Biology subjects

Schepers, J.

Publications and source records attributed to Schepers, J..

6 recordsLinked to original sources

bioRxiv2026

Beyond air-seeding: Dynamic, multiphase interactionsreveal a two-step mechanism of embolism propagation inangiosperm xylem

BackgroundThe mechanism underlying drought-induced embolism in angiosperm xylem has been attributed to air-seeding. This concept describes the bulk flow of gas from embolised to neighbouring conduits through the penetration of gas-liquid menisci across pores in interconduit pit membranes. While there is compelling evidence for the spatial propagation of embolism, air-seeding rests on various simplifying assumptions. Among others, air-seeding presumes that xylem sap has physical properties comparable to pure water, that pit membranes can be approximated as structures with simple pores, and that embolism occurs whenever a gas-liquid interface crosses a pit membrane. ScopeRecent experimental and theoretical work demonstrates that the biophysical conditions and processes governing gas-liquid interactions at interconduit pit membranes are fundamentally more dynamic and complex than assumed by air-seeding. These phenomena include: (1) gas movement through constriction pore networks, (2) insoluble, polar lipids at conduit surfaces and interfaces, (3) dynamic surface tension of xylem sap that depends on the local packing density of interfacial lipids, (4) bubble snap-off dynamics within pit membranes, (5) surfactant-stabilized nanobubbles in sap that is oversaturated with dissolved gas, and (6) electrostatic interactions between charged interfaces. Importantly, embolism propagation involves bubble generation and embolism formation as distinct, temporarily and spatially separated processes. Embolism formation occurs when nanobubbles become unstable, whereas nanobubbles below critical stability thresholds can remain stable in sap-filled conduits. ConclusionsTogether, these findings reconfirm that pit membranes function as safety valves enabling water transport according to the cohesion-tension theory, and provide mechanistic insights into embolism propagation. They address the question why plants do not suffer constant embolism formation despite negative xylem pressures. We conclude that a revised framework explicitly accounting for the 3D structure of pit membranes, and multiphase, dynamic processes operating within them are required to explain the biophysics underlying water transport and embolism resistance in angiosperm xylem.

plant biology↗

bioRxiv2026

A panel of biologically contained orthoebolaviruses for the screening of broad-spectrum antivirals

Filoviruses, particularly those of the Orthoebolavirus genus, pose ongoing public health threats due to their increasing frequency and geographic spread. However, research has been impeded by the biosafety level 4 classification of filoviruses. We previously reported the generation of biologically contained Ebola, Marburg and Sudan virus as lower biosafety level-compatible filovirus systems. In the present study, we expanded this repertoire to include biologically contained Tai Forest, Bundibugyo and Reston virus, thereby creating a near-complete toolkit for currently recognized human-relevant orthoebolaviruses. VP30-deficient viruses were generated with matching VP30 expressing cell lines. More specifically, we developed and optimized a dual-reporter system in VeroE6, Huh-7 and A549 cells, combining a virus-encoded enhanced green fluorescent protein reporter as readout for viral replication with a stably cellular-expressed nuclear mCherry marker for cytotoxicity assessment. Next, we screened two repurposing-oriented compound libraries comprising 640 small molecules against Tai Forest, Bundibugyo and Sudan virus, and subsequently cross-validated against Reston and Ebola virus. This approach identified multiple candidates with broad-spectrum activity across orthoebolaviruses, while also revealing virus-specific antivirals, with robust activity observed in both primate- and human-derived cell lines. Together, this work establishes a versatile and experimentally tractable lower biosafety level-compatible platform for the study of human-relevant orthoebolaviruses and the systematic discovery of broad-spectrum antiviral countermeasures against filoviruses.

microbiology↗

bioRxiv2026

An optimized RNA polymerase II minigenome system for Nipah virus

Nipah virus is a highly lethal, zoonotic paramyxovirus that has caused recurring outbreaks in several South and Southeast Asian countries since its discovery in Malaysia in 1998. Symptoms of infection include severe respiratory and neurological disease, often resulting in death. As no approved vaccines or antivirals are currently available to reduce the burden of this virus, it is classified as a biosafety level 4 pathogen. There is an urgent need for systems that enable research in a lower biocontainment setting, especially since the World Health Organization declared Nipah virus a priority pathogen for pandemic concern. In the past, several minigenome systems have already been developed as safe alternatives to working with infectious virus; however, these systems remain relatively inefficient and lack robustness and reliability for further applications. Therefore, we developed novel optimized RNA polymerase II-driven minigenomes with nanoluciferase or enhanced green fluorescent protein reporter genes. Both systems outperform previously designed Nipah virus minigenomes, are easily operable, and can be implemented for antiviral compound screenings.

