Wells C

References (8)

Title : Design, synthesis and discovery of picomolar selective alpha4beta2 nicotinic acetylcholine receptor ligands - Yenugonda_2013_J.Med.Chem_56_8404
Author(s) : Yenugonda VM , Xiao Y , Levin ED , Rezvani AH , Tran T , Al-Muhtasib N , Sahibzada N , Xie T , Wells C , Slade S , Johnson JE , Dakshanamurthy S , Kong HS , Tomita Y , Liu Y , Paige M , Kellar KJ , Brown ML
Ref : Journal of Medicinal Chemistry , 56 :8404 , 2013
Abstract : Developing novel and selective compounds that desensitize alpha4beta2 nicotinic acetylcholine receptors (nAChRs) could provide new effective treatments for nicotine addiction, as well as other disorders. Here we report a new class of nAChR ligands that display high selectivity and picomolar binding affinity for alpha4beta2 nicotinic receptors. The novel compounds have Ki values in the range of 0.031-0.26 nM and properties that should make them good candidates as drugs acting in the CNS. The selected lead compound 1 (VMY-2-95) binds with high affinity and potently desensitizes alpha4beta2 nAChRs. At a dose of 3 mg/kg, compound 1 significantly reduced rat nicotine self-administration. The overall results support further characterizations of compound 1 and its analogues in preclinical models of nicotine addiction and perhaps other disorders involving nAChRs.
ESTHER : Yenugonda_2013_J.Med.Chem_56_8404
PubMedSearch : Yenugonda_2013_J.Med.Chem_56_8404
PubMedID: 24047231

Title : The high-quality draft genome of peach (Prunus persica) identifies unique patterns of genetic diversity, domestication and genome evolution - Verde_2013_Nat.Genet_45_487
Author(s) : Verde I , Abbott AG , Scalabrin S , Jung S , Shu S , Marroni F , Zhebentyayeva T , Dettori MT , Grimwood J , Cattonaro F , Zuccolo A , Rossini L , Jenkins J , Vendramin E , Meisel LA , Decroocq V , Sosinski B , Prochnik S , Mitros T , Policriti A , Cipriani G , Dondini L , Ficklin S , Goodstein DM , Xuan P , Del Fabbro C , Aramini V , Copetti D , Gonzalez S , Horner DS , Falchi R , Lucas S , Mica E , Maldonado J , Lazzari B , Bielenberg D , Pirona R , Miculan M , Barakat A , Testolin R , Stella A , Tartarini S , Tonutti P , Arus P , Orellana A , Wells C , Main D , Vizzotto G , Silva H , Salamini F , Schmutz J , Morgante M , Rokhsar DS
Ref : Nat Genet , 45 :487 , 2013
Abstract : Rosaceae is the most important fruit-producing clade, and its key commercially relevant genera (Fragaria, Rosa, Rubus and Prunus) show broadly diverse growth habits, fruit types and compact diploid genomes. Peach, a diploid Prunus species, is one of the best genetically characterized deciduous trees. Here we describe the high-quality genome sequence of peach obtained from a completely homozygous genotype. We obtained a complete chromosome-scale assembly using Sanger whole-genome shotgun methods. We predicted 27,852 protein-coding genes, as well as noncoding RNAs. We investigated the path of peach domestication through whole-genome resequencing of 14 Prunus accessions. The analyses suggest major genetic bottlenecks that have substantially shaped peach genome diversity. Furthermore, comparative analyses showed that peach has not undergone recent whole-genome duplication, and even though the ancestral triplicated blocks in peach are fragmentary compared to those in grape, all seven paleosets of paralogs from the putative paleoancestor are detectable.
ESTHER : Verde_2013_Nat.Genet_45_487
PubMedSearch : Verde_2013_Nat.Genet_45_487
PubMedID: 23525075
Gene_locus related to this paper: prupe-a0a251pfr7 , prupe-a0a251r634 , prupe-m5x0p5 , prupe-m5xkg4 , prupe-m5x0q4 , prupe-m5vqa7 , prupe-m5wiw5 , prupe-a0a0u2wu32 , prupe-a0a251mtk1 , prupe-m5vl29 , prupe-m5vn82 , prupe-m5vq88 , prupe-m5y2s7 , prupe-m5wye7 , prupe-m5wxm4 , prupe-m5xqp6 , prupe-m5x4q4 , prupe-m5x4m1 , prupe-m5x6b3 , prupe-m5vlb6 , prupe-m5w4h3 , prupe-m5vlu4 , prupe-m5vln3 , prupe-a0a251myy7 , prupe-a0a251mws4 , prupe-m5vi18 , prupe-m5vh66 , prupe-m5xd54 , prupe-m5xqn2 , prupe-m5xr64 , prupe-m5vrm7 , prupe-m5vrk6 , prupe-m5vqp6 , prupe-a0a251nbb1 , prupe-a0a251nbd3 , prupe-a0a251nbb3 , prupe-a0a251nba0 , prupe-a0a251ndd4 , prupe-a0a251nbb6 , prupe-m5w315 , prupe-a0a251mwh1 , prupe-a0a251qn57 , prupe-m5vzh8 , prupe-m5xpz7 , prupe-m5xrp5 , prupe-m5wsr5 , prupe-m5xs20 , prupe-m5vl10 , prupe-a0a251nay9 , prupe-a0a251ndz1 , prupe-a0a251puf0 , prupe-m5wr61 , prupe-a0a251nyu6 , prupe-m5vl63

