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  1. Artikel ; Online: Pan-cancer analysis of the interplay between mutational signatures and cellular signaling.

    Hakobyan, Anna / Meyenberg, Mathilde / Vardazaryan, Nelli / Hancock, Joel / Vulliard, Loan / Loizou, Joanna I / Menche, Jörg

    iScience

    2024  Band 27, Heft 6, Seite(n) 109873

    Abstract: Cancer is a multi-faceted disease with intricate relationships between mutagenic processes, alterations in cellular signaling, and the tissue microenvironment. To date, these processes have been largely studied in isolation. A systematic understanding of ...

    Abstract Cancer is a multi-faceted disease with intricate relationships between mutagenic processes, alterations in cellular signaling, and the tissue microenvironment. To date, these processes have been largely studied in isolation. A systematic understanding of how they interact and influence each other is lacking. Here, we present a framework for systematically characterizing the interaction between pairs of mutational signatures and between signatures and signaling pathway alterations. We applied this framework to large-scale data from TCGA and PCAWG and identified multiple positive and negative interactions, both cross֊tissue and tissue֊specific, that provide new insights into the molecular routes observed in tumorigenesis and their respective drivers. This framework allows for a more fine-grained dissection of common and distinct etiology of mutational signatures. We further identified several interactions with both positive and negative impacts on patient survival, demonstrating their clinical relevance and potential for improving personalized cancer care.
    Sprache Englisch
    Erscheinungsdatum 2024-05-02
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2024.109873
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Complex Networks in Health and Disease

    Vulliard, Loan / Menche, Jörg

    Reference Module in Biomedical Sciences

    Abstract: From protein interactions to signal transduction, from metabolism to the nervous system: Virtually all processes in health and disease rely on the careful orchestration of a large number of diverse individual components ranging from molecules to cells ... ...

    Abstract From protein interactions to signal transduction, from metabolism to the nervous system: Virtually all processes in health and disease rely on the careful orchestration of a large number of diverse individual components ranging from molecules to cells and entire organs. Networks provide a powerful framework for describing and understanding these complex systems in a wholistic fashion. They offer a unique combination of a highly intuitive, qualitative description, and a plethora of analytical, quantitative tools. Here we provide a brief introduction to the emerging field of network medicine. After an overview of the core concepts for connecting network characteristics to biological functions, we review commonly used networks, ranging from the molecular interaction networks that form the basis of all biological processes in the cell to the global transportation networks that govern the spread of global epidemics. Lastly, we highlight current conceptual and practical challenges.
    Schlagwörter covid19
    Verlag Elsevier; PMC
    Dokumenttyp Artikel ; Online
    DOI 10.1016/b978-0-12-801238-3.11640-x
    Datenquelle COVID19

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  3. Artikel: A versatile information retrieval framework for evaluating profile strength and similarity.

    Kalinin, Alexandr A / Arevalo, John / Vulliard, Loan / Serrano, Erik / Tsang, Hillary / Bornholdt, Michael / Rajwa, Bartek / Carpenter, Anne E / Way, Gregory P / Singh, Shantanu

    bioRxiv : the preprint server for biology

    2024  

    Abstract: In profiling assays, thousands of biological properties are measured in a single test, yielding biological discoveries by capturing the state of a cell population, often at the single-cell level. However, for profiling datasets, it has been challenging ... ...

    Abstract In profiling assays, thousands of biological properties are measured in a single test, yielding biological discoveries by capturing the state of a cell population, often at the single-cell level. However, for profiling datasets, it has been challenging to evaluate the phenotypic activity of a sample and the phenotypic consistency among samples, due to profiles' high dimensionality, heterogeneous nature, and non-linear properties. Existing methods leave researchers uncertain where to draw boundaries between meaningful biological response and technical noise. Here, we developed a statistical framework that uses the well-established mean average precision (mAP) as a single, data-driven metric to bridge this gap. We validated the mAP framework against established metrics through simulations and real-world data applications, revealing its ability to capture subtle and meaningful biological differences in cell state. Specifically, we used mAP to assess both phenotypic activity for a given perturbation (or a sample) as well as consistency within groups of perturbations (or samples) across diverse high-dimensional datasets. We evaluated the framework on different profile types (image, protein, and mRNA profiles), perturbation types (CRISPR gene editing, gene overexpression, and small molecules), and profile resolutions (single-cell and bulk). Our open-source software allows this framework to be applied to identify interesting biological phenomena and promising therapeutics from large-scale profiling data.
    Sprache Englisch
    Erscheinungsdatum 2024-04-02
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2024.04.01.587631
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Morphological profiling of human T and NK lymphocytes by high-content cell imaging.

