Biology subjects

Krieg, C.

Publications and source records attributed to Krieg, C..

7 recordsLinked to original sources

bioRxiv2026

A comparison of female competitive traits: Female aggression peaks at nest building but female song spans multiple contexts in a temperate songbird

Female-female competition is increasingly recognized as a key driver of female ornamentation, including birdsong, which often functions in intrasexual competition. However, the specific resources females use elaborate traits to compete for remain unclear. In addition, few studies have simultaneously investigated the use of multiple competitive traits in females, despite growing independent interest in these traits (e.g., female song and aggression). We investigated the competitive contexts of female song, aggression and calling behavior in northern house wrens (Troglodytes aedon) to determine which resources females compete for across the breeding season. We simulated conspecific territorial intrusions using female song at three breeding stages representing different contexts: arrival (mate and territory acquisition), nest building (nest site and breeding status defense), and egg laying (brood defense). We tested whether female song and physical aggression varied as reproductive resources shifted across the breeding cycle. Females were significantly more aggressive during nest building, showing 5.8 times greater odds of a higher-intensity aggressive response during nest building compared to arrival. Female song output was similar across early stages but declined during egg laying, though this was not statistically significant after correction for multiple comparisons and individuals varied substantially in overall singing propensity. Non-song vocalizations varied by call type and breeding stage. Calls associated with aggression occurred most frequently during nest building, consistent with peak physical aggression responses. Together, these results identify nest building as the stage of highest female aggression, consistent with heightened competition over nest cavities and associated breeding status in this cavity-nesting species. In contrast, female song occurred across all stages and appears to function in multiple competitive contexts. This study provides evidence for context and mode-specific female signaling in a temperate songbird and highlights that females strategically use aggression, calls, and song to mediate social conflict across breeding contexts.

animal behavior and cognition↗

bioRxiv2026

Resolving sialylated N Glycans and immune cell landscapes using a unified same-section IMC-MSI workflow

Integrating antibody-based imaging with mass spectrometry imaging (MSI) on the same formalin-fixed paraffin-embedded (FFPE) tissue section offers powerful opportunities for multimodal spatial analysis but remains analytically challenging due to cross-platform chemical and physical interference. In particular, chemically aggressive on-tissue derivatization strategies required for isomer-resolved glycan MSI may compromise downstream antibody detection. Here, we systematically evaluate the analytical compatibility and acquisition order of imaging mass cytometry (IMC) and sialic-acid-linkage-resolving N-glycan MALDI-MSI using an Amidation-Activation-X-Linkage (AAXL) derivatization strategy on the same FFPE tissue section. Two same-section workflows were compared: AAXL-MALDI MSI followed by IMC (MALDI-first) and IMC followed by AAXL-MALDI MSI (IMC-first). We find that AAXL-first processing results in severe and widespread loss of IMC anti-body signal across epithelial, immune, and nuclear markers, rendering subsequent antibody-based analysis unreliable. In contrast, IMC-first acquisition preserves quantitative antibody performance while maintaining spatial glycan distributions, relative abundance structure, and isomer-specific signal integrity in downstream AAXL-MALDI MSI. Using high-precision co-registration, we further demonstrate that IMC-first sequencing enables analytically robust integration of IMC and MSI data at both domain and pixel levels. These results establish IMC-first acquisition as the preferred same-section strategy for workflows combining antibody imaging with chemically intensive, isomer-resolved glycan MSI and provide generalizable guidance for the design of multimodal spatial mass spectrometry experiments.

immunology↗

bioRxiv2025

Spatially-smoothed quantification improves cell typing in imaging mass cytometry datasets

Accurate cell type annotation in imaging mass cytometry (IMC) and related technologies critically depends on preprocessing steps such as normalization, segmentation, and marker aggregation. More distinct separation between negative and positive signals enables more precise cell boundary inference and more robust marker assignment to single cells. However, inherent limitations in spatial resolution and uncertain cell boundaries can lead to spillover, where signal leaks from one cell to a neighboring cell, distorting marker intensities and leading to incorrect cell type annotation. To address these challenges, we first systematically investigated the impact of spatial resolution and segmentation variability on per-cell marker aggregation using simulated IMC datasets, establishing upper limits for reliable marker separation in cell type annotation. We further analyzed technical biases in large scale studies, demonstrating that appropriate normalization approaches can significantly reduce batch effects without compromising biological variability. Finally, we benchmarked multiple spillover correction strategies across both (semi-)simulated and real IMC datasets. Our results revealed two simple methods: spatial smoothing of intensity images followed by mean marker aggregation, or resampling of cell masks followed by mean marker aggregation and median calculation, both of which improved annotation performance. Other methods often performed worse than the baseline of simple mean aggregation. Together, these findings underscore the central importance of spatial resolution, normalization, and marker aggregation in IMC data preprocessing for accurate single-cell annotation.

