Biology subjects

Mertens, D.

Publications and source records attributed to Mertens, D..

6 recordsLinked to original sources

bioRxiv2026

Digital-twin optimized transcranial temporal interference electrical stimulation alters rat brain activity patterns and metabolism including deep structures

Non-invasive deep-brain stimulation (DBS) using transcranial alternating current stimulation (tACS) with temporal interference (TI) has emerged as a promising approach for therapeutic applications in motor and neuropsychiatric disorders. Here, we present a preclinical TI tACS protocol for adult rats that follows a systems approach: an anatomically realistic finite-element digital twin of the rat head is used to optimize electrode placement and injected currents for a deep target, and the model predictions are then tested in vivo. We combine, minimal invasive TI tACS with functional MRI (fMRI) to characterize stimulation-related brain-wide neural responses, alterations in functional connectivity, and changes in neurotransmitter levels. The optimized montage targeted in particular the ventral (motor-related) thalamus. Stimulation-evoked fMRI revealed robust bilateral activation across both subcortical and cortical regions, such as the thalamus, hippocampus, amygdala, retrosplenial and anterior cingulate cortex, which, in turn, reflects direct and indirect activations of brain circuitries by TI tACS. Changes in the connectivity patterns during resting-state fMRI were limited (e.g., fimbria of the hippocampus), but partially overlapped with regional stimulation-evoked fMRI. Therefore, we assume only a short-term influence of TI on neural networks following a single stimulation. MR spectroscopy indicated a trend towards an increased glutamate/GABA ratio in the thalamus. Overall, we demonstrate that TI is a feasible and effective approach for non-invasive DBS in rodents, and that digital twin-based optimization combined with in vivo validation provides a workflow towards individualized stimulation and a foundation for future mechanistic and translational studies in disease models.

neuroscience↗

bioRxiv2024

Herbivore prevalence poorly predicts yield in diverse cropping systems

Industrialized agriculture needs sustainable alternatives to pesticides to avoid negative impacts on the environment and human health. Crop diversification is known to decrease pest pressure in agricultural crops. Up till now, effects of insect herbivores on crop yield are often assumed equal among cropping systems. Here, we show that cropping system alters the effect that herbivores have on cabbage crop yield, where more herbivores do not necessarily lead to reduced yields. Our most diverse cropping system had simultaneously the highest number of herbivores and highest crop yield. Conversely, in a cultivar mixture we observed negative impacts of herbivores on yield. Our study shows that, in addition to the time of arrival and type of herbivore, cropping system should be considered when assessing how insect herbivores affect crop yield. We emphasize how our perception of herbivorous insects as pests is flawed and limits conservation efforts and sustainable farming practices.

ecology↗

bioRxiv2022

Nucleosome repositioning in chronic lymphocytic leukaemia

The location of nucleosomes in the human genome determines the primary chromatin structure and regulates access to regulatory regions. However, genome-wide information on deregulated nucleosome occupancy and its implications in primary cancer cells is scarce. Here, we performed a systematic comparison of high-resolution nucleosome maps in peripheral-blood B-cells from patients with chronic lymphocytic leukaemia (CLL) and healthy individuals at single base pair resolution. Our investigation uncovered significant changes of both nucleosome positioning and packing in CLL. Globally, the spacing between nucleosomes (the nucleosome repeat length, NRL) was shortened in CLL. This effect was stronger in the more aggressive IGHV-unmutated than IGHV-mutated CLL subtype. Changes in nucleosome occupancy at specific sites were linked to active chromatin remodelling and reduced DNA methylation. Nucleosomes lost or gained in CLL in comparison with non-malignant B-cells marked differential binding of 3D chromatin organisers such as CTCF as well as immune response-related transcription factors, allowing delineating epigenetic mechanisms affected in CLL. Furthermore, patients could be better assigned to CLL subtypes according to nucleosome occupancy at cancer-specific sites than based on DNA methylation or gene expression. Thus, nucleosome positioning constitutes a novel readout to dissect molecular mechanisms of disease progression and to stratify patients. Furthermore, we anticipate that the global nucleosome positioning changes detected in our study, like the reduced NRL, can be exploited for liquid biopsy applications based on cell-free DNA to monitor disease progression.

genomics↗

bioRxiv2022

Priority effects in herbivore communities vary in effect on plant development and reproduction in four Brassicaceae plant species

