Schneider C

References (7)

Title : Metabolism of remimazolam in primary human hepatocytes during continuous long-term infusion in a 3-D bioreactor system - Freyer_2019_Drug.Des.Devel.Ther_13_1033
Author(s) : Freyer N , Knospel F , Damm G , Greuel S , Schneider C , Seehofer D , Stohr T , Petersen KU , Zeilinger K
Ref : Drug Des Devel Ther , 13 :1033 , 2019
Abstract : Background: Remimazolam is an ultra-short acting benzodiazepine under development for procedural sedation and general anesthesia. It is hydrolyzed by CES1 to an inactive metabolite (CNS7054). Purpose: In this study, the effect of continuous remimazolam exposure on its metabolism and on CES1 expression was investigated in a dynamic 3-D bioreactor culture model inoculated with primary human hepatocytes. Methods: Remimazolam was continuously infused into bioreactors for 5 days at a final concentration of 3,000 ng/ml (6.8 microM). In parallel, 2-D cultures were run with cells from the same donors, but with discontinuous exposure to remimazolam. Results: Daily measurement of clinical chemistry parameters (glucose, lactate, urea, ammonia, and liver enzymes) in culture supernatants indicated no noxious effect of remimazolam on hepatocyte integrity as compared to untreated controls. Concentrations of remimazolam reached steady-state values of around 250 ng/ml within 8 hours in 3-D bioreactors whereas in 2-D cultures remimazolam concentrations declined to almost zero within the same time frame. Levels of CNS7054 showed an inverse time-course reaching average values of 1,350 ng/ml in perfused 3-D bioreactors resp. 2,800 ng/ml in static 2-D cultures. Analysis of mRNA expression levels of CES1 indicated no changes in gene expression over the culture period. Conclusion: The results indicated a stable metabolism of remimazolam during 5 days of continuous exposure to clinically relevant concentrations of the drug. Moreover, there was no evidence for a harmful effect of remimazolam exposure on the integrity and metabolic activity of in vitro cultivated primary human hepatocytes.
ESTHER : Freyer_2019_Drug.Des.Devel.Ther_13_1033
PubMedSearch : Freyer_2019_Drug.Des.Devel.Ther_13_1033
PubMedID: 31037028

Title : Highly efficient cyclosarin degradation mediated by a beta-cyclodextrin derivative containing an oxime-derived substituent - Zengerle_2011_Beilstein.J.Org.Chem_7_1543
Author(s) : Zengerle M , Brandhuber F , Schneider C , Worek F , Reiter G , Kubik S
Ref : Beilstein J Org Chem , 7 :1543 , 2011
Abstract : The potential of appropriately substituted cyclodextrins to act as scavengers for neurotoxic organophosphonates under physiological conditions was evaluated. To this end, a series of derivatives containing substituents with an aldoxime or a ketoxime moiety along the narrow opening of the beta-cyclodextrin cavity was synthesized, and the ability of these compounds to reduce the inhibitory effect of the neurotoxic organophosphonate cyclosarin on its key target, acetylcholinesterase, was assessed in vitro. All compounds exhibited a larger effect than native beta-cyclodextrin, and characteristic differences were noted. These differences in activity were correlated with the structural and electronic parameters of the substituents. In addition, the relatively strong effect of the cyclodextrin derivatives on cyclosarin degradation and, in particular, the observed enantioselectivity are good indications that noncovalent interactions between the cyclodextrin ring and the substrate, presumably involving the inclusion of the cyclohexyl moiety of cyclosarin into the cyclodextrin cavity, contribute to the mode of action. Among the nine compounds investigated, one exhibited remarkable activity, completely preventing acetylcholinesterase inhibition by the (-)-enantiomer of cyclosarin within seconds under the conditions of the assay. Thus, these investigations demonstrate that decoration of cyclodextrins with appropriate substituents represents a promising approach for the development of scavengers able to detoxify highly toxic nerve agents.
ESTHER : Zengerle_2011_Beilstein.J.Org.Chem_7_1543
PubMedSearch : Zengerle_2011_Beilstein.J.Org.Chem_7_1543
PubMedID: 22238531

