Biology subjects

Wesseling, J.

Publications and source records attributed to Wesseling, J..

5 recordsLinked to original sources

bioRxiv2025

Immune responses to human pathogens exposed to simulated Mars conditions

The identification of health risks associated with long-term crewed missions to Mars is critical for mission planning and crew safety. Human-associated pathogens can be part of the microbiome and are likely to be transported during these missions. This study examines the immunological responses of human immune cells stimulated with non-fastidious bacterial species that cause opportunistic infections, i.e. Klebsiella pneumoniae and Serratia marcescens, after exposure to simulated Martian conditions, including UV radiation, desiccation and atmospheric pressure. We observed that exposure of the bacteria to these conditions altered cytokine secretion, reactive oxygen species (ROS) production, and phagocytic activity in human peripheral blood mononuclear cells (PBMCs). Specifically, exposure to desiccation reduced cytokines and ROS production, indicating impaired innate immune recognition and stimulation. Notably, the altered immune response was partially restored when desiccated bacteria were regrown in standard media. Flow cytometry revealed decreased bacterial size and complexity of both species post-exposure. These findings indicate that Martian conditions induce bacterial morphological and physiological changes, which could impair immune recognition and response. Expanding these studies to in vivo models and a broader range of potentially pathogenic microorganisms is essential to estimate infection risks during Mars missions, which is vital for developing strategies to mitigate infection risks and maintain astronaut health during long-term space travel. ImportanceSince Yuri Gagarins 1961 flight, human space exploration has expanded, unintentionally transporting microorganisms, including pathogens, into space environments. Our previous studies demonstrated that opportunistic pathogens like Klebsiella pneumoniae and Serratia marcescens can survive simulated Mars conditions. With upcoming Mars missions, it is crucial to understand how such conditions influence these pathogens and their interaction with the human immune system. This research evaluates immune responses to bacteria pathogens exposed to Martian stressors such as UV radiation and desiccation, revealing significant changes of the immune responses to the exposed bacteria. These findings provide essential insights into the health risks that astronauts may face if infected with Mars-adapted pathogens. Understanding these interactions will help to develop preventive strategies and therapeutic measures, ensuring the safety and health of crew members during long-term missions. Ultimately, this work contributes to the broader objective of safe human exploration and colonization of Mars.

immunology↗

bioRxiv2024

Overlapping role of synaptophysin and synaptogyrin family proteins in determining the small size of synaptic vesicles

Members of the synaptophysin and synaptogyrin family are vesicle proteins with four transmembrane domains. In spite of their abundance in synaptic vesicle (SV) membranes, their role remains elusive and only mild defects at the cellular and organismal level are observed in mice lacking one or more family members. Here, we show that co-expression with synapsin of each of the four brain-enriched members of this family - synaptophysin, synaptoporin, synaptogyrin1 and synaptogyrin3 - in fibroblasts is sufficient to generate clusters of small vesicles in the same size range of SVs. Moreover, mice lacking all these four proteins have larger SVs. We conclude that synaptophysin and synaptogyrin family proteins play an overlapping function in the biogenesis of SVs and in determining their small size.

neuroscience↗

bioRxiv2024

Presynaptic occlusion of long lasting NMDAR-dependent potentiation in Synaptophysin family knockouts

Baseline synaptic strength is elevated in knockouts missing the synaptophysin family of synaptic vesicle proteins because of increased probability of release of release-ready vesicles. Here we show that the longest lasting component of long-term potentiation (LTP) is: (a) eliminated at Schaffer collateral synapses under standard conditions; (b) rescued by reducing extracellular Ca2+ enough to lower baseline synaptic strength to wildtype levels; and, (c) eliminated at wildtype synapses by increasing Ca2+ enough to elevate baseline to knockout levels. Next, an earlier component of LTP, lasting less than 1 hr, was eliminated first at knockouts and then wildtype by elevating baseline further. And, the LTP that was eliminated could be recovered by subsequently reducing extracellular Ca2+ back to the permissive level. In sum, NMDA receptor-dependent LTP maintenance and expression are separable mechanisms at extensively studied Schaffer collateral synapses, and expression of multiple components can be occluded by enhancing the mechanism that catalyzes synaptic vesicle exocytosis from presynaptic terminals.

neuroscience↗

bioRxiv2023

Absence of Lipopolysccharide (LPS) expression in Breast Cancer Cells

The association between bacterial activity and tumorigenesis has gained attention in recent years, alongside the well-established link between viruses and cancer. A recent study proposed the presence of intracellular bacteria in cancer cells, particularly in melanomas and breast cancers, with detectable bacterial DNA. The authors suggested that these bacteria contribute to the tumors development. We sought to replicate these findings using the same experimental methods on different tissue microarrays. Our investigation included 129 breast cancer samples, but we found no evidence of LPS expression within cancer cells. Instead, LPS immunoreactivity was observed in ducts or immune cells, specifically macrophages. The discrepancies in LPS staining warrant caution in interpreting the reported observations, and further research is needed to elucidate the potential role of intracellular bacteria in cancer development.

pathology↗

bioRxiv2020

Parallel processing of quickly and slowly mobilized reserve vesicles in hippocampal synapses

Vesicles within presynaptic terminals are thought to be segregated into a variety of readily releasable and reserve pools. The nature of the pools and trafficking between them is not well understood, but pools that are slow to mobilize when synapses are active are often assumed to feed pools that are mobilized more quickly, in a series. However, electrophysiological studies of synaptic transmission have suggested instead a parallel organization where vesicles within slowly and quickly mobilized reserve pools would separately feed independent reluctant- and fast-releasing subdivisions of the readily releasable pool. Here we use FM-dyes to confirm the existence of multiple reserve pools at hippocampal synapses and a parallel organization that prevents intermixing between the pools, even when stimulation is intense enough to drive exocytosis at the maximum rate. The experiments additionally demonstrate extensive heterogeneity among synapses in the relative sizes of the slowly and quickly mobilized reserve pools, which suggests equivalent heterogeneity in the numbers of reluctant and fast-releasing readily releasable vesicles that may be relevant for understanding information processing and storage.

neuroscience↗