Biology subjects

Kaufmann, A.

Publications and source records attributed to Kaufmann, A..

6 recordsLinked to original sources

bioRxiv2026

Tuning the mechanical properties of polymer-based surrogate materials for articular cartilage and vocal fold repair

The macroscopic biomechanical characteristics of soft and ultrasoft tissues, such as articular cartilage and vocal folds, significantly determine their physiological function. Treatments of widespread tissue degradations due to osteoarthritis in the knee or vocal fold impairment remain an unresolved challenge. For the design of implants for tissue repair after injury or disease, it is key to thoroughly understand the unique biomechanical properties of native tissues and potential substitute materials. We use multimodal mechanical testing methods combined with hyperelastic nonlinear continuum mechanics modeling, and finite element simulations to determine the macroscopic behavior of surrogate materials for human articular cartilage in the knee and human vocal folds. Our cyclic loading experiments reveal qualitative similarities for both tissues and their surrogates, including a nonlinear stress-strain behavior, hysteresis, and conditioning. We demonstrate the tunability of biomimetic and biosimilar stiffnesses of synthetic articular cartilage and vocal fold surrogates through tissue-specific process-material combinations. Our results demonstrate the feasibility of synthetic metamaterials in replicating essential passive biomechanical functions with great potential for future treatment options.

bioengineering↗

bioRxiv2026

Inositol hexakisphosphate Functions as a Cofactor and Modulator of ADAR1 Activity

Adenosine-to-inosine (A-to-I) RNA editing by ADAR1 is a key post-transcriptional modification, and mutations in ADAR1 lead to Aicardi-Goutieres syndrome (AGS), an autoimmune disorder. Despite its biological and clinical relevance, the regulation of ADAR1 activity remains incompletely understood. Using a combination of biochemical approaches, inositol-pentakisphosphate 2-kinase (IPPK)-knockout cells, molecular dynamics simulations, and a cell-permeable inositol hexakisphosphate (IP6) prodrug (Pro-IP6), we demonstrate that IP6 depletion drastically reduces global RNA editing, while supplementation with Pro-IP6 restores and even enhances editing levels. Furthermore, we identify the C6-phosphate of IP6 as a critical determinant of ADAR1 catalytic efficiency, functioning within a hydrogen-bonding network that indirectly coordinates a Zn{superscript 2}-ion. Finally, we show that the AGS-associated ADAR1 mutation N907S impairs RNA editing activity, most likely by altering the hydrogen-bond interaction network linking IP6 to the ADAR1 catalytic center. Together, these findings identify IP6 as an essential cofactor and regulator of ADAR1 activity and highlight cofactor availability and interaction networks as strategies for therapeutically modulating RNA editing.

molecular biology↗

bioRxiv2025

Proteins are a source of glycans found in preparations of glycoRNA

Recent discoveries show that RNA can be modified with sialylated glycans (termed glycoRNA), thus broadening our understanding of cellular glycosylation beyond traditional proteins and lipids. However, the pathway of RNA-glycosylation and its biological function remain elusive. Following the original glycoRNA isolation protocol, we also detect labelled glycans in small RNA preparations. However, glycosylated molecules showed resistance to treatment with RNase A/T1 but were sensitive to proteinase K digestion under denaturing conditions. Using liquid chromatography-mass spectrometry (LC-MS) based proteomics, we detect various proteins that co-purify with small but not large RNA preparations isolated from human or murine cells, including the glycosylated membrane protein LAMP1. Importantly, we further demonstrate that recombinant soluble LAMP1 can be purified following the glycoRNA isolation method. These findings suggest that glycoproteins co-purify with RNA using current glycoRNA purification protocols, thus representing a considerable source of glycans in samples of glycoRNA.

molecular biology↗

bioRxiv2024

Decomposition of L-glutamine and accumulation of ammonium in cell culture media inhibit infectivity of influenza viruses