    German, Yolla / Vulliard, Loan / Kamnev, Anton / Pfajfer, Laurène / Huemer, Jakob / Mautner, Anna-Katharina / Rubio, Aude / Kalinichenko, Artem / Boztug, Kaan / Ferrand, Audrey / Menche, Jörg / Dupré, Loïc

    Cell reports

    2021  Band 36, Heft 1, Seite(n) 109318

    Abstract: The immunological synapse is a complex structure that decodes stimulatory signals into adapted lymphocyte responses. It is a unique window to monitor lymphocyte activity because of development of systematic quantitative approaches. Here we demonstrate ... ...

    Abstract The immunological synapse is a complex structure that decodes stimulatory signals into adapted lymphocyte responses. It is a unique window to monitor lymphocyte activity because of development of systematic quantitative approaches. Here we demonstrate the applicability of high-content imaging to human T and natural killer (NK) cells and develop a pipeline for unbiased analysis of high-definition morphological profiles. Our approach reveals how distinct facets of actin cytoskeleton remodeling shape immunological synapse architecture and affect lytic granule positioning. Morphological profiling of CD8
    Mesh-Begriff(e) Actin-Related Protein 2-3 Complex/deficiency ; Actin-Related Protein 2-3 Complex/metabolism ; Adolescent ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/drug effects ; Cell Line ; Cell Shape/drug effects ; Cytoskeleton/drug effects ; Cytoskeleton/metabolism ; Exocytosis/drug effects ; Humans ; Imaging, Three-Dimensional ; Immunological Synapses/drug effects ; Immunological Synapses/metabolism ; Killer Cells, Natural/cytology ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/metabolism ; Male ; Organoselenium Compounds/pharmacology ; Organosilicon Compounds/pharmacology ; Single-Cell Analysis ; T-Lymphocytes/cytology ; T-Lymphocytes/drug effects ; T-Lymphocytes/metabolism ; Thiones/pharmacology ; Uracil/analogs & derivatives ; Uracil/pharmacology ; Wiskott-Aldrich Syndrome Protein/deficiency ; Wiskott-Aldrich Syndrome Protein/metabolism
    Chemische Substanzen ARPC1B protein, human ; Actin-Related Protein 2-3 Complex ; CK-869 ; Organoselenium Compounds ; Organosilicon Compounds ; SMIFH2 compound ; Thiones ; Wiskott-Aldrich Syndrome Protein ; Uracil (56HH86ZVCT)
    Sprache Englisch
    Erscheinungsdatum 2021-07-07
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.109318
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: BioProfiling.jl: profiling biological perturbations with high-content imaging in single cells and heterogeneous populations.

    Vulliard, Loan / Hancock, Joel / Kamnev, Anton / Fell, Christopher W / Ferreira da Silva, Joana / Loizou, Joanna I / Nagy, Vanja / Dupré, Loïc / Menche, Jörg

    Bioinformatics (Oxford, England)

    2021  Band 38, Heft 6, Seite(n) 1692–1699

    Abstract: Motivation: High-content imaging screens provide a cost-effective and scalable way to assess cell states across diverse experimental conditions. The analysis of the acquired microscopy images involves assembling and curating raw cellular measurements ... ...

    Abstract Motivation: High-content imaging screens provide a cost-effective and scalable way to assess cell states across diverse experimental conditions. The analysis of the acquired microscopy images involves assembling and curating raw cellular measurements into morphological profiles suitable for testing biological hypotheses. Despite being a critical step, general-purpose and adaptable tools for morphological profiling are lacking and no solution is available for the high-performance Julia programming language.
    Results: Here, we introduce BioProfiling.jl, an efficient end-to-end solution for compiling and filtering informative morphological profiles in Julia. The package contains all the necessary data structures to curate morphological measurements and helper functions to transform, normalize and visualize profiles. Robust statistical distances and permutation tests enable quantification of the significance of the observed changes despite the high fraction of outliers inherent to high-content screens. This package also simplifies visual artifact diagnostics, thus streamlining a bottleneck of morphological analyses. We showcase the features of the package by analyzing a chemical imaging screen, in which the morphological profiles prove to be informative about the compounds' mechanisms of action and can be conveniently integrated with the network localization of molecular targets.
    Availability and implementation: The Julia package is available on GitHub: https://github.com/menchelab/BioProfiling.jl. We also provide Jupyter notebooks reproducing our analyses: https://github.com/menchelab/BioProfilingNotebooks. The data underlying this article are available from FigShare, at https://doi.org/10.6084/m9.figshare.14784678.v2.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    Mesh-Begriff(e) Software ; Programming Languages ; Microscopy
    Sprache Englisch
    Erscheinungsdatum 2021-12-20
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btab853
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Assessment of community efforts to advance network-based prediction of protein-protein interactions.

