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A series of novel benzotriazole derivatives containing iodine atom(s) were synthesized. The binding of these compounds to the catalytic subunit of human protein kinase CK2 was evaluated using differential scanning fluorimetry. The obtained thermodynamic data were compared with those determined previously for the brominated and chlorinated benzotriazole analogues to get a deeper insight into the thermodynamic contribution of iodine substitution to the free energy of ligand binding. We have shown that iodine atom(s) attached to the benzene ring of benzotriazole enhance(s) its binding by the target protein. This effect is the strongest when two iodine atoms are attached at positions peripheral to the triazole ring, which according to the structures deposited in protein data bank may be indicative for the formation of the halogen bond between iodine and carbonyl groups of residues located in the hinge region of the protein. Finally, quantitative structure-activity relationship analysis pointed the solute hydrophobicity as the main factor contributing to the binding affinity. © 2020 International Union of Biochemistry and Molecular Biology.Development of precision medicine for malignant pleural mesothelioma (MPM) requires a deep knowledge of tumor heterogeneity. Histologic and molecular classifications and histo-molecular gradients have been proposed to describe heterogeneity, but a deeper understanding of gene mutations in the context of MPM heterogeneity is required and the associations between mutations and clinical data need to be refined. We characterized genetic alterations on one of the largest MPM series (266 tumor samples), well annotated with histologic, molecular and clinical data of patients. Targeted next-generation sequencing was performed focusing on the major MPM mutated genes and the TERT promoter. Molecular heterogeneity was characterized using predictors allowing classification of each tumor into the previously described molecular subtypes and the determination of the proportion of epithelioid-like and sarcomatoid-like components (E/S.scores). The mutation frequencies are consistent with literature data, but this study emphasized that TERT promoter, not considered by previous large sequencing studies, was the third locus most affected by mutations in MPM. Mutations in TERT promoter, NF2, and LATS2 were more frequent in nonepithelioid MPM and positively associated with the S.score. BAP1, NF2, TERT promoter, TP53, and SETD2 mutations were enriched in some molecular subtypes. NF2 mutation rate was higher in asbestos unexposed patient. TERT promoter, NF2, and TP53 mutations were associated with a poorer overall survival. Our findings lead to a better characterization of MPM heterogeneity by identifying new significant associations between mutational status and histologic and molecular heterogeneity. Strikingly, we highlight the strong association between new mutations and overall survival. © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.The partial fluorination of polycyclic aromatic hydrocarbons often produces a layered crystal packing, where fluorinated aromatic surfaces are stacked over nonfluorinated aromatic surfaces. Herein, we report the synthesis and crystal packing of partially fluorinated [4]helicenes with steric congestion resulting from H and F atoms in the fjord region. F6-[4]Helicene forms head-to-tail columnar stacks consisting of an alternate arrangement of perfluorinated and nonfluorinated naphthalene moieties. With decreasing fluorine content, aromatic stacking switched from arene-fluoroarene (ArH-ArF) hetero-stacking to ArH-ArH/ArF-ArF homo-stacking with the help of intermolecular C-H···F contacts in the fjord region. As a result, head-to-head columnar stacks appear. Therefore, the conventional ArH-ArF stacking motif is not always applicable to Fn-[4]helicenes with twisted π-surfaces. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Uropathogenic E. coli (UPEC) infection in vivo is characterized by invasion of bladder umbrella epithelial cells followed by endosomal escape and proliferation in the cytoplasm to form intracellular bacterial communities. By contrast, UPEC infection in tissue culture models results in bacteria being trapped within Lamp1-positive endosomes where proliferation is limited. Pharmacological disruption of the actin cytoskeleton has been shown to facilitate UPEC endosomal escape in vitro and extracellular matrix stiffness is a well-characterized physiological regulator of actin dynamics; therefore, we hypothesized that substrate stiffness may play a role in UPEC endosomal escape. Using functionalized polyacrylamide substrates, we found that at physiological stiffness, UPEC escaped the endosome and proliferated rapidly in the cytoplasm of bladder epithelial cells. Dissection of the cytoskeletal signaling pathway demonstrated that inhibition of the Rho GTPase RhoB or its effector PRK1 was sufficient to increase cytoplasmic bacterial growth and that RhoB protein level was significantly reduced at physiological stiffness. Our data suggest that tissue stiffness is a critical regulator of intracellular bacterial growth. Monastrol in vivo Due to the ease of doing genetic and pharmacological manipulations in cell culture, this model system may provide a useful tool for performing mechanistic studies on the intracellular life cycle of uropathogens. © 2020 John Wiley & Sons Ltd.Biotin is an important cofactor for multiple enzymes in central metabolic processes. While many bacteria and most fungi are able to synthesise biotin de novo, Candida spp. are auxotrophic for this vitamin and thus require efficient uptake systems to facilitate biotin acquisition during infection. Here we show that Candida glabrata and Candida albicans use a largely conserved system for biotin uptake and regulation, consisting of the high-affinity biotin transporter Vht1 and the transcription factor Vhr1. Both species induce expression of biotin-metabolic genes upon in vitro biotin depletion and following phagocytosis by macrophages, indicating low biotin levels in the Candida-containing phagosome. In line with this, we observed reduced intracellular proliferation of both Candida cells pre-starved of biotin and deletion mutants lacking VHR1 or VHT1 genes. VHT1 was essential for the full virulence of C. albicans during systemic mouse infections, and the lack of VHT1 led to reduced fungal burden in C. glabrata-infected brains and C.