Institution
University of Cologne
Education•Cologne, Germany•
About: University of Cologne is a education organization based out in Cologne, Germany. It is known for research contribution in the topics: Population & Gene. The organization has 32050 authors who have published 66350 publications receiving 2210092 citations. The organization is also known as: Universität zu Köln & Universitatis Coloniensis.
Topics: Population, Gene, Transplantation, Medicine, Cancer
Papers published on a yearly basis
Papers
More filters
••
TL;DR: In this article, the authors used both single-station and array methods to determine shallow shear velocity site profiles in the vicinity of the city of Cologne, Germany from ambient vibration records.
Abstract: SUMMARY We have used both single-station and array methods to determine shallow shear velocity site profiles in the vicinity of the city of Cologne, Germany from ambient vibration records. Based on fk-analysis we assume that fundamental-mode Rayleigh waves dominate the analysed wavefield in the frequency range of 0.7‐2.2 Hz. According to this view a close relation exists between H/V spectral ratios and the ellipticity of the contributing Rayleigh waves. The inversion of the shape of H/V spectral ratios then provides quantitative information concerning the local shear wave velocity structure. However, based on tests with synthetic data believed to represent a typical situation in the Lower Rhine Embayment, dispersion curves were found to provide stronger constraints on the absolute values of the velocity‐depth model than the ellipticities. The shape of the ellipticities was found to be subject to a strong trade-off between the layer thickness and the average layer velocity. We have made use of this observation by combining the inversion schemes for dispersion curves and ellipticities such that the velocity‐depth dependence is essentially constrained by the dispersion curves while the layer thickness is constrained by the ellipticities. In order to test this method in practice, we have used array recordings of ambient vibrations from three sites where the subsurface geology is fairly well known and geotechnical information is at least partially available. In order to keep the parameter space as simple as possible we attempted to fit only a single layer over a half-space model. However, owing to earlier studies from the region, we assume a power-law depth dependence for sediment velocities. For all three sites investigated, the inversion resulted in models for which the shear wave velocity within the sediment layer both in absolute value at the surface and in depth dependence are found to be remarkably similar to the results obtained by Budny from downhole measurements. This is strong support for the interpretation of H/V spectral ratios as Rayleigh wave ellipticities. For all three sites the predicted SH-wave site amplification factors at the fundamental frequency are of the order of 5‐6 with a slightly smaller value south of Cologne.
311 citations
••
TL;DR: It is found that B cells are targeted for editing during a 2-hour delay in development at the pre-BII cell stage, and that about 25% of all antibody molecules are produced by gene replacement.
Abstract: Receptor editing, clonal deletion, and anergy are the mechanisms by which B cells maintain tolerance to self antigens. To determine the extent to which receptor editing shapes the normal antibody repertoire, we generated an immunoglobulin κ polymorphism that facilitates the detection of editing of immunoglobulin light chains in vivo. We found that B cells are targeted for editing during a 2-hour delay in development at the pre-BII cell stage, and that about 25% of all antibody molecules are produced by gene replacement. These results suggest that receptor editing represents a major force in shaping the antibody repertoire.
311 citations
••
University of Michigan1, University of Strasbourg2, Radboud University Nijmegen3, Genentech4, Utrecht University5, University of Pennsylvania6, Université de Montréal7, Mayo Clinic8, University of Birmingham9, University of Alabama at Birmingham10, University of Freiburg11, Goethe University Frankfurt12, RWTH Aachen University13, Duke University14, Baylor College of Medicine15, University of California, Los Angeles16, Johns Hopkins University17, Instituto Gulbenkian de Ciência18, Hoffmann-La Roche19, University of Cologne20, University of Paris21, Howard Hughes Medical Institute22
TL;DR: This work identifies loss of SDCCAG8 function as a cause of a retinal-renal ciliopathy and validates exome capture analysis for broadly heterogeneous single-gene disorders.
Abstract: Nephronophthisis-related ciliopathies (NPHP-RC) are recessive disorders that feature dysplasia or degeneration occurring preferentially in the kidney, retina and cerebellum. Here we combined homozygosity mapping with candidate gene analysis by performing 'ciliopathy candidate exome capture' followed by massively parallel sequencing. We identified 12 different truncating mutations of SDCCAG8 (serologically defined colon cancer antigen 8, also known as CCCAP) in 10 families affected by NPHP-RC. We show that SDCCAG8 is localized at both centrioles and interacts directly with OFD1 (oral-facial-digital syndrome 1), which is associated with NPHP-RC. Depletion of sdccag8 causes kidney cysts and a body axis defect in zebrafish and induces cell polarity defects in three-dimensional renal cell cultures. This work identifies loss of SDCCAG8 function as a cause of a retinal-renal ciliopathy and validates exome capture analysis for broadly heterogeneous single-gene disorders.
