Biology subjects

Koenig, A.

Publications and source records attributed to Koenig, A..

12 recordsLinked to original sources

bioRxiv2026

Shifts in the Maternal Gut Microbiome Across Pregnancy are Associated with Energetic Status in Phayre's Leaf Monkeys

During pregnancy, mothers experience physiological changes that support fetal development, including shifts in energy utilization and increasing insulin resistance during late gestation. While these changes benefit the fetus, they can also impose energetic costs that affect the mother's physical condition and metabolic phenotype. Previous studies suggest that the gut microbiome, a key regulator of female metabolism and energy harvest, may play a critical role in mediating these physiological challenges. In this study, metagenomic sequencing of the gut microbiome of 120 samples revealed dramatic shifts in gut bacterial composition and function associated with pregnancy and lactation in 14 wild Phayre's leaf monkeys, Trachypithecus phayrei crepusculus, from two groups at the Phu Khieo Wildlife Sanctuary, Thailand. Alpha diversity, beta diversity, and taxonomic composition all differed between cycling and the 3rd trimester. Furthermore, bacterial dissimilarity between these states was negatively correlated with postpartum physical condition; that is, mothers whose gut microbiota remained more stable during pregnancy recovered sooner after giving birth. Functional profiling revealed a depletion of pathways involved in purine salvage and glutamate degradation during the 3rd trimester. Overall, our study demonstrates that the gut microbiome undergoes substantial changes during pregnancy, and the stability of these microbial communities predicts postpartum maternal health and potentially influence lifetime reproductive output.

zoology↗

bioRxiv2026

Collateral Immune Cell Signaling Compromises the Efficacy of T-cell Engaging Therapies for Cardiac Fibrosis

Cardiac fibrosis is causally linked to heart failure progression and survival. Currently, there are no approved treatments that directly target cardiac fibrosis. Recent studies have identified a subset of activated cardiac fibroblasts distinct from myofibroblasts that are marked by fibroblast activation protein (FAP) expression, emerge in the injured and diseased heart through inflammatory signaling, and contribute to fibrosis. Using a genetic mouse model, we demonstrate the potential benefits of FAP+ fibroblast depletion following myocardial infarction. Unexpectedly, while FAP targeted bispecific T-cell engaging antibodies (BiTE(R) molecules) effectively eliminate FAP+ fibroblasts from the heart, they surprisingly lead to accelerated deterioration of cardiac function, enhanced remodeling, and increased scar size. FAP BiTE(R) molecules elicit a robust cytokine response within the heart with prominent activation of interferon gamma (IFNg) and CD40 ligand pathways. Target cell killing was independent of IFNg; and CD40L signaling and blockade of these pathways was sufficient to unmask the protective therapeutic effects of FAP+ fibroblast depletion. Mechanistically, we reveal that IFNg; signaling to fibroblasts drives the differentiation of an independent lineage of activated fibroblasts not typically found in the infarcted heart, which are responsible for the harmful effects of FAP BiTE(R) molecules. Collectively, these findings highlight a previously unrecognized cardiac liability of BiTE(R) molecules and inform the design of the next generation of therapeutics.

immunology↗

bioRxiv2026

Gravitropism Shapes the Pareto Front of Root System Architecture

The root systems of wild tomatoes (S. Pimpinellifolium) can be understood as biological networks in which the lateral roots branch from a single main root and together balance two competing objectives: minimizing the material cost of building the network (wiring cost) and minimizing the transport time from the root tips to the shoot (conduction delay). Our prior work showed that S. Pimpinellifolium root architectures cluster near the Pareto-optimal front defined by these two objectives, with morphological diversity resolving into four qualitative topologies ((Chandrasekhar and Julkowska, 2022)). That framework assumed lateral roots grow as straight lines - ignoring gradual onset of lateral root gravitropism, the tendency of roots to curve toward the gravity vector. Because curved trajectories are longer than straight lines, gravitropism directly increases both wiring cost and conduction delay, constraining which architectures are physically realizable and thereby reshaping the Pareto front itself. Here we extend the model to explicitly incorporate lateral root gravitropism, producing predicted architectures that align much more closely with observed S. Pimpinellifolium root systems. We present a computational method to infer gravitropic sensitivity directly from anatomical tracing data - without reorientation assays - and apply it to 2423 arbors across different root topologies, growth conditions, and hormone treatments. Incorporating gravitropism reveals variation invisible to the straight-line model:notably, lateral roots show reduced gravitropic sensitivity under salt stress, mirroring a phenomenon previously described only for main roots and overlooked in lateral roots until now.

