Biology subjects

Maes, D.

Publications and source records attributed to Maes, D..

12 recordsLinked to original sources

bioRxiv2026

Disease-linked mutations in hnRNPA2B1 accelerate condensate maturation and promote amyloid aggregation

Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a multifunctional RNA-binding protein that undergoes liquid-liquid phase separation (LLPS), contributing to the assembly of membraneless organelles across different cellular contexts. However, dysregulated phase separation can drive the transition from functional condensates to pathological protein aggregates. Two mutations in the low-complexity domain (LCD) of hnRNPA2B1 (D302V and P310L) have been linked to neurodegenerative diseases. How these mutations alter the interplay between LLPS and aggregation remains poorly understood. Here, we show that these disease-linked mutations accelerate condensate maturation and promote amyloid-like aggregation of hnRNPA2B1, with fibrils emerging from condensate-like cores. To dissect the mechanistic link between phase separation, aggregation, and disease, we focused on a conserved 25-amino-acid region within the LCD harboring both mutation sites. Deletion of this region markedly impairs LLPS and abolishes aggregation, revealing its contribution to both processes. Isolated peptides derived from this region have an intrinsic propensity for amyloid-like fibril formation, which is enhanced by the mutations. Although unable to phase separate, these peptides remodel condensate morphology and nucleate aggregation of the LCD. Together, our results identify a sequence-encoded mechanism linking disease-associated mutations to altered condensate behavior and amyloid aggregation, providing molecular insights into how aberrant phase transitions may contribute to hnRNPA2B1-associated disease.

biochemistry↗

bioRxiv2025

Expression and Purification of Full-Length hnRNPA2B1 for Biophysical Characterization of Liquid-Liquid Phase Separation

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) is a multifunctional RNA-binding protein involved in RNA maturation and mRNA transport. It has recently been shown to undergo liquid-liquid phase separation (LLPS), contributing to the assembly of membraneless organelles. Moreover, dysregulation of LLPS is associated with the formation of pathogenic protein aggregates, in which hnRNPA2B1 is frequently found. Despite its biological and pathological relevance, studies on the full-length protein remain limited due to its intrinsically disordered, low-complexity domain, which renders hnRNPA2B1 highly aggregation-prone and difficult to purify. In this study, we report the successful expression and purification of full-length hnRNPA2B1 with high purity and minimal nucleic acid contamination. By optimizing buffer conditions, specifically ionic strength and pH, we maintain the protein in solution following cleavage of its solubility tag. Preliminary in vitro characterization under near-physiological conditions reveals that purified hnRNPA2B1 undergoes LLPS, forming dynamic liquid-like droplets that grow and mature into amorphous aggregates. Our approach provides a robust method for purifying hnRNPA2B1 suitable for LLPS and aggregation studies. This strategy may also be useful to purify other aggregation-prone, intrinsically disordered proteins.

biochemistry↗

bioRxiv2025

The interplay of climate change, urbanization, and species traits shapes European butterfly population trends

Species populations naturally fluctuate, yet long-term trend analysis can reveal patterns of success, decline, or stability under global change pressures. While responses to climate change are well-documented, its synergy with another major global driver, urbanization, remains understudied. Here, we analyzed long-term monitoring data from over 8,400 populations of 145 butterfly species across Europe, representing a high diversity of species traits, to assess population trends in response to climate change and urbanization. We examined how population responses vary between urban and rural contexts, providing insights into the influence of site-specific conditions. Climate warming was associated with population declines, which were more pronounced in urban areas. The effect of precipitation varied between environments: increases in precipitation generally benefited populations in rural areas but had detrimental effects in urban ones. Aridity consistently drove population declines across environments, with slightly stronger effects in urban areas. Species with colder climatic niches declined the most in response to warming, increased aridity, and reduced precipitation, while trophic specialists were particularly vulnerable to aridity and precipitation changes in urban environments. Although increasing urbanization did not explain overall population trends, its effects became evident when considering species traits, with certain traits being more vulnerable to urbanization. Specifically, species with narrow climatic niches declined the most in response to urbanization in rural areas, while those and larger body sizes decline the most in urban environments. Our findings highlight the complex interplay between environmental change, landscape context, and species traits in shaping biodiversity outcomes. Importantly, our results suggest that urbanization generally amplifies the impact of climate change on insect population trends.

