Biology subjects

Kunz, M.

Publications and source records attributed to Kunz, M..

13 recordsLinked to original sources

bioRxiv2026

Competition against the intestinal microbiota selects for pathoadaptive traits in ESBL E. coli

The intestinal tract is a reservoir for Extended-Spectrum {beta}-Lactamase (ESBL)-producing Escherichia coli. Asymptomatic gut colonization by these pathobionts represents a major risk for extraintestinal infections. Despite clinical relevance, the genetic basis of gut colonization by ESBL E. coli remains poorly understood. Here, we determined how the microbiota shapes the fitness landscape of diverse ESBL E. coli strains, defining the functional requirements for intestinal colonization. In microbiota-depleted hosts, colonization relies mostly on metabolic functions. In contrast, in mice harbouring a microbiota, pathoadaptive functions associated with adhesion and biofilm formation are dominant determinants of E. coli fitness, together with accessory virulence functions. Consistent with these observations, experimental evolution in mice reveals convergent adaptation of ESBL E. coli to the presence of a complex microbiota through enhanced adhesion. These findings establish the microbiota as a major ecological driver of pathoadaptation in antibiotic-resistant pathobionts.

microbiology↗

bioRxiv2026

Sea-level and climate changes drive lineage diversification in the imperiled Venus flytrap (Dionaea muscipula J. Ellis, Droseraceae)

Venus flytrap (Dionaea muscipula) is an insectivorous plant in the monotypic genus Dionaea, endemic to the Southeastern United States, and found in a small geographic range in North and South Carolina. Its unique morphology and natural history have intrigued biologists for centuries, yet the evolution of populations has not been adequately characterized. Population decline, driven primarily by disruptive land conversion, fire suppression, and illegal harvesting/poaching underscores the urgency of defining the genetic diversity in the present population to guide species conservation. We applied a genome-wide SNP dataset to analyze admixture and population structure and used coalescent modeling to trace the ancestry and migration of geographically distinct population clusters. Our population dynamics model supports four lineages, with the North Cape Fear Arch lineage as the ancestor of all lineages and two genetically distinct Sandhills lineages derived from the South Cape Fear Arch lineage independently at [~]13 Ma and [~]3 Ma, respectively, during peak climate optima periods and maximal sea level rise. Severe population decline events occurred among all lineages, with two ancient instant bottleneck population decline events in Sandhills lineages and two recent ones in the two Cape Fear Arch lineages, which contributed to the current genetic structure. Shorter peduncle lengths in Sandhills populations correspond with suspected local adaptation to Sandhills habitats.

evolutionary biology↗

bioRxiv2026

Natural aging drives a subclinical cardiovascular phenotype in a non-human primate

Aging is an inevitable risk factor for cardiovascular disease. Profound understanding of mechanisms underlying the early stages of cardiovascular aging is essential for the development of novel therapeutics. Therefore, animal models which closely reflect the human condition are highly sought after. Here, we investigated natural cardiovascular aging in a non-human primate, comparing healthy young-adult and aged common marmosets (Callithrix jacchus). Despite preservation of most cardiac functional parameters in aged animals, significant histological alterations were found including fibrosis and microvascular rarefaction. Molecular phenotyping by single-nuclei RNA-sequencing revealed activation of cardiac stress, pro-inflammatory and fibrotic gene programs in aged hearts. Importantly, proteomic analysis of cardiac extracellular vesicles revealed a cardioprotective cargo in young animals while functionally demonstrating pro-angiogenic properties on human cardiac microvascular endothelial cells. Finally, large vessel atherosclerosis was strikingly evident in aged animals and elucidated by bulk RNA-sequencing. Overall, the aging marmoset offers a great potential for translational cardiovascular research.

physiology↗

bioRxiv2025

Oral L-arginine cures arginase 1-dependent chronic cutaneous leishmaniasis by redirecting the T helper cell response