O_LIInsect herbivores can directly affect plant reproduction by feeding on reproductive tissues, or indirectly by feeding on vegetative tissues for which plants are unable to compensate. Additionally, early arriving herbivores may have cascading effects on plant fitness by altering the richness and abundance of the later arriving community. C_LIO_LIStudies are divided on whether herbivory early in the development of plants can impact plant fitness and whether these effects are predominantly mediated through changes in plant development or subsequent herbivory. Obtaining insight into the generality and consistency of mediated effects on plant reproduction induced by early-season herbivory requires a comparative approach across plant species and environmental conditions. C_LIO_LIBy excluding the herbivore community in an exclosure experiment and by manipulating early-season herbivory in a common garden experiment replicated across four Brassicaceae species and two years, we tested whether early-season herbivory could affect plant development, reproduction, and the herbivore communities associated with individual plants. In addition, we tested a causal hypothesis to disentangle the direct effect of herbivory on plant reproduction, and their indirect effect through changes in the development of plants. C_LIO_LIEarly-season herbivory affected plant development and reproduction, but effects were highly dependent on the plant species, the inducing herbivore species, and the biotic and abiotic environment. The exploratory path analysis indicated that plant reproduction was best predicted by variation in plant development, explaining up to 90.88% of the total effect on seed production. Even though the richness and abundance of the subsequent herbivore community were conditionally affected by the initial colonising herbivore, herbivore pressure is predicted to have only minor effects on reproduction. Importantly, the effects of herbivore pressure on seed set were not direct but were mediated by changes in plant development. C_LIO_LISynthesis: Early-season herbivory has the potential to affect plant reproduction through changes in the development of plants and, less strongly, through effects mediated by the plant-associated herbivore community. However, as plants are often able to compensate and attenuate the effects induced by herbivory, the detection, sign, and strength of effects are highly dependent on the plant species and environment. C_LI

ecology↗

bioRxiv2020

Variation in insect herbivore communities on individual plants reveal phylogenetic signal in uncertainty of attack in Brassicaceae

As a result of co-evolution between plants and herbivores, related plants often interact with similar communities of herbivores. On individual plants, typically only a subset of interactions is realized. The stochasticity of realized interactions leads to uncertainty of attack on individual plants and is likely to determine adaptiveness of plant defence strategies. Here, we show that across 12 plant species in two phylogenetic lineages of the Brassicaceae, variation in realized herbivore communities reveals a phylogenetic signal in the uncertainty of attack on individual plants. Individual plants of Brassicaceae Lineage II were attacked by a larger number of herbivore species from a larger species pool, resulting in a higher uncertainty of realized antagonistic interactions compared to plants in Lineage I. We argue that uncertainty of attack in terms of realized interactions on individual plants is ecologically relevant and must therefore be considered in the evolution of plant defences.

ecology↗

bioRxiv2020

Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL

BackgroundIn cancer, normal epigenetic patterns are disturbed and contribute to gene expression changes, disease onset and progression. The cancer epigenome is composed of the epigenetic patterns present in the tumor-initiating cell at the time of transformation, and the tumor-specific epigenetic alterations that are acquired during tumor initiation and progression. The precise dissection of these two components of the tumor epigenome will facilitate a better understanding of the biological mechanisms underlying malignant transformation. Chronic lymphocytic leukemia (CLL) originates from differentiating B cells, which undergo extensive epigenetic programming. This poses the challenge to precisely determine the epigenomic ground-state of the cell-of-origin in order to identify CLL-specific epigenetic aberrations. MethodsWe developed a linear regression model, methylome-based cell-of-origin modeling (Methyl-COOM), to map the cell-of-origin for individual CLL patients based on the continuum of epigenomic changes during normal B cell differentiation. ResultsMethyl-COOM accurately maps the cell-of-origin of CLL and identifies CLL-specific aberrant DNA methylation events that are not confounded by physiologic epigenetic B cell programming. Furthermore, Methyl-COOM unmasks abnormal action of transcription factors, altered super-enhancer activities, and aberrant transcript expression in CLL. Among the aberrantly regulated transcripts were many genes that have previously been implicated in T cell biology. Flow cytometry analysis of these markers confirmed their aberrant expression on malignant B cells at the protein level. ConclusionsMethyl-COOM analysis of CLL identified disease-specific aberrant gene regulation. The aberrantly expressed genes identified in this study might play a role in immune-evasion in CLL and might serve as novel targets for immunotherapy approaches. In summary, we propose a novel framework for in silico modeling of reference DNA methylomes and for the identification of cancer-specific epigenetic changes, a concept that can be broadly applied to other human malignancies.

cancer biology↗