Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

Consolidating Heterogeneous Enterprise Data for Named Entity Linking and Web Intelligence

Linking named entities to structured knowledge sources paves the way for state-of-the-art Web intelligence applications which assign sentiment to the correct entities, identify trends, and reveal relations between organizations, persons and products. For this purpose this paper introduces Recognyze, a named entity linking component that uses background knowledge obtained from linked data repositories, and outlines the process of transforming heterogeneous data silos within an organization into a linked enterprise data repository which draws upon popular linked open data vocabularies to foster interoperability with public data sets. The presented examples use comprehensive real-world data sets from Orell Füssli Business Information, Switzerland's largest business information provider. The linked data repository created from these data sets comprises more than nine million triples on companies, the companies' contact information, key people, products and brands. We identify the major challenges of tapping into such sources for named entity linking, and describe required data pre-processing techniques to use and integrate such data sets, with a special focus on disambiguation and ranking algorithms. Finally, we conduct a comprehensive evaluation based on business news from the New Journal of Zurich and AWP Financial News to illustrate how these techniques improve the performance of the Recognyze named entity linking component

Višenukleonska emisija nakon pionske apsorpcije u N, Ar i Xe

Positive pion absorption was studied in an almost 4π geometry allowing simultaneous measurements of various charge and neutral multiplicities. Total absorption cross sections and its decomposition into the most important channels is determined. The results are presented for N, Ar and Xe nuclei at incident pion energies of 118,162 and 239 MeV. The role of multinucleon emission in the absorption process is emphasized.Proučava se pionska apsorpcija s blizu 4π detekcijom koja dozvoljava istovremeno mjerenje raznih nabojskih i neutralnih višestrukosti. Određuju se ukupni udarni presjeci i njihovo razlaganje u najvažnije kanale. Predstavljaju se rezultati za jezgre N, Ar i Xe na energijama 118,162 i 239 MeV. Ističe se uloga višenukleonske emisije u procesu apsorpcije

Pionska apsorpcija u 4He

This paper presents a large solid angle measurement of the positive pion absorption cross-section on 4He and its decomposition into partial channels. A large fraction of the absorption cross-section at incident pion kinetic energies of Tπ+ =70, 118, 162, 239, and 330 MeV is due to multinucleon channels.Daju se ishodi mjerenja pod velikim prostornim kutom udarnog presjeka za apsorpciju pozitivnih piona u He4 i razdjela na pojedine kanale. Velik dio apsorpcijskog udarnog presjeka za energije upadnih piona od Tπ+ =70, 118, 162, 239 i 330 MeV je posljedica višenukleonskih kanala

Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase

The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His–1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C–H bonds. Prolyl 4-hydroxylase (P4H) is an α-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His–1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change