Biology subjects

Rohde, G.

Publications and source records attributed to Rohde, G..

3 recordsLinked to original sources

bioRxiv2026

HERC4 limits oxidative stress-induced DNA damage during bacterial and viral-bacterial infection

Respiratory (co-)infections caused by influenza viruses and Streptococcus pneumoniae represent significant threats to global health. In our analysis of host cell ubiquitination, we identified reactive oxygen species (ROS) produced by S. pneumoniae as critical effectors in reducing the amount of intracellular polyubiquitinated proteins. Together with reduced ubiquitination we observed a downregulation of the E3 ligase HERC4 upon infection with S. pneumoniae in human alveolar epithelial and macrophage-like cells as well as in samples obtained from S. pneumoniae infected humans and mice. This was further aggravated in the viral-bacterial coinfection with influenza A. CRISPR-Cas9 deletion of HERC4 prior bacterial infection resulted in increased ROS-induced DNA damage, enhanced host cell apoptosis and reduced Histone 2B ubiquitination. In contrast, HERC4 overexpression diminished DNA damage indicating a role of HERC4 in DNA-damage-repair upon infection. By establishing a link between HERC4 expression and ROS-induced DNA damage and repair, we identified a potential marker for predicting the outcome of viral and bacterial (co-)infections. Targeting HERC4 expression defines a novel strategy to protect host cells from S. pneumoniae (co-)infection attenuating infection exacerbation.

microbiology↗

bioRxiv2025

Data Processing in Multidimensional MRI For BiomarkerIdentification: Is It Necessary?

Multidimensional MRI (MD-MRI) is an emerging technique that holds promise for identifying tissue characteristics that could be indicative of pathologies. Before these characteristics can be interpreted, MD-MRI measurements are converted into an spectrum. These spectra are then utilized to obtain some understanding of the underlying tissue microstructure, often through the use of statistical, machine learning, and mathematical modeling methods. The aim of this study was to compare outcomes of using unprocessed MDMRI signals for statistical regression in comparison to the corresponding spectra. Backed by a theoretical argument, we described an experimental procedure regressing both MDMRI signals and spectra to histological outcomes intrasubject. Through using multiple conventional ML methods, and a proposed method using convex sets, we aimed to see which yielded the highest accuracy. Both theory and experimental evidence suggest that, without a priori information, statistical regression was best performed on the MDMRI signal. We conclude, barring any a priori information regarding tissue changes, there is no significant advantage to performing regression analysis on reconstructed spectra in the process of biomarker identification.

bioengineering↗

bioRxiv2024

IGF1R is protective in pneumococcal pneumonia

BackgroundStreptococcus pneumoniae (S.pn) is the most prevalent causal bacterial pathogen in community-acquired pneumonia. Despite appropriate antimicrobial therapy, pneumococcal pneumonia can progress to acute respiratory distress syndrome where actual therapies are mainly supportive, and the discovery of new molecular targets is needed. ObjectiveTo investigate the role of IGF1R (Insulin-like Growth Factor 1 Receptor) in pneumococcal pneumonia. MethodsIgf1r-deficient (UBC-CreERT2; Igf1rfl/fl) and control (Igf1rfl/fl) mice were infected with 5x106 S.pn (PN36) or PBS (sham infected). Mice were sacrificed 48 h after infection. Pulmonary permeability, local inflammatory response, and pulmonary and extra-pulmonary bacterial loads were analyzed. Further, IGF1R protein expression was determined in human lung tissue after S.pn infection and IGF1 and IGF1R levels were determined serum of pneumonia patients. ResultsIn patients and mice infected with S.pn, IGF1 signaling was significantly altered. Igf1r-deficient mice had significantly increased pulmonary permeability after infection with increased pulmonary inflammatory cytokine levels, while inflammatory cell recruitment was not altered compared to infected Igf1rfl/fl control animals. Pulmonary bacterial load was significantly higher in Igf1r-deficient mice, and histological analysis confirmed increased alveolar edema and necrosis compared to infected Igf1rfl/fl control and sham-infected mice. Ex vivo, S.pn caused a decrease in IGF1R protein expression in human lung tissue. ConclusionOur results demonstrate a significant regulation of IGF1R in ex-vivo infected human lung tissue and in serum of S.pn pneumonia patients. Moreover, pneumonia severity was increased in Igf1r-deficient mice upon S.pn infection compared to Igf1rfl/fl control mice, suggesting that IGF1R plays a protective role in pneumococcal pneumonia.

molecular biology↗