Stadelmann-Nessler, Christine

[["dc.bibliographiccitation.artnumber","andr.13292"],["dc.bibliographiccitation.firstpage","1660"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Andrology"],["dc.bibliographiccitation.lastpage","1672"],["dc.bibliographiccitation.volume","10"],["dc.contributor.affiliation","Pinkert‐Leetsch, Diana; 1\r\nDepartment of Diagnostic and Interventional Radiology\r\nUniversity Medical Center Goettingen\r\nGoettingen Germany"],["dc.contributor.affiliation","Rost, John Uwe; 1\r\nDepartment of Diagnostic and Interventional Radiology\r\nUniversity Medical Center Goettingen\r\nGoettingen Germany"],["dc.contributor.affiliation","Schmiedeknecht, Max Ulrich Heiner; 3\r\nDepartment of Neuropathology\r\nUniversity Medical Center Goettingen\r\nGoettingen Germany"],["dc.contributor.affiliation","Stadelmann, Christine; 3\r\nDepartment of Neuropathology\r\nUniversity Medical Center Goettingen\r\nGoettingen Germany"],["dc.contributor.affiliation","Alves, Frauke; 1\r\nDepartment of Diagnostic and Interventional Radiology\r\nUniversity Medical Center Goettingen\r\nGoettingen Germany"],["dc.contributor.author","Pinkert‐Leetsch, Diana"],["dc.contributor.author","Rost, John Uwe"],["dc.contributor.author","Schmiedeknecht, Max Ulrich Heiner"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Missbach‐Guentner, Jeannine"],["dc.date.accessioned","2022-11-28T08:48:04Z"],["dc.date.available","2022-11-28T08:48:04Z"],["dc.date.issued","2022-09-15"],["dc.date.updated","2022-11-27T10:10:46Z"],["dc.description.abstract","Abstract\r\n\r\nBackground\r\nThe unique anatomy of the male reproductive organ reflects its complex function from sperm maturation to their storage for months until emission. Since light microscopy in two dimensions (2d) cannot sufficiently demonstrate its complex morphology, a comprehensive visualization is required to identify pathologic alterations in its entire anatomical context.\r\n\r\n\r\nObjectives\r\nAim of this study was to use three‐dimensional (3d) light sheet fluorescence microscopy (LSFM) to visualize entire murine testes in 3d, label‐free and at subcellular resolution, and to assign local autofluorescence to testicular and deferent structures.\r\n\r\n\r\nMaterials and methods\r\nMurine testes were fixed with four different fixatives and subsequently cleared with benzoic acid/benzyl benzoate. Hereafter, complete murine testes were scanned with LSFM with different fluorescence filter sets and subsequently embedded in paraffin for further conventional planar histology.\r\n\r\n\r\nResults\r\nAutofluorescence signals of the murine reproductive organ allowed the unambiguous identification of the testicular anatomy from the seminiferous tubules to the vas deferens with their specific stratification independent of the used fixative. Blood vessels were visualized from the pampiniform plexus to the small capillaries of single tubules. Moreover, due to the specific intrinsic fluorescence properties of the efferent ducts and the epididymis, luminal caliber, the epithelial stratification and retronuclear cytoplasmic inclusions gave a unique insight into the interface of both morphological structures. Subsequent 2d histology confirmed the identified morphological structures.\r\n\r\n\r\nDiscussion\r\nLSFM analysis of the murine reproductive organ allows due to its intrinsic fluorescence a simple, label‐free 3d assessment of its entire duct morphology, the epithelial composition, and the associated blood supply in its anatomical relation.\r\n\r\n\r\nConclusion\r\nLSFM provides the technical basis for comprehensive analyses of pathologically altered murine testes in its entirety by depicting specific autofluorescence. Thereby it facilitates mouse studies of testicular disease or their drug‐related alterations in more detail potentially for clinical translation assessing human testicular biopsies."],["dc.description.sponsorship","Bundesministerium fuer Bildung und Forschung, Deutschland"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1111/andr.13292"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117280"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-600"],["dc.relation.eissn","2047-2927"],["dc.relation.issn","2047-2919"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made."],["dc.title","The murine male reproductive organ at a glance: Three‐dimensional insights and virtual histology using label‐free light sheet microcopy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","768"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Annals of clinical and translational