Biology subjects

Visser, M.

Publications and source records attributed to Visser, M..

15 recordsLinked to original sources

bioRxiv2026

Covalent Solvatochromic Membrane Probe for Sensing Lipid Surrounding of Proteins

Plasma membranes (PM) have been traditionally studied by fluorescent probes by either labelling lipid or protein parts. Based on our MemGraft concept, we report a fluorescent probe based on solvatochromic dye Nile Red (MemGraft-NR) for sensing lipid organization in the immediate surrounding of proteins, i.e. at the protein-lipid interface. Two sequentially attached MemGraft scaffolds are required to ensure robust grafting of Nile Red to PM. In contrast to classical lipid-bound membrane probes, MemGraft-NR exhibits high resistance to the presence of serum and fixation with permeabilization. Two-color confocal imaging of MemGraft-NR in live cells reveals higher polarity at the protein-lipid interface compared to lipid-bound probe NR12A. Surprisingly, MemGraft-NR displays higher sensitivity to variation of cholesterol content in PM compared to NR12A, suggesting that protein-lipid interface is particularly impacted by changes in the lipid composition. MemGraft-NR also enabled in situ monitoring of lipid exchange and permeabilization of PM, something impossible for classical solvatochromic PM probes. Unexpectedly, MemGraft-NR reveals a dramatic decrease in the local polarity in early endosomes, suggesting that endosomal negative curvature provides strong impact on organization of the protein-lipid interface. The developed probe opens a new way to study biological membranes by sensing lipid surrounding of membrane proteins.

biochemistry↗

bioRxiv2026

City and forest great tits respond differently to artificial light at night: insights from a common garden study

Artificial light at night (ALAN) disrupts the natural light-dark cycle, which is the most important cue for synchronizing circadian clocks. If populations most exposed to ALAN adapt to get less disturbed by it, we expect forest and city populations to differ genetically. We tested this prediction in a common garden experiment using a songbird, the great tit (Parus major), originating from forest and city populations. We simulated ALAN exposure during the breeding season by keeping the birds in pairs under ALAN or dark nights for three months and then repeated the experiment in the following year with the same pairs under the opposite treatment. The advancement of daily onset under ALAN disappeared over time for city birds, but not for their forest counterparts. For these same birds, we measured their onset of daily activity under constant dim light and shift in activity in response to light pulses and showed that the city/forest difference in behavioural response was not reflected in any clock property measured. This indicates that city and forest birds differ genetically in the downstream behavioural response to ALAN, and not in the circadian clock. Thus, urbanization is unlikely to select for divergence in circadian clock properties in songbirds.

evolutionary biology↗

bioRxiv2026

Diurnal rhythmicity modulates self-blaming behaviours and neural processing of autobiographical guilt memories in the trait-like and state-like manner

Increasing evidence implicates late chronotype and higher distinctness as two diurnal dimensions associated with a risk for affective dysregulation. Nonetheless, the underlying behavioural and neural mechanisms remain poorly understood. Previous works in depressive and anxious populations have demonstrated an important role of maladaptive self-blaming processes, with pivotal contributions from superior anterior temporal lobes (sATL), involved in social conceptual knowledge, and subgenual anterior cingulate cortex (sgACC), related to self-worth and social affiliative processing. In the current study, we first tested how diurnal rhythm characteristics were associated with self-blaming emotions and related coping mechanisms through hypothetical social scenarios where participants or their close friends acted towards one another against social norms. Secondly, to probe alterations in the neural correlates of self-blaming, the participants underwent functional neuroimaging during reliving of autobiographical guilt memories. On the behavioural level, late chronotypes demonstrated decreased self-distancing and contextually-maladaptive blaming patterns, i.e. increased blaming of the action recipients rather than the agents. This was paralleled by decreased self-blame-related activity in the sATL and sgACC. Distinctness was associated with altered task-dependent sATL connectivity with hippocampus, brainstem and cerebellum. Importantly, some of the neuroimaging findings reflected interactions between the diurnal rhythm characteristics and time-of-day. As such, the current work provides plausible correlates of adverse emotional outcomes in late chronotypes. Furthermore, it suggests that affective processing reflects an interplay between stable trait-like characteristics and dynamic state-like processes varying across the day, contributing to fine-grained understanding of how emotional cognition is embedded in the brain.

