Biology subjects

Hermann, M.

Publications and source records attributed to Hermann, M..

10 recordsLinked to original sources

bioRxiv2026

Chemogenetic Hydrogen Sulfide Rescues Vascular Senescence in Ageing

Vascular senescence is a central driver of whole-body ageing, yet rescue strategies remain limited. Here we show that hydrogen sulfide (H2S) bioavailability declines in ageing and atherosclerosis and is associated with endothelial senescence. Developing a novel remote-control, endothelial-specific, mitochondria-targeted chemogenetic system, we spatiotemporally controlled H2S generation and thereby mitigated endothelial senescence-driven programs and reversed vascular remodeling in aged mice.

cell biology↗

bioRxiv2026

Gut Microbiota Production of Phenylacetate Programs Vascular Niche Senescence and Drives Atherosclerosis

Vascular senescence is a key contributor to ageing-related diseases, including atherosclerosis. Initial intervention is based on aggressive management of traditional risk factors, yet microbial metabolites remain underestimated as modifiable factors. We recently identified phenylacetate (PAA), a gut microbiota-linked metabolite, as a potent accelerator of endothelial senescence, raising the question of its causal role in atherosclerosis. Here, we show that PAA promotes vascular niche senescence and perivascular adipose tissue (PVAT) dysfunction, associated with atherosclerosis in humans and mice. Furthermore, PAA administration to atherosclerosis-prone mice was sufficient to drive atherosclerosis without altering lipid profile. Mechanistically, we found that PAA induces senescence-messaging secretome, containing IL-6, from endothelial cells, which stimulates Notch1 and disrupts insulin signaling in adipocytes. Blocking the PAA-IL-6-Notch1 axis as well as senolytics rescued adipocyte senescence and dysfunction. Identification of the strong link between PAA and atherosclerosis opens new avenues for microbiome-targeted preventive and therapeutic strategies in ageing. HighlightsO_LIAge-dependent increase in gut microbial metabolite PAA causally promotes vascular niche senescence C_LIO_LIPAA indirectly accelerates PVAT senescence through endothelial senescence-messaging secretome C_LIO_LISASP upregulates Notch1 signaling, leading to PVAT dysfunction C_LIO_LISenolytic therapy restores PVAT function C_LIO_LIPAA-induced vascular niche senescence contributes to atherosclerosis progression C_LI

cell biology↗

bioRxiv2022

Comparative analysis of genome-scale, base-resolution DNA methylation profiles across 580 animal species

Methylation of cytosines is the prototypic epigenetic modification of the DNA. It has been implicated in various regulatory mechanisms throughout the animal kingdom and particularly in vertebrates. We mapped DNA methylation in 580 animal species (535 vertebrates, 45 invertebrates), resulting in 2443 genome-scale, base-resolution DNA methylation profiles of primary tissue samples from various organs. Reference-genome independent analysis of this comprehensive dataset quantified the association of DNA methylation with the underlying genomic DNA sequence throughout vertebrate evolution. We observed a broadly conserved link with two major transitions - once in the first vertebrates and again with the emergence of reptiles. Cross-species comparisons focusing on individual organs supported a deeply conserved association of DNA methylation with tissue type, and cross-mapping analysis of DNA methylation at gene promoters revealed evolutionary changes for orthologous genes with conserved DNA methylation patterns. In summary, this study establishes a large resource of vertebrate and invertebrate DNA methylomes, it showcases the power of reference-free epigenome analysis in species for which no reference genomes are available, and it contributes an epigenetic perspective to the study of vertebrate evolution.

genomics↗

bioRxiv2022

Dispersal between interconnected patches can reduce the total population size

Human activities increasingly result in a fragmentation of natural ecosystems. However, the ecological consequences of fragmentation remain poorly understood. While some studies report that fragmentation may enhance population growth, others suggest the opposite pattern. Here we investigated how habitat connectivity affects the population size of a single species when habitat patches differ in quality. We combined dispersal experiments, in which bacterial populations of Escherichia coli were repeatedly transferred between two qualitatively different environments, with a process-based mathematical model. Both experiments and model consistently revealed that increased dispersal between patches reduced the total population size, thus demonstrating a detrimental effect of habitat connectivity on population size. This observation could be explained with a net loss of individuals upon migration from a productive to an overcrowded patch. Our findings suggest that conservation measures, which promote movement between fragmented habitats, such as dispersal corridors or stepping stones, are potentially detrimental for some species.

