Krätzner, Ralph

[["dc.bibliographiccitation.firstpage","1174"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Inherited Metabolic Disease"],["dc.bibliographiccitation.lastpage","1185"],["dc.bibliographiccitation.volume","44"],["dc.contributor.affiliation","Klemp, Henry; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Nessler, Stefan; 2\r\nInstitute of Neuropathology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Streit, Frank; 3\r\nInstitute for Clinical Chemistry, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Krätzner, Ralph; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Rosewich, Hendrik; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Gärtner, Jutta; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.author","Kettwig, Matthias"],["dc.contributor.author","Klemp, Henry"],["dc.contributor.author","Nessler, Stefan"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Krätzner, Ralph"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2021-06-01T09:42:02Z"],["dc.date.available","2021-06-01T09:42:02Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T01:43:41Z"],["dc.description.abstract","Abstract X‐linked adrenoleukodystrophy (X‐ALD) is the most common leukodystrophy. Despite intensive research in recent years, it remains unclear, what drives the different clinical disease courses. Due to this missing pathophysiological link, therapy for the childhood cerebral disease course of X‐ALD (CCALD) remains symptomatic; the allogenic hematopoietic stem cell transplantation or hematopoietic stem‐cell gene therapy is an option for early disease stages. The inclusion of dried blood spot (DBS) C26:0‐lysophosphatidylcholine to newborn screening in an increasing number of countries is leading to an increasing number of X‐ALD patients diagnosed at risk for CCALD. Current follow‐up in asymptomatic boys with X‐ALD requires repetitive cerebral MRIs under sedation. A reliable and easily accessible biomarker that predicts CCALD would therefore be of great value. Here we report the application of targeted metabolomics by AbsoluteIDQ p180‐Kit from Biocrates to search for suitable biomarkers in X‐ALD. LysoPC a C20:3 and lysoPC a C20:4 were identified as metabolites that indicate neuroinflammation after induction of experimental autoimmune encephalitis in the serum of Abcd1tm1Kds mice. Analysis of serum from X‐ALD patients also revealed different concentrations of these lipids at different disease stages. Further studies in a larger cohort of X‐ALD patient sera are needed to prove the diagnostic value of these lipids for use as early biomarkers for neuroinflammation in CCALD patients."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","Niedersächsisches Ministerium für Wissenschaft und Kultur http://dx.doi.org/10.13039/501100010570"],["dc.description.sponsorship","Germany's Excellence Strategy"],["dc.description.sponsorship","Transregional Collaborative Research Center"],["dc.identifier.doi","10.1002/jimd.12389"],["dc.identifier.pmid","33855724"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85119"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/270"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1573-2665"],["dc.relation.issn","0141-8955"],["dc.relation.workinggroup","RG Gärtner"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes."],["dc.title","Targeted metabolomics revealed changes in phospholipids during the development of neuroinflammation in Abcd1 tm1Kds mice and X‐linked adrenoleukodystrophy patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","56"],["dc.bibliographiccitation.journal","Genome Medicine"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Stalmann, Robert"],["dc.contributor.author","Dalila, Nawar"],["dc.contributor.author","Chen, Jiayin"],["dc.contributor.author","Pojar, Sherin"],["dc.contributor.author","Pereira, Joao N. dos Santos"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.date.accessioned","2018-11-07T09:55:48Z"],["dc.date.available","2018-11-07T09:55:48Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: The organic cation transporter OCT1 (SLC22A1) mediates the uptake of vitamin B1, cationic drugs, and xenobiotics into hepatocytes. Nine percent of Caucasians lack or have very low OCT1 activity due to loss-of-function polymorphisms in OCT1 gene. Here we analyzed the global genetic variability in OCT1 to estimate the therapeutic relevance of OCT1 polymorphisms in populations beyond Caucasians and to identify evolutionary patterns of the common loss of OCT1 activity in humans. Methods: We applied massively parallel sequencing to screen for coding