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Schwan, C.

Publications and source records attributed to Schwan, C..

6 recordsLinked to original sources

MDMR: Balancing Diversity and Redundancy for Annotation-Efficient Fine-Tuning of Pretrained Cell Segmentation Models

Pretrained cell segmentation models have simplified and accelerated microscopy image analysis, but they often perform poorly on new and challenging datasets. Although these models can be adapted to new datasets with only a few annotated images, the effectiveness of fine-tuning depends critically on which images are selected for annotation. To address this, we propose CGMD (Centrality-Guided Maximum Diversity), a novel algorithm that identifies a small set of images that are maximally diverse with respect to each other in the pretrained feature space. We evaluate CGMD under an extremely low annotation budget of just two images per dataset for fine-tuning the pretrained Cellpose Cyto2 model on four different 2D+t datasets from the Cell Tracking Challenge. CGMD consistently outperforms six competitive active learning and subset selection methods and approaches the performance of fully supervised fine-tuning. The results show that centrality-guided maximum diversity subset selection enables stable and annotation-efficient fine-tuning of pretrained cell segmentation models. The code is publicly available at: https://github.com/eiram-mahera/cgmd.

bioengineering↗

Borg3 / Cdc42EP5 regulates septin recruitment to primary cilia

Septin GTPases form linear hexa- or octameric rods that polymerize into higher order structures. They are incorporated into the cytoskeleton and involved in vital cellular functions. Among these, they play a role in the formation of primary cilia. Primary cilia are evolutionary conserved cellular signaling hubs. While it is accepted that septins localize to primary cilia and are involved in their formation and function, the regulation of septin assembly in the confined ciliary compartment remains elusive. Here we show, that Borg3, also known as Cdc42 effector protein 5 (Cdc42EP5), is an essential component of primary cilia. Specific Borg3 localization is facilitated by switching the Rho-GTPase Cdc42 between an inactive- and active state at the base of the primary cilium. The active form of Cdc42 has a defined localization restricted to the base of the primary cilium. Knockout of Borg3 as well as dysregulation of Cdc42 reduces septin dynamics at cilia and consequently, the formation of cilia. The study demonstrates that Borg3 is a novel and essential regulator of ciliogenesis through the spatiotemporal control of septin dynamics downstream of Cdc42.

cell biology↗

Clostridioides difficile binary toxin binding component (CDTb) increases virulence in a hamster model

Clostridioides difficile is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. We have previously shown that CDT interacts with the TLR2/6 heterodimer to induce inflammation, and in this study we further explore this interaction as well as the contribution of the separate components of CDT, CDTa and CDTb. We found that the binding component, CDTb, is capable of inducing inflammation. Additionally, complementation of a CDT-deficient C. difficile strain with CDTb alone restored virulence in a hamster model of C. difficile infection. Overall, this study demonstrates that the binding component of C. difficile binary toxin contributes to virulence during infection.

microbiology↗

Clostridium difficile binary toxin (CDT) is recognized by the TLR2/6 heterodimer to induce an NF-κB response

Clostridioides difficile infection (CDI) represents a significant burden on the health care system, one that is exacerbated by the emergence of binary toxin (CDT)-producing hypervirulent C. difficile strains. Previous work from our lab has shown that TLR2 recognizes CDT to induce inflammation. Here we explore the interactions of CDT with TLR2 and the impact on host immunity during CDI. We found that the TLR2/6 heterodimer, not TLR2/1, is responsible for CDT recognition, and that gene pathways including NF-{kappa}B and MAPK downstream of TLR2/6 are upregulated in mice with intact TLR2/6 signaling during CDI.

immunology↗

Spatiotemporal sequence of mesoderm and endoderm lineage segregation during mouse gastrulation

Anterior mesoderm (AM) and definitive endoderm (DE) progenitors represent the earliest embryonic cell types that are specified during germ layer formation at the primitive streak (PS) of the mouse embryo. Genetic experiments indicate that both lineages segregate from Eomes expressing progenitors in response to different NODAL signaling levels. However, the precise spatiotemporal pattern of the emergence of these cell types and molecular details of lineage segregation remain unexplored. We combined genetic fate labeling and imaging approaches with scRNA-seq to follow the transcriptional identities and define lineage trajectories of Eomes dependent cell types. All cells moving through the PS during the first day of gastrulation express Eomes. AM and DE specification occurs before cells leave the PS from discrete progenitor populations that are generated in distinct spatiotemporal patterns. Importantly, we dont find evidence for the existence of progenitors that co-express markers of both cell lineages suggesting an immediate and complete separation of AM and DE lineages. Summary statementCells lineages are specified in the mouse embryo already within the primitive streak where Mesp1+ mesoderm and Foxa2+ endoderm are generated in a spatial and temporal sequence from unbiased progenitors.

developmental biology↗

Post-mitotic expansion of cell nuclei requires ACTN4-mediated nuclear actin filament bundling

The actin cytoskeleton operates in a multitude of cellular processes including cell shape and migration, mechanoregulation, as well as membrane or organelle dynamics. However, its filamentous properties and functions inside the mammalian cell nucleus are less well explored. We previously described transient actin assembly at mitotic exit that promotes nuclear expansion during chromatin decondensation. Here, we identify non-muscle ACTN4 as a critical regulator to facilitate F-actin formation, reorganization and bundling during postmitotic nuclear expansion. ACTN4 binds to nuclear actin filaments and ACTN4 clusters associate with nuclear F-actin in a highly dynamic fashion. ACTN4 but not ACTN1 is required for proper postmitotic nuclear volume expansion, mediated by its actin binding domain. Using super-resolution imaging to quantify actin filament numbers and widths in individual nuclei we find that ACTN4 is necessary for postmitotic nuclear actin assembly and actin filament bundling. Our findings uncover a nuclear cytoskeletal function for ACTN4 to control nuclear size during mitotic cell division.

cell biology↗