TY  - JOUR
A1  - Iyengar, Sudha K.
A1  - Sedor, John R.
A1  - Freedman, Barry I.
A1  - Kao, W. H. Linda
A1  - Kretzler, Matthias
A1  - Keller, Benjamin J.
A1  - Abboud, Hanna E.
A1  - Adler, Sharon G.
A1  - Best, Lyle G.
A1  - Bowden, Donald W.
A1  - Burlock, Allison
A1  - Chen, Yii-Der Ida
A1  - Cole, Shelley A.
A1  - Comeau, Mary E.
A1  - Curtis, Jeffrey M.
A1  - Divers, Jasmin
A1  - Drechsler, Christiane
A1  - Duggirala, Ravi
A1  - Elston, Robert C.
A1  - Guo, Xiuqing
A1  - Huang, Huateng
A1  - Hoffmann, Michael Marcus
A1  - Howard, Barbara V.
A1  - Ipp, Eli
A1  - Kimmel, Paul L.
A1  - Klag, Michael J.
A1  - Knowler, William C.
A1  - Kohn, Orly F.
A1  - Leak, Tennille S.
A1  - Leehey, David J.
A1  - Li, Man
A1  - Malhotra, Alka
A1  - März, Winfried
A1  - Nair, Viji
A1  - Nelson, Robert G.
A1  - Nicholas, Susanne B.
A1  - O’Brien, Stephen J.
A1  - Pahl, Madeleine V.
A1  - Parekh, Rulan S.
A1  - Pezzolesi, Marcus G.
A1  - Rasooly, Rebekah S.
A1  - Rotimi, Charles N.
A1  - Rotter, Jerome I.
A1  - Schelling, Jeffrey R.
A1  - Seldin, Michael F.
A1  - Shah, Vallabh O.
A1  - Smiles, Adam M.
A1  - Smith, Michael W.
A1  - Taylor, Kent D.
A1  - Thameem, Farook
A1  - Thornley-Brown, Denyse P.
A1  - Truitt, Barbara J.
A1  - Wanner, Christoph
A1  - Weil, E. Jennifer
A1  - Winkler, Cheryl A.
A1  - Zager, Philip G.
A1  - Igo, Jr, Robert P.
A1  - Hanson, Robert L.
A1  - Langefeld, Carl D.
T1  - Genome-wide association and trans-ethnic meta-analysis for advanced diabetic kidney disease: Family Investigation of Nephropathy and Diabetes (FIND)
JF  - PLoS Genetics
N2  - Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10\(^{−9}\)). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10\(^{−8}\)), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.
KW  - diabetic kidney disease
KW  - genome-wide association study
KW  - Family Investigation of Nephropathy and Diabetes
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180545
VL  - 11
IS  - 8
ER  - 
TY  - JOUR
A1  - Sendell-Price, Ashley T.
A1  - Tulenko, Frank J.
A1  - Pettersson, Mats
A1  - Kang, Du
A1  - Montandon, Margo
A1  - Winkler, Sylke
A1  - Kulb, Kathleen
A1  - Naylor, Gavin P.
A1  - Phillippy, Adam
A1  - Fedrigo, Olivier
A1  - Mountcastle, Jacquelyn
A1  - Balacco, Jennifer R.
A1  - Dutra, Amalia
A1  - Dale, Rebecca E.
A1  - Haase, Bettina
A1  - Jarvis, Erich D.
A1  - Myers, Gene
A1  - Burgess, Shawn M.
A1  - Currie, Peter D.
