Wagner M

References (14)

Title : The clinical and molecular landscape of congenital myasthenic syndromes in Austria: a nationwide study - Krenn_2022_J.Neurol__
Author(s) : Krenn M , Sener M , Rath J , Zulehner G , Keritam O , Wagner M , Laccone F , Iglseder S , Marte S , Baumgartner M , Eisenkolbl A , Liechtenstein C , Rudnik S , Quasthoff S , Grinzinger S , Spenger J , Wortmann SB , Loscher WN , Zimprich F , Kellersmann A , Rappold M , Bernert G , Freilinger M , Cetin H
Ref : Journal of Neurology , : , 2022
Abstract : BACKGROUND: Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by genetic defects resulting in impaired neuromuscular transmission. Although effective treatments are available, CMS is probably underdiagnosed, and systematic clinico-genetic investigations are warranted. METHODS: We used a nationwide approach to collect Austrian patients with genetically confirmed CMS. We provide a clinical and molecular characterization of this cohort and aimed to ascertain the current frequency of CMS in Austria. RESULTS: Twenty-eight cases with genetically confirmed CMS were identified, corresponding to an overall prevalence of 3.1 per million (95% CI 2.0-4.3) in Austria. The most frequent genetic etiology was CHRNE (n = 13), accounting for 46.4% of the cohort. Within this subgroup, the variant c.1327del, p.(Glu443Lysfs*64) was detected in nine individuals. Moreover, causative variants were found in DOK7 (n = 4), RAPSN (n = 3), COLQ (n = 2), GMPPB (n = 2), CHAT (n = 1), COL13A1 (n = 1), MUSK (n = 1) and AGRN (n = 1). Clinical onset within the first year of life was reported in one half of the patients. Across all subtypes, the most common symptoms were ptosis (85.7%), lower limb (67.9%), upper limb (60.7%) and facial weakness (60.7%). The majority of patients (96.4%) received specific treatment, including acetylcholinesterase inhibitors in 20, adrenergic agonists in 11 and 3,4-diaminopyridine in nine patients. CONCLUSIONS: Our study presents the first systematic characterization of individuals with CMS in Austria, providing prevalence estimates and genotype-phenotype correlations that may help to improve the diagnostic approach and patient management.
ESTHER : Krenn_2022_J.Neurol__
PubMedSearch : Krenn_2022_J.Neurol__
PubMedID: 36308527

Title : A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway - Lehmann_2018_Nat.Med_24_62
Author(s) : Lehmann LH , Jebessa ZH , Kreusser MM , Horsch A , He T , Kronlage M , Dewenter M , Sramek V , Oehl U , Krebs-Haupenthal J , von der Lieth AH , Schmidt A , Sun Q , Ritterhoff J , Finke D , Volkers M , Jungmann A , Sauer SW , Thiel C , Nickel A , Kohlhaas M , Schafer M , Sticht C , Maack C , Gretz N , Wagner M , El-Armouche A , Maier LS , Londono JEC , Meder B , Freichel M , Grone HJ , Most P , Muller OJ , Herzig S , Furlong EEM , Katus HA , Backs J
Ref : Nat Med , 24 :62 , 2018
Abstract : The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely, exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific deletion of Hdac4 show reduced exercise capacity, which was characterized by cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that NR4A1 negatively regulated contractile function in a manner that depended on the HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in which epigenetic regulation of a metabolic pathway affects calcium handling. Activation of this axis during intermittent physiological stress promotes cardiac function, whereas its impairment in sustained pathological cardiac stress leads to heart failure.
ESTHER : Lehmann_2018_Nat.Med_24_62
PubMedSearch : Lehmann_2018_Nat.Med_24_62
PubMedID: 29227474