neurology"],["dc.bibliographiccitation.lastpage","783"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Malviya, Manish"],["dc.contributor.author","Barman, Sumanta"],["dc.contributor.author","Golombeck, Kristin S."],["dc.contributor.author","Planagumà, Jesús"],["dc.contributor.author","Mannara, Francesco"],["dc.contributor.author","Strutz-Seebohm, Nathalie"],["dc.contributor.author","Wrzos, Claudia"],["dc.contributor.author","Demir, Fatih"],["dc.contributor.author","Baksmeier, Christine"],["dc.contributor.author","Steckel, Julia"],["dc.contributor.author","Falk, Kim Kristin"],["dc.contributor.author","Gross, Catharina C."],["dc.contributor.author","Kovac, Stjepana"],["dc.contributor.author","Bönte, Kathrin"],["dc.contributor.author","Johnen, Andreas"],["dc.contributor.author","Wandinger, Klaus-Peter"],["dc.contributor.author","Martín-García, Elena"],["dc.contributor.author","Becker, Albert J."],["dc.contributor.author","Elger, Christian E."],["dc.contributor.author","Klöcker, Nikolaj"],["dc.contributor.author","Wiendl, Heinz"],["dc.contributor.author","Meuth, Sven G."],["dc.contributor.author","Hartung, Hans-Peter"],["dc.contributor.author","Seebohm, Guiscard"],["dc.contributor.author","Leypoldt, Frank"],["dc.contributor.author","Maldonado, Rafael"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Dalmau, Josep"],["dc.contributor.author","Melzer, Nico"],["dc.contributor.author","Goebels, Norbert"],["dc.date.accessioned","2019-07-09T11:44:45Z"],["dc.date.available","2019-07-09T11:44:45Z"],["dc.date.issued","2017-11"],["dc.description.abstract","Objective: Autoimmune encephalitis is most frequently associated with anti-NMDAR autoantibodies. Their pathogenic relevance has been suggested by passive transfer of patients' cerebrospinal fluid (CSF) in mice in vivo. We aimed to analyze the intrathecal plasma cell repertoire, identify autoantibody-producing clones, and characterize their antibody signatures in recombinant form. Methods: Patients with recent onset typical anti-NMDAR encephalitis were subjected to flow cytometry analysis of the peripheral and intrathecal immune response before, during, and after immunotherapy. Recombinant human monoclonal antibodies (rhuMab) were cloned and expressed from matching immunoglobulin heavy- (IgH) and light-chain (IgL) amplicons of clonally expanded intrathecal plasma cells (cePc) and tested for their pathogenic relevance. Results: Intrathecal accumulation of B and plasma cells corresponded to the clinical course. The presence of cePc with hypermutated antigen receptors indicated an antigen-driven intrathecal immune response. Consistently, a single recombinant human GluN1-specific monoclonal antibody, rebuilt from intrathecal cePc, was sufficient to reproduce NMDAR epitope specificity in vitro. After intraventricular infusion in mice, it accumulated in the hippocampus, decreased synaptic NMDAR density, and caused severe reversible memory impairment, a key pathogenic feature of the human disease, in vivo. Interpretation: A CNS-specific humoral immune response is present in anti-NMDAR encephalitis specifically targeting the GluN1 subunit of the NMDAR. Using reverse genetics, we recovered the typical intrathecal antibody signature in recombinant form, and proved its pathogenic relevance by passive transfer of disease symptoms from man to mouse, providing the critical link between intrathecal immune response and the pathogenesis of anti-NMDAR encephalitis as a humorally mediated autoimmune disease."],["dc.identifier.doi","10.1002/acn3.444"],["dc.identifier.pmid","29159189"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14885"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59083"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2328-9503"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.subject.ddc","610"],["dc.title","NMDAR encephalitis: passive transfer from man to mouse by a recombinant antibody."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","856"],["dc.bibliographiccitation.issue","6518"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","860"],["dc.bibliographiccitation.volume","370"],["dc.contributor.author","Cantuti-Castelvetri, Ludovico"],["dc.contributor.author","Ojha, Ravi"],["dc.contributor.author","Pedro, Liliana D."],["dc.contributor.author","Djannatian, Minou"],["dc.contributor.author","Franz, Jonas"],["dc.contributor.author","Kuivanen, Suvi"],["dc.contributor.author","van der