311 citations
••
TL;DR: It is shown here that many pre-B cells which do not produce immunoglobulin H chains and have non-functional VHDJH complexes carrying the VH and JH coding sequences in different reading frames are not dead-end products of the B-cell developmental pathway but can perform a novel VH to V HDJH joining using a 5′ VH segment to replace the Vh sequence of the VHDj−H complex.
Abstract: During B-cell development, the VH genes of immunoglobulin heavy (H) chains are assembled from three different germline components: the variable (VH) segment, the diversity (D) segment and the joining (JH) segment. The joining between two segments involves the recognition of conserved nonamer-heptamer sequences bordering each segment, double-stranded cuts at the heptamer-segment border, and the re-ligation of the two segment ends which have frequently been modified by the deletion and addition of nucleotides. The flexibility of the joint increases VHDJH variability. However, it also results in many pre-B cells which do not produce immunoglobulin H chains and have non-functional VHDJH complexes carrying the VH and JH coding sequences in different reading frames. We show here that such 'null cells' are not dead-end products of the B-cell developmental pathway but can perform a novel VH to VHDJH joining using a 5' VH segment to replace the VH sequence of the VHDJ-H complex. This process can result in the generation of a VHDJ+H complex and the subsequent expression of an immunoglobulin heavy chain.
311 citations
••
TL;DR: It is shown that phylogenomic data can substantially advance the understanding of arthropod evolution and resolve several conflicts among existing hypotheses.
Abstract: Arthropods were the first animalsto conquer land and air. They encompass more than three quarters of all described living species.Thisextraordinaryevolutionarysuccessisbasedonanastoundinglywidearrayofhighly adaptivebody organizations. A lackofrobustlyresolvedphylogeneticrelationships,however,currentlyimpedesthereliablereconstructionoftheunderlyingevolutionaryprocesses.Here,weshowthatphylogenomicdatacansubstantiallyadvanceourunderstandingofarthropod evolution and resolve several conflicts among existinghypotheses. We assembled a data set of 233 taxa and 775 genes from which an optimally informative data set of 117 taxa and 129 genes was finally selected using new heuristics and compared with the unreduced data set.We included novelexpressed sequencetag (EST) data for 11 species and allpublished phylogenomic data augmentedbyrecentlypublishedESTdata ontaxonomicallyimportantarthropodtaxa.This thorough sampling reduces the chance of obtainingspurious results due to stochastic effects of undersampling taxa and genes. Orthology prediction of genes, alignmentmasking tools, and selection of most informativegenes due to a balanced taxa–gene ratio using new heuristics were established.Our optimizeddata setrobustly resolves major arthropod relationships.We received strong supportforasistergrouprelationshipofonychophoransandeuarthropodsandstrongsupportforacloseassociationoftardigrades andcycloneuralia.Withinpancrustaceans,our analysesyieldedparaphyleticcrustaceansandmonophyletichexapods and robustly resolved monophyletic endopterygoteinsects.However, our analysesalsoshowed for few deep splitsthat were recently thought to be resolved,for example,the positionofmyriapods, a remarkable sensitivitytomethods of analyses.
310 citations
Authors
Showing all 32558 results
Name | H-index | Papers | Citations |
---|---|---|---|
Julie E. Buring | 186 | 950 | 132967 |
Stuart H. Orkin | 186 | 715 | 112182 |
Cornelia M. van Duijn | 183 | 1030 | 146009 |
Dorret I. Boomsma | 176 | 1507 | 136353 |
Frederick W. Alt | 171 | 577 | 95573 |
Donald E. Ingber | 164 | 610 | 100682 |
Klaus Müllen | 164 | 2125 | 140748 |
Klaus Rajewsky | 154 | 504 | 88793 |
Frederik Barkhof | 154 | 1449 | 104982 |
Stefanie Dimmeler | 147 | 574 | 81658 |
Detlef Weigel | 142 | 516 | 84670 |
Hidde L. Ploegh | 135 | 674 | 67437 |
Luca Valenziano | 130 | 437 | 94728 |
Peter Walter | 126 | 841 | 71580 |
Peter G. Martin | 125 | 553 | 97257 |