Institution
Charité
Healthcare•Berlin, Germany•
About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.
Topics: Population, Transplantation, Immune system, Heart failure, Cancer
Papers published on a yearly basis
Papers
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TL;DR: The data suggest that expression of Foxp3 must be stabilized by epigenetic modification to allow the development of a permanent suppressor cell lineage, a finding of significant importance for therapeutic applications involving induction or transfer of Tregs and for the understanding of long-term cell lineage decisions.
Abstract: Compelling evidence suggests that the transcription factor Foxp3 acts as a master switch governing the development and function of CD4+ regulatory T cells (Tregs). However, whether transcriptional control of Foxp3 expression itself contributes to the development of a stable Treg lineage has thus far not been investigated. We here identified an evolutionarily conserved region within the foxp3 locus upstream of exon-1 possessing transcriptional activity. Bisulphite sequencing and chromatin immunoprecipitation revealed complete demethylation of CpG motifs as well as histone modifications within the conserved region in ex vivo isolated Foxp3+CD25+CD4+ Tregs, but not in naive CD25−CD4+ T cells. Partial DNA demethylation is already found within developing Foxp3+ thymocytes; however, Tregs induced by TGF-β in vitro display only incomplete demethylation despite high Foxp3 expression. In contrast to natural Tregs, these TGF-β–induced Foxp3+ Tregs lose both Foxp3 expression and suppressive activity upon restimulation in the absence of TGF-β. Our data suggest that expression of Foxp3 must be stabilized by epigenetic modification to allow the development of a permanent suppressor cell lineage, a finding of significant importance for therapeutic applications involving induction or transfer of Tregs and for the understanding of long-term cell lineage decisions.
1,147 citations
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Leiden University Medical Center1, Ruhr University Bochum2, Ghent University Hospital3, Universidade Nova de Lisboa4, University of Zurich5, Paris Descartes University6, Sorbonne7, Semmelweis University8, VU University Medical Center9, University of Toronto10, University College London11, University of Leeds12, Erciyes University13, University of Lisbon14, University of Texas at Austin15, Charité16, Ghent University17, University of São Paulo18
TL;DR: The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA and three overarching principles and 13 recommendations deal with surgery and spinal fractures.
Abstract: To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6-8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.
1,147 citations
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University of Oxford1, University of Michigan2, Wellcome Trust Sanger Institute3, Amgen4, University of Cambridge5, University of Copenhagen6, University of Liverpool7, University of Freiburg8, Boston University9, University of Tartu10, Erasmus University Medical Center11, Leiden University Medical Center12, Pasteur Institute13, Icahn School of Medicine at Mount Sinai14, UCLA Medical Center15, Vanderbilt University Medical Center16, Wake Forest University17, National University of Singapore18, Imperial College London19, London North West Healthcare NHS Trust20, Charité21, Innsbruck Medical University22, Washington University in St. Louis23, Queen Mary University of London24, University of Southern Denmark25, National and Kapodistrian University of Athens26, Robertson Centre for Biostatistics27, University of Exeter28, Uppsala University29, University of Düsseldorf30, Steno Diabetes Center31, Aalborg University32, University of Eastern Finland33, Broad Institute34, Frederiksberg Hospital35, Lund University36, University of Bergen37, Technische Universität München38, University of North Carolina at Chapel Hill39, Ninewells Hospital40, University of Edinburgh41, University of Minnesota42, University of Glasgow43, Ludwig Maximilian University of Munich44, University of Iceland45, Aarhus University46, Stanford University47, Science for Life Laboratory48, University of Helsinki49, National Institutes of Health50, University of Dundee51, Harvard University52
TL;DR: Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.
Abstract: We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).
1,136 citations
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TL;DR: This work presents a method for prioritization of candidate genes by use of a global network distance measure, random walk analysis, for definition of similarities in protein-protein interaction networks, significantly outperforming previous methods based on local distance measures.
Abstract: The identification of genes associated with hereditary disorders has contributed to improving medical care and to a better understanding of gene functions, interactions, and pathways. However, there are well over 1500 Mendelian disorders whose molecular basis remains unknown. At present, methods such as linkage analysis can identify the chromosomal region in which unknown disease genes are located, but the regions could contain up to hundreds of candidate genes. In this work, we present a method for prioritization of candidate genes by use of a global network distance measure, random walk analysis, for definition of similarities in protein-protein interaction networks. We tested our method on 110 disease-gene families with a total of 783 genes and achieved an area under the ROC curve of up to 98% on simulated linkage intervals of 100 genes surrounding the disease gene, significantly outperforming previous methods based on local distance measures. Our results not only provide an improved tool for positional-cloning projects but also add weight to the assumption that phenotypically similar diseases are associated with disturbances of subnetworks within the larger protein interactome that extend beyond the disease proteins themselves.
1,135 citations
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TL;DR: A meta-analysis that estimates percentage of infected species based on data on the distribution of infection levels among species using a beta-binomial model and finds that within species the infection frequency follows a ‘most-or-few’ infection pattern.
Abstract: Wolbachia are intracellular bacteria found in many species of arthropods and nematodes They manipulate the reproduction of their arthropod hosts in various ways, may play a role in host speciation and have potential applications in biological pest control Estimates suggest that at least 20% of all insect species are infected with Wolbachia These estimates result from several Wolbachia screenings in which numerous species were tested for infection; however, tests were mostly performed on only one to two individuals per species The actual percent of species infected will depend on the distribution of infection frequencies among species We present a meta-analysis that estimates percentage of infected species based on data on the distribution of infection levels among species We used a beta-binomial model that describes the distribution of infection frequencies of Wolbachia, shedding light on the overall infection rate as well as on the infection frequency within species Our main findings are that (1) the proportion of Wolbachia-infected species is estimated to be 66%, and that (2) within species the infection frequency follows a ‘most-or-few’ infection pattern in a sense that the Wolbachia infection frequency within one species is typically either very high (>90%) or very low (<10%)
1,133 citations
Authors
Showing all 30787 results
Name | H-index | Papers | Citations |
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JoAnn E. Manson | 270 | 1819 | 258509 |
Yi Chen | 217 | 4342 | 293080 |
David J. Hunter | 213 | 1836 | 207050 |
Raymond J. Dolan | 196 | 919 | 138540 |
John P. A. Ioannidis | 185 | 1311 | 193612 |
Stefan Schreiber | 178 | 1233 | 138528 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Eric J. Nestler | 178 | 748 | 116947 |
Klaus Rajewsky | 154 | 504 | 88793 |
Charles B. Nemeroff | 149 | 979 | 90426 |
Andreas Pfeiffer | 149 | 1756 | 131080 |
Rinaldo Bellomo | 147 | 1714 | 120052 |
Jean Bousquet | 145 | 1288 | 96769 |
Christopher Hill | 144 | 1562 | 128098 |
Holger J. Schünemann | 141 | 810 | 113169 |