Search bioRxiv⌕ Search

Biology subjects

Steinke, H.

Publications and source records attributed to Steinke, H..

5 recordsLinked to original sources

Approach to standardized material characterization of the human lumbopelvic system - Testing and evaluation

The osseo-ligamentous lumbopelvic complex is a crucial component of the human musculoskeletal system and has been increasingly the focus of medical research and treatment planning. Numerical simulations can play a key role in better understanding the load-carrying behavior of this system, but material data in this arena remain rare. In addition, the literature lacks standardized and reproducible methods for determining biomechanical material parameters. To address these shortcomings, we obtained bone and soft tissue samples from three female and two male cadavers (average age: 77.3 years) for testing and evaluation. The elastic modulus of cortical bone averaged at 1750 MPa with a mean ultimate strength of 28.2 MPa. Whereas for trabecular bone the evaluation yields to 32.7 MPa and 1.26 MPa. Furthermore, the soft tissue specimens exhibited a mean elastic modulus of 148 MPa and an ultimate strength of 14.3 MPa for fascial tissue, in contrast to ligamentous tissue with 103 MPa and 10.7 MPa. Knowledge of these material parameters of the human pelvis, which differ from those of long bones, could, in combination with the revealed dependence on harvesting location and density, lead to more precise mechanical simulations. Such simulations might in turn promote the development of better suited implants. Together with a previous publication dealing with sample preparation, this work is intended to contribute to the standardization of mechanical testing of human tissue. Easy-to-conduct bending tests as well as direct tension and compression tests are recommended, and the proposed mechanical boundary conditions are explained and documented. These technical recommendations allow for better comparability and reproducibility in future biomechanical studies. This protocol, developed for the human pelvis, could easily be transferred to other anatomical regions.

biophysics↗

Diffusion Tensor Imaging: Influence of segmentation on fiber tracking in the supraspinatus muscle - an inter-operator reliability analysis

The ability of muscle to generate force depends on its architecture and quality. MR-based diffusion tensor imaging of muscle (mDTI) is an innovative approach for showing the fiber arrangement for the whole muscle volume. For accurate calculations of fiber metrics, muscle segmentation prior to tractography seems mandatory. Since segmentation is known to be operator dependent, it is important to understand how segmentation affects tractography. The aim of this study was to compare the results of deterministic fiber tracking based on muscle models generated by two independent operators. In addition, this study compares the results with a segmentation-free approach. Fifteen subjects underwent mDTI of the right shoulder. The results showed that mDTI can be successfully applied to complex joints such as the human shoulder. Furthermore, operators segmentation did not influence the results of fiber tracking and showed excellent intraclass correlation estimates ([≥] 0.975). As an exploratory approach, the segmentation-free fiber tracking showed significant differences in terms of mean fascicle length. Based on these findings, we assume that tractography does not require a detailed muscle segmentation. Furthermore, it implies that mDTI and automatic segmentation approaches or even a segmentation-free analysis can be considered for evaluation of muscle changes.

physiology↗

SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and brain tissue loss, raising concerns about the viruss acute and potential chronic impact on the central nervous system. In this study, we utilized mouse models and human post-mortem tissues to investigate the presence and distribution of the SARS-CoV-2 spike protein in the skull-meninges-brain axis. Our results revealed the accumulation of the spike protein in the skull marrow, brain meninges, and brain parenchyma. The injection of the spike protein alone caused cell death in the brain, highlighting a direct effect on brain tissue. Furthermore, we observed the presence of spike protein in the skull of deceased long after their COVID-19 infection, suggesting that the spikes persistence may contribute to long-term neurological symptoms. The spike protein was associated with neutrophil-related pathways and dysregulation of the proteins involved in the PI3K-AKT as well as complement and coagulation pathway. Overall, our findings suggest that SARS-CoV-2 spike protein trafficking from CNS borders into the brain parenchyma and identified differentially regulated pathways may present insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities. Graphical Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/535604v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@b223eforg.highwire.dtl.DTLVardef@15539e9org.highwire.dtl.DTLVardef@4d17a9org.highwire.dtl.DTLVardef@14c63af_HPS_FORMAT_FIGEXP M_FIG C_FIG Short SummaryThe accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis presents potential molecular mechanisms and therapeutic targets for neurological complications in long-COVID-19 patients.

neuroscience↗

Multi-omics and 3D-imaging reveal bone heterogeneity and unique calvaria cells in neuroinflammation

The meninges of the brain are an important component of neuroinflammatory response. Diverse immune cells move from the calvaria marrow into the dura mater via recently discovered skull-meninges connections (SMCs). However, how the calvaria bone marrow is different from the other bones and whether and how it contributes to human diseases remain unknown. Using multi-omics approaches and whole mouse transparency we reveal that bone marrow cells are highly heterogeneous across the mouse body. The calvaria harbors the most distinct molecular signature with hundreds of differentially expressed genes and proteins. Acute brain injury induces skull-specific alterations including increased calvaria cell numbers. Moreover, TSPO-positron-emission-tomography imaging of stroke, multiple sclerosis and neurodegenerative disease patients demonstrate disease-associated uptake patterns in the human skull, mirroring the underlying brain inflammation. Our study indicates that the calvaria is more than a physical barrier, and its immune cells may present new ways to control brain pathologies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/473988v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@978194org.highwire.dtl.DTLVardef@bc45e8org.highwire.dtl.DTLVardef@91afdborg.highwire.dtl.DTLVardef@b06bc6_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIBone marrow across the mouse body display heterogeneity in their molecular profile C_LIO_LICalvaria cells have a distinct profile that is relevant to brain pathologies C_LIO_LIBrain native proteins are identified in calvaria in pathological states C_LIO_LITSPO-PET imaging of the human skull can be a proxy of neuroinflammation in the brain C_LI Supplementary Videos can be seen at: http://discotechnologies.org/Calvaria/

cell biology↗

Cellular and Molecular Probing of Intact Transparent Human Organs

Optical tissue transparency permits cellular and molecular investigation of complex tissues in 3D, a fundamental need in biomedical sciences. Adult human organs are particularly challenging for this approach, owing to the accumulation of dense and sturdy molecules in decades-aged human tissues. Here, we introduce SHANEL method utilizing a new tissue permeabilization approach to clear and label stiff human organs. We used SHANEL to generate the first intact transparent adult human brain and kidney, and perform 3D histology using antibodies and dyes in centimeters depth. Thereby, we revealed structural details of sclera, iris and suspensory ligament in the human eye, and the vessels and glomeruli in the human kidney. We also applied SHANEL on transgenic pig organs to map complex structures of EGFP expressing beta cells in >10 cm size pancreas. Overall, SHANEL is a robust and unbiased technology to chart the cellular and molecular architecture of intact large mammalian organs.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC=\"FIGDIR/small/643908v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (89K):\norg.highwire.dtl.DTLVardef@14fea50org.highwire.dtl.DTLVardef@1a04274org.highwire.dtl.DTLVardef@6ae1fforg.highwire.dtl.DTLVardef@11b31b0_HPS_FORMAT_FIGEXP M_FIG C_FIG Supplementary Movies of SHANEL are available at http://discotechnologies.org/SHANEL/

cell biology↗