neuroscience↗

bioRxiv2026

Neutrophil-Derived Oncostatin M Contributes to Endothelial Cell Dysfunction During Treponema denticola interaction

Periodontitis (PD) is a common chronic inflammatory condition and a risk factor for cardiovascular diseases (CVD), yet underlying linking mechanisms remain unclear. The cytokine Oncostain M (OSM) is elevated in both PD and CVD and has emerged as a potential mediator linking oral inflammation to vascular dysfunction. Neutrophils represent a prominent source of OSM during PD and OSM production is elevated by the periodontal pathobiont Treponema denticola (Td). This study investigated the role of exogenous and neutrophil-derived OSM in endothelial cell (EC) dysfunction and the contribution of heterogenous oral Treponema species in OSM production. Human aortic endothelial cells (HAoEC) were used to evaluate the effects of exogenous purified OSM and neutrophil-derived OSM on endothelial cell function. Endothelial permeability, neutrophil transmigration, cytokine production, cell activation and junctional integrity were assessed using transwell assays, ELISAs, real-time PCR, immunoblotting and immunofluorescence microscopy. Exogenous OSM significantly increased HAoEC permeability, neutrophil transmigration and promoted endothelial activation; characterized by increased E-selectin, ICAM-1 and IL-6 expression. Mechanistically, OSM activated OSMR-STAT3 signaling and altered organization of VE-cadherin in adherens junctions and decreased expression of occludin in tight-junctions. Heterogenous oral Treponema species promote OSM production from mouse and human neutrophils in vitro and in vivo using a mouse air pouch model of infection. T. denticola most robustly induced OSM release, likely independent of prominent virulence factors dentilisin and Msp. Co-culture model experiments revealed conditioned media from T. denticola-stimulated neutrophils promoted endothelial cell permeability and IL-6 while reducing endothelial nitric oxide synthase (eNOS) production. These effects were abolished by antibody neutralization of OSM, supporting a casual role of neutrophil-derived OSM. Overall, these findings provide mechanistic insight into putative links between PD and adverse cardiovascular events and identify OSM signaling as critical mediator in inflammation-driven endothelial dysfunction.

microbiology↗

bioRxiv2025

Additive effects of environmental and demographic variation shape the repeatability of evolution across replicated experiments

The repeatability of evolution is fundamentally important for understanding the origin and diversification of life as well as for developing evolutionary forecasting tools. Repeatability is limited by stochasticity, here defined as changes that are independent of genotypic fitness effects. Over short timescales, the two main sources of stochasticity of evolutionary change are environmental stochasticity and demographic (life-history) stochasticity. Quantifying the relative importance of these two sources of stochasticity in driving fitness outcomes is crucially important for predicting evolutionary responses. To gain insights in the effects of stochasticity, five institutes replicated an evolutionary experiment exposing Caenorhabditis elegans to novel rearing conditions. Replication across the institutes led to variation in selective environments, e.g. through divergent microbiomes among institutes. Replication within institutes was done across demographic treatments that influence the potential for population-size dependent fluctuations in allele frequencies (drift) and genetic hitchhiking (draft). We found high among-institute variation in fitness outcomes, which was partially explained by variation in microbiota. Whereas lab-specific effects explained most of the variance in mean fitness, the repeatability of fitness outcomes depended more on demographic heterogeneity. Specifically, population bottlenecks resulted in high among-replicate variation in fitness. When combined, environmental and demographic stochasticity additively reduced repeatability, underlining their additive importance in developing evolutionary forecasting tools. These results further highlight the importance of statistically integrating heterogeneity in experimental evolution to identify factors constraining outcome repeatability and study replicability.