ecology↗

bioRxiv2025

Consistent covariation of dispersal, life history and thermal niches across terrestrial arthropods

Arthropods, as ectotherms, are experiencing global declines, with many species facing the need to either acclimate or disperse in response to climate change. Understanding to which degree life history, dispersal and thermal niche traits covary is key to improve distribution forecasting under climate change. We quantified life history, dispersal and thermal range covariation among 4000 Western European arthropod species spanning eight orders, considering phylogenetic relationships to account for common ancestry. We demonstrate the existence of two axes of life history variation: the fast-slow continuum and the reproductive strategy axis. Species at the fast end of the continuum have higher dispersal capacities and broader thermal niches than slower species. The resulting trait syndromes were surprisingly consistent across orders. These trait combinations, which generally enhance range-shifting potential, point to the emergence of two distinct groups of arthropods: those well-suited and those less equipped to mitigate the effects of future climate change.

ecology↗

bioRxiv2024

An in-depth dataset of northwestern European arthropod life histories and ecological traits

In response to the ongoing biodiversity crisis among arthropods, it is essential to implement efficient conservation strategies to safeguard both species diversity and the vital ecosystem services they provide. Developing such strategies requires reliable predictive models that can identify the species that are the most vulnerable to current and future threats, including those posed by climate and land-use change. Species life histories are central to these models, as they influence both population dynamics and spread rates. To support this effort, we compiled a dataset with key traits for arthropods based on several literature sources and expert knowledge. The dataset contains data on body size, life history, thermal niche and ecology for 4874 northwestern European species across 10 different orders. By gathering these essential trait data, we aim to create a robust foundation for predicting species vulnerability and anticipating shifts in arthropod communities in response to global change.

ecology↗

bioRxiv2023

Unravelling arthropod movement in natural landscapes: small-scale effects of body size and weather conditions

O_LIArthropod movement has been noticeably understudied compared to vertebrates. A crucial knowledge gap pertains to the factors influencing arthropod movement at habitat boundaries, which has direct implications for population dynamics and gene flow. While larger arthropod species generally achieve greater dispersal distances and large-scale movements are affected by weather conditions, the applicability of these relationships at a local scale remains uncertain. Existing studies on this subject are not only scarce but often limited to a few species or laboratory conditions. C_LIO_LITo address this knowledge gap, we conducted a field study in two nature reserves in Belgium, focusing on both flying and cursorial (non-flying) arthropods. Over 200 different arthropod species were captured and released within a circular setup placed in a resource-poor environment, allowing quantification of movement speed and direction. By analysing the relationship between these movement variables and morphological (body size) as well as environmental factors (temperature and wind), we aimed to gain insights into the mechanisms driving arthropod movement at natural habitat boundaries. C_LIO_LIFor flying species, movement speed was positively correlated with both body size and tailwind speed. In contrast, movement speed of cursorial individuals was solely positively related with temperature. Notably, movement direction was biased towards the vegetated areas where the arthropods were originally caught, suggesting an internal drive to move towards suitable habitat. This tendency was particularly strong in larger flying individuals and under tailwind conditions. Furthermore, both flying and cursorial taxa were hindered from moving towards the habitat by strong upwind. C_LIO_LIIn conclusion, movement speed and direction at patch boundaries are dependent on body size and prevailing weather conditions, and reflect an active decision-making process. C_LI

ecology↗

bioRxiv2023

Competition between induced fit and conformational selection binding: how different flux-based approaches may help clarifying their interplay.