ecology↗

bioRxiv2021

Physical phenotype of blood cells is altered in COVID-19

Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by rapid spreading and high mortality worldwide. While the pathology is not yet fully understood, hyper-inflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage. Here we report an evaluation of multiple physical parameters including the mechanical features of five frequent blood cell types, namely erythrocytes, lymphocytes, monocytes, neutrophils, and eosinophils. More than 4 million blood cells of 17 COVID-19 patients at different levels of severity, 24 volunteers free from infectious or inflammatory diseases, and 14 recovered COVID-19 patients were analyzed. We found significant changes in erythrocyte deformability, lymphocyte stiffness, monocyte size, and neutrophil size and deformability. While some of these changes recovered to normal values after hospitalization, others persisted for months after hospital discharge, evidencing the long-term imprint of COVID-19 on the body.

biophysics↗

bioRxiv2020

Obligate mutualistic cooperation limits evolvability

Cooperative mutualisms are widespread in nature and play fundamental roles in many ecosystems. Due to the often obligate nature of these interactions, the Darwinian fitness of the participating individuals is not only determined by the information encoded in their own genomes, but also the traits and capabilities of their corresponding interaction partners. Thus, a major outstanding question is how obligate cooperative mutualisms affect the ability of organisms to respond to environmental change with evolutionary adaptation. Here we address this issue using a mutualistic cooperation between two auxotrophic genotypes of Escherichia coli that reciprocally exchange costly amino acids. Amino acid-supplemented monocultures and unsupplemented cocultures were exposed to stepwise increasing concentrations of different antibiotics. This selection experiment revealed that metabolically interdependent bacteria were generally less able to adapt to environmental stress than autonomously growing strains. Moreover, obligate cooperative mutualists frequently regained metabolic autonomy, thus resulting in a collapse of the mutualistic interaction. Together, our results identify a limited evolvability as a significant evolutionary cost that individuals have to pay when entering into an obligate mutualistic cooperation.

evolutionary biology↗

bioRxiv2019

Effects of breed, management and personality on cortisol reactivity in sport horses

Sport horses need to fulfill high physical and psychological requirements during training and competition. These as well as certain conditions of modern husbandry may affect their wellbeing. Here we aimed to (1) evaluate effects of demographic and management factors as well as personality traits on stress reactivity of sport horses, (2) investigate if elite sport horses have elevated stress levels compared to amateur sport horses, and (3) assess whether different equestrian disciplines differentially influence horses adrenal cortex responsiveness. For this purpose, we visited 149 healthy elite (n=94) and amateur (n=54) sport horses in Switzerland and performed an adrenocorticotropic hormone (ACTH) stimulation test. Additionally, a person who was familiar with the horse completed a questionnaire about demographic and management factors and horses personality traits. Linear models were calculated to assess associations between the questionnaire data and salivary cortisol 60 and 90 minutes after ACTH stimulation. While the model at T90 was not significant, post-stimulatory cortisol after 60 min appears most informative in line with a previous study and was significantly affected by the horses breed and by three management factors: "number of riders", "hours spent outside" and "group housing" (adjusted r2 =15%, p<0.001). Thoroughbred and Warmblood horses displayed an increased adrenal response compared to Franches-Montagnes horses. Horses with several riders had a less pronounced reaction than horses with one rider, and horses that spent more time outside had a decreased response compared to horses that were stabled most of the time. Horses living in groups showed higher post-stimulatory cortisol values than horses that were housed singly. However, no significant associations of cortisol responsiveness with personality traits were found, and neither the horses use as elite or as amateur sport horses nor the discipline had an effect on the cortisol response. This suggests that optimizing husbandry conditions may be more important for improving horses welfare than changing their use.

