Biology subjects

Wirth, R.

Publications and source records attributed to Wirth, R..

5 recordsLinked to original sources

bioRxiv2026

Most metagenomic vanT calls are not vancomycin resistance genes

Metagenomic resistome surveys frequently report vanTG as the dominant glycopeptide resistance gene, but these calls rely on homology without verifying catalytic residues or operon context. By analyzing 107,008 metagenome-assembled genomes, we demonstrate that only 3.7% of predicted vanTG genes possess the required active-site substitution, with the vast majority being misannotated alanine racemases. Incorporating structural and genomic context corrections reveals a novel split-architecture lineage in gut-associated Erysipelotrichales missed by current profiling tools.

microbiology↗

bioRxiv2026

Lab-on-a-chip device integrating a human stem cell-based blood-brain barrier model with neural organoids for translational research

For advanced biomedical research, complex, well-described human blood-brain barrier (BBB) models are crucial for studying central nervous system pathologies and brain targeting of nanotherapeutics. Our aim was to establish and characterize a complex lab-on-a-chip (LOC) system integrating a BBB model with neural organoids (NO). We optimized the conditions for BBB-NO models under static and dynamic circumstances. The combination of a human stem cell-derived BBB co-culture model with human midbrain organoids in a microfluidic LOC allowed the observation of BBB and neural tissue changes and the separate analysis of the barrier and brain units. The LOC design enabled phase contrast and fluorescent microscopy on the whole brain endothelial culture surface, barrier integrity and permeability measurements across the BBB model, and molecule passage into NOs. BBB-specific endothelial morphology, gene and protein expression, and good barrier integrity were demonstrated, corroborating the strength of the LOC engineering and cellular design. The transport of targeted nanoparticles across the BBB model followed by their entry to neural organoids validated the barrier integrity and transporter functionality of the dynamic integrated complex model. As a proof-of-concept experiment to confirm the translational value of the BBB-NO model integrated in the LOC device, we examined a clinically used hyperosmolar iodinated contrast agent, iopamidol, with confirmed neurological side effects. We corroborated that iopamidol induces transient BBB dysfunction and neural effects in the complex system, not only validating the complex dynamic BBB-NO model but also pointing to the necessity to study BBB changes together with NO functions.

cell biology↗

bioRxiv2026

Atta Leafcutter Ants are Fine-Scale Bioindicators of Geographic and Seasonal Climate Changes Across the Americas

AimWe develop Atta leafcutter-ants as bioindicators that respond at fine scales to geographic and seasonal climate changes in the Americas, thereby addressing the paucity of versatile insect bioindicator systems capable of monitoring climate in both Southern and Northern Hemispheres. LocationAmerican tropics and sub-tropics from latitudes S33.6{degrees} to N33.2{degrees}, with case studies from Colombia, Mexico, and southern USA. Time Period2012-2024. Taxon StudiedAtta leafcutter-ants. MethodsWe elucidate biogeographic patterns of mating-flight phenology of Atta leafcutter-ants across the entire Atta range from Uruguay/Argentina to the USA, using 2335 records of Atta reproductives from the community database iNaturalist, then ground-truth these patterns by comparison with (i) mating-flight records (n=806) from the Atta literature; and (ii) mating-flight observations (n=836) accumulated by a consortium of experts who have researched Atta for a combined 1000+ work-years. Onset of mating flights can be timed with great precision in Atta populations because mass-mating flights are synchronized and triggered by the first major rainfall of a rainy season. ResultsBiogeographic patterns in climate-dependent mating-flight phenologies recorded at iNaturalist are corroborated by observations accumulated in the literature and by Atta experts. Analyses reveal so-far unknown gradients in mating-flight phenology (e.g., Colombia to USA) that are correlated to geographic climate gradients, and season switches of mating flights from early to late in the year between proximate Atta populations (e.g., 200 kilometers apart), for example in the climatically complex Andean regions of Colombia. Regional differences in Atta mating-flight phenology correspond to temporal differences in rainfall between ecoregions of Colombia. Main ConclusionsAtta ants are tractable insect bioindicators to monitor climate impacts with detailed spatial and temporal resolution across a 9200-kilometer trans-equatorial transect in the Americas. We outline future research directions to explore climate-dependent biology using the continuously growing, and now ground-truthed, information at iNaturalist on Atta mating behavior.

ecology↗

bioRxiv2025

A complex osteoporotic milieu is associated with arterial stiffening and PDGF-BB-mediated calcification of human smooth muscle cells

Accumulating evidence links skeletal and vascular aging, yet the pathological cross-talk between osteoporotic bone and vascular calcification remains insufficiently understood. In this retrospective exploratory study, we show that osteoporotic individuals exhibit a distinct systemic milieu characterized by elevated eosinophil, neutrophil, and platelet counts, as well as altered levels of sCD40L, PDGF-BB, osteopontin, and SDF-1. These changes correlate with both bone metabolism and arterial stiffness, indicating a multifactorial bone-vascular interplay. Moreover, osteoporotic sera accelerated calcification of human vascular smooth muscle cells in vitro, with PDGF-BB emerging as a central mediator. Inhibition of PDGF-BB downstream signaling blocked this effect, suggesting a mechanistic role of PDGF-BB in linking the osteoporotic milieu to vascular calcification. Conceptualizing this cross-talk as a complex adaptive system advances our understanding of the disease dynamics between localized bone loss and vascular pathologies. Furthermore, it may guide therapeutic strategies, with PDGF-BB as a potential target, to support healthier aging.

cell biology↗

bioRxiv2023

Inter-kingdom microbial interactions revealed by a comparative machine-learning guided multi-omics analysis of industrial-scale biogas plants

Multi-omics analysis is a powerful tool for the detection and study of inter-kingdom interactions, such as those between bacterial and archaeal members of complex biogas-producing microbial communities. In the present study, the microbiomes of three industrial-scale biogas digesters, each fed with different substrates, were analysed using a machine-learning guided genome-centric metagenomics framework complemented with metatranscriptome data. This data permitted us to elucidate the relationship between abundant core methanogenic communities and their syntrophic bacterial partners. In total, we detected 297 high-quality, non-redundant metagenome-assembled genomes (nrMAGs). Moreover, the assembled 16S rRNA gene profiles of these nrMAGs showed that the phylum Firmicutes possessed the highest copy number, while the representatives of the Archaeal domain had the lowest. Further investigation of the three anaerobic microbial communities showed characteristic alterations over time but remained specific to each industrial-scale biogas plant. The relative abundance of various microbes as revealed by metagenome data were independent from corresponding metatranscriptome activity data. Interestingly, Archaea showed considerably higher activity than was expected from their abundance. We detected 53 nrMAGs that were present in all three biogas plant microbiomes with different abundances. The core microbiome correlated with the main chemical fermentation parameters and no individual parameter emerged as a predominant shaper of community composition. Various interspecies H2/electron transfer mechanisms were assigned to hydrogenotrophic methanogens in the biogas plants that ran on agricultural biomass and wastewater. Analysis of metatranscriptome data revealed that methanogenesis pathways were the most active of all main metabolic pathways. These findings highlight the importance of a combinatorial omics data framework to identify and characterise the activity of specific microbes in complex environments.

microbiology↗