microbiology↗

bioRxiv2024

Brain responses vary in duration - modelingstrategies and challenges

AO_SCPLOWBSTRACTC_SCPLOWTypically, event-related brain responses are calculated invariant to the underlying event duration, even in cases where event durations observably vary: with reaction times, fixation durations, word lengths, or varying stimulus durations. Additionally, an often co-occurring consequence of differing event durations is a variable overlap of the responses to subsequent events. While the problem of overlap e.g. in fMRI and EEG is successfully addressed using linear overlap correction, it is unclear whether overlap correction and duration covariate modeling can be jointly used, as both are dependent on the same inter-event-distance variability. Here, we first show that failing to explicitly account for event durations can lead to spurious results and thus are important to consider. Next, we propose and compare several methods based on multiple regression to explicitly account for stimulus durations. Using simulations, we find that non-linear spline regression of the duration effect outperforms other candidate approaches. Finally, we show that non-linear event duration modeling is compatible with linear overlap correction in time, making mass-univariate models combining non-linear spline regression of duration and linear overlap correction a flexible and appropriate tool to model overlapping brain signals. This allows us to reconcile the analysis of brain responses to stimuli in situations where durations differ between conditions, e.g. different reaction times, different stimulus durations, or fixation-related potentials with different fixation durations. While in this paper we focus on EEG analyses, we additionally show that our findings generalize to fMRI BOLD-responses, and argue that they should generalize to other overlapping signals such as LFPs, or pupil dilation responses.

neuroscience↗

bioRxiv2022

Development and optimization of biologically contained Marburg virus for high-throughput antiviral screening

Comparable to the related Ebola virus, Marburg virus is an emerging zoonotic pathogen that causes hemorrhagic fever with a high mortality rate. Therefore, handling of Ebola virus and Marburg virus is limited to biosafety level 4 facilities, of which only a limited number exists worldwide. However, researchers have developed several virus alternatives that are safe to handle in lower biosafety settings. One particularly interesting approach is the engineering of biologically contained Ebola virus by removing an essential gene from the virus genome and providing this missing gene in trans in a specific cell line. Because the virus is confined to this specific cell line, this results in a system that is safe to handle. So far, Ebola virus is the only virus for which biological containment has been reported. Here, we describe the first successful rescue of biologically contained Marburg virus and demonstrate that biological containment is also feasible for other filoviruses. Specifically, we describe the development of containment cell lines for Marburg virus through lentiviral transduction and show the growth and safety characteristics of eGFP-expressing, biologically contained Marburg virus in these cell lines. Additionally, we exploited this newly established Marburg virus system to screen over 500 compounds from available libraries. Lastly, we also validated the applicability of our biologically contained Marburg virus system in a 384-well format, to further illustrate the usefulness of this novel system as an alternative for high-throughput MARV screening of compound libraries.

microbiology↗

bioRxiv2021

Identification of novel Ebola virus inhibitors using biologically contained virus

Despite recent advancements in the development of vaccines and monoclonal antibody therapies for Ebola virus disease, treatment options remain limited. Moreover, management and containment of Ebola virus outbreaks is often hindered by the remote nature of the locations in which the outbreaks originate. Small-molecule compounds offer the advantage of being relatively cheap and easy to produce, transport and store, making them an interesting modality for the development of novel therapeutics against Ebola virus disease. Furthermore, the repurposing of small-molecule compounds, previously developed for alternative applications, can aid in reducing the time needed to bring potential therapeutics from bench to bedside. For this purpose, the Medicines for Malaria Venture provides collections of previously developed small-molecule compounds for screening against other infectious diseases. In this study, we used biologically contained Ebola virus to screen over 4,200 small-molecule drugs and drug-like compounds provided by the Medicines for Malaria Venture (i.e., the Pandemic Response Box and the COVID Box) and the Centre for Drug Design and Discovery (CD3, KU Leuven, Belgium). In addition to confirming known Ebola virus inhibitors, illustrating the validity of our screening assays, we identified eight novel selective Ebola virus inhibitors. Although the inhibitory potential of these compounds remains to be validated in vivo, they represent interesting compounds for the study of potential interventions against Ebola virus disease and might serve as a basis for the development of new therapeutics.

microbiology↗