bioinformatics↗

bioRxiv2025

MIMIC: a flexible pipeline to register and summarize IMC-MSI experiments

Spatial omics is transforming our ability to interrogate local tissue microenvironments by enabling spatially resolved measurement of biomolecules such as transcripts, proteins, and metabolites. However, capturing the full biological complexity of tissues often requires combining multiple modalities, which introduces both experimental as well as computational challenges. To address computational difficulties due to differences in resolution, noise levels, and available channels, we present MIMIC: a reproducible, semi-automated workflow that integrates Mass Spectrometry Imaging and Imaging Mass Cytometry for joint downstream analysis. MIMIC incorporates rigorous quality control, including registration error assessment, and supports pixel-level modeling to delineate analyte-cell type associations. We demonstrate the power of our approach with a proof-of-concept study on artificial tissue and apply it to human liver tissue affected by metabolic dysfunction-associated steatotic liver disease. Despite integration challenges, MIMIC provides a robust framework that successfully recovers known molecular associations and reveals novel spatial relationships across modalities.

bioinformatics↗

bioRxiv2023

Innate immune receptor C5aR1 regulates cancer cell fate and can be targeted to improve radiotherapy in tumours with immunosuppressive microenvironments

An immunosuppressive microenvironment causes poor tumour T-cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumours is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identify complement receptor C5aR1 as a druggable target which when inhibited improves radiotherapy even in tumours displaying immunosuppressive features and poor CD8+ T-cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we find that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumour-cell specific functions. C5aR1 targeting results in increased NF-{kappa}B-dependent apoptosis specifically in tumours and not normal tissues; indicating that in malignant cells, C5aR1 primarily regulates cell fate. Collectively, these data reveal that increased complement gene expression is part of the stress response mounted by irradiated tumours and that targeting C5aR1 can improve radiotherapy even in tumours displaying immunosuppressive features.

cancer biology↗

bioRxiv2022

Use of CD122+ natural killer cell precursors for superior anti-leukemia responses.

Acute Myeloid Leukemia (AML) is an aggressive blood cancer in adults. Intensive induction therapy successfully induces a complete response in up to 80% of the adult patients but a fraction of them is refractory or relapses. The fraction of non-responsive or relapsing patients is especially high amongst medically unfit and older patients, who cannot undergo aggressive chemotherapy treatment. Therefore, offering patients failing on first line intensive chemotherapy and medically unfit and older patients an effective treatment option for long-term control or even cure of disease represents a significant yet unmet clinical need. As a component of the innate immunity, NK cells have recently shown great promise for the treatment of patients with different malignancies. Here, we show that injection of human interleukin-2 (IL-2) complexes (IL-2cx) induce the de novo generation and massive expansion of NK cell precursors in vivo. Furthermore, IL-2cx-expanded NK cells exert effector functions with the capacity to control the growth of non-self MHC class I-deficient RMA-S lymphoma cells in vivo, while remaining tolerant towards MHC class-expressing self RMA cells. In an experimental setup mimicking the clinical case of refractory patients after intensive AML induction therapy, IL-2cx treatment mediated strong anti-AML responses following haploidentical bone marrow transplantation without the need for adoptive transfer of donor-derived or in vitro autologous expanded NK cells. Thus, this study demonstrates that IL-2cx immunotherapy allows the in vivo generation and expansion of functionally mature NK cells to achieve long-term response in AML paving the way to an effective treatment option.

immunology↗

bioRxiv2021

Loss of C3aR induces immune infiltration and inflammatory microbiota in a novel spontaneous model of colon cancer

Several lines of evidence suggest that inflammation plays a pivotal role in the development and progression of colorectal cancer (CRC) and can be unleashed by the loss of innate immunosurveillance. The complement system is a well characterized first line of defense against pathogens and a central component of the immune response. Emerging evidence suggests that complement anaphylatoxin C3a produced upon complement activation and acting via its receptor (C3aR) may play a role in intestinal homeostasis. However, to date, it is unknown whether and how the C3a/C3aR axis can affect CRC. By mining publicly available datasets, we found that CpG island methylation of c3ar1 occurs in CRC patients and is associated with significant downregulation of C3aR. By reverse-translating this finding we were able to shift in APCMin/+ mice the tumorigenesis from the small intestine to the colon therefore generating a novel mouse model, which more closely mirrors the CRC in humans. Transcriptomic analysis on colorectal polyps from our newly developed genetic mouse model revealed a significant increase in innate and adaptive immune signatures in absence of C3aR. Furthermore, loss of C3aR significantly impacted the fecal and tumor-associated microbiota and supported the blooming of pro-inflammatory bacterial species as confirmed by experiments of fecal microbiota transplantation. Future studies will elucidate whether loss of C3aR can be exploited as a biomarker for sub-groups of CRC and whether the C3a/C3aR axis may be exploited for the generation of more effective therapeutic interventions.

immunology↗