Country Perspectives on Hay-Making Landscapes as Part of the European Agricultural Heritage

This paper provides an overview of traditional hay-making structures and the related agricultural landscapes in Europe. The information was collected using a standardised questionnaire that was completed by experts from different countries. What all countries had in common was that hay production with its corresponding structures was widespread. However, the scope and importance differed among the countries today. We found differences in type and extent, in degree of awareness, and in the cultural meaning of hay-making structures. The differences were connected with built structures, as well as with other tangible and intangible aspects of cultural heritage. The distribution of the broad variety of hay-making-related structures, especially semipermanent ones, has changed throughout history, as well as the hay-making techniques, as a result of agrarian specialisation, land reclamation, and consolidation. Today, in some countries, the relevance of hay-making was mainly connected to horse keeping and landscape management (like in Germany and Hungary), while in others (like Slovakia and Slovenia), it was still predominantly used for cattle and sheep

Chemical Probes that Competitively and Selectively Inhibit Stat3 Activation

Signal transducer and activator of transcription (Stat) 3 is an oncogene constitutively activated in many cancer systems where it contributes to carcinogenesis. To develop chemical probes that selectively target Stat3, we virtually screened 920,000 small drug-like compounds by docking each into the peptide-binding pocket of the Stat3 SH2 domain, which consists of three sites—the pY-residue binding site, the +3 residue-binding site and a hydrophobic binding site, which served as a selectivity filter. Three compounds satisfied criteria of interaction analysis, competitively inhibited recombinant Stat3 binding to its immobilized pY-peptide ligand and inhibited IL-6-mediated tyrosine phosphorylation of Stat3. These compounds were used in a similarity screen of 2.47 million compounds, which identified 3 more compounds with similar activities. Examination of the 6 active compounds for the ability to inhibit IFN-γ-mediated Stat1 phosphorylation revealed that 5 of 6 were selective for Stat3. Molecular modeling of the SH2 domains of Stat3 and Stat1 bound to compound revealed that compound interaction with the hydrophobic binding site was the basis for selectivity. All 5 selective compounds inhibited nuclear-to-cytoplasmic translocation of Stat3, while 3 of 5 compounds induced apoptosis preferentially of breast cancer cell lines with constitutive Stat3 activation. Thus, virtual ligand screening of compound libraries that targeted the Stat3 pY-peptide binding pocket identified for the first time 3 lead compounds that competitively inhibited Stat3 binding to its pY-peptide ligand; these compounds were selective for Stat3 vs. Stat1 and induced apoptosis preferentially of breast cancer cells lines with constitutively activated Stat3

Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2

Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease—a disease endemic especially in the Asia-Pacific region1. Scavenger receptor class B member 2 (SCARB2) is the major receptor of EV71, as well as several other enteroviruses responsible for hand, foot and mouth disease, and plays a key role in cell entry2. The isolated structures of EV71 and SCARB2 are known3,4,5,6, but how they interact to initiate infection is not. Here, we report the EV71–SCARB2 complex structure determined at 3.4 Å resolution using cryo-electron microscopy. This reveals that SCARB2 binds EV71 on the southern rim of the canyon, rather than across the canyon, as predicted3,7,8. Helices 152–163 (α5) and 183–193 (α7) of SCARB2 and the viral protein 1 (VP1) GH and VP2 EF loops of EV71 dominate the interaction, suggesting an allosteric mechanism by which receptor binding might facilitate the low-pH uncoating of the virus in the endosome/lysosome. Remarkably, many residues within the binding footprint are not conserved across SCARB2-dependent enteroviruses; however, a conserved proline and glycine seem to be key residues. Thus, although the virus maintains antigenic variability even within the receptor-binding footprint, the identification of binding ‘hot spots’ may facilitate the design of receptor mimic therapeutics less likely to quickly generate resistance

Stabilization of a diamagnetic ScIBr molecule in a sandwich-like structure

Reaction of a new beta-diketiminato derivative of scandium, LScBr2 (L = Et2NCH2CH2NC(Me)CHC-(Me)NCH2CH2NEt2), with (C3H5)MgBr gave the unexpected scandium complex (LMgBr)(2)ScBr (1), whose structure was established by X-ray analysis, liquid and solid-state NMR, EPR, UV-vis, and magnetic measurements. Correlation of all results leads to the conclusion that the formal oxidation state of scandium in this complex is one (Sc(I)) having no unpaired electrons

Stabilization of a diamagnetic (ScBr)-Br-I molecule in a sandwich-like structure

Reaction of a new beta-diketiminato derivative of scandium, LScBr2 (L = Et2NCH2CH2NC(Me)CHC-(Me)NCH2CH2NEt2), with (C3H5)MgBr gave the unexpected scandium complex (LMgBr)(2)ScBr (1), whose structure was established by X-ray analysis, liquid and solid-state NMR, EPR, UV-vis, and magnetic measurements. Correlation of all results leads to the conclusion that the formal oxidation state of scandium in this complex is one (Sc(I)) having no unpaired electrons

Vanadium complexes incorporating the beta-diketiminato ligand L. Syntheses and structures of LV(OSO2CF3)(2) and LVPPh2

The reaction of LLi (where L = N, N'-bis(2-diethylaminoethyl)-2,4-pentanediimine- ate(-1)) with VCl3.3THF yielded LVCl2, which was characterized by EI-MS and elemental analysis. Subsequent reactions of LVCl2 with AgOSO2CF3 and KPPh2 afforded two new complexes, LV(OSO2CF3)(2) and LVPPh2 which were characterized by F-19, P-31 NMR spectroscopy, EI-MS, elemental analysis, and single crystal X-ray structural analysis