polymorphisms in 1,079 unrelated individuals from 53 populations worldwide. The obtained data was combined with the existing 1000 Genomes data comprising an additional 1,092 individuals from 14 populations. The identified OCT1 variants were characterized in vitro regarding their cellular localization and their ability to transport 10 known OCT1 substrates. Both the population genetics data and transport data were used in tandem to generate a world map of loss of OCT1 activity. Results: We identified 16 amino acid substitutions potentially causing loss of OCT1 function and analyzed them together with five amino acid substitutions that were not expected to affect OCT1 function. The variants constituted 16 major alleles and 14 sub-alleles. Six major alleles showed improper subcellular localization leading to substrate-wide loss in activity. Five major alleles showed correct subcellular localization, but substrate-specific loss of activity. Striking differences were observed in the frequency of loss of OCT1 activity worldwide. While most East Asian and Oceanian individuals had completely functional OCT1, 80 % of native South American Indians lacked functional OCT1 alleles. In East Asia and Oceania the average nucleotide diversity of the loss-of-function variants was much lower than that of the variants that do not affect OCT1 function (ratio of 0.03) and was significantly lower than the theoretically expected heterozygosity (Tajima's D=-1.64, P < 0.01). Conclusions: Comprehensive genetic analyses showed strong global variations in the frequency of loss of OCT1 activity with selection pressure for maintaining OCT1 activity in East Asia and Oceania. These results not only enable pharmacogenetically-based optimization of drug treatment worldwide, but may help elucidate the functional role of human OCT1."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2015"],["dc.identifier.doi","10.1186/s13073-015-0172-0"],["dc.identifier.isi","000357566500001"],["dc.identifier.pmid","26157489"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13466"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36829"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1756-994X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Global genetic analyses reveal strong inter-ethnic variability in the loss of activity of the organic cation transporter OCT1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1321"],["dc.bibliographiccitation.journal","Acta Crystallographica Section D Biological Crystallography"],["dc.bibliographiccitation.lastpage","1335"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Sidhu, Navdeep S."],["dc.contributor.author","Schreiber, Kathrin"],["dc.contributor.author","Proepper, Kevin"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Uson, Isabel"],["dc.contributor.author","Sheldrick, George M."],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Steinfeld, Robert"],["dc.date.accessioned","2017-09-07T11:46:15Z"],["dc.date.available","2017-09-07T11:46:15Z"],["dc.date.issued","2014"],["dc.description.abstract","Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 A resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder."],["dc.identifier.doi","10.1107/S1399004714002739"],["dc.identifier.gro","3142131"],["dc.identifier.isi","000335952500014"],["dc.identifier.pmid","24816101"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12116"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4888"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1399-0047"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","773"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Nature Genetics"],["dc.bibliographiccitation.lastpage","775"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Henneke, Marco"],["dc.contributor.author","Diekmann, Simone"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Kaiser, Jens"],["dc.contributor.author","Engelbrecht, Volkher"],["dc.contributor.author","Kohlschuetter, Alfried"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Madruga-Garrido, Marcos"],["dc.contributor.author","Mayer, Michele"],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Rodriguez, Diana"],["dc.contributor.author","Rueschendorf, Franz"],["dc.contributor.author","Schumacher, Johannes"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Thoms, Sven"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:46:53Z"],["dc.date.available","2017-09-07T11:46:53Z"],["dc.date.issued","2009"],["dc.description.abstract","Congenital cytomegalovirus brain infection without symptoms at birth can cause a static encephalopathy with characteristic