Meer, Franziska"],["dc.contributor.author","Kallio, Katri"],["dc.contributor.author","Kaya, Tuğberk"],["dc.contributor.author","Anastasina, Maria"],["dc.contributor.author","Smura, Teemu"],["dc.contributor.author","Levanov, Lev"],["dc.contributor.author","Szirovicza, Leonora"],["dc.contributor.author","Tobi, Allan"],["dc.contributor.author","Kallio-Kokko, Hannimari"],["dc.contributor.author","Österlund, Pamela"],["dc.contributor.author","Joensuu, Merja"],["dc.contributor.author","Meunier, Frédéric A."],["dc.contributor.author","Butcher, Sarah J."],["dc.contributor.author","Winkler, Martin Sebastian"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Helenius, Ari"],["dc.contributor.author","Gokce, Ozgun"],["dc.contributor.author","Teesalu, Tambet"],["dc.contributor.author","Hepojoki, Jussi"],["dc.contributor.author","Vapalahti, Olli"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Balistreri, Giuseppe"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2021-04-14T08:31:26Z"],["dc.date.available","2021-04-14T08:31:26Z"],["dc.date.issued","2020"],["dc.description.abstract","The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention."],["dc.identifier.doi","10.1126/science.abd2985"],["dc.identifier.pmid","33082293"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83594"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/73"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/8"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | A06: The role of lipid-sensing nuclear receptors as checkpoints in regulating phagocyte function during recovery from demyelinating injury"],["dc.relation.eissn","1095-9203"],["dc.relation.issn","0036-8075"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.relation.workinggroup","RG Cantuti"],["dc.relation.workinggroup","RG Gokce (Systems Neuroscience – Cell Diversity)"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.rights","CC BY 4.0"],["dc.title","Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity"],["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","6940"],["dc.bibliographiccitation.issue","27"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","6945"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Töpperwien, Mareike"],["dc.contributor.author","Meer, Franziska van der"],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2020-03-11T09:06:18Z"],["dc.date.available","2020-03-11T09:06:18Z"],["dc.date.issued","2018"],["dc.description.abstract","To quantitatively evaluate brain tissue and its corresponding function, knowledge of the 3D cellular distribution is essential. The gold standard to obtain this information is histology, a destructive and labor-intensive technique where the specimen is sliced and examined under a light microscope, providing 3D information at nonisotropic resolution. To overcome the limitations of conventional histology, we use phase-contrast X-ray tomography with optimized optics, reconstruction, and image analysis, both at a dedicated synchrotron radiation endstation, which we have equipped with X-ray waveguide optics for coherence and wavefront filtering, and at a compact laboratory source. As a proof-of-concept demonstration we probe the 3D cytoarchitecture in millimeter-sized punches of unstained human cerebellum embedded in paraffin and show that isotropic subcellular resolution can be reached at both setups throughout the specimen. To enable a quantitative analysis of the reconstructed data, we demonstrate automatic cell segmentation and localization of over 1 million neurons within the cerebellar cortex. This allows for the analysis of the spatial organization and correlation of cells in all dimensions by borrowing concepts from condensed-matter physics, indicating a strong short-range order and local clustering of the cells in the granular layer. By quantification of 3D neuronal \"packing,\" we can hence shed light on how the human cerebellum accommodates 80% of the total neurons in the brain in only 10% of its volume. In addition, we show that the distribution of neighboring neurons in the granular layer is anisotropic with respect to the Purkinje cell dendrites."],["dc.identifier.doi","10.1073/pnas.1801678115"],["dc.identifier.pmid","29915047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63291"],["dc.language.iso","en"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.title","Three-dimensional virtual histology of human cerebellum by X-ray phase-contrast tomography"],["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","471"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical & Experimental Metastasis"],["dc.bibliographiccitation.lastpage","482"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Rietkoetter, Eva"],["dc.contributor.author","Wegner, Christiane"],["dc.contributor.author","Kramer, Franz-Josef"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Stadelmann, Chr."],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T09:26:31Z"],["dc.date.available","2018-11-07T09:26:31Z"],["dc.date.issued","2013"],["dc.description.abstract","An