Leishmania (L.) mexicana-induced cutaneous leishmaniasis (CL) is a neglected tropical disease characterized by localized chronic ulcers (LCL) and, in rare cases, by disseminated skin lesions (DCL). The therapeutic options for CL are currently limited, and the immune dysregulation leading to chronicity of disease is poorly understood. Here, we identified interleukin (IL)-10-dependent upregulation of arginase 1 (ARG1) in cutaneous CX3CR1+ myeloid cells as central immunometabolic determinant of chronic CL in L. mexicana-infected C57BL/6 wild-type (WT) mice. Deletion of Arg1 in myeloid cells (Arg1{Delta}Cx3cr1) enabled parasite control and clinical healing. Single-cell RNA sequencing revealed that ARG1, together with interferon-{gamma} produced by T-helper 1 (Th1) cells, caused pathologic differentiation of Ly6Chigh monocytes into inflammatory macrophages (iMACs) that simultaneously expressed ARG1, nitric oxide synthase type 2 (NOS2) and the chemokines CXCL9/10. These Arg1+Nos2+Cxcl9/10+iMACs induced a lasting depletion of L-arginine in the skin, served as parasite niche, and maintained a self-perpetuating cycle of host cell recruitment. In Arg1{Delta}Cx3cr1 mice, the ARG1+NOS2+ host cell niche for the parasite was diminished. Prophylactic or therapeutic oral L-arginine supplementation restored tissue arginine levels, reduced parasite burden, and prevented or resolved chronic disease. L-arginine-treated mice showed enhanced T cell expansion and Th1 differentiation, remained free of clinical relapses, and were resistant to reinfection. As skin lesion biopsies from L. mexicana-infected LCL and DCL patients demonstrated a similar pattern of Th1/Th2 cytokine, Arg1 and Nos2 mRNA expression as seen in mice, we suggest metabolic reprogramming by oral L-arginine as a promising and easy-to-apply host-directed therapy for human L. mexicana CL. ONE SENTENCE SUMMARYArginase 1-mediated arginine depletion accounts for chronic cutaneous leishmaniasis, which can be prevented and even cured by oral L-arginine therapy.

immunology↗

bioRxiv2024

The Immunoregulatory Architecture of the Adult Oral Cavity

The immunoregulatory architecture of human oral tissues remains poorly defined despite their central role as barrier interfaces. We present the first integrated single-cell and dual-platform spatial-proteotranscriptomic atlas of oral tissues, profiling >250,000 single-cell transcriptomes and >4 million spatially-resolved cells across 13 niches. Using our AI-enabled AstroSuite (TACIT, Constellation, STARComm, hist2omics), we defined tissue cellular neighborhoods (TCNs) and multicellular interaction modules (MCIMs) in health, revealing peri-epithelial fibroblast-centered hubs enriched for effector cytokines. We harmonized eight fibroblast subtypes (universal, immune, peri-epithelial, peri-vascular, peri-neural, APC-like, stress-responsive, and myofibroblasts) with stress-responsive subtypes partitioning between mucosae (Type I) and glands (Type II). Spatial multiomics mapped receptor-ligand circuits and showed mucosal stress-responsive fibroblasts as immunoregulatory hubs. In chronic periodontitis, niche-aware integration of healthy and diseased datasets revealed rewiring of fibroblast phenotypes and ligand::receptor networks into interdigitated inflammatory and reparative niches. Disease neighborhoods exhibited fragmentation, expansion of MHC-I, MHC-II, and PD-L1 fibroblasts, and predicted spatial engagement with T cells at ectopic lymphoid structures. Drug2Cell analysis highlighted druggable stromal::immune networks. Together, this proteotranscriptomic atlas positions fibroblasts as central architects of structural immunity in human oral tissues and establishes a scalable framework for precision targeting of stromal::immune ecosystems across other barrier organs in health and chronic disease.

cell biology↗

bioRxiv2024

Biomass allocation of trees in response to mono- and heterospecific neighbourhoods

Carbon sequestration by trees is crucial to mitigate the effects of the current climate crisis. The extent to trees sequester and allocate carbon to above- or belowground structures in turn is mediated by neighbouring species. Although many studies have demonstrated positive effects of diverse neighbourhoods on a trees productivity, little is known about biomass allocation responses to mono-vs. heterospecific neighbourhoods. In the present study we quantified above- and belowground biomass production and root-to-shoot ratios (RSR) of trees grown in mono- and heterospecific neighbourhoods. To this end we analysed growth of mono- and heterospecific tree species pairs (TSPs) established in a greenhouse and a field experiment. In the greenhouse experiment response variables were measured after one year of growth after sapling harvest. In the field experiment, conducted in the context of a forest biodiversity experiment in subtropical China, we analysed biomass density and RSR over three years using terrestrial laser scanner and minirhizotrons. RSR of trees in heterospecific TSPs were significantly higher than in monospecific TSPs. In the greenhouse experiment, this was related to a stronger below-than aboveground overyielding in heterospecific TSPs. In the field experiment, trees in heterospecific TSPs showed a stronger increase in aboveground investments over time than in monospecific TSPs, indicating that positive diversity effects became stronger for aboveground structures with progressing tree development. Our findings are consistent with the optimal biomass partitioning theory and highlight the importance of tree-tree interactions on biomass allocation. Higher RSR in mixtures further suggest a higher resistance or resilience of tree saplings against environmental stressors related to climate change (drought, heat waves).

ecology↗

bioRxiv2024

Polybacterial Intracellular Macromolecules Shape Single-Cell Epikine Profiles in Upper Airway Mucosa

