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Empirical evidence of the relationship between social support and post-disaster mental health provides support for a general beneficial effect of social support (main-effect model; Wheaton, 1985). From a theoretical perspective, a buffering effect of social support on the negative relationship between disaster-related stress and mental health also seems plausible (stress-buffering model; Wheaton, 1985). Previous studies, however, (a) have paid less attention to the buffering effect of social support and (b) have mainly relied on interpersonal support (but not collective-level support such as community resilience) when investigating this issue. This previous work might have underestimated the effect of support on post-disaster mental health. Building on a sample of residents in Germany recently affected by flooding (N = 118), we show that community resilience to flooding (but not general interpersonal social support) buffered against the negative effects of flooding on post-disaster mental health. The results support the stress-buffering model and call for a more detailed look at the relationship between support and resilience and post-disaster adjustment, including collective-level variables.
The ability to reflect is considered an essential element of Education for Sustainable Development (ESD) and a key competence for learners and educators in ESD (UNECE Strategy for ESD, 2012). In contrast to its high importance, little is known about how reflective thinking can be identified, influenced or increased in the classroom. Therefore, the objective of this study is to address this need by developing an empirical multi-stage model designed to help educators diagnose different levels of reflective thinking and to identify factors that influence students’ reflective thinking about sustainability. Based on a 4–8-week project with grade 10 and 11 students studying sustainability, reflective thinking performance using weblogs as reflective journals was analysed. In addition, qualitative semi-structured interviews were conducted with the teachers to comprehend the learning environment and the personal value they assigned to ESD in their geography class. To determine the levels of reflective thinking achieved by the students, the study built on the work of Dewey (1933) and pre-existing multi-stage models of reflective thinking (Bain, Ballantyne, & Packer, 1999; Chen, Wei, Wu, & Uden, 2009). Using a qualitative, iterative data analysis, the study adapted the stage models to be applicable in ESD and found great differences in the students’ reflection levels. Furthermore, the study identified eight factors that influence students’ reflective thinking about sustainability. The outcomes of this study may be valuable for educators in high school and higher education, who seek to diagnose their students’ reflective thinking performance and facilitate reflection about sustainability.
The Social War (91-88 BCE) is one of the most significant episodes in Roman history: from this war, in which Rome fought against her Italic allies, emerged the elite that would lead the Republic in the last decades of its existence and that would provide the senatorial aristocracy of the early imperial age. The Italic rebels were defeated militarily, yet they achieved their political aims. As such, this war – and its elaboration and memorialization in Roman cultural memory – provides a very interesting case study about how "victory" and "defeat" are constructed discursively after a disruptive war, and how its narration is "functionalized" for a re-foundation of the civic body.
Wiesner-Reinhold, Melanie ; Barknowitz, Gitte ; Florian, Simone ; Mewis, Inga ; Schumacher, Fabian ; Schreiner, Monika ; Glatt, Hansruedi
We previously showed that purified 1-methoxy-3-indolylmethyl (1-MIM) glucosinolate, a secondary plant metabolite in Brassica species, is mutagenic in various in vitro systems and forms DNA and protein adducts in mouse models. In the present study, we administered 1-MIM glucosinolate in a natural matrix to mice, by feeding a diet containing pak choi powder and extract. Groups of animals were killed after 1, 2, 4 and 8 days of pak choi diet, directly or, in the case of the 8-day treatment, after 0, 8 and 16 days of recovery with pak choi-free diet. DNA adducts [N-2-(1-MIM)-dG, N-6-(1-MIM)-dA] in six tissues, as well as protein adducts [tau N-(1-MIM)-His] in serum albumin (SA) and hemoglobin (Hb) were determined using UPLC-MS/MS with isotopically labeled internal standards. None of the samples from the 12 control animals under standard diet contained any 1-MIM adducts. All groups receiving pak choi diet showed DNA adducts in all six tissues (exception: lung of mice treated for a single day) as well as SA and Hb adducts. During the feeding period, all adduct levels continuously increased until day 8 (in the jejunum until day 4). During the 14-day recovery period, N-2-(1-MIM)-dG in liver, kidney, lung, jejunum, cecum and colon decreased to 52, 41, 59, 11, 7 and 2%, respectively, of the peak level. The time course of N-6-(1-MIM)-dA was similar. Immunohistochemical analyses indicated that cell turnover is a major mechanism of DNA adduct elimination in the intestine. In the same recovery period, protein adducts decreased more rapidly in SA than in Hb, to 0.7 and 37%, respectively, of the peak level, consistent with the differential turnover of these proteins. In conclusion, the pak choi diet lead to the formation of high levels of adducts in mice. Cell and protein turnover was a major mechanism of adduct elimination, at least in gut and blood.