patterns of brain abnormalities. Here we show that loss-of-function mutations in the gene encoding the RNASET2 glycoprotein lead to cystic leukoencephalopathy, an autosomal recessive disorder with an indistinguishable clinical and neuroradiological phenotype. Congenital cytomegalovirus infection and RNASET2 deficiency may both interfere with brain development and myelination through angiogenesis or RNA metabolism."],["dc.identifier.doi","10.1038/ng.398"],["dc.identifier.gro","3143090"],["dc.identifier.isi","000267786200005"],["dc.identifier.pmid","19525954"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6147"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/565"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1061-4036"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infection"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"],["local.message.claim","2020-08-07T08:23:16.626+0000|||rp114519|||submit_approve|||dc_contributor_author|||None"]]

[["dc.bibliographiccitation.firstpage","347"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Metabolites"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Klemp, Henry Gerd"],["dc.contributor.author","Kettwig, Matthias"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Krätzner, Ralph"],["dc.date.accessioned","2021-08-12T07:46:01Z"],["dc.date.available","2021-08-12T07:46:01Z"],["dc.date.issued","2021"],["dc.description.abstract","Peroxisomes are central hubs for cell metabolism and their dysfunction is linked to devastating human disorders, such as peroxisomal biogenesis disorders and single peroxisomal enzyme/protein deficiencies. For decades, biochemical diagnostics have been carried out using classical markers such as very long-chain fatty acids (VLCFA), which can be inconspicuous in milder and atypical cases. Holistic metabolomics studies revealed several potentially new biomarkers for peroxisomal disorders for advanced laboratory diagnostics including atypical cases. However, establishing these new markers is a major challenge in routine diagnostic laboratories. We therefore investigated whether the commercially available AbsoluteIDQ p180 kit (Biocrates Lifesciences), which utilizes flow injection and liquid chromatography mass spectrometry, may be used to reproduce some key results from previous global metabolomics studies. We applied it to serum samples from patients with mutations in peroxisomal target genes PEX1, ABCD1, and the HSD17B4 gene. Here we found various changes in sphingomyelins and lysophosphatidylcholines. In conclusion, this kit can be used to carry out extended diagnostics for peroxisomal disorders in routine laboratories, even without access to a metabolomics unit."],["dc.description.abstract","Peroxisomes are central hubs for cell metabolism and their dysfunction is linked to devastating human disorders, such as peroxisomal biogenesis disorders and single peroxisomal enzyme/protein deficiencies. For decades, biochemical diagnostics have been carried out using classical markers such as very long-chain fatty acids (VLCFA), which can be inconspicuous in milder and atypical cases. Holistic metabolomics studies revealed several potentially new biomarkers for peroxisomal disorders for advanced laboratory diagnostics including atypical cases. However, establishing these new markers is a major challenge in routine diagnostic laboratories. We therefore investigated whether the commercially available AbsoluteIDQ p180 kit (Biocrates Lifesciences), which utilizes flow injection and liquid chromatography mass spectrometry, may be used to reproduce some key results from previous global metabolomics studies. We applied it to serum samples from patients with mutations in peroxisomal target genes PEX1, ABCD1, and the HSD17B4 gene. Here we found various changes in sphingomyelins and lysophosphatidylcholines. In conclusion, this kit can be used to carry out extended diagnostics for peroxisomal disorders in routine laboratories, even without access to a metabolomics unit."