evolutionary biology↗

bioRxiv2025

Subclinical anxiety is associated with reduced self-distancing and enhanced guilt-related connectivity between anterior temporal and subgenual cingulate cortices

Excessive self-blaming emotions are commonly observed in anxiety disorders, with qualitatively similar symptomatology reported in subclinical populations. Interpretation of moral information requires assessing the social conceptual information, a process overseen by the superior anterior temporal lobe (sATL). Feelings of self-blame evoke interactions of sATL and socio-affective regions, and previous research shows that subclinical anxiety modulates the organisation of the self-blame circuitry. This study aimed to extend these findings by exploring links of trait-anxiety with (i) self-blaming emotions and associated behaviours in an experimental task, and (ii) self-blame-dependent neural activity and connectivity, as observed during reliving of autobiographical guilt memories. We also explored the role of resting-state fMRI in linking these phenomena. Increased anxiety was linked to stronger self-blaming emotions, and more pronounced self-attacking and hiding. When experiencing negative emotions about themselves (i.e. shame and self-anger), anxious individuals were also less likely to disengage from self-focused thoughts. These behavioural findings were paralleled by enhanced self-blame-related connectivity between the left sATL and bilateral posterior subgenual cingulate cortex. Distinct patterns of activity and connectivity within the ATL-related circuitry were furthermore linked to individual differences in intensity of the self-blaming emotions and approach-avoidance motivation towards the guilt memories. As such, the results of the current study link stronger self-blaming emotions in anxious individuals with specific maladaptive patterns of behaviour. Furthermore, the work provides robust evidence for the important role of ATL-related circuitry in self-blame processing, supporting its broader involvement in social conceptual processing and its alterations in subclinical anxiety.

neuroscience↗

bioRxiv2025

Socio-emotional difficulties observed in alexithymia reflect altered interactions of the semantic and monoaminergic neuromodulatory brain networks

Alexithymia is a multidimensional construct characterized by difficulties in identifying and describing feelings and reduced ability to engage in abstract thinking. Although often co-occurring with other psychological and neurodevelopmental conditions such as anxiety, depression and autism spectrum disorders, alexithymia is believed to be associated with unique alterations within the socio-emotional brain networks. With the semantic and neuromodulatory brainstem systems playing a key role in social and affective cognition, the current work aimed to study their contributions to alexithymia in unprecedented detail. First, we attempted to identify resting-state functional connectivity patterns of the social semantic hubs (superior anterior temporal lobe) and monoamine-producing regions (dorsal raphe, ventral tegmental area and locus coeruleus) linked to each alexithymia domain. Secondly, by deploying tractography and graph analysis of the associated structural network, we intended to identify their potential anatomical correlates. Alexithymia was strongly associated with dysconnectivity within the semantic network, and altered functional connectivity between the neuromodulatory brainstem regions and cortical areas crucial for social cognition and emotion regulation, including medial prefrontal cortex and inferior parietal lobule. On the anatomical level, these findings were paralleled by negative links with network modularity, suggestive of less specialised neural processing, and decreased clustering coefficient of the semantic node in the left posterior middle temporal gyrus. Despite observing associations with trait-anxiety and emotion suppression for some of the highlighted findings, these phenomena did not mediate the effects of alexithymia. Therefore, the current work highlights the existence of functional and structural alterations within socio-emotional networks as neural markers of alexithymia.

neuroscience↗

bioRxiv2025

Size in the city: morphological differences between city and forest great tits have a genetic basis

