Biology subjects

Schuermann, M.

Publications and source records attributed to Schuermann, M..

4 recordsLinked to original sources

bioRxiv2024

Evaluation of intracochlear pressure and distribution during fluid application in cochlea models and human petrous bone

IntroductionThe important factor during the application of substances for an inner ear therapy is the atraumatic execution as well as a homogeneous distribution over the cochlea in a reasonable time frame. Since faster delivery can be obtained with higher pressure but, higher pressure will lead to traumatic execution, there are certain constrains for the delivery process. Because of this, an optimized procedure for intracochlear delivery is needed, which enables reduction of intracochlear pressure during perfusion in reasonable time. Hence, the aim of this study was to compare different techniques of substance application and their effects on intracochlear pressure in different models. Material and MethodsIntracochlear pressure was measured by fiberoptic pressure sensors in artificial cochlea models and in a human temporal bone. The pressure sensor was introduced into the inner ear models via an additional channel or the lateral arcade of the temporal bone. In all models the substance was applied by means of an inner ear catheter (MED-EL, Innsbruck, Austria) via the round window with methylene blue with or without second access to the cochlea (helicotrema/oval window). ResultsThe application of substances showed significant differences in intracochlear pressure and substance distribution at the same velocity between the models with and without second access. ConclusionUsing a second-hole technique leads to a faster homogeneous distribution, as well as a lower intracochlear pressure, which can be assumed to be an essential factor for hearing preservation during substance application.

biophysics↗

bioRxiv2024

Musicians' brains at rest: Multilayer network analysis of MEG data

The ability to proficiently play a musical instrument requires a fine-grained synchronisation between several sensorimotor and cognitive brain regions. Previous studies have demonstrated that the brain undergoes functional changes with musical training, identifiable also in resting-state data. These studies analysed fMRI or electrophysiological frequency-specific brain networks in isolation. While the analysis of such "mono-layer" networks has proven useful, it fails to capture the complexities of multiple interacting networks. To this end, we applied a multilayer network framework for analysing publicly available data (Open MEG Archive) obtained with magnetoencephalography (MEG). We investigated resting-state differences between participants with musical training (n=31) and those without (n=31). While single-layer analysis did not demonstrate any group differences, multilayer analysis revealed that musicians show a modular organisation that spans visuomotor and frontotemporal areas, known to be involved in musical performance execution, which is significantly different from non-musicians. Differences between the two groups are primarily observed in the theta (6.5-8Hz), alpha1 (8.5-10Hz) and beta1 (12.5-16Hz) frequency bands. We demonstrate that the multilayer method provides additional information that single-layer analysis cannot. Overall, the multilayer network method provides a unique opportunity to explore the pan-spectral nature of oscillatory networks, with studies of brain plasticity as a potential future application.

neuroscience↗

bioRxiv2023

Head and neck cancer cells terminally differentiate reflecting their tissue of origin: a rationale for differentiation therapies

BackgroundHuman papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease with high death rates that have remained substantially unaltered for decades. Therefore, new treatment approaches are urgently needed. Human papillomavirus-negative tumors harbor areas of terminally differentiated tissue that are characterized by cornification. Dissecting this intrinsic ability of HNSCC cells to irreversibly differentiate into non-malignant cells may have striking tumor-targeting potential. MethodsWe modeled the cornification of HNSCC cells in a primary spheroid model and analyzed the mechanisms underlying differentiation by RNA-seq and ATAC-seq. Results were verified by immunofluorescence using human HNSCC tissue of distinct anatomical locations. ResultsHNSCC cell differentiation was accompanied by cell adhesion, proliferation stop, diminished tumor-initiating potential in immunodeficient mice, and activation of a wound healing-associated signaling program. Small promoter accessibility increased despite overall chromatin closure. Differentiating cells upregulated KRT17 and cornification markers. Although KRT17 represents a basal stem-cell marker in normal mucosa, we confirm KRT17 to represent an early differentiation marker in HNSCC tissue and dysplastic mucosa. Cornification was observed to frequently surround necrotic and immune-infiltrated areas in human tumors, indicating an involvement of pro-inflammatory stimuli. Indeed, inflammatory mediators were found to activate the HNSCC cell differentiation program. ConclusionsDistinct cell differentiation states create a common tissue architecture in normal mucosa and HNSCCs. Our data demonstrate a loss of cell malignancy upon HNSCC cell differentiation, indicating that targeted differentiation approaches may be therapeutically valuable. Moreover, we describe KRT17 to be a candidate biomarker for HNSCC cell differentiation and early tumor detection.

cancer biology↗

bioRxiv2018

Standardized microgel beads as elastic cell mechanical probes

Cell mechanical measurements are gaining increasing interest in biological and biomedical studies. However, there are no standardized calibration particles available that permit the cross-comparison of different measurement techniques operating at different stresses and time-scales. Here we present the rational design, production, and comprehensive characterization of poly-acylamide (PAAm) microgel beads mimicking biological cells. We produced mono-disperse beads at rates of 20 - 60 kHz by means of a microfluidic droplet generator, where the pre-gel composition was adjusted to tune the beads elasticity in the range of cell and tissue relevant mechanical properties. We verified bead homogeneity by optical diffraction tomography and Brillouin microscopy. Consistent elastic behavior of microgel beads at different shear rates was confirmed by AFM-enabled nanoindentation and real-time deformability cytometry (RT-DC). The remaining inherent variability in elastic modulus was rationalized using polymer theory and effectively reduced by sorting based on forward-scattering using conventional flow cytometry. Our results show that PAAm microgel beads can be standardized as mechanical probes, to serve not only for validation and calibration of cell mechanical measurements, but also as cell-scale stress sensors.\n\nSignificance StatementOften vastly different cell mechanical properties are reported even for the same cell type when employing different measurement techniques. This discrepancy shows the urgent need for standardized calibration particles to cross-compare and validate techniques. Microgel beads can serve this purpose, but they have to fulfil specific requirements such as homogeneity, sizes and elasticities in the range of the cells, and they have to provide comparable results independent of the method applied. Here we demonstrate the standardized production of polyacrylamide microgel beads with all the features an elastic cell-mimic should have. These can not only be used as method calibration particles, but can also serve as cell-scale sensors to quantify normal and shear stresses exerted by other cells and inside tissues, enabling many new applications.

biophysics↗