TY - JOUR A1 - Guber, Christoph Rudolf A1 - Richter, Philipp A1 - Wendt, Martin T1 - Multiple origins for the DLA at zabs = 0.313 toward PKS 1127–145 indicated by a complex dust depletion pattern of Ca, Ti, and Mn JF - Astronomy and astrophysics : an international weekly journal N2 - Aims: We aim to investigate the dust depletion properties of optically thick gas in and around galaxies and its origin we study in detail the dust depletion patterns of Ti, Mn, and Ca in the multi-component damped Lyman alpha (DLA) absorber at z(abs) = 0.313 toward the quasar PKS 1127-145. Methods: We performed a detailed spectral analysis of the absorption profiles of Ca II, Mn II, TIII, and Na I associated with the DLA toward PKS 1127-145, based on optical high-resolution data obtained with the UVES instrument at the Very Large Telescope. We obtained column densities and Doppler-parameters for the ions listed above and determine their gas-phase abundances, from which we conclude on their dust depletion properties. We compared the Ca and Ti depletion properties of this DLA with that of other DLAs. Results: One of the six analyzed absorption components (component 3) shows a striking underabundance of Ti and Mn in the gas-phase, indicating the effect of dust depletion for these elements and a locally enhanced dust-to-gas ratio. In this DLA and in other similar absorbers, the Mn II abundance follows that of Ti II very closely, implying that both ions are equally sensitive to the dust depletion effects. Conclusions: Our analysis indicates that the DLA toward PKS 1127 145 has multiple origins. With its narrow line width and its strong dust depletion, component 3 points toward the presence of a neutral gas disk from a faint LSB galaxy in front of PKS 1127 145, while the other, more diffuse and dust-poor, absorption components possibly are related to tidal gas features from the interaction between the various, optically confirmed galaxy-group members. In general, the Mn/Ca II ratio in sub-DLAs and DLAs possibly serves as an important indicator to discriminate between dust-rich and dust-poor in neutral gas in and around galaxies. KW - quasars: absorption lines KW - galaxies: abundances KW - intergalactic medium KW - quasars: individual: PKS1127-145 KW - dust, extinction KW - ISM: kinematics and dynamics Y1 - 2018 U6 - https://doi.org/10.1051/0004-6361/201730984 SN - 1432-0746 VL - 609 PB - EDP Sciences CY - Les Ulis ER - TY - JOUR A1 - Zirafi, Onofrio A1 - Kim, Kyeong-Ae A1 - Ständker, Ludger A1 - Mohr, Katharina B. A1 - Sauter, Daniel A1 - Heigele, Anke A1 - Kluge, Silvia F. A1 - Wiercinska, Eliza A1 - Chudziak, Doreen A1 - Richter, Rudolf A1 - Möpps, Barbara A1 - Gierschik, Peter A1 - Vas, Virag A1 - Geiger, Hartmut A1 - Lamla, Markus A1 - Weil, Tanja A1 - Burster, Timo A1 - Zgraja, Andreas A1 - Daubeuf, Francois A1 - Frossard, Nelly A1 - Hachet-Haas, Muriel A1 - Heunisch, Fabian A1 - Reichetzeder, Christoph A1 - Galzi, Jean-Luc A1 - Perez-Castells, Javier A1 - Canales-Mayordomo, Angeles A1 - Jimenez-Barbero, Jesus A1 - Gimenez-Gallego, Guillermo A1 - Schneider, Marion A1 - Shorter, James A1 - Telenti, Amalio A1 - Hocher, Berthold A1 - Forssmann, Wolf-Georg A1 - Bonig, Halvard A1 - Kirchhoff, Frank A1 - Münch, Jan T1 - Discovery and Characterization of an Endogenous CXCR4 Antagonist JF - Cell reports N2 - CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation. Y1 - 2015 U6 - https://doi.org/10.1016/j.celrep.2015.03.061 SN - 2211-1247 VL - 11 IS - 5 SP - 737 EP - 747 PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Forssmann, Wolf-Georg A1 - Tillmann, Hanns-Christian A1 - Hock, Dieter A1 - Forssmann, Kristin A1 - Bernasconi, Corrado A1 - Forssmann, Ulf A1 - Richter, Rudolf A1 - Hocher, Berthold A1 - Pfuetzner, Andreas T1 - Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37 JF - German politics N2 - Background/Aims: Parathyroid hormone (PTH) derivatives exert pronounced renal and osteoanabolic properties when given intermittently. The current study was performed to assess the pharmacokinetic and pharmacodynamic properties as well as safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy subjects. Methods: This randomized, double-blind, dose-escalating, placebo and active comparator controlled study was conducted in 33 healthy postmenopausal women. Subjects were allocated to one of five treatment options: 10, 20, or 40 mu g PTH-1-37, 20 mu g PTH-1-34 or placebo, administered as once daily subcutaneous doses for three days. Plasma drug concentrations and serum levels of endogenous PTH-1-84, and calcium as markers of biological activity were monitored during the treatment. Results: PTH was absorbed rapidly from the subcutaneous tissue with a median t(max) of 30 minutes for 20 and 40 mu g of PTH-1-37. t(max) was 45 minutes for 20 mu g PTH-1-34. Elimination half-lives were estimated as 76 +/- 34 min and 70 +/- 13 min for 20 mu g and 40 mu g PTH-1-37 (mean +/- SD), and 78 +/- 34 for 20 mu g PTH-1-34. Both PTH fragments (PTH-1-37 and PTH-1-34) increased serum calcium. For PTH-1-37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH-1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the study period, the subjects experienced no unexpected or serious adverse events. Conclusions: PTH-1-37 is rapidly absorbed after s.c. injection, has a short plasma elimination half-life, and does not accumulate during multiple dosing. Biological activity was demonstrated by rising serum calcium and decreasing endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and safe. Our investigation presents data that PTH-1-37 is an excellent drug candidate for intervening with syndromes of dysregulation of calcium metabolism. (C) 2016 The Author(s) Published by S. Karger AG, Basel KW - Pharmacokinetics Y1 - 2016 U6 - https://doi.org/10.1159/000443453 SN - 1420-4096 SN - 1423-0143 VL - 41 SP - 507 EP - 518 PB - Karger CY - Basel ER -