essential function of the transcription factors LEF1/TCF4 in cerebral metastases of lung adenocarcinomas has been described in mouse models, suggesting a WNT/beta-catenin effect as potential mechanism. Their role in humans is still unclear, thus we analyzed LEF1, TCF4, beta-catenin, and early stage prognostic markers in 25 adenocarcinoma brain metastases using immunohistochemistry (IHC). IHC revealed nuclear TCF4 in all adenocarcinoma samples, whereas only 36 % depicted nuclear LEF1 and nuclear beta-catenin signals. Samples with nuclear LEF1 as well as high TCF4 (++++) expression were associated with a shorter survival (p = 0.01, HR = 6.68), while nuclear beta-catenin had no significant impact on prognosis and did not significantly correlate with nuclear LEF1. High proliferation index Ki67 was associated with shorter survival in late-stage disease (p = 0.03, HR 3.27). Additionally, we generated a LEF1/TCF4 as well as an AXIN2 signature, the latter as representative of WNT/beta-catenin activity, following a bioinformatics approach with a gene expression dataset of cerebral metastases in lung adenocarcinoma. To analyze the prognostic relevance in primary lung adenocarcinomas, we applied both signatures to a microarray dataset of 58 primary lung adenocarcinomas. Only the LEF1/TCF4 signature was able to separate clusters with impact on survival (p = 0.01, HR = 0.32). These clusters displayed diverging enrichment patterns of the cell cycle pathway. In conclusion, our data show that LEF1/TCF4, but not beta-catenin, have prognostic relevance in primary and cerebrally metastasized human lung adenocarcinomas. In contrast to the previous in vivo findings, these results indicate that LEF1/TCF4 act independently of beta-catenin in this setting."],["dc.identifier.doi","10.1007/s10585-012-9552-7"],["dc.identifier.isi","000317297400011"],["dc.identifier.pmid","23224985"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10341"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30319"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1573-7276"],["dc.relation.issn","0262-0898"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Nuclear LEF1/TCF4 correlate with poor prognosis but not with nuclear beta-catenin in cerebral metastasis of lung adenocarcinomas"],["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.artnumber","69"],["dc.bibliographiccitation.journal","Retrovirology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Roebke, Christina"],["dc.contributor.author","Wahl, Silke"],["dc.contributor.author","Laufer, Georg"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Sauter, Marlies"],["dc.contributor.author","Mueller-Lantzsch, Nikolaus"],["dc.contributor.author","Mayer, Jens"],["dc.contributor.author","Ruprecht, Klemens"],["dc.date.accessioned","2018-11-07T08:40:17Z"],["dc.date.available","2018-11-07T08:40:17Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: We previously showed that the envelope (env) sequence of a human endogenous retrovirus (HERV)W locus on chromosome Xq22.3 is transcribed in human peripheral blood mononuclear cells. The env open reading frame (ORF) of this locus is interrupted by a premature stop at codon 39, but otherwise harbors a long ORF for an N-terminally truncated 475 amino acid Env protein, starting at an in-frame ATG at codon 68. We set out to characterize the protein encoded by that ORF. Results: Transient expression of the 475 amino acid Xq22.3 HERV-W env ORF produced an N-terminally truncated HERV-W Env protein, as detected by the monoclonal anti-HERV-W Env antibodies 6A2B2 and 13H5A5. Remarkably, reversion of the stop at codon 39 in Xq22.3 HERV-W env reconstituted a full-length HERV-W Xq22.3 Env protein. Similar to the full-length HERV-W Env protein Syncytin-1, reconstituted full-length Xq22.3 HERV-W Env is glycosylated, forms oligomers, and is expressed at the cell surface. In contrast, Xq22.3 HERV-W Env is unglycosylated, does not form oligomers, and is located intracellularly, probably due to lack of a signal peptide. Finally, we reconfirm by immunohistochemistry that monoclonal antibody 6A2B2 detects an antigen expressed in placenta and multiple sclerosis brain lesions. Conclusions: A partially defective HERV-W env gene located on chromosome Xq22.3, which we propose to designate ERVWE2, has retained coding capacity and can produce ex vivo an N-terminally truncated Env