TY - JOUR A1 - Wu, Hao A1 - Han, Yijie A1 - Rodriguez Sillke, Yasmina A1 - Deng, Hongzhang A1 - Siddiqui, Sophiya A1 - Treese, Christoph A1 - Schmidt, Franziska A1 - Friedrich, Marie A1 - Keye, Jacqueline A1 - Wan, Jiajia A1 - Qin, Yue A1 - Kühl, Anja A. A1 - Qin, Zhihai A1 - Siegmund, Britta A1 - Glauben, Rainer T1 - Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages JF - EMBO molecular medicine N2 - Tumor-associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long-chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en-route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate-induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro-tumoral myeloid cells on a metabolic level. KW - cancer immunotherapy KW - lipid droplets KW - lipid metabolism KW - tumor microenvironment KW - tumor-associated macrophage Y1 - 2019 U6 - https://doi.org/10.15252/emmm.201910698 SN - 1757-4676 SN - 1757-4684 VL - 11 IS - 11 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Burschel, Sabrina A1 - Decovic, Doris Kreuzer A1 - Nuber, Franziska A1 - Stiller, Marie A1 - Hofmann, Maud A1 - Zupok, Arkadiusz A1 - Siemiatkowska, Beata A1 - Gorka, Michal Jakub A1 - Leimkühler, Silke A1 - Friedrich, Thorsten T1 - Iron-sulfur cluster carrier proteins involved in the assembly of Escherichia coli NADH BT - ubiquinone oxidoreductase (complex I) JF - Molecular microbiology N2 - The NADH:ubiquinone oxidoreductase (respiratory complex I) is the main entry point for electrons into the Escherichia coli aerobic respiratory chain. With its sophisticated setup of 13 different subunits and 10 cofactors, it is anticipated that various chaperones are needed for its proper maturation. However, very little is known about the assembly of E. coli complex I, especially concerning the incorporation of the iron-sulfur clusters. To identify iron-sulfur cluster carrier proteins possibly involved in the process, we generated knockout strains of NfuA, BolA, YajL, Mrp, GrxD and IbaG that have been reported either to be involved in the maturation of mitochondrial complex I or to exert influence on the clusters of bacterial complex. We determined the NADH and succinate oxidase activities of membranes from the mutant strains to monitor the specificity of the individual mutations for complex I. The deletion of NfuA, BolA and Mrp led to a decreased stability and partially disturbed assembly of the complex as determined by sucrose gradient centrifugation and native PAGE. EPR spectroscopy of cytoplasmic membranes revealed that the BolA deletion results in the loss of the binuclear Fe/S cluster N1b. Y1 - 2018 U6 - https://doi.org/10.1111/mmi.14137 SN - 0950-382X SN - 1365-2958 VL - 111 IS - 1 SP - 31 EP - 45 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Maass, Friedrich A1 - Utecht, Manuel Martin A1 - Stremlau, Stephan A1 - Gille, Marie A1 - Schwarz, Jutta A1 - Hecht, Stefan A1 - Klamroth, Tillmann A1 - Tegeder, Petra T1 - Electronic structure changes during the on-surface synthesis of nitrogen-doped chevron-shaped graphene nanoribbons JF - Physical review : B, Condensed matter and materials physics N2 - Utilizing suitable precursor molecules, a thermally activated and surface-assisted synthesis results in the formation of defect-free graphene nanoribbons (GNRs), which exhibit electronic properties that are not present in extended graphene. Most importantly, they have a band gap in the order of a few electron volts, depending on the nanoribbon width. In this study, we investigate the electronic structure changes during the formation of GNRs, nitrogen-doped (singly and doubly N-doped) as well as non-N-doped chevron-shaped CGNRs on Au(111). Thus we determine the optical gaps of the precursor molecules, the intermediate nonaromatic polymers, and finally the aromatic GNRs, using high-resolution electron energy loss spectroscopy and density functional theory calculations. As expected, we find no influence of N-doping on the size of the optical gaps. The gap of the precursor molecules is around 4.5 eV. Polymerization leads to a reduction of the gap to a value of 3.2 eV due to elongation and thus enhanced delocalization. The CGNRs exhibit a band gap of 2.8 eV, thus the gap is further reduced in the nanoribbons, since they exhibit an extended delocalized pi-electron system. Y1 - 2017 U6 - https://doi.org/10.1103/PhysRevB.96.045434 SN - 2469-9950 SN - 2469-9969 VL - 96 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Lange, Maik A1 - Braune, Steffen A1 - Luetzow, Karola A1 - Richau, Klaus A1 - Scharnagl, Nico A1 - Weinhart, Marie A1 - Neffe, Axel T. A1 - Jung, Friedrich A1 - Haag, Rainer A1 - Lendlein, Andreas T1 - Surface functionalization of poly(ether imide) membranes with linear, methylated oligoglycerols for reducing thrombogenicity JF - Macromolecular rapid communications N2 - Materials for biomedical applications are often chosen for their bulk properties. Other requirements such as a hemocompatible surface shall be fulfilled by suitable chemical functionalization. Here we show, that linear, side-chain methylated oligoglycerols (OGMe) are more stable to oxidation than oligo(ethylene glycol) (OEG). Poly(ether imide) (PEI) membranes functionalized with OGMes perform at least as good as, and partially better than, OEG functionalized PEI membranes in view of protein resistance as well as thrombocyte adhesion and activation. Therefore, OGMes are highly potent surface functionalizing molecules for improving the hemocompatibility of polymers. KW - hemocompatibility KW - poly(ethylene glycol) KW - polyglycerol KW - polyimides KW - surface chemistry Y1 - 2012 U6 - https://doi.org/10.1002/marc.201200426 SN - 1022-1336 VL - 33 IS - 17 SP - 1487 EP - 1492 PB - Wiley-VCH CY - Weinheim ER -