Shainyan, Bagrat A. ; Suslova, Elena N. ; Tran Dinh Phien ; Shlykov, Sergey A. ; Heydenreich, Matthias ; Kleinpeter, Erich
1-Methylthio-1-phenyl-1-silacyclohexane 1, the first silacyclohexane with the sulfur atom at silicon, was synthesized and its molecular structure and conformational preferences studied by gas-phase electron diffraction (GED) and low temperature C-13 and Si-29 NMR spectroscopy (LT NMR). Quantum-chemical calculations were carried out both for the isolated species and solvate complexes in gas and in polar medium. The predominance of the 1-MeSaxPheq conformer in gas phase (1-Ph-eq :1-Ph-ax = 55:45, Delta G degrees = 0.13 kcal/mol) determined from GED is consistent with that measured in the freon solution by LT NMR (1-Ph-eq:1-Ph-ax = 65:35, Delta G degrees = 0.12 kcal/mol), the experimentally measured ratios being close to that estimated by quantum chemical calculations at both the DFT and MP2 levels of theory. (C) 2019 Elsevier Ltd. All rights reserved.
1989 in Berlin
(2019)
Als Hauptstadt der DDR war Ost-Berlin ein wichtiges Zentrum der Friedlichen Revolution von 1989. Ingo Juchler nimmt die Leserinnen und Leser mit zu den zentralen Schauplätzen der Ereignisse, wobei er den Bogen vom 17. Juni 1953 über die Protestbewegung der 1970er Jahre bis hin zu den Demonstrationen im Herbst 1989 und den Ereignissen rund um den Mauerfall schlägt.
Informative Texte zu den Hintergründen, zahlreiche Abbildungen und eine Übersichtskarte machen das Buch zu einem anschaulichen Zeitreiseführer in die jüngere deutsche Geschichte.
1989 in Deutschland
(2019)
Kaum ein Ereignis in der zweiten Hälfte des 20. Jahrhunderts war so bedeutsam wie die Friedliche Revolution von 1989, mit der die Bevölkerung der DDR sich vom SED - Regime befreite.
Dieses Buch nimmt die Leserinnen und Leser mit zu den zentralen Schauplätzen der Protestbewegung in Deutschland – in Leipzig, Berlin, Dresden, Chemnitz, Plauen, Rostock, Potsdam, Stendal und an vielen anderen Orten. Informative Texte zu den Hintergründen der Ereignisse und umfangreiches Bildmaterial machen das Buch zu einem anschaulichen Zeitreiseführer in die jüngere deutsche Geschichte.