BackgroundBinding kinetics has become a popular discipline in pharmacology. Yet, it was recommended a decade ago to look on ligand-target binding in terms of fluxes instead of rate constants. Like product formation in enzymology, these binding fluxes stand for the rate/velocity by which the target converts form one state into another. Several thereon-based approaches can be used for studying the functioning binding mechanisms. ObjectivesAlthough the relative contribution/importance of the induced fit and conformational selection binding pathways within a thermodynamic cycle is still hotly debated, only a single flux-based approach is customarily addressed for such calculations. There is a need to better understand the relevance of this peculiar approach. MethodsThe present findings relied on differential equation-based simulations, using the provided forward- and reverse rate constants for four reported cases as input. ResultsBoth pathways may act in unison and even in tandem rather than being mutually exclusive. Also, calculating their relative contribution by distinct flux-based approaches may yield different outcomes for some of the cases under pre-equilibrium as well as equilibrium conditions. Additional flux-based approaches offer a rationale for the occurrence of those disparities. ConclusionsThe interplay between the induced fit- and conformational selection pathways is even more intricate than hitherto expected. It may me preferable to quantitate their relative contribution in terms of target occupancies instead of binding fluxes when genuine equilibrium can be reached. PerspectivesCompared to the often-used elaborate algebraic equations, combining different binding flux-based approaches may offer better intuitive and visual insight into the functioning of complex binding mechanisms. More attention should also be paid to physiologically more relevant non-equilibrium situations.

pharmacology and toxicology↗

bioRxiv2023

Strong gene flow across an urbanized coastal landscape in a dune specialist digger wasp

ContextGenetic connectivity is often disrupted by anthropogenic habitat fragmentation, and therefore often a focus in landscape-scale conservation. Landscape genetics methods allow for studying functional connectivity in heterogenous landscapes in detail and have the potential to inform conservation measures for a species regional persistence. Yet, for insects, functional connectivity through landscape genetics remains largely unexplored. ObjectivesWe aimed to assess the functional connectivity in the dune-specialist digger wasp Bembix rostrata, in a human-altered 15 km section along the Belgian coast, based on landscape genetics methods. MethodsWe optimised landscape resistance distances according to individual genetic distances with the package ResistanceGA. We combined this with a multi-model inference approach to deduce relative conductance or resistance of gene flow to natural and anthropogenic landscape types. ResultsOverall, the populations of this dune-specialist insect are genetically well-connected. We detected-- on top of the prominent background process of isolation-by-distance--a weak but consistent signal of urban features facilitating gene flow. ConclusionsUrban areas are not a barrier to genetic connectivity of the dune-specialist insect B. rostrata in the focal human-altered landscape. However, because urbanisation leads to larger scale fragmentation, its impact on the distribution of populations in the landscape and related effective regional gene flow remains substantial. As this species depends on early-succession dune vegetations, restoring and increasing sand dynamics at the local and landscape scale should be the focus of conservation aimed at the regional species persistence, rather than trying to increase habitat connectivity in this human-altered dune ecosystem.

ecology↗

bioRxiv2023

C9orf72-linked arginine-rich dipeptide repeats aggravate pathological phase separation of G3BP1

Ras GTPase-activating protein-binding protein 1 (G3BP1) is the key protein driving the formation of cytoplasmic stress granules (SGs) by liquid-liquid phase separation (LLPS). It is a switch-like protein held in a closed and inactive state by intramolecular electrostatic interactions competitively opened by RNA, activating the protein and initiating its LLPS. Here we show that C9orf72-derived arginine-rich dipeptide repeats PR30 and GR30 (R-DPRs) present in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), also bind to G3BP1, switching it to an LLPS-competent open state much more effectively than RNA. Whereas RNA binds G3BP1 with micromolar affinity, and cannot initiate LLPS without crowding agents, R-DPRs exhibit a thousand-fold stronger binding to G3BP1, eliciting rapid LLPS even without crowding. The pathogenic effect of R-DPRs is also underscored by the slow transition of R-DPR-G3BP1 liquid droplets to aggregated, ThS-positive states that can recruit the ALS-linked protein hnRNPA2. Deletion constructs and molecular simulations show that R-DPR binding and LLPS are mediated via binding through the negatively charged intrinsically disordered region 1 (IDR1) of the protein, allosterically regulated by the positively charged IDR3. Bioinformatic analyses point to the strong mechanistic parallels of these effects with the interaction of R-DPRs with nuclear nucleophosmin (NPM1) and also suggest that R-DPRs also interact with many other similar nucleolar and stress-granule proteins, extending the underlying mechanism of R-DPR toxicity in cells.