A1  - Andersson, Leif
A1  - Schartl, Manfred
T1  - Low mutation rate in epaulette sharks is consistent with a slow rate of evolution in sharks
JF  - Nature Communications
N2  - Sharks occupy diverse ecological niches and play critical roles in marine ecosystems, often acting as apex predators. They are considered a slow-evolving lineage and have been suggested to exhibit exceptionally low cancer rates. These two features could be explained by a low nuclear mutation rate. Here, we provide a direct estimate of the nuclear mutation rate in the epaulette shark (Hemiscyllium ocellatum). We generate a high-quality reference genome, and resequence the whole genomes of parents and nine offspring to detect de novo mutations. Using stringent criteria, we estimate a mutation rate of 7×10\(^{−10}\) per base pair, per generation. This represents one of the lowest directly estimated mutation rates for any vertebrate clade, indicating that this basal vertebrate group is indeed a slowly evolving lineage whose ability to restore genetic diversity following a sustained population bottleneck may be hampered by a low mutation rate.
KW  - evolutionary genetics
KW  - genomics
KW  - molecular evolution
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357827
VL  - 14
ER  - 
TY  - JOUR
A1  - Hassouna, I.
A1  - Ott, C.
A1  - Wüstefeld, L.
A1  - Offen, N.
A1  - Neher, R. A.
A1  - Mitkovski, M.
A1  - Winkler, D.
A1  - Sperling, S.
A1  - Fries, L.
A1  - Goebbels, S.
A1  - Vreja, I. C.
A1  - Hagemeyer, N.
A1  - Dittrich, M.
A1  - Rossetti, M. F.
A1  - Kröhnert, K.
A1  - Hannke, K.
A1  - Boretius, S.
A1  - Zeug, A.
A1  - Höschen, C.
A1  - Dandekar, T.
A1  - Dere, E.
A1  - Neher, E.
A1  - Rizzoli, S. O.
A1  - Nave, K.-A.
A1  - Sirén, A.-L.
A1  - Ehrenreich, H.
T1  - Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus
JF  - Molecular Psychiatry
N2  - Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of similar to 20%. Under constant cognitive challenge, neuron numbers remained elevated until >6 months of age. Surprisingly, this increase occurred in absence of altered cell proliferation or apoptosis. After feeding a \(^{15}\)N-leucine diet, we used nanoscopic secondary ion mass spectrometry, and found that in EPO-treated mice, an equivalent number of neurons was defined by elevated \(^{15}\)N-leucine incorporation. In EPO-treated NG2-Cre-ERT2 mice, we confirmed enhanced differentiation of preexisting oligodendrocyte precursors in the absence of elevated DNA synthesis. A corresponding analysis of the neuronal lineage awaits the identification of suitable neuronal markers. In cultured neurospheres, EPO reduced Sox9 and stimulated miR124, associated with advanced neuronal differentiation. We are discussing a resulting working model in which EPO drives the differentiation of non-dividing precursors in both (NG2+) oligodendroglial and neuronal lineages. As endogenous EPO expression is induced by brain injury, such a mechanism of adult neurogenesis may be relevant for central nervous system regeneration.
KW  - neural stem-cells
KW  - recombinat-human-erythropoietin
KW  - cognitive functions
KW  - pyramidal neurons
KW  - nervous-sytem
KW  - brain-injury
KW  - mouse-brain
KW  - progenitors
KW  - mice
KW  - memory
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186669
VL  - 21
IS  - 12
ER  - 
TY  - JOUR
A1  - Lutz, Werner K.
A1  - Winkler, F. K.
A1  - Dunitz, J. D.
T1  - Crystal structure of the antibiotic monensin similarities and differences betweeen free acid and metal complex
N2  - The structure of monensin, C36H620 11 , has been deterrnined by X-ray analysis of its crystalline monohydrate (orthorhombic, a = 15.15, b = 23.61, c = 10.65 A, Z = 4, space group P212121). Phases were assigned by direct methods, malring use of the 'tangent formula'. Although the conformation of the free acid resembles that of the silver salt in being cyclic, there are differences in the hydrogen bonding pattern. These featurcs are discussed in relation to the cornplexation of metal ions by m.onensin.
KW  - Toxikologie
Y1  - 1971
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61228
ER  -