The upper airway, particularly the nasal and oral mucosal epithelium, serves as a primary barrier for microbial interactions throughout life. Specialized niches like the anterior nares and the tooth are especially susceptible to dysbiosis and chronic inflammatory diseases. To investigate host-microbial interactions in mucosal epithelial cell types, we reanalyzed our single-cell RNA sequencing atlas of human oral mucosa, identifying polybacterial signatures (20% Gram-positive, 80% Gram-negative) within both epithelial- and stromal-resident cells. This analysis revealed unique responses of bacterial-associated epithelia when compared to two inflammatory disease states of mucosa. Single-cell RNA sequencing, in situ hybridization, and immunohistochemistry detected numerous persistent macromolecules from Gram-positive and Gram-negative bacteria within human oral keratinocytes (HOKs), including bacterial rRNA, mRNA and glycolipids. Epithelial cells with higher concentrations of 16S rRNA and glycolipids exhibited enhanced receptor-ligand signaling in vivo. HOKs with a spectrum of polybacterial intracellular macromolecular (PIM) concentrations were challenged with purified exogenous lipopolysaccharide, resulting in the synergistic upregulation of select innate (CXCL8, TNFSF15) and adaptive (CXCL17, CCL28) epikines. Notably, endogenous lipoteichoic acid, rather than lipopolysaccharide, directly correlated with epikine expression in vitro and in vivo. Application of the Drug2Cell algorithm to health and inflammatory disease data suggested altered drug efficacy predictions based on PIM detection. Our findings demonstrate that PIMs persist within mucosal epithelial cells at variable concentrations, linearly driving single-cell effector cytokine expression and influencing drug responses, underscoring the importance of understanding host-microbe interactions and the implications of PIMs on cell behavior in health and disease at single-cell resolution. One-sentence summaryThis study reveals how persistent intracellular bacterial macromolecules in mucosal epithelial cells drive inflammatory signaling, offering new insights into microbial-host interactions and their potential impact on inflammatory disease treatment and drug efficacy.

cell biology↗

bioRxiv2024

Diversity-enhanced canopy space occupation and leaf functional diversity jointly promote overyielding in tropical tree communities

Understanding the mechanisms that drive biodiversity-productivity relationships is critical for guiding forest restoration. Although complementarity among trees in the canopy space has been suggested as a key mechanism for greater productivity in mixed-species tree communities, empirical evidence remains limited. Here, we used data from a tropical tree diversity experiment to disentangle the effects of tree species richness and community functional characteristics (community-weighted mean and functional diversity of leaf traits) on canopy space filling, and how these effects are related to overyielding. We found that canopy space filling was largely explained by species identity effects rather than tree diversity effects. Communities with a high abundance of species with conservative leaf traits were those with most densely packed canopies. Overall, a higher canopy space filling translated into an enhanced wood productivity, with communities associated with a high taxonomic and functional diversity being the most productive. Importantly, most communities (83%) produced more wood volume than the average of their constituent species in monoculture (i.e. most communities overyielded). Our results show that overyielding increased with leaf functional diversity and positive net biodiversity effects on canopy space filling, which mainly arose due to a high taxonomic diversity. These findings suggest that both taxonomic diversity-enhanced canopy space filling and canopy leaf diversity are important drivers for overyielding in mixed-species forests. Consequently, restoration initiatives should promote stands with functionally diverse canopies by selecting tree species with large interspecific differences in leaf nutrition, as well as leaf and branch morphology to optimize carbon capture in young forest stands.

ecology↗

bioRxiv2024

A pluripotent stem cell platform for in vitro systems genetics studies of mouse development

The directed differentiation of pluripotent stem cells (PSCs) from panels of genetically diverse individuals is emerging as a powerful experimental system for characterizing the impact of natural genetic variation on developing cell types and tissues. Here, we establish new PSC lines and experimental approaches for modeling embryonic development in a genetically diverse, outbred mouse stock (Diversity Outbred mice). We show that a range of inbred and outbred PSC lines can be stably maintained in the primed pluripotent state (epiblast stem cells -- EpiSCs) and establish the contribution of genetic variation to phenotypic differences in gene regulation and directed differentiation. Using pooled in vitro fertilization, we generate and characterize a genetic reference panel of Diversity Outbred PSCs (n = 230). Finally, we demonstrate the feasibility of pooled culture of Diversity Outbred EpiSCs as "cell villages", which can facilitate the differentiation of large numbers of EpiSC lines for forward genetic screens. These data can complement and inform similar efforts within the stem cell biology and human genetics communities to model the impact of natural genetic variation on phenotypic variation and disease-risk.