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3390/metabo11060347"],["dc.identifier.pii","metabo11060347"],["dc.identifier.pmid","34072483"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88599"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/413"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2218-1989"],["dc.relation.orgunit","Klinik für Kinder- und Jugendmedizin"],["dc.relation.workinggroup","RG Gärtner"],["dc.rights","CC BY 4.0"],["dc.title","LC-MS Based Platform Simplifies Access to Metabolomics for Peroxisomal Disorders"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","354"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","363"],["dc.bibliographiccitation.volume","85"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Helms, Gunther"],["dc.contributor.author","Dechent, Peter"],["dc.contributor.author","Wevers, Ron"],["dc.contributor.author","Grosso, Salvatore"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2019-07-09T11:52:56Z"],["dc.date.available","2019-07-09T11:52:56Z"],["dc.date.issued","2009"],["dc.description.abstract","Sufficient folate supplementation is essential for a multitude of biological processes and diverse organ systems. At least five distinct inherited disorders of folate transport and metabolism are presently known, all of which cause systemic folate deficiency.We identified an inherited brain-specific folate transport defect that is caused by mutations in the folate receptor 1 (FOLR1) gene coding for folate receptor alpha (FRa). Three patients carrying FOLR1 mutations developed progressive movement disturbance, psychomotor decline, and epilepsy and showed severely reduced folate concentrations in the cerebrospinal fluid (CSF). Brain magnetic resonance imaging (MRI) demonstrated profound hypomyelination, and MR-based in vivo metabolite analysis indicated a combined depletion of white-matter choline and inositol. Retroviral transfection of patient cells with either FRa or FRb could rescue folate binding. Furthermore, CSF folate concentrations, as well as glial choline and inositol depletion, were restored by folinic acid therapy and preceded clinical improvements. Our studies not only characterize a previously unknown and treatable disorder of early childhood, but also provide new insights into the folate metabolic pathways involved in postnatal myelination and brain development."],["dc.identifier.doi","10.1016/j.ajhg.2009.08.005."],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6177"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60304"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Folate Receptor Alpha Defect Causes Cerebral Folate Transport Deficiency: A Treatable Neurodegenerative Disorder Associated with Disturbed Myelin Metabolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","13540"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.affiliation","Buentzel, Judith; 1Department of Hematology and Medical Oncology, University Medical Center Goettingen, 37075 Goettingen, Germany; mschulz@gdwg.de (M.S.); annalen.bleckmann@ukmuenster.de (A.B.); claudia.binder@med.uni-goettingen.de (C.B.)"],["dc.contributor.affiliation","Klemp, Henry Gerd; 2Department of Pediatrics and Adolescent Medicine, University Medical Center Goettingen, 37075 Goettingen, Germany; henrygerd.klemp@stud.uni-goettingen.de (H.G.K.); rkraetzner@gwdg.de (R.K.)"],["dc.contributor.affiliation","Kraetzner, Ralph; 2Department of Pediatrics and Adolescent Medicine, University Medical Center Goettingen, 37075 Goettingen, Germany; henrygerd.klemp@stud.uni-goettingen.de (H.G.K.); rkraetzner@gwdg.de (R.K.)"],["dc.contributor.affiliation","Schulz, Matthias; 1Department of Hematology and Medical Oncology, University Medical Center Goettingen, 37075 Goettingen, Germany; mschulz@gdwg.de (M.S.); annalen.bleckmann@ukmuenster.de (A.B.); claudia.binder@med.uni-goettingen.de (C.B.)"],["dc.contributor.affiliation","Dihazi, Gry Helene; 3Metabolomics Platform, Department of Clinical Chemistry, University Medical Center Goettingen, 37075 Goettingen, Germany; gryhelene.dihazi@med.uni-goettingen.de (G.H.D.); frank.streit@med.uni-goettingen.de (F.S.)"],["dc.contributor.affiliation","Streit, Frank; 3Metabolomics Platform, Department of Clinical Chemistry, University Medical Center Goettingen, 37075 Goettingen, Germany; gryhelene.dihazi@med.uni-goettingen.de (G.H.D.); frank.streit@med.uni-goettingen.de (F.S.)"],["dc.contributor.affiliation","Bleckmann, Annalen; 1Department of Hematology and Medical Oncology, University Medical Center Goettingen, 37075 Goettingen, Germany; mschulz@gdwg.de (M.S.); annalen.bleckmann@ukmuenster.de (A.B.); claudia.binder@med.uni-goettingen.de (C.B.)"],["dc.contributor.affiliation","Menck, Kerstin; 4Department of Medicine A (Hematology, Oncology, Hemostaseology and Pulmonology), University Hospital Muenster, 48149 Muenster, Germany; kerstin.menck@ukmuenster.de"],["dc.contributor.affiliation","Wlochowitz, Darius; 5Medical Bioinformatics, University Medical Center Goettingen, 37075 Goettingen, Germany; dwl@bioinf.med.uni-goettingen.de"],["dc.contributor.affiliation","Binder, Claudia; 1Department of Hematology and Medical Oncology, University Medical Center