Gholamrezaie, Ershad ; Scheck-Wenderoth, Magdalena ; Bott, Judith ; Heidbach, Oliver ; Strecker, Manfred
Abstract. The Sea of Marmara, in northwestern Turkey, is a transition zone where the dextral North Anatolian Fault zone (NAFZ) propagates westward from the Anatolian Plate to the Aegean Sea Plate. The area is of interest in the context of seismic hazard of Istanbul, a metropolitan area with about 15 million inhabitants. Geophysical observations indicate that the crust is heterogeneous beneath the Marmara basin, but a detailed characterization of the crustal heterogeneities is still missing. To assess if and how crustal heterogeneities are related to the NAFZ segmentation below the Sea of Marmara, we develop new crustal-scale 3-D density models which integrate geological and seismological data and that are additionally constrained by 3-D gravity modeling. For the latter, we use two different gravity datasets including global satellite data and local marine gravity observation. Considering the two different datasets and the general non-uniqueness in potential field modeling, we suggest three possible “end-member” solutions that are all consistent with the observed gravity field and illustrate the spectrum of possible solutions. These models indicate that the observed gravitational anomalies originate from significant density heterogeneities within the crust. Two layers of sediments, one syn-kinematic and one pre-kinematic with respect to the Sea of Marmara formation are underlain by a heterogeneous crystalline crust. A felsic upper crystalline crust (average density of 2720 kgm⁻³) and an intermediate to mafic lower crystalline crust (average density of 2890 kgm⁻³) appear to be cross-cut by two large, dome-shaped mafic highdensity bodies (density of 2890 to 3150 kgm⁻³) of considerable thickness above a rather uniform lithospheric mantle (3300 kgm⁻³). The spatial correlation between two major bends of the main Marmara fault and the location of the highdensity bodies suggests that the distribution of lithological heterogeneities within the crust controls the rheological behavior along the NAFZ and, consequently, maybe influences fault segmentation and thus the seismic hazard assessment in the region.
Gholamrezaie, Ershad ; Scheck-Wenderoth, Magdalena ; Bott, Judith ; Heidbach, Oliver ; Strecker, Manfred
Abstract. The Sea of Marmara, in northwestern Turkey, is a transition zone where the dextral North Anatolian Fault zone (NAFZ) propagates westward from the Anatolian Plate to the Aegean Sea Plate. The area is of interest in the context of seismic hazard of Istanbul, a metropolitan area with about 15 million inhabitants. Geophysical observations indicate that the crust is heterogeneous beneath the Marmara basin, but a detailed characterization of the crustal heterogeneities is still missing. To assess if and how crustal heterogeneities are related to the NAFZ segmentation below the Sea of Marmara, we develop new crustal-scale 3-D density models which integrate geological and seismological data and that are additionally constrained by 3-D gravity modeling. For the latter, we use two different gravity datasets including global satellite data and local marine gravity observation. Considering the two different datasets and the general non-uniqueness in potential field modeling, we suggest three possible “end-member” solutions that are all consistent with the observed gravity field and illustrate the spectrum of possible solutions. These models indicate that the observed gravitational anomalies originate from significant density heterogeneities within the crust. Two layers of sediments, one syn-kinematic and one pre-kinematic with respect to the Sea of Marmara formation are underlain by a heterogeneous crystalline crust. A felsic upper crystalline crust (average density of 2720 kgm⁻³) and an intermediate to mafic lower crystalline crust (average density of 2890 kgm⁻³) appear to be cross-cut by two large, dome-shaped mafic highdensity bodies (density of 2890 to 3150 kgm⁻³) of considerable thickness above a rather uniform lithospheric mantle (3300 kgm⁻³). The spatial correlation between two major bends of the main Marmara fault and the location of the highdensity bodies suggests that the distribution of lithological heterogeneities within the crust controls the rheological behavior along the NAFZ and, consequently, maybe influences fault segmentation and thus the seismic hazard assessment in the region.
