Biology subjects

Kohl, M.

Publications and source records attributed to Kohl, M..

7 recordsLinked to original sources

bioRxiv2026

Cyclic uremia without kidney injury drives cardiovascular disease with rapid onset of immunosenescence and heart failure

End-stage kidney disease (ESKD) is a major driver of cardiovascular disease (CVD) and requires dialysis treatment leading to a unique metabolic phenotype with cyclic transitions between accumulation and clearance of uremic toxins. Although ESKD patients display the highest cardiovascular mortality among CKD patients, the effect of cyclic uremia on cardiovascular disease remains subject to discussion. Existing mouse models rely on induction of kidney injury and do not resolve the interconnected pathophysiological effects of metabolic, hypertensive and endocrine renal failure. They are therefore unable to distinguish uremia-driven effects from well-established drivers of cardiovascular disease such as hypertension. Here, we established a simple, reproducible, and sex-inclusive mouse model of uremia in absence of kidney injury or hypertension leveraging a bistable vesico-peritoneal shunt (VPS). Strikingly, we identify cyclic uremia as an independent driver of ESKD-induced CVD, that induces heart failure with preserved ejection fraction (HFpEF), vascular inflammation and immunosenescence. As such, the VPS represents the first preclinical model that enables investigation of cyclic uremia as a driver of cardiovascular disease.

systems biology↗

bioRxiv2025

Complete post-transcriptional modification profiles in individual Staphylococcus aureus tRNA species

Transfer RNAs play a critical role in protein synthesis by matching mRNA codons to their corresponding amino acids. Their post-transcriptional modifications, shaping structure, stability, and codon decoding, are now recognized as key regulators of translation and cellular adaptation, including in bacterial pathogens. Here, we provide a comprehensive analysis of tRNA modifications in Staphylococcus aureus using extensive oligonucleotide mass spectrometry and deep-sequencing methods, generating a high-confidence modification map for each individual tRNA species, including the non-proteogenic tRNAGly. While the overall tRNA modification landscape is conserved among Gram-positive bacteria, our data uncovered unexpected S. aureus-specific features. These include the absence of [m2A]37 in tRNAs despite the presence of the methyltransferase RlmN, a single multi-site DusB2 enzyme catalyzing all tRNA dihydrouridylation, and a dedicated pseudouridine synthase responsible for [{Psi}]32 formation. Besides, heterogenous modification patterns were observed in tRNALeu(UAA) and tRNALys(CAA), highlighting a complex interplay in anticodon hypermodification. Integration of ribosome profiling and Nanopore tRNA sequencing offered a global view of the decoding properties of the reduced S. aureus tRNA set, revealing efficient four-way wobble recognition, slower translation of rare codons by low abundant tRNAs, and distinctive decoding dynamics of Gly codons potentially influenced by the unusual modification status of tRNAGly(UCC). This work establishes a framework for future research aimed at dissecting the role of specific tRNA modifications in S. aureus physiology and pathogenesis.

molecular biology↗

bioRxiv2025

Proteomic Remodeling During Tumor Cell-Induced Platelet Aggregation Unveils Metastatic Drivers in Colorectal Cancer

BackgroundColorectal cancer (CRC) is frequently associated with metastasis, resulting in high mortality rates. Platelets are known to play a crucial role in the metastatic cascade influencing tumor microenvironment remodeling, promoting cell transformation, facilitating metastatic niche formation, and shielding circulating tumor cells from immune surveillance. However, platelet proteomic alterations during tumor cell-induced platelet aggregation (TCIPA) remain largely unexplored. This study aims to characterize the proteomic profile of TCIPA in CRC using an in vitro model that recapitulates key aspects of CRC metastasis. MethodsTCIPA was assessed via light transmission aggregometry using an in vitro model incorporating paired primary and metastatic cell cultures. Stable Isotope Labeling with Amino Acids in Cell culture (SILAC) allowed for the discrimination of healthy platelet and tumor cell proteomes prior to and following TCIPA. Data-independent acquisition mass spectrometry was employed to analyze intra- and extracellular tumor and platelet proteomes. Comparative proteomic profiling was performed using a range of bioinformatic analyses, including clustering, differential expression, and Gene Set Enrichment Analyses (GSEA). ResultsComparison of the baseline proteome profiles of the CRC cell lines SW480 and SW620 identified 263 significant differentially expressed proteins (FDR [≤] 0.05, log2FC [≥] 1). The GSEA demonstrated enrichment of the epithelial-mesenchymal transition (FDR: 5.617 x 10-5) gene set in SW480 cells. While SW480 exhibited rapid TCIPA, SW620 did not consistently interact with healthy platelets. Following TCIPA, 34 tumor proteins showed differential expression compared to their naive status (without platelet-exposure). Notably, 17 of these proteins were significantly associated with CRC progression, particularly in the promotion of EMT, metastasis, tumor cell survival, proliferation, and metabolic reprogramming. ConclusionsThis study successfully characterized the proteomic profiles of platelets, platelet secretomes, and colorectal tumor cells following TCIPA-induced activation. The findings highlight the significant role of several tumor proteins and their metabolic effects in colorectal cancer progression, particularly with regard to metastasis.

cancer biology↗

bioRxiv2023

Ready-to-use nanopore platform for ethanolamine quantification using an aptamer-based strand displacement assay.