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 : Mutations associated with a congenital form of ichthyosis (NCIE) inactivate the epidermal lipoxygenases 12R-LOX and eLOX3 - Yu_2005_Biochim.Biophys.Acta_1686_238
Author(s) : Yu Z , Schneider C , Boeglin WE , Brash AR
Ref : Biochimica & Biophysica Acta , 1686 :238 , 2005
Abstract : Non-bullous congenital ichthyosiform erythroderma (NCIE) is one of the main clinical forms of ichthyosis. Genetic studies indicated that 12R-lipoxygenase (12R-LOX) or epidermal lipoxygenase-3 (eLOX3) was mutated in six families affected by NCIE [F. Jobard, C. Lefevre, A. Karaduman, C. Blanchet-Bardon, S. Emre, J. Weissenbach, M. Ozguc, M. Lathrop, J.F. Prud'homme, J. Fischer, Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1, Hum. Mol. Genet. 11 (2002) 107-113.], but the impact of these mutations on LOX function has not been defined. To explore this, we overexpressed the wild-type or mutated enzymes in E. coli and COS7 cells and then analyzed the essential catalytic properties. We showed recently that human eLOX3 is a hydroperoxide isomerase (hepoxilin synthase) that converts the product of 12R-LOX, 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE) to a specific epoxyalcohol. Using incubations with [(14)C]-labeled substrates and HPLC analyses, we found that the naturally occurring mutations totally eliminate the lipoxygenase activity of 12R-LOX and the hydroperoxide isomerase activity of eLOX3. We further demonstrate that the 12R-LOX/eLOX3-derived 8R-hydroxy-11R,12R-epoxide is converted by an epoxide hydrolase in COS7 cells and in human keratinocytes to a single isomer of 8,11,12-trihydroxyeicosa-5,9,14-trienoic acid. Taken together, the results support the hypothesis that 12R-LOX, eLOX3, and perhaps an epoxide hydrolase function together in the normal process of skin differentiation, and that the loss of function mutations are the basis of the LOX-dependent form of NCIE.
ESTHER : Yu_2005_Biochim.Biophys.Acta_1686_238
PubMedSearch : Yu_2005_Biochim.Biophys.Acta_1686_238
PubMedID: 15629692

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

Title : Association of acetylcholine receptor alpha-subunit gene expression in mixed thymoma with myasthenia gravis - Wilisch_1999_Neurology_52_1460
Author(s) : Wilisch A , Gutsche S , Hoffacker V , Schultz A , Tzartos SJ , Nix W , Schalke B , Schneider C , Muller-Hermelink HK , Marx A
Ref : Neurology , 52 :1460 , 1999
Abstract : OBJECTIVE: To investigate the association of MG with the transcription of muscular or neuronal acetylcholine receptor (AChR) subunit genes in thymomas. BACKGROUND: Many steps in the pathogenesis of MG have been elucidated but, with rare exceptions, its etiology is unknown. In patients with MG with thymoma, the tumor probably elicits autoimmunity to AChR, but it is enigmatic why MG develops in some patients but not in others.
METHODS: Reverse transcriptase (RT)-PCR, immunohistochemistry, and immunofluorescence studies were carried out to investigate AChR expression in 35 patients with thymoma. Statistical analysis was used to specify significant differences between thymoma subtypes.
RESULTS: Considering all thymomas (n = 35), no correlation was found between MG status and AChR gene expression as detected by RT-PCR. However, when histologically defined thymoma subtypes were studied separately, transcription of the muscular AChR P3A- alpha-subunit gene was significantly associated (alpha < 0.01) with the occurrence of MG in mixed thymomas (n = 17), but not in thymomas of the cortical type. For the other muscular AChR subunits (P3A+ alpha isoform, beta, gamma, delta, and epsilon) and the alpha2 and beta4 neuronal AChR subunits, no such correlation was detected.
CONCLUSIONS: Expression of the P3A AChR alpha-subunit gene might be important for the pathogenesis of MG in mixed thymomas, suggesting etiologic heterogeneity of paraneoplastic MG among patients with histologically different thymoma subtypes.
ESTHER : Wilisch_1999_Neurology_52_1460
PubMedSearch : Wilisch_1999_Neurology_52_1460
PubMedID: 10227635