Guillemoteau, Julien ; Simon, Francois-Xavier ; Hulin, Guillaume ; Dousteyssier, Bertrand ; Dacko, Marion ; Tronicke, Jens
The in-phase response collected by portable loop-loop electromagnetic induction (EMI) sensors operating at low and moderate induction numbers (<= 1) is typically used for sensing the magnetic permeability (or susceptibility) of the subsurface. This is due to the fact that the in-phase response contains a small induction fraction and a preponderant induced magnetization fraction. The magnetization fraction follows the magneto-static equations similarly to the magnetic method but with an active magnetic source. The use of an active source offers the possibility to collect data with several loop-loop configurations, which illuminate the subsurface with different sensitivity patterns. Such multiconfiguration soundings thereby allows the imaging of subsurface magnetic permeability/susceptibility variations through an inversion procedure. This method is not affected by the remnant magnetization and theoretically overcomes the classical depth ambiguity generally encountered with passive geomagnetic data. To invert multiconfiguration in-phase data sets, we propose a novel methodology based on a full-grid 3-D multichannel deconvolution (MCD) procedure. This method allows us to invert large data sets (e.g. consisting of more than a hundred thousand of data points) for a dense voxel-based 3-D model of magnetic susceptibility subject to smoothness constraints. In this study, we first present and discuss synthetic examples of our imaging procedure, which aim at simulating realistic conditions. Finally, we demonstrate the applicability of our method to field data collected across an archaeological site in Auvergne (France) to image the foundations of a Gallo-Roman villa built with basalt rock material. Our synthetic and field data examples demonstrate the potential of the proposed inversion procedure offering new and complementary ways to interpret data sets collected with modern EMI instruments.
Gomez-Garcia, Angela Maria ; Meeßen, Christian ; Scheck-Wenderoth, Magdalena ; Monsalve, Gaspar ; Bott, Judith ; Bernhardt, Anne ; Bernal, Gladys
Geophysical data acquisition in oceanic domains is challenging, implying measurements with low and/or nonhomogeneous spatial resolution. The evolution of satellite gravimetry and altimetry techniques allows testing 3-D density models of the lithosphere, taking advantage of the high spatial resolution and homogeneous coverage of satellites. However, it is not trivial to discretise the source of the gravity field at different depths. Here, we propose a new method for inferring tectonic boundaries at the crustal level. As a novelty, instead of modeling the gravity anomalies and assuming a flat Earth approximation, we model the vertical gravity gradients (VGG) in spherical coordinates, which are especially sensitive to density contrasts in the upper layers of the Earth. To validate the methodology, the complex oceanic domain of the Caribbean region is studied, which includes different crustal domains with a tectonic history since Late Jurassic time. After defining a lithospheric starting model constrained by up-to-date geophysical data sets, we tested several a-priory density distributions and selected the model with the minimum misfits with respect to the VGG calculated from the EIGEN-6C4 data set. Additionally, the density of the crystalline crust was inferred by inverting the VGG field. Our methodology enabled us not only to refine, confirm, and/or propose tectonic boundaries in the study area but also to identify a new anomalous buoyant body, located in the South Lesser Antilles subduction zone, and high-density bodies along the Greater, Lesser, and Leeward Antilles forearcs.
Ibarra, Federico ; Liu, Sibiao ; Meeßen, Christian ; Prezzi, Claudia Beatriz ; Bott, Judith ; Scheck-Wenderoth, Magdalena ; Sobolev, Stephan Vladimir ; Strecker, Manfred
We present a new three-dimensional density model of the Central Andes characterizing the structure and composition of the lithosphere together with a geodynamic simulation subjected to continental intraplate shortening. The principal aim of this study is to assess the link between heterogeneities in the lithosphere and different deformation patterns and styles along the orogen-foreland system of the Central Andes. First, we performed a 3D integration of new geological and geophysical data with previous models through forward modelling of Bouguer anomalies. Subsequently, a geodynamic model was set-up and parametrized from the previously obtained 3D structure and composition. We do not find a unambigous correlation between the resulting density configuration and terrane boundaries proposed by other authors. Our models reproduce the observed Bouguer anomaly and deformation patterns in the foreland. We find that thin-skinned deformation in the Subandean fold-and thrust belt is controlled by a thick sedimentary layer and coeval underthrusting of thin crust of the foreland beneath the thick crust of the Andean Plateau. In the adjacent thick-skinned deformation province of the inverted Cretaceous extensional Santa Barbara System sedimentary strata are much thinner and crustal thickness transitions from greater values in the Andean to a more reduced thickness in the foreland. Our results show that deformation processes occur where the highest gradients of lithospheric strength are present between the orogen and the foreland, thus suggesting a spatial correlation between deformation and lithospheric strength.
