Muller S

References (10)

Title : In vitro and in vivo toxicological studies of V nerve agents: molecular and stereoselective aspects - Reiter_2015_Toxicol.Lett_232_438
Author(s) : Reiter G , Muller S , Hill I , Weatherby K , Thiermann H , Worek F , Mikler J
Ref : Toxicol Lett , 232 :438 , 2015
Abstract : In vitro inhibition data of cholinesterases (ChEs) and reactivation with HI 6 are presented for separated VX and VR enantiomers with high purity (enantiomer excess >99.999%). Inhibition rate constants for (-)-VR were fourfold higher than for (-)-VX. Marked higher stereoselectivity of ChEs inhibition was observed for VR compared with VX enantiomers. Low/no reactivation was determined for respective (+)-enantiomers. Results were related to orientation of (-)- and (+)-enantiomers in ChEs active sites. In vivo in swine, absorption rate constants were practically identical for VX and VR enantiomers after percutaneous application of 3xLD(5)(0) underlining relevance of amine group and postulated equilibria shifts between charged, uncharged, open and cyclic form (skin depot). In vivo toxicokinetics of VX and VR enantiomers differed markedly after 4h. Elimination of VX was much slower compared with VR. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition in vivo differed for VX and VR. In vivo spontaneous reactivation was not observed for VX-inhibited AChE while VR-inhibited AChE was much faster spontaneously reactivated than expected and AChE inhibition by VR was slower than expected. Progredient BChE inhibition was detected after VX application while VR inhibited BChE weakly. Possible explanation may be impact of the agents on hemodynamics and different metabolisms. Thus, due to increase of the V agents' blood concentration after atropine administration (depot release) the present standard therapy should be thoroughly reconsidered.
ESTHER : Reiter_2015_Toxicol.Lett_232_438
PubMedSearch : Reiter_2015_Toxicol.Lett_232_438
PubMedID: 25448275

Title : Functionalized cyclodextrins bearing an alpha nucleophile - A promising way to degrade nerve agents - Estour_2013_Chem.Biol.Interact_203_202
Author(s) : Estour F , Letort S , Muller S , Kalakuntla RK , Le Provost R , Wille T , Reiter G , Worek F , Lafont O , Gouhier G
Ref : Chemico-Biological Interactions , 203 :202 , 2013
Abstract : Organophosphorus nerve agents are irreversible inhibitors of acetylcholinesterase. Current treatment of nerve agent poisoning has limited efficacy and more efficient medical countermeasures need to be developed. A promising approach is to design chemical scavengers more stable during storage and less immunogenic than bioscavengers. Furthermore, they could be produced at lowest production costs. Cyclodextrins are attractive cyclic oligosaccharides that can be used to develop chemical scavengers of organophosphorus nerve agents. Their abilities to form inclusion and non-inclusion complexes with organic substrates are useful to trap chemical warfare agents. Selective introduction of an alpha-nucleophile residue on the secondary face of beta-cyclodextrin allowed to obtain supramolecular derivatives active against organophosphorus compounds. The degradation activity of these monosubstituted cyclodextrins was determined against paraoxon and chemical warfare agents. These tests showed that the structure of the scavengers mainly influences the interaction between the organophosphorus substrate, or its reaction products, and the cyclodextrin moiety. All the tested G-type agents were efficiently degraded. According to the binding modes of cyclosarin, some oligosaccharidic scavengers led to an enantioselective degradation of this nerve agent. These promising derivatives open the way to further investigations of new structural modifications to reach more sophisticated and efficient scavengers for prophylactic and curative medical applications.
ESTHER : Estour_2013_Chem.Biol.Interact_203_202
PubMedSearch : Estour_2013_Chem.Biol.Interact_203_202
PubMedID: 23123247