protein, named N-Trenv. Detection of an antigen by 6A2B2 in placenta and multiple sclerosis lesions opens the possibility that N-Trenv could be expressed in vivo. More generally, our findings are compatible with the idea that defective HERV elements may be capable of producing incomplete HERV proteins that, speculatively, may exert functions in human physiology or pathology."],["dc.description.sponsorship","HOMFOR; DFG"],["dc.identifier.doi","10.1186/1742-4690-7-69"],["dc.identifier.isi","000282565000001"],["dc.identifier.pmid","20735848"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5661"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19194"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1742-4690"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","An N-terminally truncated envelope protein encoded by a human endogenous retrovirus W locus on chromosome Xq22.3"],["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","4331"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Biomedical Optics Express"],["dc.bibliographiccitation.lastpage","4347"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Carboni, Eleonora"],["dc.contributor.author","Nicolas, Jan-David"],["dc.contributor.author","Töpperwien, Mareike"],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2017-11-09T09:25:21Z"],["dc.date.accessioned","2021-10-11T11:31:15Z"],["dc.date.available","2017-11-09T09:25:21Z"],["dc.date.available","2021-10-11T11:31:15Z"],["dc.date.issued","2017"],["dc.description.abstract","We have used scanning X-ray diffraction (XRD) and X-ray fluorescence (XRF) with micro-focused synchrotron radiation to study histological sections from human substantia nigra (SN). Both XRF and XRD mappings visualize tissue properties, which are inaccessible by conventional microscopy and histology. We propose to use these advanced tools to characterize neuronal tissue in neurodegeneration, in particular in Parkinson's disease (PD). To this end, we take advantage of the recent experimental progress in x-ray focusing, detection, and use automated data analysis scripts to enable quantitative analysis of large field of views. XRD signals are recorded and analyzed both in the regime of small-angle (SAXS) and wide-angle x-ray scattering (WAXS). The SAXS signal was analyzed in view of the local myelin structure, while WAXS was used to identify crystalline deposits. PD tissue scans exhibited increased amounts of crystallized cholesterol. The XRF analysis showed increased amounts of iron and decreased amounts of copper in the PD tissue compared to the control."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1364/BOE.8.004331"],["dc.identifier.gro","3142465"],["dc.identifier.pmid","29082068"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14826"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90600"],["dc.language","eng"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","2156-7085"],["dc.relation.orgunit","Fakultät für Physik"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.uri","https://goedoc.uni-goettingen.de/licenses"],["dc.subject","170.6510) Spectroscopy, tissue diagnostics; (170.6935) Tissue characterization; (180.5810) Scanning microscopy; (180.7460) X-ray microscopy"],["dc.subject.ddc","530"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","x-ray scattering"],["dc.title","Imaging of neuronal tissues by x-ray diffraction and x-ray fluorescence microscopy: evaluation of contrast and biomarkers for neurodegenerative diseases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9495"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.affiliation","Rajendran, Ranjithkumar; \t\t \r\n\t\t Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany, Ranjithkumar.rajendran@neuro.med.uni-giessen.de"],["dc.contributor.affiliation","Rajendran, Vinothkumar; \t\t \r\n\t\t Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany, vinothkumar.rajendran@neuro.med.uni-giessen.de"],["dc.contributor.affiliation","Giraldo-Velasquez, Mario; \t\t \r\n\t\t Department of Neurology, Sozialstiftung Bamberg, Buger Strasse 80, 96049 Bamberg, Germany, Mario.Giraldo@sozialstiftung-bamberg.de"],["dc.contributor.affiliation","Megalofonou, Fevronia-Foivi; \t\t \r\n\t\t Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany, Fevronia.F.Megalofonou@med.uni-giessen.de"],["dc.contributor.affiliation","Gurski, Fynn; \t\t \r\n\t\t Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany, fynn.gurski@med.uni-giessen.de"],["dc.contributor.affiliation","Stadelmann, Christine; \t\t \r\n\t\t Institute of