Title : The genome of the ammonia-oxidizing Candidatus Nitrososphaera gargensis: insights into metabolic versatility and environmental adaptations - Spang_2012_Environ.Microbiol_14_3122
Author(s) : Spang A , Poehlein A , Offre P , Zumbragel S , Haider S , Rychlik N , Nowka B , Schmeisser C , Lebedeva EV , Rattei T , Bohm C , Schmid M , Galushko A , Hatzenpichler R , Weinmaier T , Daniel R , Schleper C , Spieck E , Streit WR , Wagner M
Ref : Environ Microbiol , 14 :3122 , 2012
Abstract : The cohort of the ammonia-oxidizing archaea (AOA) of the phylum Thaumarchaeota is a diverse, widespread and functionally important group of microorganisms in many ecosystems. However, our understanding of their biology is still very rudimentary in part because all available genome sequences of this phylum are from members of the Nitrosopumilus cluster. Here we report on the complete genome sequence of Candidatus Nitrososphaera gargensis obtained from an enrichment culture, representing a different evolutionary lineage of AOA frequently found in high numbers in many terrestrial environments. With its 2.83 Mb the genome is much larger than that of other AOA. The presence of a high number of (active) IS elements/transposases, genomic islands, gene duplications and a complete CRISPR/Cas defence system testifies to its dynamic evolution consistent with low degree of synteny with other thaumarchaeal genomes. As expected, the repertoire of conserved enzymes proposed to be required for archaeal ammonia oxidation is encoded by N. gargensis, but it can also use urea and possibly cyanate as alternative ammonia sources. Furthermore, its carbon metabolism is more flexible at the central pyruvate switch point, encompasses the ability to take up small organic compounds and might even include an oxidative pentose phosphate pathway. Furthermore, we show that thaumarchaeota produce cofactor F420 as well as polyhydroxyalkanoates. Lateral gene transfer from bacteria and euryarchaeota has contributed to the metabolic versatility of N. gargensis. This organisms is well adapted to its niche in a heavy metal-containing thermal spring by encoding a multitude of heavy metal resistance genes, chaperones and mannosylglycerate as compatible solute and has the genetic ability to respond to environmental changes by signal transduction via a large number of two-component systems, by chemotaxis and flagella-mediated motility and possibly even by gas vacuole formation. These findings extend our understanding of thaumarchaeal evolution and physiology and offer many testable hypotheses for future experimental research on these nitrifiers.
ESTHER : Spang_2012_Environ.Microbiol_14_3122
PubMedSearch : Spang_2012_Environ.Microbiol_14_3122
PubMedID: 23057602
Gene_locus related to this paper: nitgg-k0im51

Title : Complete genome sequences of Desulfosporosinus orientis DSM765T, Desulfosporosinus youngiae DSM17734T, Desulfosporosinus meridiei DSM13257T, and Desulfosporosinus acidiphilus DSM22704T - Pester_2012_J.Bacteriol_194_6300
Author(s) : Pester M , Brambilla E , Alazard D , Rattei T , Weinmaier T , Han J , Lucas S , Lapidus A , Cheng JF , Goodwin L , Pitluck S , Peters L , Ovchinnikova G , Teshima H , Detter JC , Han CS , Tapia R , Land ML , Hauser L , Kyrpides NC , Ivanova NN , Pagani I , Huntmann M , Wei CL , Davenport KW , Daligault H , Chain PS , Chen A , Mavromatis K , Markowitz V , Szeto E , Mikhailova N , Pati A , Wagner M , Woyke T , Ollivier B , Klenk HP , Spring S , Loy A
Ref : Journal of Bacteriology , 194 :6300 , 2012
Abstract : Desulfosporosinus species are sulfate-reducing bacteria belonging to the Firmicutes. Their genomes will give insights into the genetic repertoire and evolution of sulfate reducers typically thriving in terrestrial environments and able to degrade toluene (Desulfosporosinus youngiae), to reduce Fe(III) (Desulfosporosinus meridiei, Desulfosporosinus orientis), and to grow under acidic conditions (Desulfosporosinus acidiphilus).
ESTHER : Pester_2012_J.Bacteriol_194_6300
PubMedSearch : Pester_2012_J.Bacteriol_194_6300
PubMedID: 23105050
Gene_locus related to this paper: desaj-i4dc82 , desmd-j7j1v2 , desod-g7wg97 , desaj-i4d5q8