    Wang, Xu-Wen / Madeddu, Lorenzo / Spirohn, Kerstin / Martini, Leonardo / Fazzone, Adriano / Becchetti, Luca / Wytock, Thomas P / Kovács, István A / Balogh, Olivér M / Benczik, Bettina / Pétervári, Mátyás / Ágg, Bence / Ferdinandy, Péter / Vulliard, Loan / Menche, Jörg / Colonnese, Stefania / Petti, Manuela / Scarano, Gaetano / Cuomo, Francesca /
    Hao, Tong / Laval, Florent / Willems, Luc / Twizere, Jean-Claude / Vidal, Marc / Calderwood, Michael A / Petrillo, Enrico / Barabási, Albert-László / Silverman, Edwin K / Loscalzo, Joseph / Velardi, Paola / Liu, Yang-Yu

    Nature communications

    2023  Band 14, Heft 1, Seite(n) 1582

    Abstract: Comprehensive understanding of the human protein-protein interaction (PPI) network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Despite the remarkable experimental ... ...

    Abstract Comprehensive understanding of the human protein-protein interaction (PPI) network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Despite the remarkable experimental efforts undertaken to date to determine the structure of the human interactome, many PPIs remain unmapped. Computational approaches, especially network-based methods, can facilitate the identification of previously uncharacterized PPIs. Many such methods have been proposed. Yet, a systematic evaluation of existing network-based methods in predicting PPIs is still lacking. Here, we report community efforts initiated by the International Network Medicine Consortium to benchmark the ability of 26 representative network-based methods to predict PPIs across six different interactomes of four different organisms: A. thaliana, C. elegans, S. cerevisiae, and H. sapiens. Through extensive computational and experimental validations, we found that advanced similarity-based methods, which leverage the underlying network characteristics of PPIs, show superior performance over other general link prediction methods in the interactomes we considered.
    Mesh-Begriff(e) Animals ; Humans ; Protein Interaction Mapping/methods ; Saccharomyces cerevisiae ; Caenorhabditis elegans ; Protein Interaction Maps ; Computational Biology/methods
    Sprache Englisch
    Erscheinungsdatum 2023-03-22
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-37079-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Assessment of community efforts to advance network-based prediction of protein–protein interactions

    Xu-Wen Wang / Lorenzo Madeddu / Kerstin Spirohn / Leonardo Martini / Adriano Fazzone / Luca Becchetti / Thomas P. Wytock / István A. Kovács / Olivér M. Balogh / Bettina Benczik / Mátyás Pétervári / Bence Ágg / Péter Ferdinandy / Loan Vulliard / Jörg Menche / Stefania Colonnese / Manuela Petti / Gaetano Scarano / Francesca Cuomo /
    Tong Hao / Florent Laval / Luc Willems / Jean-Claude Twizere / Marc Vidal / Michael A. Calderwood / Enrico Petrillo / Albert-László Barabási / Edwin K. Silverman / Joseph Loscalzo / Paola Velardi / Yang-Yu Liu

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Band 14

    Abstract: Comprehensive understanding of the human protein-protein interaction network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Here the authors summarize the community ... ...

    Abstract Comprehensive understanding of the human protein-protein interaction network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Here the authors summarize the community efforts initiated by the International Network Medicine Consortium to benchmark the ability of 26 representative network-based methods to predict protein-protein interactions.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2023-03-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

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  8. Artikel ; Online: Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers.

    Schick, Sandra / Rendeiro, André F / Runggatscher, Kathrin / Ringler, Anna / Boidol, Bernd / Hinkel, Melanie / Májek, Peter / Vulliard, Loan / Penz, Thomas / Parapatics, Katja / Schmidl, Christian / Menche, Jörg / Boehmelt, Guido / Petronczki, Mark / Müller, André C / Bock, Christoph / Kubicek, Stefan

    Nature genetics

    2019  Band 51, Heft 9, Seite(n) 1399–1410

    Abstract: Aberrations in genes coding for subunits of the BRG1/BRM associated factor (BAF) chromatin remodeling complexes are highly abundant in human cancers. Currently, it is not understood how these mostly loss-of-function mutations contribute to cancer ... ...

    Abstract Aberrations in genes coding for subunits of the BRG1/BRM associated factor (BAF) chromatin remodeling complexes are highly abundant in human cancers. Currently, it is not understood how these mostly loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer-type-specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knockout cell lines deficient for 22 BAF subunits. We observe strong, specific and sometimes discordant alterations dependent on the targeted subunit and show that these explain intracomplex codependencies, including the synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest approaches to therapeutically target BAF-mutant cancers.
    Mesh-Begriff(e) Chromatin Assembly and Disassembly/genetics ; DNA Helicases/genetics ; DNA Helicases/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Humans ; Mutation ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptome
    Chemische Substanzen ARID2 protein, human ; DNA-Binding Proteins ; Nuclear Proteins ; SMARCC1 protein, human ; SMARCC2 protein, human ; Transcription Factors ; SMARCA4 protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
    Sprache Englisch
    Erscheinungsdatum 2019-08-19
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-019-0477-9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Mutational landscape of the transcriptome offers putative targets for immunotherapy of myeloproliferative neoplasms.

