Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small‐molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure‐ and ligand‐based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4‐aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.     

Imide‐containing ladder polyphenylsilsesquioxanes with high thermal stability and thermoplastic properties

This work reports for the first time the synthesis of ladder polyphenylsilsesquioxanes containing imide building blocks as parts of the main parallel chains. The ladder structure of the synthesized polymers was documented by means of small angle X‐ray scattering (SAXS) measurements. The obtained ladder polymers exhibit stability with respect to decomposition up to temperatures as high as 460°C; additionally, they have melting points far below their decomposition temperatures, which make them interesting candidate materials for thermoplastic processing. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40085.     

Blended Learning – ein innovatives Weiterbildungskonzept für die Technische Chemie

The ever‐increasing and ever‐changing challenges of the job market require professionals to constantly attend extra occupational education programs. Professionals furthermore express their desire for a compatibility of family and work. Therefore, a general concept for extended vocational training in the field of natural science and technology was developed based on blended learning. As an example, the concept was implemented and tested on the basis of the extended vocational training course “tc‐compact^BL” in Chemical Technology.     

Rapeseed Proteins for Paperboard Coating

Protein samples of rapeseed were prepared with different compositions as protein isolate, protein concentrate and acetylated protein concentrate. They showed functional properties which are consolidated in the coating. The manufactured protein samples were tested in a pilot‐scale paperboard coating plant. The results indicated that the use of rapeseed proteins in the coating preparation is technically feasible and that the color and roughness of the coated paperboard show no negative effect on the quality. Industry printing experiments with this coated paperboard achieved the standard quality.     

Occurrence of perfluoroalkyl compounds in surface waters from the North Pacific to the Arctic Ocean

Perfluoroalkyl compounds (PFCs) were determined in 22 surface water samples (39-76°N) and three sea ice core and snow samples (77-87°N) collected from North Pacific to the Arctic Ocean during the fourth Chinese Arctic Expedition in 2010. Geographically, the average concentration of ∑PFC in surface water samples were 560 ± 170 pg L(-1) for the Northwest Pacific Ocean, 500 ± 170 pg L(-1) for the Arctic Ocean, and 340 ± 130 pg L(-1) for the Bering Sea, respectively. The perfluoroalkyl carboxylates (PFCAs) were the dominant PFC class in the water samples, however, the spatial pattern of PFCs varied. The C(5), C(7) and C(8) PFCAs (i.e., perfluoropentanoate (PFPA), perfluoroheptanoate (PFHpA), and perfluorooctanoate (PFOA)) were the dominant PFCs in the Northwest Pacific Ocean while in the Bering Sea the PFPA dominated. The changing in the pattern and concentrations in Pacific Ocean indicate that the PFCs in surface water were influenced by sources from the East-Asian (such as Japan and China) and North American coast, and dilution effect during their transport to the Arctic. The presence of PFCs in the snow and ice core samples indicates an atmospheric deposition of PFCs in the Arctic. The elevated PFC concentration in the Arctic Ocean shows that the ice melting had an impact on the PFC levels and distribution. In addition, the C(4) and C(5) PFCAs (i.e., perfluorobutanoate (PFBA), PFPA) became the dominant PFCs in the Arctic Ocean indicating that PFBA is a marker for sea ice melting as the source of exposure.     

TcdB of Clostridioides difficile Mediates RAS-Dependent Necrosis in Epithelial Cells

A Clostridioides difficile infection (CDI) is the most common nosocomial infection worldwide. The main virulence factors of pathogenic C. difficile are TcdA and TcdB, which inhibit small Rho-GTPases. The inhibition of small Rho-GTPases leads to the so-called cytopathic effect, a reorganization of the actin cytoskeleton, an impairment of the colon epithelium barrier function and inflammation. Additionally, TcdB induces a necrotic cell death termed pyknosis in vitro independently from its glucosyltransferases, which are characterized by chromatin condensation and ROS production. To understand the underlying mechanism of this pyknotic effect, we conducted a large-scale phosphoproteomic study. We included the analysis of alterations in the phosphoproteome after treatment with TcdA, which was investigated for the first time. TcdA exhibited no glucosyltransferase-independent necrotic effect and was, thus, a good control to elucidate the underlying mechanism of the glucosyltransferase-independent effect of TcdB. We found RAS to be a central upstream regulator of the glucosyltransferase-independent effect of TcdB. The inhibition of RAS led to a 68% reduction in necrosis. Further analysis revealed apolipoprotein C-III (APOC3) as a possible crucial factor of CDI-induced inflammation in vivo.     

Polysilazane derived micro/nano Si3N4/SiC composites

The pyrolised polysilazanes poly(hydridomethyl)silazane NCP 200 and poly(urea)silazane CERASET derived Si–C–N amorphous powders were used for preparation of micro/nano Si₃N₄/SiC composites by hot pressing. Y₂O₃–Al₂O₃ and Y₂O₃–Yb₂O₃ were used, as sintering aids. The resulting ceramic composites of all compositions were dense and polycrystalline with fine microstructure of average grain size <1 μm of both Si₃N₄ and SiC phases. The fine SiC nano-inclusions were identified within the Si₃N₄ micrograins. Phase composition of both composites consist of , β modifications of Si₃N₄ and SiC. High weight loss was observed during the hot pressing cycle, 12 and 19 wt.% for NCP 200 and CERASET precursors, respectively. The fracture toughness of both nanocomposites (NCP 2000 and CERASET derived) was not different. Indentation method measured values are from 5 to 6 MPa m^1/2, with respect to the sintering additive system. Fracture toughness is slightly sensitive to the SiC content of the nanocomposite. Hardness increases with the content of SiC in the nanocomposite. The highest hardness was achieved for pyrolysed CERASET precursor with 2 wt.% Y₂O₃ and 6 wt.% Yb₂O₃, HV 23 GPa. This is a consequence of the highest SiC content as well as the chemical composition of additives.