Biology subjects

Beckmann, A.

Publications and source records attributed to Beckmann, A..

3 recordsLinked to original sources

bioRxiv2025

Degradation of rutin and genistein and the effect on human bacterial fecal populations of obese and non-obese

This study re-evaluates the microbial degradation of rutin and genistein, emphasizing health-related metabotypes and novel degradation and transformation products of these compounds. In silico predictions and calculations were made to determine the molecular formulae of metabolites derived from precursor molecules by methylation, sulfation, and dehydroxylation. To validate these, anaerobic, ex vivo experiments were conducted with pooled fecal samples of obese and non-obese test persons (n=7 per group) over 48 hours, followed by 16S rRNA gene sequencing and semi-targeted high-resolution mass spectrometry analysis. We identified 46 rutin and 23 genistein metabolites, including novel methylated and sulfated derivatives. Microbial analysis revealed that the plant compounds influenced 34 bacterial families and 83 genera. Rutin inhibited obesity-associated genera while promoting butyrate-producing bacteria in BMI >40 samples, but reduced health-associated bifidobacteria and increased enterobacteria. Both compounds stimulated Eggerthella. These findings highlight significant microbial and metabolic shifts induced by plant-derived compounds, suggesting potential health implications.

microbiology↗

bioRxiv2021

Pathogenic tau disrupts the cellular program that maintains neuronal identity

Neurons in human Alzheimers disease acquire phenotypes that are also present in various cancers, including over-stabilization of the cytoskeleton, nuclear pleomorphism, decondensation of constitutive heterochromatin, and aberrant activation of the cell cycle. Unlike in cancer, in which cell cycle activation drives tumor formation, activation of the cell cycle in post-mitotic neurons is sufficient to induce neuronal death. Multiple lines of evidence suggest that abortive cell cycle activation is a consequence of pathogenic forms of tau, a protein that drives neurodegeneration in Alzheimers disease and related "tauopathies." We have combined network analysis of human Alzheimers disease and mouse tauopathy with mechanistic studies in Drosophila to discover that pathogenic forms of tau drive abortive cell cycle activation by disrupting the cellular program that maintains neuronal identity. Mechanistically, we identify Moesin, a prognostic biomarker for cancer and mediator of the epithelial-mesenchymal transition (EMT), as a major effector of tau-induced neurotoxicity. We find that aberrant activation of Moesin in neurons acts through the actin cytoskeleton to dysregulate the cellular program that maintains neuronal identity. Our study identifies mechanistic parallels between tauopathy and cancer and sets the stage for novel therapeutic approaches.

neuroscience↗

bioRxiv2020

A proteogenomics workflow to uncover the world of small proteins in Staphylococcus aureus

Small proteins play diverse and essential roles in bacterial physiology and virulence. Despite their importance, automated genome annotation algorithms still cannot accurately annotate all respective small open reading frames (sORFs), as they usually provide insufficient sequence information for domain and homology searches, tend to be species specific and only a few experimentally validated examples are covered in standard proteomics studies. The accuracy and reliability of genome annotations, particularly for sORFs, can be significantly improved by integrating protein evidence from experimental approaches that enrich for small proteins. Here we present a highly optimized and flexible workflow for bacterial proteogenomics, which covers all steps from (i) creation of protein databases, (ii) database searches, (iii) peptide-to-genome mapping to (iv) result interpretation and whose automated execution is supported by two open source tools (SALT & Pepper). We used the workflow to identify high quality peptide spectrum matches (PSMs) for both annotated and unannotated small proteins ([≤] 100 aa; SP100) in Staphylococcus aureus Newman. Proteins isolated from cells at the exponential and stationary growth phase were digested with different endopeptidases (trypsin, Lys-C, AspN), the resulting peptides fractionated by gel-based and gel-free methods and measured with highly sensitive mass spectrometers. PSMs or sORF predictions from sORFfinder were stringently filtered allowing us to detect 185 soluble SP100, 69 of which were missing in the used genome annotation. Most interestingly, almost half of the identified SP100 were basic, suggesting a role in binding to more acidic molecules such as nucleic acids or phospholipids. In addition, phage-related functions were proposed for 30 SP100, based on the localization of their coding sequences in the genome.

genomics↗