Goettingen, 37075 Goettingen, Germany; mschulz@gdwg.de (M.S.); annalen.bleckmann@ukmuenster.de (A.B.); claudia.binder@med.uni-goettingen.de (C.B.)"],["dc.contributor.author","Buentzel, Judith"],["dc.contributor.author","Klemp, Henry Gerd"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Dihazi, Gry Helene"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Wlochowitz, Darius"],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2022-01-11T14:05:29Z"],["dc.date.available","2022-01-11T14:05:29Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-03T19:53:04Z"],["dc.description.abstract","Malignant cells differ from benign ones in their metabolome and it is largely unknown whether this difference is reflected in the metabolic profile of their microvesicles (MV), which are secreted into the blood of cancer patients. Here, they are present together with MV from the various blood and endothelial cells. Harvesting MV from 78 breast cancer patients (BC) and 30 controls, we characterized the whole blood MV metabolome using targeted and untargeted mass spectrometry. Especially (lyso)-phosphatidylcholines and sphingomyelins were detected in a relevant abundance. Eight metabolites showed a significant discriminatory power between BC and controls. High concentrations of lysoPCaC26:0 and PCaaC38:5 were associated with shorter overall survival. Comparing BC subtype-specific metabolome profiles, 24 metabolites were differentially expressed between luminal A and luminal B. Pathway analysis revealed alterations in the glycerophospholipid metabolism for the whole cancer cohort and in the ether lipid metabolism for the molecular subtype luminal B. Although this mixture of blood-derived MV contains only a minor number of tumor MV, a combination of metabolites was identified that distinguished between BC and controls as well as between molecular subtypes, and was predictive for overall survival. This suggests that these metabolites represent promising biomarkers and, moreover, that they may be functionally relevant for tumor progression."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3390/ijms222413540"],["dc.identifier.pii","ijms222413540"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97673"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Metabolomic Profiling of Blood-Derived Microvesicles in Breast Cancer Patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8733"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","8742"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Thorn, Andrea"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Ziegenbein, Marc"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Sheldrick, George M."],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Kraetzner, Ralph"],["dc.date.accessioned","2017-09-07T11:48:25Z"],["dc.date.available","2017-09-07T11:48:25Z"],["dc.date.issued","2012"],["dc.description.abstract","Mutations in the gene of human RNase T2 are associated with white matter disease of the human brain. Although brain abnormalities (bilateral temporal lobe cysts and multifocal white matter lesions) and clinical symptoms (psychomotor impairments, spasticity and epilepsy) are well characterized, the pathomechanism of RNase T2 deficiency remains unclear. RNase T2 is the only member of the Rh/T2/S family of acidic hydrolases in humans. In recent years, new functions such as tumor suppressing properties of RNase T2 have been reported that are independent of its catalytic activity. We determined the X-ray structure of human RNase T2 at 1.6 A resolution. The alpha+beta core fold shows high similarity to those of known T2 RNase structures from plants, while, in contrast, the external loop regions show distinct structural differences. The catalytic features of RNase T2 in presence of bivalent cations were analyzed and the structural consequences of known clinical mutations were investigated. Our data provide further insight into the function of human RNase T2 and may prove useful in understanding its mode of action independent of its enzymatic activity."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2012"],["dc.identifier.doi","10.1093/nar/gks614"],["dc.identifier.gro","3142467"],["dc.identifier.isi","000309464300054"],["dc.identifier.pmid","22735700"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7944"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8607"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0305-1048"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Structure and activity of the only human RNase T2"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]