Remote Sensing technologies allow to map biophysical, biochemical, and earth surface parameters of the land surface. Of especial interest for various applications in environmental and urban sciences is the combination of spectral and 3D elevation information. However, those two data streams are provided separately by different instruments, namely airborne laser scanner (ALS) for elevation and a hyperspectral imager (HSI) for high spectral resolution data. The fusion of ALS and HSI data can thus lead to a single data entity consistently featuring rich structural and spectral information. In this study, we present the application of fusing the first pulse return information from ALS data at a sub-decimeter spatial resolution with the lower-spatial resolution hyperspectral information available from the HSI into a hyperspectral point cloud (HSPC). During the processing, a plausible hyperspectral spectrum is assigned to every first-return ALS point. We show that the complementary implementation of spectral and 3D information at the point-cloud scale improves object-based classification and information extraction schemes. This improvements have great potential for numerous land cover mapping and environmental applications.
Already for decades it has been known that the winds of massive stars are inhomogeneous (i.e. clumped). To properly model observed spectra of massive star winds it is necessary to incorporate the 3-D nature of clumping into radiative transfer calculations. In this paper we present our full 3-D Monte Carlo radiative transfer code for inhomogeneous expanding stellar winds. We use a set of parameters to describe dense as well as the rarefied wind components. At the same time, we account for non-monotonic velocity fields. We show how the 3-D density and velocity wind inhomogeneities strongly affect the resonance line formation. We also show how wind clumping can solve the discrepancy between P v and H alpha mass-loss rate diagnostics.
Hepcidin-25 (Hep-25) plays a crucial role in the control of iron homeostasis. Since the dysfunction of the hepcidin pathway leads to multiple diseases as a result of iron imbalance, hepcidin represents a potential target for the diagnosis and treatment of disorders of iron metabolism. Despite intense research in the last decade targeted at developing a selective immunoassay for iron disorder diagnosis and treatment and better understanding the ferroportin-hepcidin interaction, questions remain. The key to resolving these underlying questions is acquiring exact knowledge of the 3D structure of native Hep-25. Since it was determined that the N-terminus, which is responsible for the bioactivity of Hep-25, contains a small Cu(II)-binding site known as the ATCUN motif, it was assumed that the Hep-25-Cu(II) complex is the native, bioactive form of the hepcidin. This structure has thus far not been elucidated in detail. Owing to the lack of structural information on metal-bound Hep-25, little is known about its possible biological role in iron metabolism. Therefore, this work is focused on structurally characterizing the metal-bound Hep-25 by NMR spectroscopy and molecular dynamics simulations. For the present work, a protocol was developed to prepare and purify properly folded Hep-25 in high quantities. In order to overcome the low solubility of Hep-25 at neutral pH, we introduced the C-terminal DEDEDE solubility tag. The metal binding was investigated through a series of NMR spectroscopic experiments to identify the most affected amino acids that mediate metal coordination. Based on the obtained NMR data, a structural calculation was performed in order to generate a model structure of the Hep-25-Ni(II) complex. The DEDEDE tag was excluded from the structural calculation due to a lack of NMR restraints. The dynamic nature and fast exchange of some of the amide protons with solvent reduced the overall number of NMR restraints needed for a high-quality structure. The NMR data revealed that the 20 Cterminal Hep-25 amino acids experienced no significant conformational changes, compared to published results, as a result of a pH change from pH 3 to pH 7 and metal binding. A 3D model of the Hep-25-Ni(II) complex was constructed from NMR data recorded for the hexapeptideNi(II) complex and Hep-25-DEDEDE-Ni(II) complex in combination with the fixed conformation of 19 C-terminal amino acids. The NMR data of the Hep-25-DEDEDE-Ni(II) complex indicates that the ATCUN motif moves independently from the rest of the structure. The 3D model structure of the metal-bound Hep-25 allows for future works to elucidate hepcidin’s interaction with its receptor ferroportin and should serve as a starting point for the development of antibodies with improved selectivity.