Title : Assessing the effects of chronic sazetidine-A delivery on nicotine self-administration in both male and female rats - Johnson_2012_Psychopharmacology.(Berl)_222_269
Author(s) : Johnson JE , Slade S , Wells C , Petro A , Sexton H , Rezvani AH , Brown ML , Paige MA , McDowell BE , Xiao Y , Kellar KJ , Levin ED
Ref : Psychopharmacology (Berl) , 222 :269 , 2012
Abstract : RATIONALE: Sazetidine-A is a selective alpha4beta2 nicotinic receptor desensitizing agent and partial agonist. It has been shown in previous studies to significantly reduce nicotine self-administration in rats after acute or repeated injections. However, the effects of continuous chronic infusions of sazetidine-A on maintenance of nicotine self-administration and relapse after abstinence have yet to be examined. OBJECTIVES: This study evaluated the efficacy of continuous sazetidine-A infusions (sc) over a period of 4 weeks to reduce nicotine self-administration in male and female Sprague-Dawley rats.
METHODS: Sazetidine-A was administered via Alzet osmotic minipumps to young adult female and male rats at doses of 0, 2 or 6 mg/kg/day for 4 weeks. The effects of sazetidine-A on IV nicotine self-administration were examined in repeated 3-h sessions over the first 2 weeks of infusion followed by 1 week of forced abstinence from nicotine and 1 week of resumed nicotine access.
RESULTS: The 6 mg/kg/day sazetidine-A dose significantly reduced overall nicotine self-administration compared with vehicle control across the sessions for both male (p < 0.001) and female (p < 0.05) rats. The lower 2 mg/kg/day sazetidine-A infusion dose was effective in reducing nicotine self-administration for male (p < 0.001), but not female rats. No attenuation in sazetidine-A effectiveness was seen over the course of the 4-week treatment. In the vehicle control group, male rats self-administered significantly (p < 0.001) more nicotine than females.
CONCLUSIONS: The continuing effectiveness of sazetidine-A in reducing nicotine self-administration in both male and female rats supports its promise as a new treatment to help people successfully quit smoking.
ESTHER : Johnson_2012_Psychopharmacology.(Berl)_222_269
PubMedSearch : Johnson_2012_Psychopharmacology.(Berl)_222_269
PubMedID: 22297831

