14 results on '"Sontheimer K"'
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2. Das Gewicht der (antidemokratischen) Traditionen
- Author
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Sontheimer, K. and Iwand, Wolf Michael
- Published
- 1985
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3. Von antidemokratischen Traditionen zur intellektuellen Kulturrevolution — Politische Kultur als ‚Stabilitätsreserve‘
- Author
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Sontheimer, K. and Iwand, Wolf Michael
- Published
- 1985
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4. Struktur der deutschen Gesellschaft und deutsches Sozialverhalten
- Author
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Sontheimer, K. and Iwand, Wolf Michael
- Published
- 1985
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5. Nuclear measurements for type 3 replacement cores for SM-1, SM-1A and PM-2A CE-3
- Author
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Raby, T. M., primary, Walthousen, L. D., additional, Kemp, S. N., additional, McCool, W. J., additional, Sontheimer, K. C., additional, and Robinson, R. A., additional
- Published
- 1962
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6. NUCLEAR MEASUREMENTS FOR DEVELOPMENT OF HIGH PERFORMANCE REPLACEMENT CORES FOR ARMY REACTORS
- Author
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Sontheimer, K
- Published
- 1961
7. Multiscale co-simulation design pattern for neuroscience applications.
- Author
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Kusch L, Diaz-Pier S, Klijn W, Sontheimer K, Bernard C, Morrison A, and Jirsa V
- Abstract
Integration of information across heterogeneous sources creates added scientific value. Interoperability of data, tools and models is, however, difficult to accomplish across spatial and temporal scales. Here we introduce the toolbox Parallel Co-Simulation, which enables the interoperation of simulators operating at different scales. We provide a software science co-design pattern and illustrate its functioning along a neuroscience example, in which individual regions of interest are simulated on the cellular level allowing us to study detailed mechanisms, while the remaining network is efficiently simulated on the population level. A workflow is illustrated for the use case of The Virtual Brain and NEST, in which the CA1 region of the cellular-level hippocampus of the mouse is embedded into a full brain network involving micro and macro electrode recordings. This new tool allows integrating knowledge across scales in the same simulation framework and validating them against multiscale experiments, thereby largely widening the explanatory power of computational models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kusch, Diaz-Pier, Klijn, Sontheimer, Bernard, Morrison and Jirsa.)
- Published
- 2024
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8. Effect of enzyme-assisted hydrolysis on protein pattern, technofunctional, and sensory properties of lupin protein isolates using enzyme combinations.
- Author
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Schlegel K, Sontheimer K, Eisner P, and Schweiggert-Weisz U
- Abstract
The modification of lupin protein isolates (LPI) by means of enzymatic hydrolysis ( Lupinus angustifolius cultivar Boregine) was performed with four enzyme preparations (Alcalase 2.4 L, Papain, Corolase 7089, and Neutrase 0.8 L) in a one- and two-step process to determine the efficacy for the destruction of major IgE-reactive polypeptides and the evaluation of the technofunctional and sensory properties of lupin protein hydrolysates. Combinations of Alcalase 2.4 L and Papain were most effective in the degradation of polypeptides in L. angustifolius as measured by sodium dodecylsulfate-polyacrylamide gel electrophoresis. The enzymatic hydrolysis of the LPI increased their technofunctional properties such as protein solubility, foam activity, and emulsifying capacity almost independently of the enzyme preparation used. The sensory results showed a significant increase in bitterness from 1.9 for LPI to 5.7 for the combination of Alcalase 2.4 L and Papain in one-step process. The aroma attributes of the hydrolysates were very similar to untreated LPI. The results of this study show the possibility of enzymatic hydrolysis of LPI to destroy the major IgE-reactive polypeptides that increase the technofunctional properties of the isolates and thus their use in human nutrition as food ingredients., Competing Interests: The authors declare that they have no conflict of interest., (© 2019 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.)
- Published
- 2019
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9. Enzymatic hydrolysis of lupin protein isolates-Changes in the molecular weight distribution, technofunctional characteristics, and sensory attributes.
