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Start date: 2024 × DDC: 610 ×

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    PIEZO1-mediated mechanosensing governs NK cell killing efficiency and infiltration in three-dimensional matrices
    ([Cold Spring Harbor] : Cold Spring Harbor Laboratory (CSHL), 2024) Yanamandra, Archana K.; Zhang, Jingnan; Montalvo, Galia; Zhou, Xiangda; Biedenweg, Doreen; Zhao, Renping; Sharma, Shulagna; Hoth, Markus; Lautenschläger, Franziska; Otto, Oliver; del Campo, Aránzazu; Qu, Bin
    Natural killer (NK) cells play a vital role in eliminating tumorigenic cells. Efficient locating and killing of target cells in complex three-dimensional (3D) environments are critical for their functions under physiological conditions. However, the role of mechanosensing in regulating NK cell killing efficiency in physiologically relevant scenarios is poorly understood. Here, we report that the responsiveness of NK cells is regulated by tumor cell stiffness. NK cell killing efficiency in 3D is impaired against softened tumor cells, while it is enhanced against stiffened tumor cells. Notably, the durations required for NK cell killing and detachment are significantly shortened for stiffened tumor cells. Furthermore, we have identified PIEZO1 as the predominantly expressed mechanosensitive ion channel among the examined candidates in NK cells. Perturbation of PIEZO1 abolishes stiffness-dependent NK cell responsiveness, significantly impairs the killing efficiency of NK cells in 3D, and substantially reduces NK cell infiltration into 3D collagen matrices. Conversely, PIEZO1 activation enhances NK killing efficiency as well as infiltration. In conclusion, our findings demonstrate that PIEZO1-mediated mechanosensing is crucial for NK killing functions, highlighting the role of mechanosensing in NK cell killing efficiency under 3D physiological conditions and the influence of environmental physical cues on NK cell functions.
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    Expanding the genetic programmability of Lactiplantibacillus plantarum
    (Oxford : Wiley-Blackwell, 2024) Blanch‐Asensio, Marc; Dey, Sourik; Tadimarri, Varun Sai; Sankaran, Shrikrishnan
    Lactobacilli are ubiquitous in nature and symbiotically provide health benefits for countless organisms including humans, animals and plants. They are vital for the fermented food industry and are being extensively explored for healthcare applications. For all these reasons, there is considerable interest in enhancing and controlling their capabilities through the engineering of genetic modules and circuits. One of the most robust and reliable microbial chassis for these synthetic biology applications is the widely used Lactiplantibacillus plantarum species. However, the genetic toolkit needed to advance its applicability remains poorly equipped. This mini-review highlights the genetic parts that have been discovered to achieve food-grade recombinant protein production and speculates on lessons learned from these studies for L. plantarum engineering. Furthermore, strategies to identify, create and optimize genetic parts for real-time regulation of gene expression and enhancement of biosafety are also suggested.
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    Semantic units: organizing knowledge graphs into semantically meaningful units of representation
    (London : BioMed Central, 2024) Vogt, Lars; Kuhn, Tobias; Hoehndorf, Robert
    Background In today’s landscape of data management, the importance of knowledge graphs and ontologies is escalating as critical mechanisms aligned with the FAIR Guiding Principles—ensuring data and metadata are Findable, Accessible, Interoperable, and Reusable. We discuss three challenges that may hinder the effective exploitation of the full potential of FAIR knowledge graphs. Results We introduce “semantic units” as a conceptual solution, although currently exemplified only in a limited prototype. Semantic units structure a knowledge graph into identifiable and semantically meaningful subgraphs by adding another layer of triples on top of the conventional data layer. Semantic units and their subgraphs are represented by their own resource that instantiates a corresponding semantic unit class. We distinguish statement and compound units as basic categories of semantic units. A statement unit is the smallest, independent proposition that is semantically meaningful for a human reader. Depending on the relation of its underlying proposition, it consists of one or more triples. Organizing a knowledge graph into statement units results in a partition of the graph, with each triple belonging to exactly one statement unit. A compound unit, on the other hand, is a semantically meaningful collection of statement and compound units that form larger subgraphs. Some semantic units organize the graph into different levels of representational granularity, others orthogonally into different types of granularity trees or different frames of reference, structuring and organizing the knowledge graph into partially overlapping, partially enclosed subgraphs, each of which can be referenced by its own resource. Conclusions Semantic units, applicable in RDF/OWL and labeled property graphs, offer support for making statements about statements and facilitate graph-alignment, subgraph-matching, knowledge graph profiling, and for management of access restrictions to sensitive data. Additionally, we argue that organizing the graph into semantic units promotes the differentiation of ontological and discursive information, and that it also supports the differentiation of multiple frames of reference within the graph.
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    Lebensqualität bei Krebserkrankungen – Integration in die Versorgung (working paper von Versorgern und Betroffenen)
    (Hannover : Technische Informationsbibliothek, 2024) Beutter, C. N. L.; Block, N.; Berger, S.; Edo-Ferrando, P.; Heinz, B.; Läufer, K.; Lang, B.; Mächtlen, K.; Münkel, S.; Rannert, D.; Zwerenz-Kopp, F.; Fegeler, C.
    Im Rahmen einer Projektgruppe haben sich sowohl Versorger (ÄrztInnen, KrebsberatungsstellenmitarbeiterInnen oder PsychoonkologInnen) sowie Betroffene mit einer regulären Integration von Lebensqualitätsdaten in der Versorgung befasst. Dabei wurde ein digitales System konzipiert, dass eine alltagsnahe und longitudinale Erhebung ermöglicht. Im working paper wurde über alle Teilnehmenden hinweg eine Problemidentifikation der derzeitigen IST-Situation integriert, um anhand dieser Probleme und Hemmschwellen ein übergreifendes Lösungskonzept zu erarbeiten. Im Lösungsraum wurden sowohl spezifische Anforderungen seitens der Versorger als auch PatientInnen zusammengefasst und gegenübergestellt. Dabei wurde ebenfalls die Vernetzung der einzelnen Akteure untereinander beleuchtet sowie die Thematik der Datenspende angerissen.