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  1. Article ; Online: Bystander activation in memory and antigen-inexperienced memory-like CD8 T cells.

    Paprckova, Darina / Salyova, Eva / Michalik, Juraj / Stepanek, Ondrej

    Current opinion in immunology

    2023  Volume 82, Page(s) 102299

    Abstract: Antigen-induced memory T cells undergo counterintuitive activation in an antigen-independent manner, which is called bystander response. Although it is well documented that memory ... ...

    Abstract Antigen-induced memory T cells undergo counterintuitive activation in an antigen-independent manner, which is called bystander response. Although it is well documented that memory CD8
    MeSH term(s) Humans ; CD8-Positive T-Lymphocytes ; Lymphocyte Activation ; Antigens ; Cytokines ; Immunologic Memory
    Chemical Substances Antigens ; Cytokines
    Language English
    Publishing date 2023-03-11
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2023.102299
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    Zs.A 2773: Show issues Location:
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  2. Article ; Online: IL-2-driven CD8

    Niederlova, Veronika / Tsyklauri, Oksana / Kovar, Marek / Stepanek, Ondrej

    Trends in immunology

    2023  Volume 44, Issue 11, Page(s) 890–901

    Abstract: The therapeutic potential of interleukin (IL)-2 in cancer treatment has been known for decades, yet its widespread adoption in clinical practice remains limited. Recently, chimeric proteins of an anti-PD-1 antibody and suboptimal IL-2 variants were shown ...

    Abstract The therapeutic potential of interleukin (IL)-2 in cancer treatment has been known for decades, yet its widespread adoption in clinical practice remains limited. Recently, chimeric proteins of an anti-PD-1 antibody and suboptimal IL-2 variants were shown to stimulate potent antitumor and antiviral immunity by inducing unique effector CD8
    MeSH term(s) Mice ; Animals ; CD8-Positive T-Lymphocytes ; Interleukin-2/therapeutic use ; Interleukin-2/metabolism ; Immunotherapy ; T-Lymphocytes, Cytotoxic ; T-Lymphocytes, Regulatory ; Phenotype
    Chemical Substances Interleukin-2
    Language English
    Publishing date 2023-10-10
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2023.09.003
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  3. Article ; Online: A LoCK at the T cell dock.

    Horkova, Veronika / Stepanek, Ondrej

    Science (New York, N.Y.)

    2021  Volume 372, Issue 6546, Page(s) 1038–1039

    MeSH term(s) Biochemical Phenomena ; Peptides ; Receptors, Antigen, T-Cell ; Signal Transduction ; T-Lymphocytes
    Chemical Substances Peptides ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2021-06-02
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abj2937
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  4. Article ; Online: Identification of GC-rich LAT genes in birds.

    Janusova, Sarka / Krchlikova, Veronika / Hron, Tomas / Elleder, Daniel / Stepanek, Ondrej

    PloS one

    2023  Volume 18, Issue 4, Page(s) e0283431

    Abstract: Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we ... ...

    Abstract Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we show that LAT gene is present in genomes of multiple extant birds. It was not properly assembled previously because of its GC-rich content. LAT expression is enriched in lymphoid organs in chicken. The analysis of the coding sequences revealed a strong conservation of key signaling motifs in LAT between chicken and human. Overall, our data indicate that mammalian and avian LAT genes are functional homologues with a common role in T-cell signaling.
    MeSH term(s) Animals ; Humans ; Adaptor Proteins, Signal Transducing/genetics ; Membrane Proteins/genetics ; T-Lymphocytes/metabolism ; Genome ; Chickens/genetics ; Chickens/metabolism ; Mammals/genetics ; Phosphoproteins/metabolism
    Chemical Substances Adaptor Proteins, Signal Transducing ; Membrane Proteins ; Phosphoproteins
    Language English
    Publishing date 2023-04-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0283431
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  5. Article ; Online: Identification of GC-rich LAT genes in birds.