- Author
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Schlegel K, Sontheimer K, Hickisch A, Wani AA, Eisner P, and Schweiggert-Weisz U
- Abstract
Enzymatic hydrolysis of lupin protein isolates (LPI; Lupinus angustifolius L.) was performed with nine different protease preparations to investigate their effect on technofunctionality, sensory properties, and the integrity of the proteins to estimate the reduction of the immunoreactivity. Alcalase 2.4 L, papain, and pepsin were most effective in the degradation of the α- and β-conglutin examined by SDS-PAGE analysis, although the degree of hydrolysis only slightly increased. The technofunctional properties of LPI-solubility, emulsifying, and foaming activity-were improved by most of the proteolytic enzymes with the most impressive increase from 980% foam activity for LPI up to 3,614% foam activity for pepsin hydrolysate. The formation of bitterness, most likely linked to generation of bitter peptides, was pronounced in the Alcalase hydrolysate, while the other hydrolysates did not show an extensive increase in bitterness compared to the LPI. Other sensory attributes of the hydrolysates-with the exception of Alcalase treatment-were also very similar to the LPI. The results of this study show the potential of enzymatic degradation of LPI to modify the IgE-reacting polypeptides and to improve the technofunctionality of the isolates and therefore their use as food ingredients., Competing Interests: The authors declare that they have no conflict of interest.
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- 2019
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10. Interleukin 21-induced granzyme B-expressing B cells infiltrate tumors and regulate T cells.
- Author
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Lindner S, Dahlke K, Sontheimer K, Hagn M, Kaltenmeier C, Barth TF, Beyer T, Reister F, Fabricius D, Lotfi R, Lunov O, Nienhaus GU, Simmet T, Kreienberg R, Möller P, Schrezenmeier H, and Jahrsdörfer B
- Subjects
- Apoptosis drug effects, B-Lymphocytes, Regulatory metabolism, CD5 Antigens metabolism, Cell Communication drug effects, Cells, Cultured, Humans, Immunophenotyping, Lymphocyte Activation drug effects, Lymphocyte Activation immunology, Lymphocytes, Tumor-Infiltrating drug effects, Lymphocytes, Tumor-Infiltrating enzymology, Lymphocytes, Tumor-Infiltrating immunology, Phenotype, Receptors, Antigen, T-Cell, gamma-delta metabolism, Signal Transduction drug effects, T-Lymphocyte Subsets metabolism, Toll-Like Receptors metabolism, Tumor Microenvironment drug effects, Tumor Microenvironment immunology, B-Lymphocytes, Regulatory drug effects, B-Lymphocytes, Regulatory immunology, Granzymes metabolism, Interleukins pharmacology, Neoplasms enzymology, Neoplasms immunology, T-Lymphocyte Subsets immunology
- Abstract
The pathogenic impact of tumor-infiltrating B cells is unresolved at present, however, some studies suggest that they may have immune regulatory potential. Here, we report that the microenvironment of various solid tumors includes B cells that express granzyme B (GrB, GZMB), where these B cells can be found adjacent to interleukin (IL)-21-secreting regulatory T cells (Treg) that contribute to immune tolerance of tumor antigens. Because Tregs and plasmacytoid dendritic cells are known to modulate T-effector cells by a GrB-dependent mechanism, we hypothesized that a similar process may operate to modulate regulatory B cells (Breg). IL-21 induced outgrowth of B cells expressing high levels of GrB, which thereby limited T-cell proliferation by a GrB-dependent degradation of the T-cell receptor ζ-chain. Mechanistic investigations into how IL-21 induced GrB expression in B cells to confer Breg function revealed a CD19(+)CD38(+)CD1d(+)IgM(+)CD147(+) expression signature, along with expression of additional key regulatory molecules including IL-10, CD25, and indoleamine-2,3-dioxygenase. Notably, induction of GrB by IL-21 integrated signals mediated by surface immunoglobulin M (B-cell receptor) and Toll-like receptors, each of which were enhanced with expression of the B-cell marker CD5. Our findings show for the first time that IL-21 induces GrB(+) human Bregs. They also establish the existence of human B cells with a regulatory phenotype in solid tumor infiltrates, where they may contribute to the suppression of antitumor immune responses. Together, these findings may stimulate novel diagnostic and cell therapeutic approaches to better manage human cancer as well as autoimmune and graft-versus-host pathologies., (©2013 AACR.)