Neuropathology, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, Germany, cstadelmann@med.uni-goettingen.de"],["dc.contributor.affiliation","Karnati, Srikanth; \t\t \r\n\t\t Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstrasse 6, 97080 Würzburg, Germany, srikanth.karnati@uni-wuerzburg.de"],["dc.contributor.affiliation","Berghoff, Martin; \t\t \r\n\t\t Experimental Neurology, Department of Neurology, University of Giessen, Klinikstrasse 33, 35385 Giessen, Germany, martin.berghoff@neuro.med.uni-giessen.de"],["dc.contributor.author","Rajendran, Ranjithkumar"],["dc.contributor.author","Rajendran, Vinothkumar"],["dc.contributor.author","Giraldo-Velasquez, Mario"],["dc.contributor.author","Megalofonou, Fevronia-Foivi"],["dc.contributor.author","Gurski, Fynn"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Karnati, Srikanth"],["dc.contributor.author","Berghoff, Martin"],["dc.date.accessioned","2021-10-01T09:58:26Z"],["dc.date.available","2021-10-01T09:58:26Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-03T18:44:06Z"],["dc.description.abstract","Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS). MS commonly affects the cerebellum causing acute and chronic symptoms. Cerebellar signs significantly contribute to clinical disability, and symptoms such as tremor, ataxia, and dysarthria are difficult to treat. Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in demyelinating pathologies such as MS. In autopsy tissue from patients with MS, increased expression of FGF1, FGF2, FGF9, and FGFR1 was found in lesion areas. Recent research using mouse models has focused on regions such as the spinal cord, and data on the expression of FGF/FGFR in the cerebellum are not available. In recent EAE studies, we detected that oligodendrocyte-specific deletion of FGFRs results in a milder disease course, less cellular infiltrates, and reduced neurodegeneration in the spinal cord. The objective of this study was to characterize the role of FGFR1 in oligodendrocytes in the cerebellum. Conditional deletion of FGFR1 in oligodendrocytes (Fgfr1ind−/−) was achieved by tamoxifen application, EAE was induced using the MOG35-55 peptide. The cerebellum was analyzed by histology, immunohistochemistry, and western blot. At day 62 p.i., Fgfr1ind−/− mice showed less myelin and axonal degeneration compared to FGFR1-competent mice. Infiltration of CD3(+) T cells, Mac3(+) cells, B220(+) B cells and IgG(+) plasma cells in cerebellar white matter lesions (WML) was less in Fgfr1ind−/−mice. There were no effects on the number of OPC or mature oligodendrocytes in white matter lesion (WML). Expression of FGF2 and FGF9 associated with less myelin and axonal degeneration, and of the pro-inflammatory cytokines IL-1β, IL-6, and CD200 was downregulated in Fgfr1ind−/− mice. The FGF/FGFR signaling protein pAkt, BDNF, and TrkB were increased in Fgfr1ind−/− mice. These data suggest that cell-specific deletion of FGFR1 in oligodendrocytes has anti-inflammatory and neuroprotective effects in the cerebellum in the EAE disease model of MS."],["dc.description.abstract","Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS). MS commonly affects the cerebellum causing acute and chronic symptoms. Cerebellar signs significantly contribute to clinical disability, and symptoms such as tremor, ataxia, and dysarthria are difficult to treat. Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in demyelinating pathologies such as MS. In autopsy tissue from patients with MS, increased expression of FGF1, FGF2, FGF9, and FGFR1 was found in lesion areas. Recent research using mouse models has focused on regions such as the spinal cord, and data on the expression of FGF/FGFR in the cerebellum are not available. In recent EAE studies, we detected that oligodendrocyte-specific deletion of FGFRs results in a milder disease course, less cellular infiltrates, and reduced neurodegeneration in the spinal cord. The objective of this study was to characterize the role of FGFR1 in oligodendrocytes in the cerebellum. Conditional deletion of FGFR1 in oligodendrocytes (Fgfr1ind−/−) was achieved by tamoxifen application, EAE was induced using the MOG35-55 peptide. The cerebellum was analyzed by histology, immunohistochemistry, and western blot. At day 62 p.i., Fgfr1ind−/− mice showed less myelin and axonal degeneration compared to FGFR1-competent mice. Infiltration of CD3(+) T cells, Mac3(+) cells, B220(+) B cells and IgG(+) plasma cells in cerebellar white matter lesions (WML) was less in Fgfr1ind−/−mice. There were no effects on the number of OPC or mature oligodendrocytes in white matter lesion (WML). Expression of FGF2 and FGF9 associated with less