molecular biology↗

bioRxiv2022

Asymmetrical gene flow between coastal and inland dunes in a threatened digger wasp

1.Connectivity is a species- and landscape-specific measure that is key to species conservation in fragmented landscapes. However, information on connectivity is often lacking, especially for insects which are known to be severely declining. Patterns of gene flow constitute an indirect measure of functional landscape connectivity. We studied the population genetic structure of the rare digger wasp Bembix rostrata in coastal and inland regions in and near Belgium. The species is restricted to sandy pioneer vegetations for nesting and is well known for its philopatry as it does not easily colonize vacant habitat. It has markedly declined in the last century, especially in the inland region where open sand habitat has decreased in area and became highly fragmented. To assess within and between region connectivity, we used mating system independent population genetic methods suitable for haplodiploid species. We found more pronounced genetic structure in the small and isolated inland populations as compared to the well-connected coastal region. We also found a pattern of asymmetrical gene flow from coast to inland, including a few rare dispersal distances up to 200 to 300 km based on assignment tests. We point to demography, wind and difference in dispersal capacities as possible underlying factors that can explain the discrepancy in connectivity and asymmetrical gene flow between the different regions. Despite B. rostrata being a poor colonizer, gene flow between existing populations appeared not highly restricted, especially at the coast. Therefore, to improve the conservation status of B. rostrata, the primary focus should be to preserve and create sufficient habitat for this species to increase the number and quality of (meta)populations, rather than focusing on landscape connectivity itself.

ecology↗

bioRxiv2021

High heritabilities for antibiotic usage show potential to breed for disease resistance in finishing pigs

The use of antimicrobials in animal production is under public debate, mainly due to the risk of transfer of resistance to pathogenic bacteria in humans. Therefore, measures have been taken during the last decades to reduce antibiotic usage in animals, for instance by national monitoring programmes and by improving animal health management. Although some initiatives exist in molecular genetic selection, quantitative genetic selection of animals towards decreased antibiotic usage is an underexplored area to reduce antibiotic usage. However, this strategy could yield cumulative effects. In this study we derived new phenotypes from on-farm parenteral antibiotic records from commercially grown crossbred finishing pigs used in the progeny test of Pietrain terminal sires to investigate the heritability of antibiotics usage. Parenteral antibiotic records, production parameters and pedigree records of 2238 fullsib pens from two experimental farms in Belgium between 2014 and 2020 were analysed. Heritability estimates were moderate (18-44%) for phenotypes derived from all antibiotic treatments, and low (1-15%) for phenotypes derived from treatments against respiratory diseases only. Moreover, genetic correlations between these new phenotypes and mortality were low to moderate (0.08-0.60) and no strong adverse genetic correlations with production traits were found. The high heritabilities and favourable genetic correlations suggest these new phenotypes derived from on-farm antibiotics records to be promising for inclusion in future pig breeding programs to breed for a decrease in antibiotics usage.

genetics↗

bioRxiv2019

A generic approach for studying the kinetics of liquid-liquid phase separation under near-native conditions

Understanding the kinetics and underlying physicochemical forces of liquid-liquid phase separation (LLPS) is of paramount importance in cell biology, requiring reproducible methods for the analysis of often severely aggregation-prone proteins. Frequently applied approaches, such as dilution of the protein from an urea-containing solution or cleavage of its fused solubility tag, however, often lead to very different kinetic behaviors. Here we suggest that at extreme pH values even proteins such as the low-complexity domain (LCD) of hnRNPA2, TDP-43, and NUP-98 can be kept in solution, and then their LLPS can be induced by a jump to native pH, resulting in a system that can be easily controlled. This approach represents a generic method for studying LLPS under near native conditions, providing a platform for studying the phase-separation behavior of diverse proteins.

molecular biology↗