- Published
- 2013
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11. Human B cells differentiate into granzyme B-secreting cytotoxic B lymphocytes upon incomplete T-cell help.
- Author
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Hagn M, Sontheimer K, Dahlke K, Brueggemann S, Kaltenmeier C, Beyer T, Hofmann S, Lunov O, Barth TF, Fabricius D, Tron K, Nienhaus GU, Simmet T, Schrezenmeier H, and Jahrsdörfer B
- Subjects
- B-Lymphocytes metabolism, CD40 Ligand, Cells, Cultured, Humans, Immunity, Cellular, Interleukin-2 pharmacology, Interleukins pharmacology, B-Lymphocytes cytology, Cell Differentiation immunology, Granzymes metabolism, T-Lymphocytes, Helper-Inducer immunology
- Abstract
Recently, CD4(+) T helper cells were shown to induce differentiation of human B cells into plasma cells by expressing interleukin (IL-)21 and CD40 ligand (CD40L). In the present study we show, that in the absence of CD40L, CD4(+) T cell-derived IL-21 induces differentiation of B cells into granzyme B (GzmB)-secreting cytotoxic cells. Using fluorescence-activated cell sorting (FACS) analysis, ELISpot and confocal microscopy, we demonstrate that CD4(+) T cells, activated via their T-cell receptor without co-stimulation, can produce IL-21, but do not express CD40L and rapidly induce GzmB in co-cultured B cells in an IL-21 receptor-dependent manner. Of note, we confirmed these results with recombinant reagents, highlighting that CD40L suppresses IL-21-induced GzmB induction in B cells in a dose-dependent manner. Surprisingly, although GzmB-secreting B cells did not express perforin, they were able to transfer active GzmB to tumor cell lines, thereby effectively inducing apoptosis. In contrast, no cytotoxic effects were found when effector B cells were activated with IL-2 instead of IL-21 or when target cells were cultured with IL-21 alone. Our findings suggest GzmB(+) cytotoxic B cells may have a role in early cellular immune responses including tumor immunosurveillance, before fully activated, antigen-specific cytotoxic T cells are on the spot. CD40 ligand determines whether IL-21 induces differentiation of B cells into plasma cells or into granzyme B-secreting cytotoxic cells.
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- 2012
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12. CD5+ B cells from individuals with systemic lupus erythematosus express granzyme B.
- Author
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Hagn M, Ebel V, Sontheimer K, Schwesinger E, Lunov O, Beyer T, Fabricius D, Barth TF, Viardot A, Stilgenbauer S, Hepp J, Scharffetter-Kochanek K, Simmet T, and Jahrsdörfer B
- Subjects
- Adolescent, Adult, Aged, B-Lymphocytes immunology, B-Lymphocytes pathology, CD5 Antigens biosynthesis, Cell Proliferation, Cell Survival immunology, Female, Granzymes genetics, Humans, Immune Tolerance, Interleukins blood, Interleukins genetics, Interleukins immunology, Lupus Erythematosus, Systemic blood, Male, Middle Aged, Receptor Cross-Talk immunology, Receptors, Antigen, B-Cell immunology, Receptors, Interleukin-21 biosynthesis, Receptors, Interleukin-21 genetics, B-Lymphocytes metabolism, Granzymes metabolism, Interleukins biosynthesis, Lupus Erythematosus, Systemic immunology, Receptors, Antigen, B-Cell metabolism
- Abstract
Recently, we reported that IL-21 induces granzyme B (GzmB) and GzmB-dependent apoptosis in malignant CD5(+) B cells from patients with chronic lymphocytic leukemia. Several autoimmune diseases (AD) are associated with enhanced frequencies of CD5(+) B cells. Since AD are also associated with elevated IL-21 and GzmB levels, we postulated a link between CD5(+) B cells, IL-21 and GzmB. Here, we demonstrate that IL-21 and GzmB serum levels are highly correlated in subjects with systemic lupus erythematosus (SLE) and that freshly isolated CD5(+) SLE B cells constitutively express GzmB. IL-21 directly induced GzmB expression and secretion by CD5(+) B cells from several AD and from cord blood in vitro, and the simultaneous presence of BCR stimulation strongly enhanced this process. Furthermore, IL-21 suppressed both viability and expansion of CD5(+) B cells from SLE individuals. In summary, our study may explain the elevated levels of IL-21 and GzmB in SLE and other AD. Moreover, our data suggest that IL-21 may have disease-modifying characteristics by inducing GzmB in CD5(+) B cells and by suppressing their expansion. Our results provide the rationale for further evaluation of the therapeutic potential of IL-21 in certain AD such as SLE.