    Schischlik, Fiorella / Jäger, Roland / Rosebrock, Felix / Hug, Eva / Schuster, Michael / Holly, Raimund / Fuchs, Elisabeth / Milosevic Feenstra, Jelena D / Bogner, Edith / Gisslinger, Bettina / Schalling, Martin / Rumi, Elisa / Pietra, Daniela / Fischer, Gottfried / Faé, Ingrid / Vulliard, Loan / Menche, Jörg / Haferlach, Torsten / Meggendorfer, Manja /
    Stengel, Anna / Bock, Christoph / Cazzola, Mario / Gisslinger, Heinz / Kralovics, Robert

    Blood

    2019  Band 134, Heft 2, Seite(n) 199–210

    Abstract: Ph-negative myeloproliferative neoplasms (MPNs) are hematological cancers that can be subdivided into entities with distinct clinical features. Somatic mutations ... ...

    Abstract Ph-negative myeloproliferative neoplasms (MPNs) are hematological cancers that can be subdivided into entities with distinct clinical features. Somatic mutations in
    Mesh-Begriff(e) Aged ; Antigens, Neoplasm/genetics ; Calreticulin/genetics ; Female ; Humans ; Immunotherapy/methods ; Male ; Middle Aged ; Mutation ; Myeloproliferative Disorders/genetics ; Receptors, Thrombopoietin/genetics ; Sequence Analysis, RNA/methods ; Transcriptome
    Chemische Substanzen Antigens, Neoplasm ; CALR protein, human ; Calreticulin ; Receptors, Thrombopoietin ; MPL protein, human (143641-95-6)
    Sprache Englisch
    Erscheinungsdatum 2019-05-07
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2019000519
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Environmental arginine controls multinuclear giant cell metabolism and formation.

    Brunner, Julia S / Vulliard, Loan / Hofmann, Melanie / Kieler, Markus / Lercher, Alexander / Vogel, Andrea / Russier, Marion / Brüggenthies, Johanna B / Kerndl, Martina / Saferding, Victoria / Niederreiter, Birgit / Junza, Alexandra / Frauenstein, Annika / Scholtysek, Carina / Mikami, Yohei / Klavins, Kristaps / Krönke, Gerhard / Bergthaler, Andreas / O'Shea, John J /
    Weichhart, Thomas / Meissner, Felix / Smolen, Josef S / Cheng, Paul / Yanes, Oscar / Menche, Jörg / Murray, Peter J / Sharif, Omar / Blüml, Stephan / Schabbauer, Gernot

    Nature communications

    2020  Band 11, Heft 1, Seite(n) 431

    Abstract: Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. MGC generation is energy intensive to enforce membrane fusion and cytoplasmic expansion. Using receptor activator of nuclear factor ... ...

    Abstract Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. MGC generation is energy intensive to enforce membrane fusion and cytoplasmic expansion. Using receptor activator of nuclear factor kappa-Β ligand (RANKL) induced osteoclastogenesis to model MGC formation, here we report RANKL cellular programming requires extracellular arginine. Systemic arginine restriction improves outcome in multiple murine arthritis models and its removal induces preosteoclast metabolic quiescence, associated with impaired tricarboxylic acid (TCA) cycle function and metabolite induction. Effects of arginine deprivation on osteoclastogenesis are independent of mTORC1 activity or global transcriptional and translational inhibition. Arginine scarcity also dampens generation of IL-4 induced MGCs. Strikingly, in extracellular arginine absence, both cell types display flexibility as their formation can be restored with select arginine precursors. These data establish how environmental amino acids control the metabolic fate of polykaryons and suggest metabolic ways to manipulate MGC-associated pathologies and bone remodelling.
    Mesh-Begriff(e) Animals ; Arginine/metabolism ; Arthritis/genetics ; Arthritis/metabolism ; Arthritis/physiopathology ; Bone Remodeling ; Citric Acid Cycle ; Female ; Giant Cells/cytology ; Giant Cells/immunology ; Humans ; Interleukin-4/metabolism ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Mice, Inbred C57BL ; Osteoclasts/cytology ; Osteoclasts/metabolism ; Osteogenesis ; RANK Ligand/genetics ; RANK Ligand/metabolism
    Chemische Substanzen RANK Ligand ; Interleukin-4 (207137-56-2) ; Arginine (94ZLA3W45F) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
    Sprache Englisch
    Erscheinungsdatum 2020-01-22
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-14285-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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