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https://www.selleckchem.com/products/pcna-i1.html Our study suggests possibilities for therapeutic intervention abrogating tissue priming without immunosuppression.A big challenge in natural product research of today is rapid dereplication of already known substances, to free capacities for the exploration of new agents. Prompt information on bioactivities and mode of action (MOA) speeds up the lead discovery process and is required for rational compound optimization. Here, we present a bioreporter approach as a versatile strategy for combined bioactivity- and MOA-informed primary screening for antimicrobials. The approach is suitable for directly probing producer strains grown on agar, without need for initial compound enrichment or purification, and works along the entire purification pipeline with culture supernatants, extracts, fractions, and pure substances. The technology allows for MOA-informed purification to selectively prioritize activities of interest. In combination with high-resolution mass spectrometry, the biosensor panel is an efficient and sensitive tool for compound deconvolution. Concomitant information on the affected metabolic pathway enables the selection of appropriate follow-up assays to elucidate the molecular target.The central pathogen-immune interface in tuberculosis is the granuloma, a complex host immune structure that dictates infection trajectory and physiology. Granuloma macrophages undergo a dramatic transition in which entire epithelial modules are induced and define granuloma architecture. In tuberculosis, relatively little is known about the host signals that trigger this transition. Using the zebrafish-Mycobacterium marinum model, we identify the basis of granuloma macrophage transformation. Single-cell RNA-sequencing analysis of zebrafish granulomas and analysis of Mycobacterium tuberculosis-infected macaques reveal that, even in the presence of robust type 1 immune responses, countervailing type 2 signals associate with macrop

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