Biology subjects

Visser, J.

Publications and source records attributed to Visser, J..

5 recordsLinked to original sources

bioRxiv2025

AAV6-HCN4t-mediated biological pacing as a potential life-saving therapy for congenital complete heart block

Congenital complete heart block (CCHB) is a life-threatening condition in fetuses due to severe bradycardia. Maternal administration of {beta}-adrenergic agonists is used to increase fetal heart rates, but its effectiveness is limited and lost over time most likely due to insufficient expression of HCN channels in some individuals. We report the development of an injectable gene therapy that produces reliable cardiac pacemaker function in the presence of {beta}-adrenergic stimulation. Intramyocardial injection of adeno-associated viral serotype 6 vectors expressing HCN4t (AAV6-HCN4t) into the left ventricular apex significantly increased ectopic pacing frequency and heart rate in response to isoproterenol in rats with complete heart block, and this effect remained stable throughout the 4 weeks of follow-up. Injection of AAV6-HCN4t showed similar reliable biological pacing in complete heart block pigs. These results suggest that AAV6-HCN4t generates robust biological pacing in the presence of isoproterenol, providing the foundation for a potentially life-saving therapy for in utero CCHB.

physiology↗

bioRxiv2024

Unveiling the Functional Connectivity of Astrocytic Networks with AstroNet, a Graph Reconstruction Algorithm Coupled to Image Processing

Astrocytes form extended intercellular networks, displaying complex calcium activity. However, the specific organization of these astrocytic networks and the precise extent of their functional connectivity in different brain areas remain unexplored. To unveil the functional architecture of astrocytic networks, we developed, using a data-driven methodology, a novel algorithm called AstroNet that uses two-photon calcium imaging to map temporal correlations in activation events among neighboring astro-cytes. Our approach involves reconstructing functional astrocytic networks by organizing individual astrocyte activation events chronologically. This chronological order creates activity paths that enable the extraction of local astrocyte functional correlations. Ultimately, by tallying the occurrences of direct co-activations between pairs of cells along these pathways, we construct a graph that mirrors the underlying astrocyte functional network. By applying this method to two distinct brain regions (CA1 hippocampus and motor cortex), we identified notable differences in local network organizations in sub-regions of around 20-40 astrocytes. Specifically, the cortex exhibited a lower connectivity, while astrocytes in the hippocampus displayed stronger connections. Moreover, we found that in both regions, astrocytic networks consist of smaller, tightly connected sub-networks embedded within a larger, more loosely connected one. Altogether, our innovative method enables the identification of activation paths among astrocytes, facilitates the characterization of local network functional connectivity, and quantifies distinct connectivity patterns among astrocytes from different brain regions. This approach sheds light on the heterogeneous functional organization of astrocytic networks within the brain, pointing to region-specific astrocyte connectivity.

neuroscience↗

bioRxiv2024

On the diversity of nematode antagonists in an agricultural soil, and their steerability by root-knot nematode density and cover crops

Plant-parasitic nematodes are harmful pathogens for many agricultural crops. Within this category, root-knot nematodes (RKN, Meloidogyne spp.) are worldwide regarded as the most impactful because of their wide geographical distribution and their polyphagous nature. Host plant resistances against RKN have been successfully introduced in a few crops only. As the use of nematicides is becoming increasingly restricted because of environmental and human health concerns, there is a need for alternative strategies to control RKN. One such approach is the stimulation of local nematode antagonists. We investigated this in an experimental field setting with two main variables: density of the Columbia root-knot nematode Meloidogyne chitwoodi, and the type of cover of crop. For each of the three M. chitwoodi densities, the effects of ten cover crop treatments were tested on both the resident (DNA) and the active (RNA) fractions of the bacterial and fungal communities. In our analyses, we focussed on changes in the abundance of plant-parasitic nematode antagonists. From the eight bacterial and 26 fungal genera known from global literature to harbour potential antagonists of plant-parasitic nematodes, we detected respectively five and 14 genera in our agricultural field. Among the bacterial genera, four included bacterial species for which nematode antagonism has been documented. The fungal genera included facultative nematode parasites (e.g., Arthrobotrys spp.), endophytes strengthening host defences (e.g., Acremonium spp.), as well as multiple obligatory nematophagous species. This study revealed that conventionally managed arable fields may harbour an unexpectedly high diversity of nematode antagonists. Multiple antagonists were stimulated by cover crops in a cover crop-specific manner, and, to a lesser extent, by increased RKN densities. The richness in putative nematode antagonists did not translate into M. chitwoodi suppression probably because most antagonists have a facultative nematophagous lifestyle and will only predate nematodes under poorer nutritional conditions.

ecology↗

bioRxiv2022

Astrocytes in the retinorecipient superior colliculus display unique cellular and structural properties

Astrocytes have long been considered to be a largely homogeneous cell population. Recent studies however suggest that astrocytes are highly adapted to the local neuronal circuitry. Glucose utilization in the retinorecipient superior colliculus (SC) is one of the highest in the brain. Since metabolic support to neurons is a major function of astrocytes, they could be of particular relevance in this region and display specific features. However, little is known about astrocytes and their interactions with neurons in this multisensory brain area. We thus here investigated region-specific cellular and structural properties of astrocytes in the visual layer of the SC. Using morphological reconstructions, fluorescent recovery after photobleaching (FRAP) and superresolution imaging, we found that astrocytes from the visual layers of the SC are highly distinct with a higher cellular density, a more complex morphology and a stronger proximity to synapses compared to astrocytes from the primary visual cortex and the hippocampus. These data point to astroglial diversity and specialization within neural circuits integrating sensory information in the adult brain.

neuroscience↗

bioRxiv2020

Physiological synaptic activity and recognition memory are fueled by astroglial glutamine

Presynaptic glutamate replenishment is fundamental to brain function. In high activity regimes, such as epileptic episodes, this process is thought to rely on the glutamate-glutamine cycle between neurons and astrocytes. However the presence of an astroglial glutamine supply, as well as its functional relevance in vivo in the healthy brain remain controversial, partly due to a lack of tools that can directly examine glutamine transfer. Here, we generated a novel fluorescent probe that tracks glutamine in live cells, which provided direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein with both gap-junction and hemichannel functions, and is essential for synaptic transmission and object recognition memory. Our findings uncover an indispensable recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes.

neuroscience↗