Biology subjects

de Jong, C.

Publications and source records attributed to de Jong, C..

4 recordsLinked to original sources

bioRxiv2026

Stromal innervation is prognostic in non-muscle-invasive bladder cancer and predicted by a distinct microenvironmental transcriptomic signature

Peripheral nerves are increasingly recognized as active components of the tumor microenvironment (TME). Yet, their role in non-muscle-invasive bladder cancer (NMIBC) and response to Bacillus Calmette-Guerin (BCG) remains poorly defined. Using multispectral imaging, we characterized autonomic and sensory nerve populations within the tumor-adjacent stroma of 241 treatment-naive high-risk NMIBC tumor regions from 141 patients. Stromal tumor-associated nerve (STaN) abundance varied substantially across patients and was associated with aggressive clinicopathological features, BCG failure, and disease progression. Unsupervised clustering resolved distinct STaN phenotypic groups with differential clinical and spatial associations. Noradrenergic and a neurochemically heterogeneous STaN populations showed the strongest associations with adverse outcomes. In contrast, a mixed population of nerves with high expression of the synaptic vesicle protein synaptophysin exhibited prominent spatial remodeling associated with BCG failure, despite limited prognostic value by abundance alone. Integration with an independent single-cell atlas nominated cancer-associated fibroblasts and mast cells as candidate cellular intermediaries of neural communication within the TME. Matched transcriptomic profiling revealed coordinated neuronal, extracellular matrix, lipid metabolism, and immune programs in STaN-high tumors, whereas STaN-low tumors preferentially enriched proliferative and hypoxic stress-response pathways. Leveraging these transcriptional features, we developed a transcriptomic classifier that distinguished STaN-high from STaN-low tumors in an independent test cohort (AUC = 0.87) and stratified clinical outcomes in additional patient cohorts. Together, these findings establish tumor innervation as a heterogeneous and clinically relevant feature of the NMIBC microenvironment, with neural abundance, phenotype, and spatial organization capturing distinct aspects of tumor behavior and clinical outcome.

cancer biology↗

bioRxiv2025

Lipid nanoparticle supplementation enhances host metabolism in a model symbiotic cnidarian

Stable cnidarian-dinoflagellate symbiosis provides the trophic foundation of coral reef ecosystems. Understanding nutrient exchange underpinning this symbiosis grows increasingly urgent as reefs face accelerating threats from climate change, and the need for time-critical interventions to improve coral health via aquaculture. Lipid nanoparticles (LNPs), widely used as delivery vehicles in biomedical science, are emerging as a promising tool to supplement coral nutrition. However, physiological impacts of LNPs on cnidarians, including uptake, nutritional value, and holobiont response, remain largely unexplored. Here, we delivered empty, phosphatidylcholine LNPs to both symbiotic and aposymbiotic Exaiptasia diaphana, an anemone model for corals, and analyzed the host proteomic response via mass spectrometry. LNP supplementation elicited broad proteome shifts, with notable overlap between symbiosis- and LNP-induced protein expression. Proteins involved in lipid catabolism, lipid transport, {beta}-oxidation, lysosomal function, and protein translation were significantly more abundant, consistent with enhanced lipid processing and metabolic activity. LNP supplementation, like symbiosis, suppressed both asexual reproduction and the expression of a suite of predation- and digestion-associated venom proteins and proteases, suggesting a conserved "sated" phenotype in response to lipid supply. Variations in feeding frequency with Artemia had minimal impact, indicating that LNPs can be a robust supplement irrespective of primary feeding regime. These data demonstrate that adult Exaiptasia are capable of direct uptake of LNPs, offering a tool for probing lipid metabolism, signaling and symbiotic function in cnidarians. Moreover, the ability to manipulate host physiology using defined lipid formulations holds significant potential for advancing coral aquaculture stress resilience, including reef restoration strategies.

zoology↗

bioRxiv2023

Sentinels for future coral reef conditions: assessment of environmental variability and water quality in semi-enclosed inland bays in the southern Caribbean

The mangrove-seagrass-coral reef continuum is of immense ecological and socio-economic importance, supporting biodiversity, carbon storage, coastal protection, fisheries, and tourism. The presence of extreme environmental conditions along this continuum could support adaptive refugia for climate-sensitive taxa such as reef-building corals but physicochemical conditions are rarely assessed at sufficient spatiotemporal resolution. Furthermore, coastal development and low water quality increasingly threaten these interconnected coastal ecosystems. Yet, time-integrated pollution monitoring is absent at most locations. Here, we used a multi-disciplinary approach to assess benthic cover, coral diversity, and >20 abiotic parameters characterizing two mangrove- and seagrass-dominated inland bays and two nearby coral reefs in Curacao (southern Caribbean) during the cool, dry season and warm, wet season. This was combined with time-integrated pollution monitoring using bioindicators to assess nutrients and trace metal pollution (inland bays only), and passive samplers and bioassays to assess organic chemical pollution (all four sites) during the wet season. This approach revealed a previously undocumented extent of strong diel and seasonal environmental variability in the two inland bays, with temperature, pH and dissolved oxygen frequently reaching values predicted under moderate-to-severe future climate scenarios. In addition, the inland bays had greater nutrient concentrations (especially ammonium) and ecotoxicological risks than the nearby reefs during the wet season due to run-off, industrial- and wastewater effluents, ports and boating. Overall, our findings show that Curacaos inland bays have significant potential to serve as natural laboratories to study the effects of future ocean conditions on resident taxa in situ. This however applies within the context of strong diel fluctuations and with the caveat of co-occurring stressors. Our work confirms the important role of mangrove and seagrass habitats as resilience hotspots for climate-sensitive taxa but also highlights the urgent need to improve monitoring, water quality and protection of these valuable habitats along the mangrove-seagrass-coral reef continuum.

ecology↗

bioRxiv2018

Spirometric indices in primary ciliary dyskinesia: systematic review and meta-analysis

Primary ciliary dyskinesia (PCD) is a genetic, heterogeneous disease caused by dysfunction of cilia. Evidence is sparse and reports of lung function of PCD patients ranges from normal to severe impairment. This systematic review and meta-analysis of studies of lung function of PCD patients examines the spirometric indices of PCD patients and differences by age group and sex.\n\nWe searched PubMed, Embase, and Scopus for studies that described lung function in [≥]10 patients with PCD. We performed meta-analyses and metaregression to explain heterogeneity. We included 24 studies, ranging from 13-158 patients per study. The most commonly reported spirometric indices were forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) presented as mean and standard deviation of percent of predicted values. We found considerable heterogeneity for both parameters (I2 range 94-96%). The heterogeneity remained when we stratified the analysis by age; however, FEV1 in adult patients was lower. Even after taking into account explanatory factors, the largest part of the between-studies variance remained unexplained. Heterogeneity could be explained by genetic differences between study populations, methodological factors related to the variability of study inclusion criteria, or details on the performance and evaluation of lung function measurements that we could not account for. Prospective studies therefore need to use standardised protocols and international reference values. These results underline the possibility of distinct PCD phenotypes as in other chronic respiratory diseases. Detailed characterisation of these phenotypes and related genotypes is needed in order to better understand the natural history of PCD.

epidemiology↗