developmental biology↗

bioRxiv2023

Tree diversity increases forest temperature buffering

Global warming is increasing the frequency and intensity of climate extremes. Forests may buffer such extreme events by creating their own microclimate below their canopy via cooling hot and insulating against cold macroclimate air temperatures. This buffering capacity of forests may be increased by tree diversity and may itself maintain forest functioning and biodiversity. However, despite its relevance for many ecosystem processes, the effect of tree diversity on temperature buffering is largely unexplored. Here, we show that tree species richness consistently increases forest temperature buffering across daily, monthly, and annual scales over six years. This finding is based on data from a large-scale tree diversity experiment covering a species richness gradient of 1 to 24 tree species. We found that species richness strengthened both components of forest temperature buffering: the attenuation of hot and of cold macroclimate air temperatures, with the cooling effect being more pronounced. The buffering effect of tree species richness was mediated by canopy density and structural diversity, assessed as leaf area index and stand structural complexity index, respectively. Safeguarding and planting diverse forests may thus mitigate negative effects of global warming and climate extremes on ecosystem functions and communities below the tree canopy.

ecology↗

bioRxiv2023

Facial expression is a distinctive behavioural marker of pain processing in the brain

Pain is a private experience observable through various verbal and non-verbal behavioural manifestations, each of which may relate to different pain-related functions. Despite the importance of understanding the cerebral mechanisms underlying those manifestations, there is currently limited knowledge on the neural correlates of the facial expression of pain. In this functional magnetic resonance imaging (fMRI) study, noxious heat stimulation was applied in healthy volunteers and we tested if previously published brain signatures of pain were sensitive to pain expression. We then applied a multivariate pattern analysis to the fMRI data to predict the facial expression of pain. Results revealed the inability of previously developed pain neurosignatures to predict the facial expression of pain. We thus propose a Facial Expression of Pain Signature (FEPS) conveying distinctive information about the brain response to nociceptive stimulations with minimal or no overlap with other pain-relevant brain signatures associated with nociception, pain ratings, thermal pain aversiveness, or pain valuation. The FEPS may provide a distinctive functional characterization of the distributed cerebral response to nociceptive pain associated with the socio-communicative role of non-verbal pain expression. This underscores the complexity of pain phenomenology by reinforcing the view that neurosignatures conceived as biomarkers must be interpreted in relation to the specific pain manifestation(s) predicted and their underlying function(s). Future studies should explore other pain-relevant manifestations and assess the specificity of the FEPS against simulated pain expressions and other types of aversive or emotional states.

neuroscience↗

bioRxiv2021

Hydraulic diversity stabilizes productivity in a large-scale subtropical tree biodiversity experiment

Extreme climatic events threaten forests and their climate mitigation potential globally. Understanding the drivers promoting ecosystem stability is therefore considered crucial to mitigate adverse climate change effects on forests. Here, we use structural equation models to explain how tree species richness, asynchronous species dynamics and diversity in hydraulic traits affect the stability of forest productivity along an experimentally manipulated biodiversity gradient ranging from 1 to 24 tree species. Tree species richness improved stability by increasing species asynchrony. That is, at higher species richness, inter-annual variation in productivity among tree species buffered the community against stress-related productivity declines. This effect was mediated by the diversity of species hydraulic traits regarding drought tolerance and stomatal control, but not by the community-weighted means of these traits. The identified mechanisms by which tree species richness stabilizes forest productivity emphasize the importance of hydraulically diverse, mixed-species forests to adapt to climate change.

ecology↗

bioRxiv2019

The exotic species Senecio inaequidens pays the price for arriving late in temperate European grasslands

The South African ragwort (Senecio inaequidens DC.) is one of the fastest exotic plant invaders in Central Europe but, despite its large distribution area, it is still not commonly found in European grasslands. In order to better understand the mechanisms behind invasion resistance of grassland communities to S. inaequidens, we determined (1) to what extent the timing of arrival of S. inaequidens in the community affected its invasiveness as well as the performance of the native species, and (2) how the direction and strength of priority effects were affected by the composition of the native community being invaded, particularly with regard to the presence of N2-fixing species (legumes). In a greenhouse experiment, we manipulated the timing of arrival of the exotic species in the community and the composition of the native background community to test the influence of these factors on the productivity and N content of exotic and native species. Using a set of interaction indices, we also investigated if the plant species origin (native or exotic) and the native community composition affected the benefit of arriving early and the cost of arriving late (i.e., priority effects) in the community. We showed that both exotic and native species created inhibitory priority effects for late-arriving species. The establishment success of S. inaequidens strongly depended on its timing of arrival in a grassland community. On average, S. inaequidens benefited more from arriving early than the natives. We did not find any evidence to support that the presence of legumes in the background community would favour invasion by S. inaequidens. When natives arrived later than S. inaequidens, however, priority effects were weaker when legumes were present in the native community. Synthesis: we showed that priority effects created by natives can lower the risk of invasion by S. inaequidens and are an important mechanism to explain why this exotic species is not commonly found in European grasslands yet. Our results suggest that an early arrival of this species at a site with low native species abundance (e.g., following a disturbance) is a scenario that could favour invasion by S. inaequidens.

ecology↗