Title : New modified beta-cyclodextrin derivatives as detoxifying agents of chemical warfare agents (I). Synthesis and preliminary screening: Evaluation of the detoxification using a half-quantitative enzymatic assay - Kalakuntla_2013_Toxicol.Lett_216_200
Author(s) : Kalakuntla RK , Wille T , Le Provost R , Letort S , Reiter G , Muller S , Thiermann H , Worek F , Gouhier G , Lafont O , Estour F
Ref : Toxicol Lett , 216 :200 , 2013
Abstract : Current treatments of organophosphorus nerve agents poisoning are imperfect, and more efficient medical countermeasures need to be developed. Chemical scavengers based on beta-cyclodextrin displayed promising results, but further investigations have to be performed to evaluate the possibility of application of substituted cyclodextrins as potential detoxification agents. Herein, five new cyclodextrins scavengers were synthesized. New optimal conditions for regioselectively monosubstitution of beta-cyclodextrin at O-2 position were then studied to access to key intermediates. After these optimizations, a new series of three permethylated derivatives was developed, and two compounds bearing an alpha-nucleophilic group via a three carbon atoms linker were prepared. The ability of these five scavengers to detoxify nerve agents (cyclosarin, soman, tabun and VX) was evaluated by a semi-quantitative biological assay. All the modified cyclodextrins significantly decreased the inhibitory effect of chemical warfare G agents on acetylcholinesterase activity. For this purpose, we showed that the specific interactions between the organophosphorus compound and the oligosaccharidic moiety of the scavenger played a pivotal role in the detoxification process.
ESTHER : Kalakuntla_2013_Toxicol.Lett_216_200
PubMedSearch : Kalakuntla_2013_Toxicol.Lett_216_200
PubMedID: 23201439

Title : Optimized strategies to synthesize beta-cyclodextrin-oxime conjugates as a new generation of organophosphate scavengers - Le Provost_2011_Org.Biomol.Chem_9_3026
Author(s) : Le Provost R , Wille T , Louise L , Masurier N , Muller S , Reiter G , Renard PY , Lafont O , Worek F , Estour F
Ref : Org Biomol Chem , 9 :3026 , 2011
Abstract : A new generation of organophosphate (OP) scavengers was obtained by synthesis of beta-cyclodextrin-oxime derivatives 8-12. Selective monosubstitution of beta-cyclodextrin was the main difficulty in order to access these compounds, because reaction onto the oligosaccharide was closely related to the nature of the incoming group. For this purpose, non-conventional activation conditions were also evaluated. Intermediates 5 and 7 were then obtained with the better yields under ultrasounds irradiation. Finally, the desired compounds 8-10 were obtained from 5-7 in high purity by desilylation using potassium fluoride. Quaternarisation of compounds 8 and 9 was carried out. OP hydrolytic activity of compounds 8-12 was evaluated against cyclosarin (GF) and VX. None of the tested compounds was active against VX, but these five cyclodextrin derivatives detoxified GF, and the most active scavengers 10 and 11 allowed an almost complete hydrolysis of GF within 10 min. Even more fascinating is the fact that compounds 9 and 10 were able to hydrolyze enantioselectively GF.
ESTHER : Le Provost_2011_Org.Biomol.Chem_9_3026
PubMedSearch : Le Provost_2011_Org.Biomol.Chem_9_3026
PubMedID: 21373706

Title : In vitro detoxification of cyclosarin (GF) by modified cyclodextrins - Muller_2011_Toxicol.Lett_200_53
Author(s) : Muller S , Koller M , Le Provost R , Lafont O , Estour F , Wille T , Thiermann H , Worek F , Reiter G
Ref : Toxicol Lett , 200 :53 , 2011
Abstract : Developing potent detoxification strategies for prophylaxis and therapy against organophosphate (OP) intoxication still represents a challenging task. Clinical application of numerous investigated substances including enzymes and low molecular scavengers like metal ions or nucleophiles could not yet be realised due to profound disadvantages. Presenting a promising attempt, cyclodextrins (CDs) efficiently enhance the degradation of some organophosphorus compounds. The present study examined the in vitro GF degradation mediated by three CDs and a nucleophilic precursor performed by mass spectrometric detection with ammonia chemical ionisation. All four compounds caused a notable enhancement of GF detoxification that was synergistically accelerated in the case of 2-O-(3-carboxy-4-iodosobenzyl)-beta-cyclodextrin (IBA-beta-CD) with the alpha-nucleophile 2-iodosobenzoic acid (IBA) grafted on the secondary face of beta-cyclodextrin (beta-CD). In vitro toxicokinetic investigations of CD derivatives are needed to evaluate the effect of slow terminal elimination phase of the more toxic (-)-GF shown for two CD-derivatives underlining the necessity of detecting the complete kinetic course of inactivation. The observed effect of fast high affinity binding (20-30%) represents an additional therapeutic option of an extremely rapid reduction of GF concentration in vivo. Distinctive differences in the course of reaction are detected depending on beta-CD-derivatives, allowing a first inference of possible mechanisms and relevance of attached substituents. However, further profound investigation needs to be done to evaluate the basis of a clinical application of substituted CDs as potential detoxification agents.
ESTHER : Muller_2011_Toxicol.Lett_200_53
PubMedSearch : Muller_2011_Toxicol.Lett_200_53
PubMedID: 21035528