Title : Sazetidine-A, a selective alpha4beta2 nicotinic receptor desensitizing agent and partial agonist, reduces nicotine self-administration in rats - Levin_2010_J.Pharmacol.Exp.Ther_332_933
Author(s) : Levin ED , Rezvani AH , Xiao Y , Slade S , Cauley M , Wells C , Hampton D , Petro A , Rose JE , Brown ML , Paige MA , McDowell BE , Kellar KJ
Ref : Journal of Pharmacology & Experimental Therapeutics , 332 :933 , 2010
Abstract : Adequate treatment of tobacco addiction remains problematic. Part of the problem with treatment is a poor understanding of the pharmacologic aspects of nicotine contributing to addiction. In addition to activating nicotinic acetylcholine receptors, nicotine also desensitizes them. It is currently not known how much of each of nicotine's actions contribute to its particular behavioral effects. Sazetidine-A (saz-A) is a novel nicotinic receptor-desensitizing agent and partial agonist with high selectivity for alpha4beta2 receptors. The current experiments were conducted to determine whether saz-A would reduce nicotine self-administration in rats and to characterize its ancillary effects. Adult male Sprague-Dawley rats were allowed to self-administer nicotine. After initial food pellet training followed by 10 sessions of nicotine self-administration training, the rats were administered saz-A (0.1-3 mg/kg s.c.) or the saline vehicle in a repeated-measures counterbalanced design. Saz-A at the 3 mg/kg dose significantly decreased nicotine self-administration relative to performance of the same rats after saline injections. In a second study, long-term administration of this dose of sazetidine-A over the course of 10 sessions significantly reduced nicotine self-administration with no apparent diminution of effect. Saz-A in this dose range had only modest effects on locomotor activity, without any overall decrease in activity over a 1-h-long session. Saz-A significantly reduced food self-administration, but this effect was smaller than its effect on nicotine self-administration. Saz-A, which is a selective alpha4beta2-desensitizing agent and partial agonist, effectively reduces nicotine self-administration. This type of treatment holds promise for a new therapy to aid smoking cessation.
ESTHER : Levin_2010_J.Pharmacol.Exp.Ther_332_933
PubMedSearch : Levin_2010_J.Pharmacol.Exp.Ther_332_933
PubMedID: 20007754

Title : Effects of sazetidine-A, a selective alpha4beta2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats - Rezvani_2010_Psychopharmacology.(Berl)_211_161
Author(s) : Rezvani AH , Slade S , Wells C , Petro A , Lumeng L , Li TK , Xiao Y , Brown ML , Paige MA , McDowell BE , Rose JE , Kellar KJ , Levin ED
Ref : Psychopharmacology (Berl) , 211 :161 , 2010
Abstract : RATIONALE: Manipulations of nicotinic cholinergic receptors have been shown to influence both alcohol and nicotine intake. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound that potently and selectively desensitizes alpha4beta2 nicotinic receptors with only modest receptor activation. OBJECTIVES: The goal of the present study was to examine the effects of sazetidine-A on alcohol and nicotine self-administration in alcohol-preferring (P) rats.
METHODS: P rats were given the choice of water or alcohol. Once stable baselines were established, the acute (0, 0.1, 0.3, 1, and 3 mg/kg, s.c.) and chronic (3 mg/kg for 10 days) effects of sazetidine-A on alcohol intake were assessed. Naltrexone (2.5 mg/kg) served as a positive control. The effect of sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on saccharin (0.2%) preference was also assessed. In addition, the acute effects of sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on alcohol intake after alcohol deprivation were evaluated. In another experiment, the effects of sazetidine-A (0, 1, or 3 mg/kg) on i.v. nicotine self-administration in P and NP rats were assessed.
RESULTS: Sazetidine-A caused a dose-dependent reduction in alcohol intake. Chronic sazetidine-A also effectively reduced alcohol intake until the seventh day of treatment, when partial tolerance appeared to develop. In the post-deprivation study, sazetidine-A significantly reduced alcohol intake and preference. Sazetidine-A at 3 mg/kg significantly reduced nicotine self-administration in both lines.
CONCLUSIONS: Sazetidine-A significantly reduced alcohol and nicotine intake in P rats that self-administer higher levels of both drugs. Sazetidine-A may hold promise for the treatment of alcohol and nicotine addiction.
ESTHER : Rezvani_2010_Psychopharmacology.(Berl)_211_161
PubMedSearch : Rezvani_2010_Psychopharmacology.(Berl)_211_161
PubMedID: 20535453

Title : Antisense transcription in the mammalian transcriptome - Katayama_2005_Science_309_1564
Author(s) : Katayama S , Tomaru Y , Kasukawa T , Waki K , Nakanishi M , Nakamura M , Nishida H , Yap CC , Suzuki M , Kawai J , Suzuki H , Carninci P , Hayashizaki Y , Wells C , Frith M , Ravasi T , Pang KC , Hallinan J , Mattick J , Hume DA , Lipovich L , Batalov S , Engstrom PG , Mizuno Y , Faghihi MA , Sandelin A , Chalk AM , Mottagui-Tabar S , Liang Z , Lenhard B , Wahlestedt C
Ref : Science , 309 :1564 , 2005
Abstract : Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.
ESTHER : Katayama_2005_Science_309_1564
PubMedSearch : Katayama_2005_Science_309_1564
PubMedID: 16141073
Gene_locus related to this paper: mouse-lipli , mouse-Ppgb , mouse-q3uuq7