myelin and axonal degeneration, and of the pro-inflammatory cytokines IL-1β, IL-6, and CD200 was downregulated in Fgfr1ind−/− mice. The FGF/FGFR signaling protein pAkt, BDNF, and TrkB were increased in Fgfr1ind−/− mice. These data suggest that cell-specific deletion of FGFR1 in oligodendrocytes has anti-inflammatory and neuroprotective effects in the cerebellum in the EAE disease model of MS."],["dc.identifier.doi","10.3390/ijms22179495"],["dc.identifier.pii","ijms22179495"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90062"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Oligodendrocyte-Specific Deletion of FGFR1 Reduces Cerebellar Inflammation and Neurodegeneration in MOG35-55-Induced EAE"],["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","43"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","58"],["dc.bibliographiccitation.volume","132"],["dc.contributor.author","Kinzel, Silke"],["dc.contributor.author","Lehmann-Horn, Klaus"],["dc.contributor.author","Torke, Sebastian"],["dc.contributor.author","Haeusler, Darius"],["dc.contributor.author","Winkler, Anne"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Payne, Natalie L."],["dc.contributor.author","Feldmann, Linda"],["dc.contributor.author","Saiz, Albert"],["dc.contributor.author","Reindl, Markus"],["dc.contributor.author","Lalive, Patrice H."],["dc.contributor.author","Bernard, Claude C."],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2018-11-07T10:12:20Z"],["dc.date.available","2018-11-07T10:12:20Z"],["dc.date.issued","2016"],["dc.description.abstract","In the pathogenesis of central nervous system (CNS) demyelinating disorders, antigen-specific B cells are implicated to act as potent antigen-presenting cells (APC), eliciting waves of inflammatory CNS infiltration. Here, we provide the first evidence that CNS-reactive antibodies (Ab) are similarly capable of initiating an encephalitogenic immune response by targeting endogenous CNS antigen to otherwise inert myeloid APC. In a transgenic mouse model, constitutive production of Ab against myelin oligodendrocyte glycoprotein (MOG) was sufficient to promote spontaneous experimental autoimmune encephalomyelitis (EAE) in the absence of B cells, when mice endogenously contained MOG-recognizing T cells. Adoptive transfer studies corroborated that anti-MOG Ab triggered activation and expansion of peripheral MOG-specific T cells in an Fc-dependent manner, subsequently causing EAE. To evaluate the underlying mechanism, anti-MOG Ab were added to a co-culture of myeloid APC and MOG-specific T cells. At otherwise undetected concentrations, anti-MOG Ab enabled Fc-mediated APC recognition of intact MOG; internalized, processed and presented MOG activated na < ve T cells to differentiate in an encephalitogenic manner. In a series of translational experiments, anti-MOG Ab from two patients with an acute flare of CNS inflammation likewise facilitated detection of human MOG. Jointly, these observations highlight Ab-mediated opsonization of endogenous CNS auto-antigen as a novel disease- and/or relapse-triggering mechanism in CNS demyelinating disorders."],["dc.identifier.doi","10.1007/s00401-016-1559-8"],["dc.identifier.isi","000378811600003"],["dc.identifier.pmid","27022743"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14069"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40217"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen"],["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.artnumber","e0168174"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Huhndorf, Monika"],["dc.contributor.author","Moussavi, Amir"],["dc.contributor.author","Kramann, Nadine"],["dc.contributor.author","Will, Olga Maria"],["dc.contributor.author","Hattermann, Kirsten"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Jansen, Olav"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.editor","Sherman, Jonathan H."],["dc.date.accessioned","2017-09-07T11:44:48Z"],["dc.date.available","2017-09-07T11:44:48Z"],["dc.date.issued","2017"],["dc.description.abstract","ObjectivesAngiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization.MethodsWe analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections.ResultsIn all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology.ConclusionSubstantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development."],["dc.identifier.doi","10.1371/journal.pone.0168174"],["dc.identifier.gro","3150343"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14141"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7096"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]