70 Jahre Israel
(2019)
Schon kurz nach dem Zweiten Weltkrieg wurde die These vertreten, die Shoah sei ein wichtiger, wenn nicht gar entscheidender Faktor für die Gründung des Staates Israel gewesen. Der Essay arbeitet heraus, dass der nationalsozialistische Judenmord sicherlich eine moralisch-legitimatorische Funktion gehabt hat, ein unmittelbarer kausaler Zusammenhang mit der Staatsgründung aber nicht nachzuweisen ist.
Zhang, Shuhao ; Bramski, Julia ; Tutus, Murat ; Pietruszka, Jörg ; Böker, Alexander ; Reinicke, Stefan
Aldol reactions play an important role in organic synthesis, as they belong to the class of highly beneficial C-C-linking reactions. Aldol-type reactions can be efficiently and stereoselectively catalyzed by the enzyme 2-deoxy-D-ribose-5-phosphate aldolase (DERA) to gain key intermediates for pharmaceuticals such as atorvastatin. The immobilization of DERA would open the opportunity for a continuous operation mode which gives access to an efficient, large-scale production of respective organic intermediates. In this contribution, we synthesize and utilize DERA/polymer conjugates for the generation and fixation of a DERA bearing thin film on a polymeric membrane support. The conjugation strongly increases the tolerance of the enzyme toward the industrial relevant substrate acetaldehyde while UV-cross-linkable groups along the conjugated polymer chains provide the opportunity for covalent binding to the support. First, we provide a thorough characterization of the conjugates followed by immobilization tests on representative, nonporous cycloolefinic copolymer supports. Finally, immobilization on the target supports constituted of polyacrylonitrile (PAN) membranes is performed, and the resulting enzymatically active membranes are implemented in a simple membrane module setup for the first assessment of biocatalytic performance in the continuous operation mode using the combination hexanal/acetaldehyde as the substrate.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Wuttke, Matthias ; Li, Yong ; Li, Man ; Sieber, Karsten B. ; Feitosa, Mary F. ; Gorski, Mathias ; Tin, Adrienne ; Wang, Lihua ; Chu, Audrey Y. ; Hoppmann, Anselm ; Kirsten, Holger ; Giri, Ayush ; Chai, Jin-Fang ; Sveinbjornsson, Gardar ; Tayo, Bamidele O. ; Nutile, Teresa ; Fuchsberger, Christian ; Marten, Jonathan ; Cocca, Massimiliano ; Ghasemi, Sahar ; Xu, Yizhe ; Horn, Katrin ; Noce, Damia ; Van der Most, Peter J. ; Sedaghat, Sanaz ; Yu, Zhi ; Akiyama, Masato ; Afaq, Saima ; Ahluwalia, Tarunveer Singh ; Almgren, Peter ; Amin, Najaf ; Arnlov, Johan ; Bakker, Stephan J. L. ; Bansal, Nisha ; Baptista, Daniela ; Bergmann, Sven ; Biggs, Mary L. ; Biino, Ginevra ; Boehnke, Michael ; Boerwinkle, Eric ; Boissel, Mathilde ; Böttinger, Erwin ; Boutin, Thibaud S. ; Brenner, Hermann ; Brumat, Marco ; Burkhardt, Ralph ; Butterworth, Adam S. ; Campana, Eric ; Campbell, Archie ; Campbell, Harry ; Canouil, Mickael ; Carroll, Robert J. ; Catamo, Eulalia ; Chambers, John C. ; Chee, Miao-Ling ; Chee, Miao-Li ; Chen, Xu ; Cheng, Ching-Yu ; Cheng, Yurong ; Christensen, Kaare ; Cifkova, Renata ; Ciullo, Marina ; Concas, Maria Pina ; Cook, James P. ; Coresh, Josef ; Corre, Tanguy ; Sala, Cinzia Felicita ; Cusi, Daniele ; Danesh, John ; Daw, E. Warwick ; De Borst, Martin H. ; De Grandi, Alessandro ; De Mutsert, Renee ; De Vries, Aiko P. J. ; Degenhardt, Frauke ; Delgado, Graciela ; Demirkan, Ayse ; Di Angelantonio, Emanuele ; Dittrich, Katalin ; Divers, Jasmin ; Dorajoo, Rajkumar ; Eckardt, Kai-Uwe ; Ehret, Georg ; Elliott, Paul ; Endlich, Karlhans ; Evans, Michele K. ; Felix, Janine F. ; Foo, Valencia Hui Xian ; Franco, Oscar H. ; Franke, Andre ; Freedman, Barry I. ; Freitag-Wolf, Sandra ; Friedlander, Yechiel ; Froguel, Philippe ; Gansevoort, Ron T. ; Gao, He ; Gasparini, Paolo ; Gaziano, J. Michael ; Giedraitis, Vilmantas ; Gieger, Christian ; Girotto, Giorgia ; Giulianini, Franco ; Gogele, Martin ; Gordon, Scott D. ; Gudbjartsson, Daniel F. ; Gudnason, Vilmundur ; Haller, Toomas ; Hamet, Pavel ; Harris, Tamara B. ; Hartman, Catharina A. ; Hayward, Caroline ; Hellwege, Jacklyn N. ; Heng, Chew-Kiat ; Hicks, Andrew A. ; Hofer, Edith ; Huang, Wei ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Indridason, Olafur S. ; Ingelsson, Erik ; Ising, Marcus ; Jaddoe, Vincent W. V. ; Jakobsdottir, Johanna ; Jonas, Jost B. ; Joshi, Peter K. ; Josyula, Navya Shilpa ; Jung, Bettina ; Kahonen, Mika ; Kamatani, Yoichiro ; Kammerer, Candace M. ; Kanai, Masahiro ; Kastarinen, Mika ; Kerr, Shona M. ; Khor, Chiea-Chuen ; Kiess, Wieland ; Kleber, Marcus E. ; Koenig, Wolfgang ; Kooner, Jaspal S. ; Korner, Antje ; Kovacs, Peter ; Kraja, Aldi T. ; Krajcoviechova, Alena ; Kramer, Holly ; Kramer, Bernhard K. ; Kronenberg, Florian ; Kubo, Michiaki ; Kuhnel, Brigitte ; Kuokkanen, Mikko ; Kuusisto, Johanna ; La Bianca, Martina ; Laakso, Markku ; Lange, Leslie A. ; Langefeld, Carl D. ; Lee, Jeannette Jen-Mai ; Lehne, Benjamin ; Lehtimaki, Terho ; Lieb, Wolfgang ; Lim, Su-Chi ; Lind, Lars ; Lindgren, Cecilia M. ; Liu, Jun ; Liu, Jianjun ; Loeffler, Markus ; Loos, Ruth J. F. ; Lucae, Susanne ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Magi, Reedik ; Magnusson, Patrik K. E. ; Mahajan, Anubha ; Martin, Nicholas G. ; Martins, Jade ; Marz, Winfried ; Mascalzoni, Deborah ; Matsuda, Koichi ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Metspalu, Andres ; Mikaelsdottir, Evgenia K. ; Milaneschi, Yuri ; Miliku, Kozeta ; Mishra, Pashupati P. ; Program, V. A. Million Veteran ; Mohlke, Karen L. ; Mononen, Nina ; Montgomery, Grant W. ; Mook-Kanamori, Dennis O. ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nalls, Mike A. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; Noordam, Raymond ; Olafsson, Isleifur ; Oldehinkel, Albertine J. ; Orho-Melander, Marju ; Ouwehand, Willem H. ; Padmanabhan, Sandosh ; Palmer, Nicholette D. ; Palsson, Runolfur ; Penninx, Brenda W. J. H. ; Perls, Thomas ; Perola, Markus ; Pirastu, Mario ; Pirastu, Nicola ; Pistis, Giorgio ; Podgornaia, Anna I. ; Polasek, Ozren ; Ponte, Belen ; Porteous, David J. ; Poulain, Tanja ; Pramstaller, Peter P. ; Preuss, Michael H. ; Prins, Bram P. ; Province, Michael A. ; Rabelink, Ton J. ; Raffield, Laura M. ; Raitakari, Olli T. ; Reilly, Dermot F. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Ridker, Paul M. ; Rivadeneira, Fernando ; Rizzi, Federica ; Roberts, David J. ; Robino, Antonietta ; Rossing, Peter ; Rudan, Igor ; Rueedi, Rico ; Ruggiero, Daniela ; Ryan, Kathleen A. ; Saba, Yasaman ; Sabanayagam, Charumathi ; Salomaa, Veikko ; Salvi, Erika ; Saum, Kai-Uwe ; Schmidt, Helena ; Schmidt, Reinhold ; Ben Schottker ; Schulz, Christina-Alexandra ; Schupf, Nicole ; Shaffer, Christian M. ; Shi, Yuan ; Smith, Albert V. ; Smith, Blair H. ; Soranzo, Nicole ; Spracklen, Cassandra N. ; Strauch, Konstantin ; Stringham, Heather M. ; Stumvoll, Michael ; Svensson, Per O. ; Szymczak, Silke ; Tai, E-Shyong ; Tajuddin, Salman M. ; Tan, Nicholas Y. Q. ; Taylor, Kent D. ; Teren, Andrej ; Tham, Yih-Chung ; Thiery, Joachim ; Thio, Chris H. L. ; Thomsen, Hauke ; Thorleifsson, Gudmar ; Toniolo, Daniela ; Tonjes, Anke ; Tremblay, Johanne ; Tzoulaki, Ioanna ; Uitterlinden, Andre G. ; Vaccargiu, Simona ; Van Dam, Rob M. ; Van der Harst, Pim ; Van Duijn, Cornelia M. ; Edward, Digna R. Velez ; Verweij, Niek ; Vogelezang, Suzanne ; Volker, Uwe ; Vollenweider, Peter ; Waeber, Gerard ; Waldenberger, Melanie ; Wallentin, Lars ; Wang, Ya Xing ; Wang, Chaolong ; Waterworth, Dawn M. ; Bin Wei, Wen ; White, Harvey ; Whitfield, John B. ; Wild, Sarah H. ; Wilson, James F. ; Wojczynski, Mary K. ; Wong, Charlene ; Wong, Tien-Yin ; Xu, Liang ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Weihua ; Zonderman, Alan B. ; Rotter, Jerome I. ; Bochud, Murielle ; Psaty, Bruce M. ; Vitart, Veronique ; Wilson, James G. ; Dehghan, Abbas ; Parsa, Afshin ; Chasman, Daniel I. ; Ho, Kevin ; Morris, Andrew P. ; Devuyst, Olivier ; Akilesh, Shreeram ; Pendergrass, Sarah A. ; Sim, Xueling ; Boger, Carsten A. ; Okada, Yukinori ; Edwards, Todd L. ; Snieder, Harold ; Stefansson, Kari ; Hung, Adriana M. ; Heid, Iris M. ; Scholz, Markus ; Teumer, Alexander ; Kottgen, Anna ; Pattaro, Cristian
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.