Cationic lysosomotropic molecules such as ammonium salts and chloroquine inhibit influenza A virus (IAV) infection in cell culture by counteracting endosomal acidification and hampering viral-endosomal fusion. Here, we studied the effects of storage of L-glutamine-supplemented cell culture media on accumulation of ammonium and inhibition of IAV infection. The storage-related inhibitory effect was observed in the case of DMEM and OptiMEM media, but not RPMI medium, and was more pronounced for the IAV with pH-stable hemagglutinin. Our results highlight the importance to consider potential presence of virus-inhibiting lysosomotropic agents and/or their production in culture media with negative effect on influenza virus infection.

microbiology↗

bioRxiv2024

Single-cell RNA-seq analysis profiling characterizes differences in cell composition and physiology between normal tissue, treatment-naive, and cisplatin-treated ovarian cancer

BackgroundIntense efforts have focused on identifying heterogeneity of the cellular composition in ovarian cancer. However, tissue composition and physiological conditions of cancer cells in cisplatin-sensitive ovarian cancer remains largely unknown. Moreover, comparisons of different cellular states in normal tissue, in treatment naive ovarian cancer, and in cisplatin-treated tissue after adjuvant therapy of cisplatin-sensitive ovarian cancer at the single-cell level might offer clues for ovarian cancer treatment and prevention of cisplatin-resistance formation. MethodsSingle-cell transcriptome sequencing of a cisplatin-treated ovarian cancer was performed. Data sets of non-tumorous ovarian tissues and treatment-naive ovarian cancer were downloaded from the European Genome-phenome Archive (accession number EGAS00001004987). Quality control, batch effect correction, integration, and clustering analysis of the integrated single-cell transcriptome data was done. Cell subsets were annotated based on surface marker phenotypes. Finally, the proportions of subclusters, the immune cell population, and the potential biological processes among different cellular states were compared. ResultsSixteen distinct cell subsets were identified from the integrated single-cell transcriptome sequencing data of a pool of all tissues. The composition of the three different tissue types was characterized. The proportion of fibroblasts in cisplatin-treated ovarian tumor was remarkably lower than in treatment-naive ovarian tumor (1.33% vs. 13.53%, p < 0.05). Moreover, each subjects sample had differing relative proportions of the identified cell types. In primary untreated ovarian cancer, the prevalent immune cells were B cells and myeloid-related immunosuppressive M2 macrophages. However, there were less B cells and myeloid-related immunosuppressive M2 macrophages after cisplatin-treatment, while significantly more T cells were found. The physiological cellular state in primary untreated ovarian tumors was associated with dysfunctional gene expression and modulation of cellular homeostasis, while cells from cisplatin-treated tumor showed more activation of immune and inflammatory genes as compared to healthy ovarian tissue. ConclusionOur molecular gene expression analysis allowed for the separation and identification of differences in normal ovarian tissues, treatment-naive, and cisplatin-sensitive ovarian cancer cell populations at single-cell resolution. We identified different cell type composition and discriminative marker expression concerning specific cell subsets and identified differences among their physiological cell states. This knowledge may open new possibilities for elucidating important pathogenetic features and therapeutic strategies for treating ovarian cancer.

cancer biology↗

bioRxiv2019

Developmental Reactive Oxygen Species Target Histone Methylation to Individualize Stress resistance and Lifespan

A central aspect of aging research concerns the question as to when individuality in lifespan arises and what mechanism(s) promote and potentially manifest individual differences in longevity. We have now discovered that a transient increase in reactive oxygen species (ROS), which occurs naturally during early development in a subpopulation of synchronized Caenorhabditis elegans, sets processes into motion that increase stress resistance, improve redox homeostasis and ultimately prolong lifespan in those animals. We find that these effects are linked to the global ROS-mediated decrease in developmental histone H3K4me3 levels. Studies in HeLa cells confirmed that global H3K4me3 levels are ROS-sensitive, and that depletion of H3K4me3 levels increases stress resistance in mammalian cell cultures. In vitro studies identified the Set1-MML histone methyltransferase as the redox sensitive unit of the H3K4-trimethylating COMPASS complex. Our findings imply a novel link between early-life events, ROS-sensitive epigenetic marks, stress resistance and lifespan.

molecular biology↗