Title : The transcriptional landscape of the mammalian genome - Carninci_2005_Science_309_1559
Author(s) : Carninci P , Kasukawa T , Katayama S , Gough J , Frith MC , Maeda N , Oyama R , Ravasi T , Lenhard B , Wells C , Kodzius R , Shimokawa K , Bajic VB , Brenner SE , Batalov S , Forrest AR , Zavolan M , Davis MJ , Wilming LG , Aidinis V , Allen JE , Ambesi-Impiombato A , Apweiler R , Aturaliya RN , Bailey TL , Bansal M , Baxter L , Beisel KW , Bersano T , Bono H , Chalk AM , Chiu KP , Choudhary V , Christoffels A , Clutterbuck DR , Crowe ML , Dalla E , Dalrymple BP , de Bono B , Della Gatta G , di Bernardo D , Down T , Engstrom P , Fagiolini M , Faulkner G , Fletcher CF , Fukushima T , Furuno M , Futaki S , Gariboldi M , Georgii-Hemming P , Gingeras TR , Gojobori T , Green RE , Gustincich S , Harbers M , Hayashi Y , Hensch TK , Hirokawa N , Hill D , Huminiecki L , Iacono M , Ikeo K , Iwama A , Ishikawa T , Jakt M , Kanapin A , Katoh M , Kawasawa Y , Kelso J , Kitamura H , Kitano H , Kollias G , Krishnan SP , Kruger A , Kummerfeld SK , Kurochkin IV , Lareau LF , Lazarevic D , Lipovich L , Liu J , Liuni S , McWilliam S , Madan Babu M , Madera M , Marchionni L , Matsuda H , Matsuzawa S , Miki H , Mignone F , Miyake S , Morris K , Mottagui-Tabar S , Mulder N , Nakano N , Nakauchi H , Ng P , Nilsson R , Nishiguchi S , Nishikawa S , Nori F , Ohara O , Okazaki Y , Orlando V , Pang KC , Pavan WJ , Pavesi G , Pesole G , Petrovsky N , Piazza S , Reed J , Reid JF , Ring BZ , Ringwald M , Rost B , Ruan Y , Salzberg SL , Sandelin A , Schneider C , Schonbach C , Sekiguchi K , Semple CA , Seno S , Sessa L , Sheng Y , Shibata Y , Shimada H , Shimada K , Silva D , Sinclair B , Sperling S , Stupka E , Sugiura K , Sultana R , Takenaka Y , Taki K , Tammoja K , Tan SL , Tang S , Taylor MS , Tegner J , Teichmann SA , Ueda HR , van Nimwegen E , Verardo R , Wei CL , Yagi K , Yamanishi H , Zabarovsky E , Zhu S , Zimmer A , Hide W , Bult C , Grimmond SM , Teasdale RD , Liu ET , Brusic V , Quackenbush J , Wahlestedt C , Mattick JS , Hume DA , Kai C , Sasaki D , Tomaru Y , Fukuda S , Kanamori-Katayama M , Suzuki M , Aoki J , Arakawa T , Iida J , Imamura K , Itoh M , Kato T , Kawaji H , Kawagashira N , Kawashima T , Kojima M , Kondo S , Konno H , Nakano K , Ninomiya N , Nishio T , Okada M , Plessy C , Shibata K , Shiraki T , Suzuki S , Tagami M , Waki K , Watahiki A , Okamura-Oho Y , Suzuki H , Kawai J , Hayashizaki Y
Ref : Science , 309 :1559 , 2005
Abstract : This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
ESTHER : Carninci_2005_Science_309_1559
PubMedSearch : Carninci_2005_Science_309_1559
PubMedID: 16141072
Gene_locus related to this paper: mouse-abhd1 , mouse-abhd3 , mouse-abhd4 , mouse-acot4 , mouse-adcl4 , mouse-DGLB , mouse-ephx3 , mouse-Kansl3 , mouse-lipli , mouse-LIPN , mouse-Ppgb , mouse-q3uuq7 , mouse-srac1 , mouse-Tex30 , mouse-tmco4 , mouse-tmm53 , mouse-f172a

