given a normally lethal cocaine injection (100 mg/kg, i.p.), lowered brain cocaine levels even when administered after the drug, and provided rescue after convulsions commenced. Moreover, it selectively blocked cocaine-induced reinstatement of drug seeking in rats that had previously self-administered cocaine. The enzyme treatment was well tolerated and may be worth exploring for clinical application in humans.
ESTHER : Brimijoin_2008_Neuropsychopharmacology_33_2715
PubMedSearch : Brimijoin_2008_Neuropsychopharmacology_33_2715
PubMedID: 18199998

Title : Cholinesterase inhibitors ameliorate behavioral deficits induced by MK-801 in mice - Csernansky_2005_Neuropsychopharmacology_30_2135
Author(s) : Csernansky JG , Martin M , Shah R , Bertchume A , Colvin J , Dong H
Ref : Neuropsychopharmacology , 30 :2135 , 2005
Abstract : Enhancing cholinergic function has been suggested as a possible strategy for ameliorating the cognitive deficits of schizophrenia. The purpose of this study was to examine the effects of acetylcholinesterase (AChE) inhibitors in mice treated with the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, which has been suggested as an animal model of the cognitive deficits of schizophrenia. Three separate experiments were conducted to test the effects of physostigmine, donepezil, or galantamine on deficits in learning and memory induced by MK-801. In each experiment, MK-801 (0.05 or 0.10 mg/kg) or saline was administered i.p. 20 min prior to behavioral testing over a total of 12 days. At 30 min prior to administration of MK-801 or saline, one of three doses of the AChE inhibitor (ie physostigmine-0.03, 0.10, or 0.30 mg/kg; donepezil-0.10, 0.30, or 1.00 mg/kg; or galantamine-0.25, 0.50, or 1.00 mg/kg) or saline was administered s.c. Behavioral testing was performed in all experimental animals using the following sequence: (1) spatial reversal learning, (2) locomotion, (3) fear conditioning, and (4) shock sensitivity. Both doses of MK-801 produced impairments in spatial reversal learning and in contextual and cued memory, as well as hyperlocomotion. Physostigmine and donepezil, but not galantamine, ameliorated MK-801-induced deficits in spatial reversal learning and in contextual and cued memory in a dose-dependent manner. Also, physostigmine, but not donepezil or galantamine, reversed MK-801-induced hyperlocomotion. Galantamine, but not physostigmine or donepezil, altered shock sensitivity. These results suggest that AChE inhibitors may differ in their capacity to ameliorate learning and memory deficits produced by MK-801 in mice, which may have relevance for the cognitive effects of cholinomimetic drugs in patients with schizophrenia.
ESTHER : Csernansky_2005_Neuropsychopharmacology_30_2135
PubMedSearch : Csernansky_2005_Neuropsychopharmacology_30_2135
PubMedID: 15956997

Title : Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana - Tabata_2000_Nature_408_823
Author(s) : Tabata S , Kaneko T , Nakamura Y , Kotani H , Kato T , Asamizu E , Miyajima N , Sasamoto S , Kimura T , Hosouchi T , Kawashima K , Kohara M , Matsumoto M , Matsuno A , Muraki A , Nakayama S , Nakazaki N , Naruo K , Okumura S , Shinpo S , Takeuchi C , Wada T , Watanabe A , Yamada M , Yasuda M , Sato S , de la Bastide M , Huang E , Spiegel L , Gnoj L , O'Shaughnessy A , Preston R , Habermann K , Murray J , Johnson D , Rohlfing T , Nelson J , Stoneking T , Pepin K , Spieth J , Sekhon M , Armstrong J , Becker M , Belter E , Cordum H , Cordes M , Courtney L , Courtney W , Dante M , Du H , Edwards J , Fryman J , Haakensen B , Lamar E , Latreille P , Leonard S , Meyer R , Mulvaney E , Ozersky P , Riley A , Strowmatt C , Wagner-McPherson C , Wollam A , Yoakum M , Bell M , Dedhia N , Parnell L , Shah R , Rodriguez M , See LH , Vil D , Baker J , Kirchoff K , Toth K , King L , Bahret A , Miller B , Marra M , Martienssen R , McCombie WR , Wilson RK , Murphy G , Bancroft I , Volckaert G , Wambutt R , Dusterhoft A , Stiekema W , Pohl T , Entian KD , Terryn N , Hartley N , Bent E , Johnson S , Langham SA , McCullagh B , Robben J , Grymonprez B , Zimmermann W , Ramsperger U , Wedler H , Balke K , Wedler E , Peters S , van Staveren M , Dirkse W , Mooijman P , Lankhorst RK , Weitzenegger T , Bothe G , Rose M , Hauf J , Berneiser S , Hempel S , Feldpausch M , Lamberth S , Villarroel R , Gielen J , Ardiles W , Bents O , Lemcke K , Kolesov G , Mayer K , Rudd S , Schoof H , Schueller C , Zaccaria P , Mewes HW , Bevan M , Fransz P
Ref : Nature , 408 :823 , 2000
Abstract : The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.
ESTHER : Tabata_2000_Nature_408_823
PubMedSearch : Tabata_2000_Nature_408_823
PubMedID: 11130714
Gene_locus related to this paper: arath-At5g11650 , arath-At5g16120 , arath-at5g18630 , arath-AT5G20520 , arath-At5g21950 , arath-AT5G27320 , arath-CXE15 , arath-F1N13.220 , arath-F14F8.240 , arath-q3e9e4 , arath-q8lae9 , arath-Q8LFB7 , arath-q9ffg7 , arath-q9fij5 , arath-Q9LVU7 , arath-q66gm8 , arath-SCPL34 , arath-B9DFR3 , arath-a0a1p8bcz0