animal behavior and cognition↗

bioRxiv2018

A serial dilution method for assessment of microplastic toxicity in suspension

The occurrence of microplastic (MP) in the environment is of global concern. MP risk assessment, however, is currently hampered by lacking ecotoxicological methods due to conceptual and practical problems with particle exposure. Natural particles of similar size as MP, e.g., clay and cellulose, occur abundantly in the environment. For MP risk assessment and regulation it must be established whether the addition of MP to these particles represents an additional hazard. We present a novel approach employing a serial dilution of MP and reference particles, in mixtures, which allows the differentiation of MP effects from other particulates. We demonstrate the applicability of the method using an immobilisation test with Daphnia magna exposed to polyethylene terephthalate (MP) and kaolin clay (reference material). In the concentration range of 0.1 to 10000 mg L-1 of total suspended solids (TSS), with MP contributing 0-100 %, the LC50 values for MP-kaolin mixtures were significantly lower compared to the pure kaolin suspension. MP particles were thus more harmful to daphnids than the reference material. The estimated threshold for %MP contribution above which higher mortality was observed was 1 % MP at 36 mg TSS L-1. This approach has a potential for standardisation of MP ecotoxicological testing as well as other particulate material of anthropogenic origin.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC=\"FIGDIR/small/401331_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (40K):\norg.highwire.dtl.DTLVardef@13e1153org.highwire.dtl.DTLVardef@1e37652org.highwire.dtl.DTLVardef@6d3efborg.highwire.dtl.DTLVardef@420d7a_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2018

Tobacco TGA7 mediates gene expression dependent and independent of salicylic acid

Basic region leucine zipper (bZIP) transcription factors of the TGA family control gene expression in response to diverse stimuli. Arabidopsis clade II and clade III TGA factors mediate salicylic acid (SA)-induced expression of PATHOGENESIS-RELATED GENE1 (PR-1) via interplay with NONEXPRESSOR OF PR GENES1 (NPR1, a.k.a. NIM1). Interaction with TGA factors occurs through the central ankyrin repeat domain of NPR1. In a yeast two-hybrid screen with the NPR1 bait, we identified TGA7, a novel member of the tobacco (Nt) TGA family grouping to clade III. TGA7 is most similar to NtTGA1a, and, like NtTGA1a, TGA7 displays transcription activity in yeast. Unexpectedly, TGA7 preferentially and uniquely interacts with the SA-sensitive C-terminal region of NtNPR1, demonstrating that NtNPR1 harbors multiple distinct TGA factor binding sites. Interaction with NPR1 impairs TGA7 transcription activity in yeast. Furthermore, TGA7 binding to the NtNPR1 C-terminus is outcompeted by SA-induced type 2 NIM1-INTERACTING (NIMIN) proteins. In tobacco plants, a TGA7-Gal4 DNA-binding domain chimeric protein (TGA7GBD) mediates SA-responsive reporter gene expression in young leaf tissue and spontaneous reporter activation in older leaves displaying PR-1 gene expression. Astonishingly, TGA7GBD is also able to activate the reporter independent from PR-1 gene expression in noninduced cotyledons of tobacco seedlings. Together, our findings support a model in which TGA7 mediates both SA-dependent and SA-independent gene activation controlled by the plants developmental stage and by the C-terminal region of constitutively accumulating NtNPR1.

plant biology↗

bioRxiv2018

A specific, glycomimetic Langerin ligand for human Langerhans cell targeting

Langerhans cells are a subset of dendritic cells residing in the epidermis of the human skin. As such, they are key mediators of immune regulation and have emerged as prime targets for novel transcutaneous cancer vaccines. Importantly, the induction of protective T cell immunity by these vaccines requires the efficient and specific delivery of both tumor-associated antigens and adjuvants. Langerhans cells uniquely express Langerin (CD207), an endocytic C-type lectin receptor. Here, we report the discovery of a specific, glycomimetic Langerin ligand employing a heparin-inspired design strategy that integrated NMR spectroscopy and molecular docking. The conjugation of these glycomimetics to liposomes enabled the specific and efficient targeting of Langerhans cells in the human skin. This delivery platform provides superior versatility and scalability over antibody-based approaches and thus addresses current limitations of dendritic cell-based immunotherapies.

immunology↗