Animals living in cities are smaller than their conspecifics from rural areas but whether such differences are caused by genetic differences or food constraints remains untested. We performed a multi-generation common garden study where we raised great tits (Parus major), originating from eggs collected from multiple Dutch cities and forests under the same conditions for two generations. Offspring from city birds had a smaller tarsus than forest birds in both generations, demonstrating that these morphological differences are genetic. Next, we tested whether size differences are an adaptation to the low food abundance when offspring are raised in the city. Third generation birds of both origins were given food amounts mimicking being raised in forests or cities during the second part of their nestling development. While the treatment resulted in birds in the lower feeding frequency treatment to be smaller, city and forest birds responded the same way, suggesting that city birds do not cope better with reduced food availability. Our study shows that the smaller size of urban birds has a genetic basis and is not only caused by a plastic response to restricted resources in the urban environment. Our experiment does not provide evidence that these genetic differences have evolved as an adaptive response to a reduced food availability in cities.

evolutionary biology↗

bioRxiv2025

Subjective sleep quality in healthy young adults moderates associations of sensitivity to punishment and reward with functional connectivity of regions relevant for insomnia disorder

Chronic unhealthy sleeping behaviours are a major risk factor for the emergence of mood and anxiety disorders. Nevertheless, we are still lacking understanding why some individuals are more prone than others to affective dysregulation caused by sleep disruption. With preliminary evidence suggesting that brain activity during positive and negative emotional processing might play an important modulating role, we conducted whole-brain resting-state functional connectivity analyses in a large cohort of healthy young adults (N = 155). Using regions consistently affected in insomnia disorder as seeds, we investigated sleep quality-related neural connectivity patterns that were both insensitive and sensitive to the interactions with individual measures of reward and punishment processing, additionally assessing the links with indices of emotional health. The majority of the findings reflected interactions between sleep quality and reinforcement sensitivity, with the opposite associations reported in the good and poor sleepers. One of such connections, the coupling between precentral gyrus and posterior insula, was additionally negatively linked to trait anxiety, with the lowest connectivity values observed in poor sleepers with higher sensitivity to punishment. In turn, the only finding associated solely with sleep quality, i.e. coupling between subgenual anterior cingulate cortex and thalamus, was also related to the habitual use of emotion suppression strategies. As such, the present study provides evidence that reinforcement sensitivity plays an essential role in understanding the associations of poor sleep quality with brain connectivity and emotional health, hinting at a potential link that may help explain individual differences in susceptibility to sleep-related affective dysregulation. HighlightsO_LIFunctional connectivity of insomnia-related brain regions is altered in poor sleepers C_LIO_LISleep quality interacts with reinforcement sensitivity for most of such effects C_LIO_LIDistinct sleep-related mechanisms are linked to trait anxiety and emotion suppression C_LIO_LIPoor sleep and high punishment sensitivity increase the risk of affect dysregulation. C_LI

neuroscience↗

bioRxiv2024

Rapid fluctuations in histamine associated with intake of nutritive and non-nutritive solutions

The neurotransmitter histamine is involved in control of food intake, yet its dynamics during individual feeding episodes remain unexplored. Therefore, we used the novel genetically-encoded histamine sensor, HisLightG, combined with fiber photometry to measure histamine release in two hypothalamic regions critical for the food-suppressive effects of histamine, the paraventricular nucleus of the hypothalamus (PVH), and the ventromedial hypothalamus (VMH). Male mice were tested under different conditions to assess whether hunger, time of day, or the caloric content of the solution they were given affected histamine fluctuations. We found that histamine levels changed rapidly in response to eating. These histamine fluctuations were influenced by experimental conditions, with slightly smaller responses when the test solution was sucralose (both regions) or during the light cycle (PVH only). Notable regional differences were identified, such that in the PVH histamine rebounded to baseline levels, whereas in the VMH histamine remained lower than baseline for at least 10 seconds after licking ceased. In a separate cohort of male and female mice, enhancing histamine tone via administration of a histamine precursor (L-histidine) reduced the number of licks across multiple sucrose concentrations. Together, these findings indicate that histaminergic activity is modulated rapidly during ingestive episodes, and that understanding these release patterns will give insight into histamines role in appetite suppression.