Title : Improving the promiscuous nerve agent hydrolase activity of a thermostable archaeal lactonase - Merone_2010_Bioresour.Technol_101_9204
Author(s) : Merone L , Mandrich L , Porzio E , Rossi M , Muller S , Reiter G , Worek F , Manco G
Ref : Bioresour Technol , 101 :9204 , 2010
Abstract : The thermostable Phosphotriesterase-Like Lactonase from Sulfolobus solfataricus (SsoPox) hydrolyzes lactones and, at a lower rate, neurotoxic organophosphorus compounds. The persistent demand of detoxification tools in the field of agricultural wastes and restoring of conditions after terrorist acts prompted us to exploit SsoPox as a "starter" to evolve its ancillary nerve agents hydrolytic capability. A directed evolution strategy yielded, among several variants, the single mutant W263F with k(cat) and specificity constant against paraoxon 16- and 6-fold enhanced, respectively, compared to the wild type. Furthermore, a phenomenon of enzyme activation by SDS has been observed, which allowed to increase those values 150- and 28-fold, respectively. The activity of SsoPox against the deadly nerve gas Cyclosarin has been reported for the first time and proved to be substantially unaffected for variant W263F. Finally, outperforming efficiency of W263F was demonstrated, under severe stressing conditions, with respect to the best known phosphotriesterase PTE from Brevundimonas diminuta.
ESTHER : Merone_2010_Bioresour.Technol_101_9204
PubMedSearch : Merone_2010_Bioresour.Technol_101_9204
PubMedID: 20667718

Title : Detoxification of nerve agents by a substituted beta-cyclodextrin: application of a modified biological assay - Wille_2009_Toxicology_265_96
Author(s) : Wille T , Tenberken O , Reiter G , Muller S , Le Provost R , Lafont O , Estour F , Thiermann H , Worek F
Ref : Toxicology , 265 :96 , 2009
Abstract : Chemical warfare agents (nerve agents) are still available and present a real threat to the population. Numerous in vitro and in vivo studies showed that various nerve agents, e.g. tabun and cyclosarin, are resistant towards standard therapy with atropine and oxime. Based on these facts we applied a modified biological assay for the easy, semi-quantitative testing of the detoxifying properties of the beta-cyclodextrin derivative CD-IBA. Cyclosarin, sarin, tabun and VX were incubated with CD-IBA for 1-50 min at 37 degrees C, then an aliquot was added to erythrocyte acetylcholinesterase (AChE) and the percentage of AChE inhibition was determined. The validity of the assay was confirmed by concomitant quantification of tabun by GC-MS. Different concentrations of cyclosarin were detoxified by CD-IBA in a concentration-dependent velocity. The ability to detoxify various nerve agents decreased in the order cyclosarin>sarin>tabun>>VX. Hereby, no detoxification of VX could be detected. Sarin was detoxified in a biphasic reaction with a fast reduction of inhibitory potential in the first phase and a slower detoxification in the second phase. CD-IBA detoxified tabun in a one phase decay and, compared to cyclosarin and sarin, a longer half-life was determined with tabun. The modified biological assay is appropriate for the initial semi-quantitative screening of candidate compounds for the detoxification of nerve agents. The beta-cyclodextrin derivative CD-IBA demonstrated its ability to detoxify different nerve agents.
ESTHER : Wille_2009_Toxicology_265_96
PubMedSearch : Wille_2009_Toxicology_265_96
PubMedID: 19800384