plant biology↗

bioRxiv2026

Time resolved proteomic analysis of hepatitis B virus infection

Hepatitis B virus (HBV) infection can result in progressive inflammatory liver diseases that are associated with the development of hepatocellular carcinoma. Our understanding of the HBV infection proteome is limited, and we used label-free quantitative (LFQ) proteomics to address this gap in knowledge. Kinetic sampling of mock and HBV infected human hepatoma HepG2 cells showed a time-dependent expression of the viral core (C) and Surface (S) proteins. Concomitantly, we observed altered host cell proteome dynamics, including cytoskeletal proteins, collagens, fibrinogen subunits, extracellular matrix receptor interaction and focal adhesion pathways, as well as an elevated abundance of complement proteins. Specifically, we noted evidence for elevated C5 complement protein abundance in the HBV infected cells, highlighting selective complement adaptations during infection.

microbiology↗

bioRxiv2025

The Role of SARS-CoV-2 Nucleocapsid Protein Persistence in Inducing Chronic Type I Interferon and Mitochondrial Dysfunction.

The potential mechanisms that link SARS-CoV-2 infection to post-acute sequelae of SARS-CoV-2 symptoms and ultimately transition to new onset of autoimmune disease remain poorly understood. Here, we report the consequences of SARS-CoV-2 nucleocapsid (N) protein persistence in the absence of detectable SARS-CoV-2 replication in otherwise healthy individuals, a set of systemic lupus erythematosus (SLE) patients, and a case of a 60-year-old man who developed a new onset of lupus nephritis seven months following mild COVID-19 disease. We have identified that N protein persistence in peripheral blood mononuclear cells (PBMC) did not correlate with detectable SARS-CoV-2 RNA in blood but is associated with significantly increased secretion of type I interferons (IFN) and presence of tubuloreticular structures in peripheral leukocytes. We further demonstrate that the N protein colocalizes in the mitochondrial fraction of PBMCs from individuals positive for N protein alongside mitochondrial antiviral signaling protein (MAVS). In vitro expression of the N protein in a monocytic cell line showed that the N protein itself was directly capable of interacting with MAVS in the absence of viral RNA, and this interaction was enhanced if the cell was exposed to oxidative stress. We show that the type I IFN signature in the presence of N protein expression was MAVS, but not STING signaling pathway-dependent. Our findings suggest a mechanism for the onset and promotion of type I IFN signature after COVID-19; in our model, the SARS-CoV-2 N protein can independently trigger sustained type I IFN production via direct activation of MAVS and its spontaneous oligomerization. This long-lasting type I IFN generation may create a chronic inflammatory milieu, favoring autoimmunity with SLE-like symptoms in susceptible individuals. One Sentence SummaryThe persistence of SARS-CoV-2 nucleocapsid in the absence of viral replication is associated with an induction of mitochondria-mediated inflammatory milieu, which can favor autoimmunity in susceptible individuals.

immunology↗

bioRxiv2025

A role of villin-dependent F-actin organization in peroxisome motility in Arabidopsis cells

Actin microfilaments (F-actin) serve as the track for directional movement of organelles in plants. To understand how the F-actin network is employed for the movement of peroxisomes, essential organelles in plant metabolism, we analyzed mutants of three villin (VLN) genes, which encode the primary actin-bundling factor and are most actively expressed in vegetative tissues in Arabidopsis thaliana. We found that the vln4 mutation greatly exacerbated the growth and subcellular defects in vln2 vln3. Compared to the wild-type cells, the double and triple vln mutants exhibit progressive reduction of stable F-actin bundles and rapid remodeling of the fine filaments. The defective F-actin network did not prevent peroxisomes from taking on both rapid and slow movements along the tracks but caused significantly reduced speed of movement and displacement distance of peroxisomes. Using a correlation analysis method, we classified the complex heterogeneous peroxisome movement patterns into clusters reflecting distinct movement directionalities. The vln triple mutant had significantly reduced number of peroxisomes with long-range and linear movement. Our results provide insights into how VLN-dependent F-actin organization is coupled with the complex pattern of peroxisome movement.