In recent decades, nanopores have become a promising diagnostic tool. Protein and solid-state nanopores are increasingly used for both RNA/DNA sequencing and small molecule detection. The latter is of great importance because small molecules are difficult or expensive to detect using available methods such as HPLC or LC-MS. Moreover, DNA aptamers are an excellent detection element for sensitive and specific detection of small molecules. Here, we describe a method for the quantification of ethanolamine using Oxford Nanopores ready-to-use sequencing platform. To this end, we have developed a strand displacement assay using a binding ethanolamine aptamer and magnetic beads. The displaced aptamer can be detected using the MinION(R) nanopores and analysed/quantified using our in-house developed analysis software.

molecular biology↗

bioRxiv2021

pyControl: Open source, Python based, hardware and software for controlling behavioural neuroscience experiments.

Laboratory behavioural tasks are an essential research tool. As questions asked of behaviour and brain activity become more sophisticated, the ability to specify and run richly structured tasks becomes more important. An increasing focus on reproducibility also necessitates accurate communication of task logic to other researchers. To these ends we developed pyControl, a system of open source hardware and software for controlling behavioural experiments comprising; a simple yet flexible Python-based syntax for specifying tasks as extended state machines, hardware modules for building behavioural setups, and a graphical user interface designed for efficiently running high throughput experiments on many setups in parallel, all with extensive online documentation. These tools make it quicker, easier and cheaper to implement rich behavioural tasks at scale. As important, pyControl facilitates communication and reproducibility of behavioural experiments through a highly readable task definition syntax and self-documenting features. ResourcesDocumentation: https://pycontrol.readthedocs.io Repositories: https://github.com/pyControl User support: https://groups.google.com/g/pycontrol

neuroscience↗

bioRxiv2020

Axenic in-vitro cultivation of nineteen peat-moss (Sphagnum L.) species as a resource for basic biology, biotechnology and paludiculture

O_LIThe cultivation of Sphagnum mosses reduces CO2 emissions by rewetting drained peatlands and by substituting peat with renewable biomass. Sphagnum farming requires large volumes of founder material, which can only be supplied sustainably by axenic cultivation in bioreactors. C_LIO_LIWe established axenic in-vitro cultures from sporophytes of 19 Sphagnum species collected in Austria, Germany, Latvia, Netherlands, Russia and Sweden, namely S. angustifolium, S. balticum, S. capillifolium, S. centrale, S. compactum, S. cuspidatum, S. fallax, S. fimbriatum, S. fuscum, S. lindbergii, S. medium/divinum, S. palustre, S. papillosum, S. rubellum, S. russowii, S. squarrosum, S. subnitens, S. subfulvum, and S. warnstorfii. These species cover five of the six European Sphagnum sections, namely Acutifolia, Cuspidata, Rigida, Sphagnum and Squarrosa. C_LIO_LITheir growth was measured in axenic suspension cultures, whereas their ploidy was determined by flow cytometry and compared with the genome size of Physcomitrella patens. We identified haploid and diploid Sphagnum species, found that their cells are predominantly arrested in the G1-phase of the cell cycle, and did not find a correlation between plant productivity and ploidy. C_LIO_LIWith this collection, high-quality founder material for diverse large-scale applications but also for basic Sphagnum research is available from the International Moss Stock Center (IMSC). C_LI

plant biology↗

bioRxiv2019

Distinct roles of parvalbumin and somatostatin interneurons in the synchronization of spike-times in the neocortex

Synchronization of precise spike-times across multiple neurons carries information about sensory stimuli. Inhibitory interneurons are suggested to promote this synchronization, but it is unclear whether distinct interneuron subtypes provide different contributions. To test this, we examined single-unit recordings from barrel cortex in vivo and used optogenetics to determine the contribution of two classes of inhibitory interneurons: parvalbumin (PV)- and somatostatin (SST)-positive interneurons to spike-timing synchronization across cortical layers. We found that PV interneurons preferentially promote the synchronization of spike-times when instantaneous firing-rates are low (<12 Hz), whereas SST interneurons preferentially promote the synchronization of spike-times when instantaneous firing-rates are high (>12 Hz). Furthermore, using a computational model, we demonstrate that these effects can be explained by PV and SST interneurons having preferential contribution to feedforward and feedback inhibition, respectively. Our findings demonstrate that distinct subtypes of inhibitory interneurons have frequency-selective roles in spatio-temporal synchronization of precise spike-times.

neuroscience↗