Title : The B73 maize genome: complexity, diversity, and dynamics - Schnable_2009_Science_326_1112
Author(s) : Schnable PS , Ware D , Fulton RS , Stein JC , Wei F , Pasternak S , Liang C , Zhang J , Fulton L , Graves TA , Minx P , Reily AD , Courtney L , Kruchowski SS , Tomlinson C , Strong C , Delehaunty K , Fronick C , Courtney B , Rock SM , Belter E , Du F , Kim K , Abbott RM , Cotton M , Levy A , Marchetto P , Ochoa K , Jackson SM , Gillam B , Chen W , Yan L , Higginbotham J , Cardenas M , Waligorski J , Applebaum E , Phelps L , Falcone J , Kanchi K , Thane T , Scimone A , Thane N , Henke J , Wang T , Ruppert J , Shah N , Rotter K , Hodges J , Ingenthron E , Cordes M , Kohlberg S , Sgro J , Delgado B , Mead K , Chinwalla A , Leonard S , Crouse K , Collura K , Kudrna D , Currie J , He R , Angelova A , Rajasekar S , Mueller T , Lomeli R , Scara G , Ko A , Delaney K , Wissotski M , Lopez G , Campos D , Braidotti M , Ashley E , Golser W , Kim H , Lee S , Lin J , Dujmic Z , Kim W , Talag J , Zuccolo A , Fan C , Sebastian A , Kramer M , Spiegel L , Nascimento L , Zutavern T , Miller B , Ambroise C , Muller S , Spooner W , Narechania A , Ren L , Wei S , Kumari S , Faga B , Levy MJ , McMahan L , Van Buren P , Vaughn MW , Ying K , Yeh CT , Emrich SJ , Jia Y , Kalyanaraman A , Hsia AP , Barbazuk WB , Baucom RS , Brutnell TP , Carpita NC , Chaparro C , Chia JM , Deragon JM , Estill JC , Fu Y , Jeddeloh JA , Han Y , Lee H , Li P , Lisch DR , Liu S , Liu Z , Nagel DH , McCann MC , SanMiguel P , Myers AM , Nettleton D , Nguyen J , Penning BW , Ponnala L , Schneider KL , Schwartz DC , Sharma A , Soderlund C , Springer NM , Sun Q , Wang H , Waterman M , Westerman R , Wolfgruber TK , Yang L , Yu Y , Zhang L , Zhou S , Zhu Q , Bennetzen JL , Dawe RK , Jiang J , Jiang N , Presting GG , Wessler SR , Aluru S , Martienssen RA , Clifton SW , McCombie WR , Wing RA , Wilson RK
Ref : Science , 326 :1112 , 2009
Abstract : We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.
ESTHER : Schnable_2009_Science_326_1112
PubMedSearch : Schnable_2009_Science_326_1112
PubMedID: 19965430
Gene_locus related to this paper: maize-b4ffc7 , maize-b6u7e1 , maize-c0pcy5 , maize-c0pgf7 , maize-c0pgw1 , maize-c0pfl3 , maize-b4fpr7 , maize-k7vy73 , maize-a0a096swr3 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a1d6nse2 , maize-c4j9a1 , maize-k7uba1

Title : Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis - Carlton_2007_Science_315_207
Author(s) : Carlton JM , Hirt RP , Silva JC , Delcher AL , Schatz M , Zhao Q , Wortman JR , Bidwell SL , Alsmark UC , Besteiro S , Sicheritz-Ponten T , Noel CJ , Dacks JB , Foster PG , Simillion C , Van de Peer Y , Miranda-Saavedra D , Barton GJ , Westrop GD , Muller S , Dessi D , Fiori PL , Ren Q , Paulsen I , Zhang H , Bastida-Corcuera FD , Simoes-Barbosa A , Brown MT , Hayes RD , Mukherjee M , Okumura CY , Schneider R , Smith AJ , Vanacova S , Villalvazo M , Haas BJ , Pertea M , Feldblyum TV , Utterback TR , Shu CL , Osoegawa K , de Jong PJ , Hrdy I , Horvathova L , Zubacova Z , Dolezal P , Malik SB , Logsdon JM, Jr. , Henze K , Gupta A , Wang CC , Dunne RL , Upcroft JA , Upcroft P , White O , Salzberg SL , Tang P , Chiu CH , Lee YS , Embley TM , Coombs GH , Mottram JC , Tachezy J , Fraser-Liggett CM , Johnson PJ
Ref : Science , 315 :207 , 2007
Abstract : We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the approximately 160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.
ESTHER : Carlton_2007_Science_315_207
PubMedSearch : Carlton_2007_Science_315_207
PubMedID: 17218520
Gene_locus related to this paper: triva-a2d7i4 , triva-a2d9w5 , triva-a2d766 , triva-a2dah5 , triva-a2dlx9 , triva-a2dul1 , triva-a2dy49 , triva-a2e6h5 , triva-a2e7p9 , triva-a2e9l3 , triva-a2e414 , triva-a2e613 , triva-a2e983 , triva-a2eau8 , triva-a2ekb9 , triva-a2en58 , triva-a2erp5 , triva-a2et59 , triva-a2f7u4 , triva-a2f801 , triva-a2fa76 , triva-a2fbq3 , triva-a2fe47 , triva-a2fgl0 , triva-a2fhp7 , triva-a2fie6 , triva-a2fk22 , triva-a2fla2 , triva-a2fqm0 , triva-a2fqq2 , triva-a2frq0 , triva-a2frr3 , triva-a2fsq9 , triva-a2fsz5 , triva-a2fux4 , triva-a2fz57 , triva-a2g2h0 , triva-a2g9x0 , triva-a2fqi4

