Biology subjects

van Veen, S.

Publications and source records attributed to van Veen, S..

4 recordsLinked to original sources

bioRxiv2024

Proteomic And Transcriptomic Host Biomarkers For Detection Of Pleural Tuberculosis

Current diagnosis of pleural tuberculosis (PLTB) is based on highly invasive procedures. Therefore, blood-based host biomarkers could represent a low-invasive diagnostic alternative. Plasma and pleural effusion, as well as blood-and pleural fluid mononuclear cells (PBMCs and PFMCs), were sampled from patients with PLTB and other pleural diseases (OPLDs). In pleural effusion, ApoA1, C1q, CRP, IL-6, IFN-{gamma}, IP-10, MIG, S100A12, SAA1/A2, and serpin-A3 were significantly higher in PLTB compared to OPLD, whereas only SAA1/A2 showed discriminatory potential in plasma. Increased mRNA levels were observed in PFMCs of PLTB for CD8A, GBP5, SLAMF7, CXCL10, IL2, GNLY, IL23A, PDCD1 and BCMA, whereas HMOX1, CD163, DUSP3, IGF1, GUSB and MARCO were decreased. In PBMCs of PLTB, only CCL22 expression was decreased. GBP5 was significantly higher expressed in PLTB for both cell types. This study shows the potential of transcriptomic and proteomic host biomarkers to differentiate PLTB from OPLDs also when applying low-invasive methods.

microbiology↗

bioRxiv2024

nanoFeatures: a cross-platform application to characterize nanoparticles from super-resolution microscopy images

Super-resolution microscopy and Single-Molecule Localization Microscopy (SMLM) are a powerful tool to characterize synthetic nanomaterials used for many applications such as drug delivery. In the last decade, imaging techniques like STORM, PALM, and PAINT have been used to study nanoparticle size, structure, and composition. While imaging has progressed significantly, often image analysis did not follow accordingly and many studies are limited to qualitative and semi-quantitative analysis. Therefore, it is imperative to have a robust and accurate method to analyze SMLM images of nanoparticles and extract quantitative features from them. Here we introduce nanoFeatures, a cross-platform Matlab-based app for the automatic and quantitative analysis of super-resolution images. nanoFeatures makes use of clustering algorithms to identify nanoparticles from the raw data (localization list) and extract quantitative information about size, shape, and molecular abundance at the single-particle and single-molecule levels. Moreover, it applies a series of quality controls, increasing data quality and avoiding artifacts. nanoFeatures, thanks to its intuitive interface is also accessible to non-experts and will facilitate analysis of super-resolution microscopy for materials scientists and nanotechnologies. This easy accessibility to expansive feature characterization at the single particle level will bring us one step closer to understanding the relationship between nanostructure features and their efficiency. https://github.com/n4nlab/nanoFeatures

bioinformatics↗

bioRxiv2023

ATP13A4 upregulation drives the elevated polyamine transport system in the breast cancer cell line MCF7

Polyamine homeostasis is disturbed in several human diseases, including cancer, which is hallmarked by increased intracellular polyamine levels and an upregulated polyamine transport system (PTS). So far, the polyamine transporters contributing to the elevated levels of polyamines in cancer cells have not yet been described, despite the fact that polyamine transport inhibitors are considered for cancer therapy. Here, we tested whether upregulation of candidate polyamine transporters of the P5B- transport ATPase family is responsible for the increased PTS in the well-studied breast cancer cell line MCF7 compared to the non-tumorigenic epithelial breast cell line MCF10A. We found that MCF7 cells present elevated expression of a previously uncharacterized P5B-ATPase ATP13A4, which is responsible for the elevated polyamine uptake activity. Furthermore, MCF7 cells are more sensitive to polyamine cytotoxicity, as demonstrated by cell viability, cell death and clonogenic assays. Importantly, overexpression of ATP13A4 WT in MCF10A cells induces a MCF7 polyamine phenotype, with significantly higher uptake of BODIPY-labelled polyamines and increased sensitivity to polyamine toxicity. In conclusion, we establish ATP13A4 as a new polyamine transporter in the human PTS and show that ATP13A4 may play a major role in the increased polyamine uptake of breast cancer cells. ATP13A4 therefore emerges as a candidate therapeutic target for anticancer drugs that block the PTS.

cell biology↗

bioRxiv2021

Repurposing diphenylbutylpiperidine-class antipsychotic drugs for host-directed therapy of Mycobacterium tuberculosis and Salmonella enterica infections

The persistent increase of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) infections negatively impacts Tuberculosis (TB) treatment outcomes. Host-directed therapies (HDT) pose an complementing strategy, particularly since Mtb is highly successful in evading host-defense by manipulating host-signaling pathways. Here, we screened a library containing autophagy-modulating compounds for their ability to inhibit intracellular Mtb-bacteria. Several active compounds were identified, including two drugs of the diphenylbutylpiperidine-class, Fluspirilene and Pimozide, commonly used as antipsychotics. Both molecules inhibited intracellular Mtb in pro- as well as anti-inflammatory primary human macrophages in a host-directed manner and synergized with conventional anti-bacterials. Importantly, these inhibitory effects extended to MDR-Mtb strains and the unrelated intracellular pathogen, Salmonella enterica serovar Typhimurium (Stm). Mechanistically Fluspirilene and Pimozide were shown to regulate autophagy and alter the lysosomal response, partly correlating with increased bacterial localization to autophago(lyso)somes. Pimozides and Fluspirilenes efficacy was inhibited by antioxidants, suggesting involvement of the oxidative-stress response in Mtb growth control. Furthermore, Fluspirilene and especially Pimozide counteracted Mtb-induced STAT5 phosphorylation, thereby reducing Mtb phagosome-localized CISH that promotes phagosomal acidification. In conclusion, two approved antipsychotic drugs, Pimozide and Fluspirilene, constitute highly promising and rapidly translatable candidates for HDT against Mtb and Stm and act by modulating the autophagic/lysosomal response by multiple mechanisms.

immunology↗