neuroscience↗

bioRxiv2024

Noradrenergic and Dopaminergic Neural Correlates of Trait Anxiety: Unveiling the Impact of Maladaptive Emotion Regulation

BackgroundMaladaptive emotion regulation plays a crucial role in the development and maintenance of elevated anxiety levels, both in patients and in individuals with subclinical symptomatology. While pharmacological treatments for anxiety target the emotion dysregulation through dopaminergic, noradrenergic and serotonergic systems, little is known about the underlying mechanisms. Therefore, the current study depicts the association of these neuromodulatory systems resting-state functioning with trait-anxiety, investigating the role of maladaptive emotion regulation. MethodsAmplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and whole-brain resting-state functional connectivity (rs-FC) were obtained from the ventral tegmental area (VTA), locus coeruleus (LC) and dorsal raphe, and correlated with trait-anxiety and self-reported maladaptive emotion regulation (N = 60). ResultsTrait-anxiety was positively associated with LCs fALFF and negatively with VTAs whole-brain rs-FC with the left inferior parietal lobule (L-IPL) and the left superior frontal gyrus (L-SFG). Maladaptive emotion regulation was negatively associated with VTAs rs-FC with these regions, with trait-anxiety fully mediating this association. VTA connectivity with the frontal region, but not parietal, positively predicted its amplitude of neural oscillations, an effect that was paralleled by stronger frontal dopaminergic innervation. LimitationsUse of external molecular datasets and need for replication in patients. ConclusionsNoradrenergic and dopaminergic systems appear to contribute differently to subclinical anxiety. While noradrenaline likely acts through a more general mechanism, the dopaminergic dysconnectivity with the frontoparietal control network may act as one of the mechanisms of maladaptive emotion regulation, informing the models on the disorder development. HighlightsO_LITrait-anxiety shows a positive association with the activity of locus coeruleus C_LIO_LITrait-anxiety and emotional regulation are linked to VTA-frontoparietal connectivity C_LIO_LITrait-anxiety fully mediates emotion regulations effect on VTAs connectivity C_LIO_LIStrength of connectivity with VTA is positively linked to the frontal ALFF and fALFF C_LI

neuroscience↗

bioRxiv2024

Graph analysis of the guilt network highlights associations with subclinical anxiety and self-blame

Maladaptive forms of guilt, such as excessive self-blame, are common characteristics of anxiety disorders. The associated network includes the superior anterior temporal lobe (sATL), underlying the conceptual representations of social meaning, and fronto-subcortical areas involved in the affective dimension of guilt. Nevertheless, despite understanding the anatomy of the guilt processing circuitry, network-level changes related to subclinical anxiety and self-blaming behaviour have not been depicted. To fill this gap, we used graph theory analyses on a resting-state functional and diffusion-weighted magnetic resonance imaging dataset of 78 healthy adults. Within the guilt network, we found increased functional contributions (higher clustering coefficient, local efficiency and strength) of the left sATL for individuals with higher self-blaming and trait-anxiety, while functional isolation (lower clustering coefficient and local efficiency) of the left pars opercularis and insula was related to higher trait-anxiety. Trait-anxiety was also linked to the structural networks global parameters (mean clustering coefficient), with the circuitrys architecture favouring increased local information processing in individuals with increased anxiety levels. Previous research suggests that aberrant interactions between conceptual (sATL) and affective (fronto-limbic) regions underlie maladaptive guilt and the current results align and expand on this theory by detailing network changes associated with self-blame and trait-anxiety.

neuroscience↗

bioRxiv2021

Population genetic bottleneck has only marginal effects on fitness evolution and its repeatability in dioecious C. elegans