Title : A Nitrospira metagenome illuminates the physiology and evolution of globally important nitrite-oxidizing bacteria - Lucker_2010_Proc.Natl.Acad.Sci.U.S.A_107_13479
Author(s) : Lucker S , Wagner M , Maixner F , Pelletier E , Koch H , Vacherie B , Rattei T , Damste JS , Spieck E , Le Paslier D , Daims H
Ref : Proc Natl Acad Sci U S A , 107 :13479 , 2010
Abstract : Nitrospira are barely studied and mostly uncultured nitrite-oxidizing bacteria, which are, according to molecular data, among the most diverse and widespread nitrifiers in natural ecosystems and biological wastewater treatment. Here, environmental genomics was used to reconstruct the complete genome of "Candidatus Nitrospira defluvii" from an activated sludge enrichment culture. On the basis of this first-deciphered Nitrospira genome and of experimental data, we show that Ca. N. defluvii differs dramatically from other known nitrite oxidizers in the key enzyme nitrite oxidoreductase (NXR), in the composition of the respiratory chain, and in the pathway used for autotrophic carbon fixation, suggesting multiple independent evolution of chemolithoautotrophic nitrite oxidation. Adaptations of Ca. N. defluvii to substrate-limited conditions include an unusual periplasmic NXR, which is constitutively expressed, and pathways for the transport, oxidation, and assimilation of simple organic compounds that allow a mixotrophic lifestyle. The reverse tricarboxylic acid cycle as the pathway for CO2 fixation and the lack of most classical defense mechanisms against oxidative stress suggest that Nitrospira evolved from microaerophilic or even anaerobic ancestors. Unexpectedly, comparative genomic analyses indicate functionally significant lateral gene-transfer events between the genus Nitrospira and anaerobic ammonium-oxidizing planctomycetes, which share highly similar forms of NXR and other proteins reflecting that two key processes of the nitrogen cycle are evolutionarily connected.
ESTHER : Lucker_2010_Proc.Natl.Acad.Sci.U.S.A_107_13479
PubMedSearch : Lucker_2010_Proc.Natl.Acad.Sci.U.S.A_107_13479
PubMedID: 20624973
Gene_locus related to this paper: 9bact-d8pbw6 , 9bact-d8pbw8 , 9bact-d8pch8 , 9bact-d8pdl3 , 9bact-d8pej0

Title : Deciphering the evolution and metabolism of an anammox bacterium from a community genome - Strous_2006_Nature_440_790
Author(s) : Strous M , Pelletier E , Mangenot S , Rattei T , Lehner A , Taylor MW , Horn M , Daims H , Bartol-Mavel D , Wincker P , Barbe V , Fonknechten N , Vallenet D , Segurens B , Schenowitz-Truong C , Medigue C , Collingro A , Snel B , Dutilh BE , Op den Camp HJ , van der Drift C , Cirpus I , van de Pas-Schoonen KT , Harhangi HR , van Niftrik L , Schmid M , Keltjens J , van de Vossenberg J , Kartal B , Meier H , Frishman D , Huynen MA , Mewes HW , Weissenbach J , Jetten MS , Wagner M , Le Paslier D
Ref : Nature , 440 :790 , 2006
Abstract : Anaerobic ammonium oxidation (anammox) has become a main focus in oceanography and wastewater treatment. It is also the nitrogen cycle's major remaining biochemical enigma. Among its features, the occurrence of hydrazine as a free intermediate of catabolism, the biosynthesis of ladderane lipids and the role of cytoplasm differentiation are unique in biology. Here we use environmental genomics--the reconstruction of genomic data directly from the environment--to assemble the genome of the uncultured anammox bacterium Kuenenia stuttgartiensis from a complex bioreactor community. The genome data illuminate the evolutionary history of the Planctomycetes and allow us to expose the genetic blueprint of the organism's special properties. Most significantly, we identified candidate genes responsible for ladderane biosynthesis and biological hydrazine metabolism, and discovered unexpected metabolic versatility.
ESTHER : Strous_2006_Nature_440_790
PubMedSearch : Strous_2006_Nature_440_790
PubMedID: 16598256
Gene_locus related to this paper: 9bact-q1py93 , 9bact-q1q3k9 , 9bact-q1q414

Title : Neuregulin effect on quantal content dissociated from effect on miniature endplate potential amplitude - Mann_2006_J.Neurophysiol_96_671
Author(s) : Mann MA , Das S , Zhang J , Wagner M , Fischbach GD
Ref : Journal of Neurophysiology , 96 :671 , 2006
Abstract : Members of the neuregulin family of signaling proteins increase transcription of acetylcholine receptor (AChR) subunit genes in muscle fibers and the number of AChRs in the muscle membrane. In adult mice heterozygous for targeted deletion of type I neuregulins (Ig-NRG(+/-)), postsynaptic AChR density was decreased and transmitter release was increased. We examined the relationship between functional AChR density and ACh release in postnatal day 7 (P7), P14, and adult NRG-deficient mice. Here we report that changes in postsynaptic sensitivity and transmitter release are not temporally coupled during postnatal development in Ig-NRG-deficient mice. Although miniature endplate potential (MEPP) amplitude was decreased compared with control in P7 Ig-NRG(+/-) mice, quantum content was not increased. Quantum content was increased in adult heterozygotes despite normal MEPP amplitudes. Thus, during postnatal maturation, both quantal size and quantum content were influenced by decreased Ig-NRG expression, although the effects were dissociated in time.
ESTHER : Mann_2006_J.Neurophysiol_96_671
PubMedSearch : Mann_2006_J.Neurophysiol_96_671
PubMedID: 16835362