- Published
- 2010
- Full Text
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13. Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion.
- Author
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Jahrsdörfer B, Vollmer A, Blackwell SE, Maier J, Sontheimer K, Beyer T, Mandel B, Lunov O, Tron K, Nienhaus GU, Simmet T, Debatin KM, Weiner GJ, and Fabricius D
- Subjects
- Arthritis, Juvenile pathology, Blotting, Western, Cell Differentiation, Cell Proliferation, Cells, Cultured, Child, Cytotoxicity, Immunologic, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Interleukin-3 metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor metabolism, STAT5 Transcription Factor metabolism, Signal Transduction, Arthritis, Juvenile immunology, Dendritic Cells metabolism, Granzymes physiology, Lymphocyte Activation physiology, T-Lymphocytes immunology
- Abstract
Human plasmacytoid dendritic cells (pDCs) are crucially involved in the modulation of adaptive T-cell responses in the course of neoplastic, viral, and autoimmune disorders. In several of these diseases elevated extracellular levels of the serine protease granzyme B (GrB) are observed. Here we demonstrate that human pDCs can be an abundant source of GrB and that such GrB(+) pDCs potently suppress T-cell proliferation in a GrB-dependent, perforin-independent manner, a process reminiscent of regulatory T cells. Moreover, we show that GrB expression is strictly regulated on a transcriptional level involving Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and STAT5 and that interleukin-3 (IL-3), a cytokine secreted by activated T cells, plays a central role for GrB induction. Moreover, we find that the immunosuppressive cytokine IL-10 enhances, while Toll-like receptor agonists and CD40 ligand strongly inhibit, GrB secretion by pDCs. GrB-secreting pDCs may play a regulatory role for immune evasion of tumors, antiviral immune responses, and autoimmune processes. Our results provide novel information about the complex network of pDC-T-cell interactions and may contribute to an improvement of prophylactic and therapeutic vaccinations.
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- 2010
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14. Human B cells secrete granzyme B when recognizing viral antigens in the context of the acute phase cytokine IL-21.
- Author
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Hagn M, Schwesinger E, Ebel V, Sontheimer K, Maier J, Beyer T, Syrovets T, Laumonnier Y, Fabricius D, Simmet T, and Jahrsdörfer B
- Subjects
- Acute-Phase Proteins, B-Lymphocytes immunology, Endosomes virology, Humans, Immunity, Immunophenotyping, Signal Transduction, Vaccination, Virus Internalization, Antigens, Viral immunology, B-Lymphocytes metabolism, Granzymes metabolism, Interleukins immunology
- Abstract
Human B cells are currently not known to produce the proapoptotic protease granzyme B (GrB) in physiological settings. We have discovered that BCR stimulation with either viral Ags or activating Abs in the context of the acute phase cytokine IL-21 can induce the secretion of substantial amounts of GrB by human B cells. Importantly, GrB response to viral Ags was significantly stronger in B cells from subjects recently vaccinated against the corresponding viruses as compared with unvaccinated subjects. GrB-secreting B cells featured a homogeneous CD19(+)CD20(+)CD27(-)CD38(-)IgD(-) phenotype, improved survival, and enhanced expression of costimulatory, Ag-presenting and cell-adhesion molecules. B cell-derived GrB was enzymatically active and its induction required the activation of similar signaling pathways as those in CTLs. Our findings suggest that GrB-secreting B cells support the early antiviral immune response against viruses with endosomal entry pathways, thereby counteracting overwhelming viral replication at the beginning of an infection until virus-specific T cells from draining lymph nodes arrive at the site of infection. Our data may also explain the elevated serum GrB levels found in the early phase of various viral diseases.
- Published
- 2009
- Full Text
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