plant biology↗

bioRxiv2025

Helical foldamers as selective G-quadruplex ligands

We investigated the G-quadruplex binding selectivity of short aromatic oligoamide helical foldamers comprising quinoline (Q) and pyridine (P) units. We found that the foldamers prefer parallel G-quadruplex structures, especially when the external G-quartets are sterically accessible. A crystal structure of the tetramer QQPQ with the parallel G-quadruplex formed by dTGGGTTGGGTTGGGTTGGGT shows two quinoline subunits interacting with an external G-quartet through {pi}-stacking, and solution NMR confirms that the foldamer targets the 3 and 5 ends of this G-quadruplex. Foldamers can also selectively target sequence variants of the telomeric sequences containing adenine-to-thymine mutation in the loops. The conformational selectivity of foldamers originates from the bulkiness of oligomers with four or more subunits, which imposes steric restrictions on G-quadruplex binding. The flexibility provided by the pyridine subunits was also key to improve affinity. Mixed quinoline-pyridine foldamers are thus a promising class of selective G-quadruplex ligands, and their unique modular scaffold offers new avenues to further improve their affinity and selectivity.

biophysics↗

bioRxiv2024

Soil microbes prefer organic acids over sugars in simulated root exudation

Sugars and organic acids, primary components in plant root exudates, are thought to enhance microbial decomposition of organic matter in the rhizosphere. However, their specific impacts on microbial activity and nutrient mobilisation remain poorly understood. Here, we simulated passive root exudation to investigate the distinct effects of sugars and organic acids on microbial metabolism in the rhizosphere. We released 13C- labelled sugars and/or organic acids via reverse microdialysis into intact meadow and forest soils over 6-hours. We measured substrate-induced microbial respiration, soil organic matter mineralization, metabolite concentrations, and substrate incorporation into lipid-derived fatty acids. Our results reveal a pronounced microbial preference for organic acids over sugars, with organic acids being removed faster from the exudation spot and preferentially respired by microbes. Unlike sugars, organic acids increased concentrations of microbial metabolic byproducts and cations (K, Ca, Mg) near the exudation spot. Our results challenge the prevailing assumption that sugars are the most readily available and rapidly consumed substrates for soil microbes. Microbial preference for organic acids indicates a trade-off between rapid biomass growth and ATP yield. Our findings underscore the significant role of exudate composition in influencing microbial dynamics and nutrient availability, and emphasize the importance of biotic and abiotic feedback mechanisms in the rhizosphere in regulating root exudation.

microbiology↗

bioRxiv2023

Quantitative comparison of a mobile, tablet-based and two stationary, video-based eye-trackers

AbstractThe analysis of eye-movements is a non-invasive, reliable and fast method to detect and quantify brain (dys-)functions. Here, we investigated the performance of two novel eye-trackers: the Thomas-Oculus-Motus-research mobile (TOM-rm) and the TOM-research stationary (TOM-rs) and compared it with the performance of a well-established video-based eye-tracker, i.e., the EyeLink 1000 (EL). The TOM-rm is a fully integrated, tablet-based mobile device that presents visual stimuli and records head-unrestrained eye-movements at 30Hz without additional infrared (IR) illumination. The TOM-rs is a stationary, video-based eye-tracker that records eye-movements at either high spatial or high temporal resolution. We compared the performance of all three eye-trackers in two different behavioral tasks: pro- and anti-saccade and free viewing. We collected data from human subjects while running all three eye-tracking devices in parallel. Parameters requiring a high spatial or temporal resolution (e.g., saccade latency or gain), as derived from the data, differed significantly between the EL and the TOM-rm in the pro- and anti-saccade task. In the free viewing task, larger noise and the lower frame rate of the TOM-rm caused deviations of the results with respect to the EL. Differences between results derived from the TOM-rs and the EL were most likely due to experimental conditions, which could not be optimized for both systems simultaneously. We conclude that the TOM-rm can be used for measuring eye-movements reliably at comparably low spatial and temporal resolution. The TOM-rs, on the other hand, can provide high-resolution oculomotor data at least on a par with an established reference system.

neuroscience↗

bioRxiv2022

Subsensory stochastic electrical stimulation targeting muscle afferents alters gait control during locomotor adaptations to haptic perturbations