Title : New insights into metabolic properties of marine bacteria encoding proteorhodopsins - Sabehi_2005_PLoS.Biol_3_e273
Author(s) : Sabehi G , Loy A , Jung KH , Partha R , Spudich JL , Isaacson T , Hirschberg J , Wagner M , Beja O
Ref : PLoS Biol , 3 :e273 , 2005
Abstract : Proteorhodopsin phototrophy was recently discovered in oceanic surface waters. In an effort to characterize uncultured proteorhodopsin-exploiting bacteria, large-insert bacterial artificial chromosome (BAC) libraries from the Mediterranean Sea and Red Sea were analyzed. Fifty-five BACs carried diverse proteorhodopsin genes, and we confirmed the function of five. We calculate that proteorhodopsin-exploiting bacteria account for 13% of microorganisms in the photic zone. We further show that some proteorhodopsin-containing bacteria possess a retinal biosynthetic pathway and a reverse sulfite reductase operon, employed by prokaryotes oxidizing sulfur compounds. Thus, these novel phototrophs are an unexpectedly large and metabolically diverse component of the marine microbial surface water.
ESTHER : Sabehi_2005_PLoS.Biol_3_e273
PubMedSearch : Sabehi_2005_PLoS.Biol_3_e273
PubMedID: 16008504
Gene_locus related to this paper: 9bact-q4pk85 , 9bact-q4pkb4

Title : Development and biological evaluation of acyl protein thioesterase 1 (APT1) inhibitors -
Author(s) : Deck P , Pendzialek D , Biel M , Wagner M , Popkirova B , Ludolph B , Kragol G , Kuhlmann J , Giannis A , Waldmann H
Ref : Angew Chem Int Ed Engl , 44 :4975 , 2005
PubMedID: 16003812

Title : The DNA sequence and biology of human chromosome 19 - Grimwood_2004_Nature_428_529
Author(s) : Grimwood J , Gordon LA , Olsen A , Terry A , Schmutz J , Lamerdin J , Hellsten U , Goodstein D , Couronne O , Tran-Gyamfi M , Aerts A , Altherr M , Ashworth L , Bajorek E , Black S , Branscomb E , Caenepeel S , Carrano A , Caoile C , Chan YM , Christensen M , Cleland CA , Copeland A , Dalin E , Dehal P , Denys M , Detter JC , Escobar J , Flowers D , Fotopulos D , Garcia C , Georgescu AM , Glavina T , Gomez M , Gonzales E , Groza M , Hammon N , Hawkins T , Haydu L , Ho I , Huang W , Israni S , Jett J , Kadner K , Kimball H , Kobayashi A , Larionov V , Leem SH , Lopez F , Lou Y , Lowry S , Malfatti S , Martinez D , McCready P , Medina C , Morgan J , Nelson K , Nolan M , Ovcharenko I , Pitluck S , Pollard M , Popkie AP , Predki P , Quan G , Ramirez L , Rash S , Retterer J , Rodriguez A , Rogers S , Salamov A , Salazar A , She X , Smith D , Slezak T , Solovyev V , Thayer N , Tice H , Tsai M , Ustaszewska A , Vo N , Wagner M , Wheeler J , Wu K , Xie G , Yang J , Dubchak I , Furey TS , DeJong P , Dickson M , Gordon D , Eichler EE , Pennacchio LA , Richardson P , Stubbs L , Rokhsar DS , Myers RM , Rubin EM , Lucas SM
Ref : Nature , 428 :529 , 2004
Abstract : Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G + C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.
ESTHER : Grimwood_2004_Nature_428_529
PubMedSearch : Grimwood_2004_Nature_428_529
PubMedID: 15057824