Title : Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs - Okazaki_2002_Nature_420_563
Author(s) : Okazaki Y , Furuno M , Kasukawa T , Adachi J , Bono H , Kondo S , Nikaido I , Osato N , Saito R , Suzuki H , Yamanaka I , Kiyosawa H , Yagi K , Tomaru Y , Hasegawa Y , Nogami A , Schonbach C , Gojobori T , Baldarelli R , Hill DP , Bult C , Hume DA , Quackenbush J , Schriml LM , Kanapin A , Matsuda H , Batalov S , Beisel KW , Blake JA , Bradt D , Brusic V , Chothia C , Corbani LE , Cousins S , Dalla E , Dragani TA , Fletcher CF , Forrest A , Frazer KS , Gaasterland T , Gariboldi M , Gissi C , Godzik A , Gough J , Grimmond S , Gustincich S , Hirokawa N , Jackson IJ , Jarvis ED , Kanai A , Kawaji H , Kawasawa Y , Kedzierski RM , King BL , Konagaya A , Kurochkin IV , Lee Y , Lenhard B , Lyons PA , Maglott DR , Maltais L , Marchionni L , McKenzie L , Miki H , Nagashima T , Numata K , Okido T , Pavan WJ , Pertea G , Pesole G , Petrovsky N , Pillai R , Pontius JU , Qi D , Ramachandran S , Ravasi T , Reed JC , Reed DJ , Reid J , Ring BZ , Ringwald M , Sandelin A , Schneider C , Semple CA , Setou M , Shimada K , Sultana R , Takenaka Y , Taylor MS , Teasdale RD , Tomita M , Verardo R , Wagner L , Wahlestedt C , Wang Y , Watanabe Y , Wells C , Wilming LG , Wynshaw-Boris A , Yanagisawa M , Yang I , Yang L , Yuan Z , Zavolan M , Zhu Y , Zimmer A , Carninci P , Hayatsu N , Hirozane-Kishikawa T , Konno H , Nakamura M , Sakazume N , Sato K , Shiraki T , Waki K , Kawai J , Aizawa K , Arakawa T , Fukuda S , Hara A , Hashizume W , Imotani K , Ishii Y , Itoh M , Kagawa I , Miyazaki A , Sakai K , Sasaki D , Shibata K , Shinagawa A , Yasunishi A , Yoshino M , Waterston R , Lander ES , Rogers J , Birney E , Hayashizaki Y
Ref : Nature , 420 :563 , 2002
Abstract : Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
ESTHER : Okazaki_2002_Nature_420_563
PubMedSearch : Okazaki_2002_Nature_420_563
PubMedID: 12466851
Gene_locus related to this paper: mouse-1lipg , mouse-1llip , mouse-1plrp , mouse-3neur , mouse-ABH15 , mouse-abhd4 , mouse-abhd5 , mouse-Abhd8 , mouse-Abhd11 , mouse-abhda , mouse-acot4 , mouse-adcl4 , mouse-AI607300 , mouse-BAAT , mouse-bphl , mouse-C87498 , mouse-Ldah , mouse-Ces1d , mouse-Ces2e , mouse-CMBL , mouse-DGLB , mouse-dpp9 , mouse-ES10 , mouse-F135A , mouse-FASN , mouse-hslip , mouse-hyes , mouse-Kansl3 , mouse-LIPH , mouse-LIPK , mouse-lipli , mouse-LIPM , mouse-lypla1 , mouse-lypla2 , mouse-MEST , mouse-MGLL , mouse-ndr4 , mouse-OVCA2 , mouse-pafa , mouse-pcp , mouse-ppce , mouse-Ppgb , mouse-PPME1 , mouse-q3uuq7 , mouse-Q8BLF1 , mouse-ACOT6 , mouse-Q8C1A9 , mouse-Q9DAI6 , mouse-Q80UX8 , mouse-Q8BGG9 , mouse-Q8C167 , mouse-rbbp9 , mouse-SERHL , mouse-tssp