Title : The nucleotide sequence of Saccharomyces cerevisiae chromosome IV - Jacq_1997_Nature_387_75
Author(s) : Jacq C , Alt-Morbe J , Andre B , Arnold W , Bahr A , Ballesta JP , Bargues M , Baron L , Becker A , Biteau N , Blocker H , Blugeon C , Boskovic J , Brandt P , Bruckner M , Buitrago MJ , Coster F , Delaveau T , del Rey F , Dujon B , Eide LG , Garcia-Cantalejo JM , Goffeau A , Gomez-Peris AC , Granotier C , Hanemann V , Hankeln T , Hoheisel JD , Jager W , Jimenez A , Jonniaux JL , Kramer C , Kuster H , Laamanen P , Legros Y , Louis E , Muller-Rieker S , Monnet A , Moro M , Muller-Auer S , Nussbaumer B , Paricio N , Paulin L , Perea J , Perez-Alonso M , Perez-Ortin JE , Pohl TM , Prydz H , Purnelle B , Rasmussen SW , Remacha M , Revuelta JL , Rieger M , Salom D , Saluz HP , Saiz JE , Saren AM , Schafer M , Scharfe M , Schmidt ER , Schneider C , Scholler P , Schwarz S , Soler-Mira A , Urrestarazu LA , Verhasselt P , Vissers S , Voet M , Volckaert G , Wagner G , Wambutt R , Wedler E , Wedler H , Wolfl S , Harris DE , Bowman S , Brown D , Churcher CM , Connor R , Dedman K , Gentles S , Hamlin N , Hunt S , Jones L , McDonald S , Murphy L , Niblett D , Odell C , Oliver K , Rajandream MA , Richards C , Shore L , Walsh SV , Barrell BG , Dietrich FS , Mulligan J , Allen E , Araujo R , Aviles E , Berno A , Carpenter J , Chen E , Cherry JM , Chung E , Duncan M , Hunicke-Smith S , Hyman R , Komp C , Lashkari D , Lew H , Lin D , Mosedale D , Nakahara K , Namath A , Oefner P , Oh C , Petel FX , Roberts D , Schramm S , Schroeder M , Shogren T , Shroff N , Winant A , Yelton M , Botstein D , Davis RW , Johnston M , Hillier L , Riles L , Albermann K , Hani J , Heumann K , Kleine K , Mewes HW , Zollner A , Zaccaria P
Ref : Nature , 387 :75 , 1997
Abstract : The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome IV has been determined. Apart from chromosome XII, which contains the 1-2 Mb rDNA cluster, chromosome IV is the longest S. cerevisiae chromosome. It was split into three parts, which were sequenced by a consortium from the European Community, the Sanger Centre, and groups from St Louis and Stanford in the United States. The sequence of 1,531,974 base pairs contains 796 predicted or known genes, 318 (39.9%) of which have been previously identified. Of the 478 new genes, 225 (28.3%) are homologous to previously identified genes and 253 (32%) have unknown functions or correspond to spurious open reading frames (ORFs). On average there is one gene approximately every two kilobases. Superimposed on alternating regional variations in G+C composition, there is a large central domain with a lower G+C content that contains all the yeast transposon (Ty) elements and most of the tRNA genes. Chromosome IV shares with chromosomes II, V, XII, XIII and XV some long clustered duplications which partly explain its origin.
ESTHER : Jacq_1997_Nature_387_75
PubMedSearch : Jacq_1997_Nature_387_75
PubMedID: 9169867
Gene_locus related to this paper: yeast-dlhh , yeast-ECM18 , yeast-YDL109C , yeast-YDR428C , yeast-YDR444W