    Sarka Janusova / Veronika Krchlikova / Tomas Hron / Daniel Elleder / Ondrej Stepanek

    PLoS ONE, Vol 18, Iss 4, p e

    2023  Volume 0283431

    Abstract: Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we ... ...

    Abstract Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we show that LAT gene is present in genomes of multiple extant birds. It was not properly assembled previously because of its GC-rich content. LAT expression is enriched in lymphoid organs in chicken. The analysis of the coding sequences revealed a strong conservation of key signaling motifs in LAT between chicken and human. Overall, our data indicate that mammalian and avian LAT genes are functional homologues with a common role in T-cell signaling.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
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  6. Article ; Online: Identification of GC-rich LAT genes in birds

    Sarka Janusova / Veronika Krchlikova / Tomas Hron / Daniel Elleder / Ondrej Stepanek

    PLoS ONE, Vol 18, Iss

    2023  Volume 4

    Abstract: Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we ... ...

    Abstract Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we show that LAT gene is present in genomes of multiple extant birds. It was not properly assembled previously because of its GC-rich content. LAT expression is enriched in lymphoid organs in chicken. The analysis of the coding sequences revealed a strong conservation of key signaling motifs in LAT between chicken and human. Overall, our data indicate that mammalian and avian LAT genes are functional homologues with a common role in T-cell signaling.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
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  7. Article ; Online: Narcissistic T cells: reactivity to self makes a difference.

    Paprckova, Darina / Stepanek, Ondrej

    The FEBS journal

    2020  Volume 288, Issue 6, Page(s) 1778–1788

    Abstract: It has been appreciated for more than three decades that the interactions between the T-cell antigen receptor and self-antigens are the major determinants of the cell fates of developing thymocytes and the establishment of central tolerance. However, ... ...

    Abstract It has been appreciated for more than three decades that the interactions between the T-cell antigen receptor and self-antigens are the major determinants of the cell fates of developing thymocytes and the establishment of central tolerance. However, recent evidence shows that the level of self-reactivity substantially contributes to fate choices of positively selected mature T cells in homeostasis, as well as during immune responses. This implies that individual clones of peripheral T cells are predisposed to specific functional properties based on the self-reactivity of their antigen receptors. Overall, the relative difference in the self-reactivity among peripheral T cells is an important factor contributing to the diversity of T-cell responses to foreign antigens.
    Language English
    Publishing date 2020-08-10
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.15498
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    Zs.A 260: Show issues Location:
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  8. Article ; Online: Rapid screening of ternary amorphous formulations by a spray drying robot.

    Klimša, Vojtěch / Mašková, Lucie / Kašpar, Ondřej / Ruphuy, Gabriela / Štěpánek, František

    International journal of pharmaceutics

    2023  Volume 651, Page(s) 123739

    Abstract: Spray drying is commonly used for producing amorphous solid dispersions to improve drug solubility. The development of such formulations typically relies on comprehensive excipient and composition screening, which requires the preparation of many spray- ... ...

    Abstract Spray drying is commonly used for producing amorphous solid dispersions to improve drug solubility. The development of such formulations typically relies on comprehensive excipient and composition screening, which requires the preparation of many spray-dried powder samples. This is both labour-intensive and time-consuming when carried out manually. In the present work, the formulation screening task was automated by coupling a laboratory spray dryer operated in a semi-continuous mode with custom-made add-ons, allowing for rapid, computer-controlled production of formulation samples with systematically varying composition. The practical use of the spray drying robot in formulation development was demonstrated on a case study of poorly water-soluble model drugs simvastatin and ezetimibe. Six different polymers and several drug:polymer ratios were screened for the enhancement of dissolution properties. From a pool of 28 spray-dried samples, ternary compositions containing Eudragit L100-55 were identified as the most suitable ones for further processing and characterisation. The ability to populate the formulation design space rapidly and automatically made it possible to construct maps of physico-chemical properties such as glass transition temperature or dissolution rate. The spray drying robot thus enables the acceleration of early formulation development and a deeper understanding of composition-property relationships for multi-component spray dried powders.
    MeSH term(s) Drug Compounding ; Spray Drying ; Robotics ; Solubility ; Polymers/chemistry
    Chemical Substances Polymers
    Language English
    Publishing date 2023-12-23
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 428962-6
    ISSN 1873-3476 ; 0378-5173
    ISSN (online) 1873-3476
    ISSN 0378-5173
    DOI 10.1016/j.ijpharm.2023.123739
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  9. Article ; Online: FRENCH COUNTERINSURGENCY IN MALI BEFORE AND AFTER THE COUP D'ÉTAT OF 2020