Subsensory noise stimulation targeting sensory receptors has been shown to improve balance control in healthy and impaired individuals. However, the potential for application of this technique in other contexts is still unknown. Gait control and adaptation rely heavily on the input from proprioceptive organs in the muscles and joints. Here we investigated the use of subsensory noise stimulation as a means to influence motor control by "boosting" proprioception during locomotor adaptations to forces delivered by a robot. The forces increase step length unilaterally and trigger an adaptive response that restores the original symmetry. Healthy participants performed two adaptation experiments, one with stimulation applied to the hamstring muscles and one without. We found that participants adapted faster but to a lesser extent when undergoing subsensory stimulation. We argue that this behaviour is due to the dual effect that the stimulation has on the afferents encoding position and velocity that are present in the muscle spindles.

neuroscience↗

bioRxiv2021

Donor Macrophages Modulate Rejection after Heart Transplantation

BackgroundCellular rejection after heart transplantation imparts significant morbidity and mortality. Current immunosuppressive strategies are imperfect, target recipient T-cells, and have a multitude of adverse effects. The innate immune response plays an essential role in the recruitment and activation of T-cells. Targeting the donor innate immune response would represent the earliest interventional opportunity within the immune response cascade. There is limited knowledge regarding donor immune cell types and functions in the setting of cardiac transplantation and no current therapeutics exist for targeting these cell populations. MethodsUsing genetic lineage tracing, cell ablation, and conditional gene deletion, we examined donor mononuclear phagocyte diversity and function during acute cellular rejection of transplanted hearts in mice. We performed single cell RNA sequencing on donor and recipient macrophages, dendritic cells, and monocytes at multiple timepoints after transplantation. Based on our single cell RNA sequencing data, we evaluated the functional relevance of donor CCR2+ and CCR2- macrophages using selective cell ablation strategies in donor grafts prior to transplant. Finally, we perform functional validation of our single cell-derived hypothesis that donor macrophages signal through MYD88 to facilitate cellular rejection. ResultsDonor macrophages persisted in the transplanted heart and co-existed with recipient monocyte-derived macrophages. Single-cell RNA sequencing identified donor CCR2+ and CCR2- macrophage populations and revealed remarkable diversity amongst recipient monocytes, macrophages, and dendritic cells. Temporal analysis demonstrated that donor CCR2+ and CCR2- macrophages were transcriptionally distinct, underwent significant morphologic changes, and displayed unique activation signatures after transplantation. While selective depletion of donor CCR2- macrophages reduced allograft survival, depletion of donor CCR2+ macrophages prolonged allograft survival. Pathway analysis revealed that donor CCR2+ macrophages were being activated through MYD88/NF-{beta} signaling. Deletion of MYD88 in donor macrophages resulted in reduced antigen presenting cell recruitment, decreased emergence of allograft reactive T-cells, and extended allograft survival. ConclusionsDistinct populations of donor and recipient macrophages co-exist within the transplanted heart. Donor CCR2+ macrophages are key mediators of allograft rejection and inhibition of MYD88 signaling in donor macrophages is sufficient to suppress rejection and extend allograft survival. This highlights the therapeutic potential of donor heart-based interventions.

immunology↗

bioRxiv2020

Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization

Parkinsons disease (PD) and Alzheimers disease (AD) are common neurodegenerative disorders of the elderly and, therefore, affect a growing number of patients worldwide. Both diseases share, as a common hallmark, the accumulation of characteristic protein aggregates, known as Lewy bodies (LB) in PD, and neurofibrillary tangles in AD. LBs are primarily composed of misfolded -synuclein (aSyn), and neurofibrillary tangles are primarily composed of tau protein. Importantly, upon pathological evaluation, most AD and PD/Lewy body dementia cases exhibit mixed pathology, with the co-occurrence of both Lewy bodies and neurofibrillary tangles, among other protein inclusions. Recent studies suggest that both aSyn and tau pathology can spread and propagate through neuronal connections. Therefore, it is important to investigate the mechanisms underlying aggregation and propagation of these proteins for the development of novel therapeutic strategies. Here, we assessed the effects of different pharmacological interventions on the aggregation and internalization of tau and aSyn. We found that anle138b and epigallocatechin gallate decrease aSyn aggregation, that fulvic acid attenuates aggregation of the repeat domain of tau, and that dynasore reduces tau internalization. Establishing the effects of small molecules with different chemical properties on the aggregation and spreading of aSyn and tau will be important for the development of future therapeutic interventions.

neuroscience↗