Title : Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana - Mayer_1999_Nature_402_769
Author(s) : Mayer K , Schuller C , Wambutt R , Murphy G , Volckaert G , Pohl T , Dusterhoft A , Stiekema W , Entian KD , Terryn N , Harris B , Ansorge W , Brandt P , Grivell L , Rieger M , Weichselgartner M , de Simone V , Obermaier B , Mache R , Muller M , Kreis M , Delseny M , Puigdomenech P , Watson M , Schmidtheini T , Reichert B , Portatelle D , Perez-Alonso M , Boutry M , Bancroft I , Vos P , Hoheisel J , Zimmermann W , Wedler H , Ridley P , Langham SA , McCullagh B , Bilham L , Robben J , Van der Schueren J , Grymonprez B , Chuang YJ , Vandenbussche F , Braeken M , Weltjens I , Voet M , Bastiaens I , Aert R , Defoor E , Weitzenegger T , Bothe G , Ramsperger U , Hilbert H , Braun M , Holzer E , Brandt A , Peters S , van Staveren M , Dirske W , Mooijman P , Klein Lankhorst R , Rose M , Hauf J , Kotter P , Berneiser S , Hempel S , Feldpausch M , Lamberth S , Van den Daele H , De Keyser A , Buysshaert C , Gielen J , Villarroel R , De Clercq R , van Montagu M , Rogers J , Cronin A , Quail M , Bray-Allen S , Clark L , Doggett J , Hall S , Kay M , Lennard N , McLay K , Mayes R , Pettett A , Rajandream MA , Lyne M , Benes V , Rechmann S , Borkova D , Blocker H , Scharfe M , Grimm M , Lohnert TH , Dose S , de Haan M , Maarse A , Schafer M , Muller-Auer S , Gabel C , Fuchs M , Fartmann B , Granderath K , Dauner D , Herzl A , Neumann S , Argiriou A , Vitale D , Liguori R , Piravandi E , Massenet O , Quigley F , Clabauld G , Mundlein A , Felber R , Schnabl S , Hiller R , Schmidt W , Lecharny A , Aubourg S , Chefdor F , Cooke R , Berger C , Montfort A , Casacuberta E , Gibbons T , Weber N , Vandenbol M , Bargues M , Terol J , Torres A , Perez-Perez A , Purnelle B , Bent E , Johnson S , Tacon D , Jesse T , Heijnen L , Schwarz S , Scholler P , Heber S , Francs P , Bielke C , Frishman D , Haase D , Lemcke K , Mewes HW , Stocker S , Zaccaria P , Bevan M , Wilson RK , de la Bastide M , Habermann K , Parnell L , Dedhia N , Gnoj L , Schutz K , Huang E , Spiegel L , Sehkon M , Murray J , Sheet P , Cordes M , Abu-Threideh J , Stoneking T , Kalicki J , Graves T , Harmon G , Edwards J , Latreille P , Courtney L , Cloud J , Abbott A , Scott K , Johnson D , Minx P , Bentley D , Fulton B , Miller N , Greco T , Kemp K , Kramer J , Fulton L , Mardis E , Dante M , Pepin K , Hillier L , Nelson J , Spieth J , Ryan E , Andrews S , Geisel C , Layman D , Du H , Ali J , Berghoff A , Jones K , Drone K , Cotton M , Joshu C , Antonoiu B , Zidanic M , Strong C , Sun H , Lamar B , Yordan C , Ma P , Zhong J , Preston R , Vil D , Shekher M , Matero A , Shah R , Swaby IK , O'Shaughnessy A , Rodriguez M , Hoffmann J , Till S , Granat S , Shohdy N , Hasegawa A , Hameed A , Lodhi M , Johnson A , Chen E , Marra M , Martienssen R , McCombie WR
Ref : Nature , 402 :769 , 1999
Abstract : The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.
ESTHER : Mayer_1999_Nature_402_769
PubMedSearch : Mayer_1999_Nature_402_769
PubMedID: 10617198
Gene_locus related to this paper: arath-AT4G00500 , arath-AT4G16690 , arath-AT4G17480 , arath-AT4G24380 , arath-AT4g30610 , arath-o65513 , arath-o65713 , arath-LPAAT , arath-f4jt64