    Ondřej Čábelka / Stanislav Štěpánek

    Obrana a Strategie, Vol 21, Iss 2, Pp 43-

    2021  Volume 66

    Abstract: The civil war in Mali is one of the longest-running conflicts in the African Sahel region. The conflict is now a typical example of an asymmetric conflict, with nation-state forces on one side and non-state armed actors on the other. This article ... ...

    Abstract The civil war in Mali is one of the longest-running conflicts in the African Sahel region. The conflict is now a typical example of an asymmetric conflict, with nation-state forces on one side and non-state armed actors on the other. This article describes the roots of the conflict, its evolution, France’s involvement in counterinsurgency and counterterrorism operations, and the operational activities of Task Force Takuba. Finally, it provides an assessment of the overall issue, including an assessment of whether the objectives for which Task Force Takuba was formed have been met.
    Keywords mali ; france ; task force takuba ; special forces ; coin ; counterterrorism ; Military Science ; U
    Language Czech
    Publishing date 2021-12-01T00:00:00Z
    Publisher University of Defence
    Document type Article ; Online
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  10. Article ; Online: Model-Based Evaluation of Drying Kinetics and Solvent Diffusion in Pharmaceutical Thin Film Coatings.

    Navrátil, Ondřej / Kolář, Jiří / Zadražil, Aleš / Štěpánek, František

    Pharmaceutical research

    2022  Volume 39, Issue 9, Page(s) 2017–2031

    Abstract: Purpose: Fluid-bed coating processes make it possible to manufacture pharmaceutical products with tuneable properties. The choice of polymer type and coating thickness provides control over the drug release characteristics, and multi-layer pellet ... ...

    Abstract Purpose: Fluid-bed coating processes make it possible to manufacture pharmaceutical products with tuneable properties. The choice of polymer type and coating thickness provides control over the drug release characteristics, and multi-layer pellet coatings can combine several active ingredients or achieve tailored drug release profiles. However, the fluid-bed coating is a parametrically sensitive process due to the simultaneous occurrence of polymer solution spraying and solvent evaporation. Designing a robust fluid-bed coating process requires the knowledge of thin film drying kinetics, which in turn critically depends on an accurate description of concentration-dependent solvent diffusion in the polymer.
    Methods: This work presents a mathematical model of thin film drying as an enabling tool for fluid-bed process design. A custom-built benchtop drying cell able to record and evaluate the drying kinetics of a chosen polymeric excipient has been constructed, validated, and used for data collection.
    Results: A semi-empirical mathematical model combining heat transfer, mass transfer, and film thickness evolution was formulated and used for estimating the solvent diffusion coefficient and solvent distribution in the polymer layer. The combined experimental and computational methodology was then used for analysing the drying kinetics of common polymeric excipients: poly(vinylpyrrolidone) and two grades of hydroxypropyl methylcellulose.
    Conclusions: The experimental setup together with the mathematical model represents a valuable tool for predictive modeling of pharmaceutical coating processes.
    MeSH term(s) Excipients ; Hypromellose Derivatives ; Kinetics ; Polymers ; Solvents
    Chemical Substances Excipients ; Polymers ; Solvents ; Hypromellose Derivatives (3NXW29V3WO)
    Language English
    Publishing date 2022-08-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 843063-9
    ISSN 1573-904X ; 0724-8741 ; 0739-0742
    ISSN (online) 1573-904X
    ISSN 0724-8741 ; 0739-0742
    DOI 10.1007/s11095-022-03352-5
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