Title : Complete DNA sequence of yeast chromosome II - Feldmann_1994_EMBO.J_13_5795
Author(s) : Feldmann H , Aigle M , Aljinovic G , Andre B , Baclet MC , Barthe C , Baur A , Becam AM , Biteau N , Boles E , Brandt T , Brendel M , Bruckner M , Bussereau F , Christiansen C , Contreras R , Crouzet M , Cziepluch C , Demolis N , Delaveau T , Doignon F , Domdey H , Dusterhus S , Dubois E , Dujon B , El Bakkoury M , Entian KD , Feurmann M , Fiers W , Fobo GM , Fritz C , Gassenhuber H , Glandsdorff N , Goffeau A , Grivell LA , de Haan M , Hein C , Herbert CJ , Hollenberg CP , Holmstrom K , Jacq C , Jacquet M , Jauniaux JC , Jonniaux JL , Kallesoe T , Kiesau P , Kirchrath L , Kotter P , Korol S , Liebl S , Logghe M , Lohan AJ , Louis EJ , Li ZY , Maat MJ , Mallet L , Mannhaupt G , Messenguy F , Miosga T , Molemans F , Muller S , Nasr F , Obermaier B , Perea J , Pierard A , Piravandi E , Pohl FM , Pohl TM , Potier S , Proft M , Purnelle B , Ramezani Rad M , Rieger M , Rose M , Schaaff-Gerstenschlager I , Scherens B , Schwarzlose C , Skala J , Slonimski PP , Smits PH , Souciet JL , Steensma HY , Stucka R , Urrestarazu A , van der Aart QJ , van Dyck L , Vassarotti A , Vetter I , Vierendeels F , Vissers S , Wagner G , de Wergifosse P , Wolfe KH , Zagulski M , Zimmermann FK , Mewes HW , Kleine K , Dsterhus S , Mller S , Pirard A , Schaaff-Gerstenschlger I
Ref : EMBO Journal , 13 :5795 , 1994
Abstract : In the framework of the EU genome-sequencing programmes, the complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome II (807 188 bp) has been determined. At present, this is the largest eukaryotic chromosome entirely sequenced. A total of 410 open reading frames (ORFs) were identified, covering 72% of the sequence. Similarity searches revealed that 124 ORFs (30%) correspond to genes of known function, 51 ORFs (12.5%) appear to be homologues of genes whose functions are known, 52 others (12.5%) have homologues the functions of which are not well defined and another 33 of the novel putative genes (8%) exhibit a degree of similarity which is insufficient to confidently assign function. Of the genes on chromosome II, 37-45% are thus of unpredicted function. Among the novel putative genes, we found several that are related to genes that perform differentiated functions in multicellular organisms of are involved in malignancy. In addition to a compact arrangement of potential protein coding sequences, the analysis of this chromosome confirmed general chromosome patterns but also revealed particular novel features of chromosomal organization. Alternating regional variations in average base composition correlate with variations in local gene density along chromosome II, as observed in chromosomes XI and III. We propose that functional ARS elements are preferably located in the AT-rich regions that have a spacing of approximately 110 kb. Similarly, the 13 tRNA genes and the three Ty elements of chromosome II are found in AT-rich regions. In chromosome II, the distribution of coding sequences between the two strands is biased, with a ratio of 1.3:1. An interesting aspect regarding the evolution of the eukaryotic genome is the finding that chromosome II has a high degree of internal genetic redundancy, amounting to 16% of the coding capacity.
ESTHER : Feldmann_1994_EMBO.J_13_5795
PubMedSearch : Feldmann_1994_EMBO.J_13_5795
PubMedID: 7813418
Gene_locus related to this paper: yeast-LDH1 , yeast-MCFS2 , yeast-yby9