Title : Illuminating the evolutionary history of chlamydiae - Horn_2004_Science_304_728
Author(s) : Horn M , Collingro A , Schmitz-Esser S , Beier CL , Purkhold U , Fartmann B , Brandt P , Nyakatura GJ , Droege M , Frishman D , Rattei T , Mewes HW , Wagner M
Ref : Science , 304 :728 , 2004
Abstract : Chlamydiae are the major cause of preventable blindness and sexually transmitted disease. Genome analysis of a chlamydia-related symbiont of free-living amoebae revealed that it is twice as large as any of the pathogenic chlamydiae and had few signs of recent lateral gene acquisition. We showed that about 700 million years ago the last common ancestor of pathogenic and symbiotic chlamydiae was already adapted to intracellular survival in early eukaryotes and contained many virulence factors found in modern pathogenic chlamydiae, including a type III secretion system. Ancient chlamydiae appear to be the originators of mechanisms for the exploitation of eukaryotic cells.
ESTHER : Horn_2004_Science_304_728
PubMedSearch : Horn_2004_Science_304_728
PubMedID: 15073324
Gene_locus related to this paper: paruw-q6m9q5 , paruw-q6m9q7 , paruw-q6mcu6 , paruw-q6mev0

Title : Structure-activity relationships of new analogues of arecaidine propargyl ester at muscarinic M1 and M2 receptor subtypes - Moser_1989_Br.J.Pharmacol_96_319
Author(s) : Moser U , Lambrecht G , Wagner M , Wess J , Mutschler E
Ref : British Journal of Pharmacology , 96 :319 , 1989
Abstract : 1. The potency of arecaidine propargyl ester (APE) and of several analogues containing a modified ester side chain has been assessed at M1 and M2 muscarinic receptor subtypes. APE was shown to act as a potent agonist at ganglionic M1 receptors in the pithed rat, at M2 receptors in guinea-pig isolated atria (-log EC50 = 8.22) and ileum (-log EC50 = 7.77). 2. The arecaidine 2-butynyl and 2-pentynyl esters were approximately equipotent with APE at M1 and M2 receptors, whereas the 2-hexynyl derivative was found to be less potent than APE in atria (-log EC50 = 6.80) and ileum (-log EC50 = 6.70) by about one order of magnitude. The 2-heptynyl and 3-phenyl propargyl esters exhibited no agonist actions in atria and ileum. 3. Shifting the triple bond from the 2 to the 3 position and introducing a bulky group at position 1 of the ester side chain of APE and analogues resulted in competitive antagonists (pA2 ranging from 4.9 to 7.3). 4. APE and its 2-butynyl analogue showed some agonistic selectivity for cardiac M2 receptors (potency ratio, ileum/atria = 2.8 and 4.6 respectively). All antagonists in this series of compounds were not selective in terms of affinity since their pA2 values at cardiac and ileal M2 receptors were similar (potency ratios, ileum/atria = 0.4 to 1.2).
ESTHER : Moser_1989_Br.J.Pharmacol_96_319
PubMedSearch : Moser_1989_Br.J.Pharmacol_96_319
PubMedID: 2924082

Title : Poster: Antimuscarinic potencies of olefinic analogues related to hexahydro-difenidol at three muscarinic receptor subtypes -
Author(s) : Choo LK , Wagner M , Unterhalt B , Middelberg C , Tacke R , Strohmann C , Tafel A , Mutschler E , Lambrecht G
Ref : Trends in Pharmacological Sciences , Suppl :113 , 1989

Title : [The effect of the systemic and intraventricular application of orotic acid on monosynaptic evoked potentials in the dentate gyrus in free-moving rats] - Krug_1985_Biomed.Biochim.Acta_44_623
Author(s) : Krug M , Ruthrich H , Wagner M , Matthies R , Ott T
Ref : Biomedica Biochimica Acta , 44 :623 , 1985
Abstract : In 20 freely moving Wistar rats the influence of systemically and intraventricularly applied orotic acid derivatives on monosynaptically evoked field potentials registered in the dentate gyrus on the stimulation of the medial entorhinal cortex was investigated. Both, methylglucamine-orotate and tris-orotate led to an increase of the amplitude of the population spike. The slope function of the field EPSP, however, remained unchanged. The effect has been observed to begin 2 h after application and had a duration of 6-10 h. The data obtained in a monosynaptic pathway targeting on a brain structure which is known to play a crucial role in memory formation support earlier findings of a transient effect of orotic acid on cerebral excitation processes. An influence on mechanisms of spike generation or other postsynaptic membrane processes might be assumed.
ESTHER : Krug_1985_Biomed.Biochim.Acta_44_623
PubMedSearch : Krug_1985_Biomed.Biochim.Acta_44_623
PubMedID: 4026817