The predictability of evolution is expected to depend on the relative contribution of deterministic and stochastic processes. This ratio is modulated by effective population size. Smaller effective populations harbor less genetic diversity and stochastic processes are generally expected to play a larger role, leading to less repeatable evolutionary trajectories. Empirical insight into the relationship between effective population size and repeatability is limited and focused mostly on asexual organisms. Here, we tested whether fitness evolution was less repeatable after a population bottleneck in obligately outcrossing populations of Caenorhabditis elegans. Replicated populations founded by 500, 50, or 5 individuals (no/moderate/strong bottleneck) were exposed to a novel environment with a different bacterial prey. As a proxy for fitness, population size was measured after one week of growth before and after 15 weeks of evolution. Surprisingly, we found no significant differences among treatments in their fitness evolution. Even though the strong bottleneck reduced the relative contribution of selection to fitness variation, this did not translate to a significant reduction in the repeatability of fitness evolution. Thus, although a bottleneck reduced the contribution of deterministic processes, we conclude that the predictability of evolution may not universally depend on effective population size, especially in sexual organisms.

evolutionary biology↗

bioRxiv2020

Artificial light at night shifts the circadian system but still leads to physiological disruption in a wild bird

Globally increasing levels of artificial light at night (ALAN) are associated with shifts in circadian rhythms of behaviour in many wild species. However, it is still unclear whether changes in behavioural timing are underlined by parallel shifts in the molecular clock, and whether such internal shifts may differ between different tissues and physiological pathways, which could highlight circadian disruption. We tackled these questions in a comprehensive study that integrated behavioural, gene expression and metabolomic analyses. We exposed captive male great tits (Parus major) to three ALAN intensities or to dark nights, recorded their activity rhythms and obtained mid-day and midnight samples of brain, liver, spleen and blood. ALAN advanced wake-up time, and this shift was paralleled by an advance in the expression of the clock gene BMAL1 in all tissues, suggesting close links of brain and peripheral clock gene expression with activity rhythms. However, several metabolic and immune genes were desynchronised the shifted BMAL1 expression, suggesting circadian disruption of behaviour and physiology. This result was reinforced by untargeted metabolomic profiling, which showed that only 9.7% of the 755 analysed metabolites followed the behavioural shift. We suggest circadian as a key mediator of the health impacts of ALAN on wild animals.

zoology↗

bioRxiv2020

Real-time tracking of Tomato brown rugose fruit virus (ToBRFV) outbreaks in the Netherlands using Nextstrain

Tomato brown rugose fruit virus (ToBRFV) is a Tobamovirus that was first observed in 2014 and 2015 on tomato plants in Israel and Jordan causing discolorations and deformation of leaves and fruits. Apart from tomato, damage in pepper fruits has been reported. Since the first description, the virus has been found on all continents except Oceania and Antarctica. In October 2019, the Dutch National Plant Protection Organization received a tomato sample suspected to be infected with ToBRFV as part of an official specific survey of tomato fruit growers in the Netherlands carried out July to October 2019. During the survey 124 companies were visited and inspected for possible ToBRFV symptoms. Of the 47 samples tested, one sample tested positive with ELISA and test plants, which was verified using real-time RT-PCR and Illumina RNAseq data. A follow-up survey was initiated to determine the extent of ToBRFV presence in the Dutch tomato horticulture and identify possible linkages between ToBRFV genotypes, companies and epidemiological traits. We used Nextstrain to visualize these potential connections. Genomic diversity of ToBRFV isolates found in the Netherlands group in three main clusters which are hypothesized to represent three sources. No correlation was found between genotypes, companies and epidemiological traits such as rootstock and scion varieties, seed batches and nurseries, and the source(s) of the Dutch outbreak remain unknown. This paper describes a Nextstrain build containing ToBRFV genomes up to and including November 2019. The NPPO-NL has committed itself to maintain and improve the build. Sharing data with this interactive online tool will enable the regulatory plant virology field to better understand and communicate the diversity and spread of this new virus. Other organizations are stimulated to share data or materials for inclusion in the Nextstrain build, which can be accessed at //40.91.255.14/ToBRFV/20191231.

evolutionary biology↗