Institution
University of Kiel
Education•Kiel, Germany•
About: University of Kiel is a education organization based out in Kiel, Germany. It is known for research contribution in the topics: Population & Crystal structure. The organization has 27816 authors who have published 57114 publications receiving 2061802 citations. The organization is also known as: Christian Albrechts University & Christian-Albrechts-Universität zu Kiel.
Topics: Population, Crystal structure, Transplantation, Gene, Receptor
Papers published on a yearly basis
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Dresden University of Technology1, Brigham and Women's Hospital2, University of California, San Francisco3, University of Düsseldorf4, University of Pisa5, Northwestern University6, Medical University of Vienna7, University of Cyprus8, National and Kapodistrian University of Athens9, Medical University of South Carolina10, University of Cambridge11, University of Barcelona12, University Health Network13, The Feinstein Institute for Medical Research14, Toronto Western Hospital15, University of California, Los Angeles16, Humboldt University of Berlin17, Copenhagen University Hospital18, University of Michigan19, Harvard University20, University of the Basque Country21, University of Crete22, University of Kiel23, University Hospital Centre Zagreb24, University of Paris-Sud25, University of Hong Kong26, University of Calgary27, Hospital for Special Surgery28, University of Pécs29, University of Padua30, Medical University of Graz31, National Institutes of Health32, New York University33, Université Paris-Saclay34, University Hospital Complex Of Vigo35, University of Occupational and Environmental Health Japan36, University of Porto37, University of Leeds38, Leeds Teaching Hospitals NHS Trust39, Cedars-Sinai Medical Center40, Istanbul Bilim University41, McMaster University42, University of Paris43, University of Toronto44
TL;DR: These new classification criteria for systemic lupus erythematosus have excellent sensitivity and specificity, and were developed using rigorous methodology with multidisciplinary and international input.
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.
606 citations
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University of Cambridge1, Brigham and Women's Hospital2, Kangwon National University3, University of Kiel4, Complutense University of Madrid5, Innsbruck Medical University6, Nara Institute of Science and Technology7, Gunma University8, International Vaccine Institute9, Beth Israel Deaconess Medical Center10
TL;DR: Genetically and environmentally controlled UPR function within Paneth cells may set the threshold for the development of intestinal inflammation upon hypomorphic ATG16L1 function and implicate ileal Crohn’s disease as a specific disorder ofPaneth cells.
Abstract: The recognition of autophagy related 16-like 1 (ATG16L1) as a genetic risk factor has exposed the critical role of autophagy in Crohn's disease. Homozygosity for the highly prevalent ATG16L1 risk allele, or murine hypomorphic (HM) activity, causes Paneth cell dysfunction. As Atg16l1(HM) mice do not develop spontaneous intestinal inflammation, the mechanism(s) by which ATG16L1 contributes to disease remains obscure. Deletion of the unfolded protein response (UPR) transcription factor X-box binding protein-1 (Xbp1) in intestinal epithelial cells, the human orthologue of which harbours rare inflammatory bowel disease risk variants, results in endoplasmic reticulum (ER) stress, Paneth cell impairment and spontaneous enteritis. Unresolved ER stress is a common feature of inflammatory bowel disease epithelium, and several genetic risk factors of Crohn's disease affect Paneth cells. Here we show that impairment in either UPR (Xbp1(ΔIEC)) or autophagy function (Atg16l1(ΔIEC) or Atg7(ΔIEC)) in intestinal epithelial cells results in each other's compensatory engagement, and severe spontaneous Crohn's-disease-like transmural ileitis if both mechanisms are compromised. Xbp1(ΔIEC) mice show autophagosome formation in hypomorphic Paneth cells, which is linked to ER stress via protein kinase RNA-like endoplasmic reticulum kinase (PERK), elongation initiation factor 2α (eIF2α) and activating transcription factor 4 (ATF4). Ileitis is dependent on commensal microbiota and derives from increased intestinal epithelial cell death, inositol requiring enzyme 1α (IRE1α)-regulated NF-κB activation and tumour-necrosis factor signalling, which are synergistically increased when autophagy is deficient. ATG16L1 restrains IRE1α activity, and augmentation of autophagy in intestinal epithelial cells ameliorates ER stress-induced intestinal inflammation and eases NF-κB overactivation and intestinal epithelial cell death. ER stress, autophagy induction and spontaneous ileitis emerge from Paneth-cell-specific deletion of Xbp1. Genetically and environmentally controlled UPR function within Paneth cells may therefore set the threshold for the development of intestinal inflammation upon hypomorphic ATG16L1 function and implicate ileal Crohn's disease as a specific disorder of Paneth cells.
602 citations
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TL;DR: The pooled ABP records of 1141 healthy children and adolescents with a body height between 115 and 185 cm provided well-based limits of normal ABP in mid-European children.
601 citations
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TL;DR: Time‐lapse cinematography revealed that late endosomes/lysosomes as well as phagosomes lacking LAMP‐1 and LAMP-2 had reduced ability to move toward the microtubule‐organizing center, likely precluding their interaction with each other.
Abstract: Lysosome-associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2) are delivered to phagosomes during the maturation process. We used cells from LAMP-deficient mice to analyze the role of these proteins in phagosome maturation. Macrophages from LAMP-1- or LAMP-2-deficient mice displayed normal fusion of lysosomes with phagosomes. Because ablation of both the lamp-1 and lamp-2 genes yields an embryonic-lethal phenotype, we were unable to study macrophages from double knockouts. Instead, we reconstituted phagocytosis in murine embryonic fibroblasts (MEFs) by transfection of FcγIIA receptors. Phagosomes formed by FcγIIA-transfected MEFs obtained from LAMP-1- or LAMP-2- deficient mice acquired lysosomal markers. Remarkably, although FcγIIA-transfected MEFs from double-deficient mice ingested particles normally, phagosomal maturation was arrested. LAMP-1 and LAMP-2 double-deficient phagosomes acquired Rab5 and accumulated phosphatidylinositol 3-phosphate, but failed to recruit Rab7 and did not fuse with lysosomes. We attribute the deficiency to impaired organellar motility along microtubules. Time-lapse cinematography revealed that late endosomes/lysosomes as well as phagosomes lacking LAMP-1 and LAMP-2 had reduced ability to move toward the microtubule-organizing center, likely precluding their interaction with each other.
601 citations
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TL;DR: The concepts and mechanisms of microbial resilience against dietary, antibiotic or bacteriotherapy-induced perturbations and the implications for human health are discussed.
Abstract: The resilience of the microbiota can protect us from disease, but a resilient dysbiotic microbiota may also cause disease. This Opinion article discusses the concepts and mechanisms of microbial resilience against dietary, antibiotic or bacteriotherapy-induced perturbations and the implications these have for human health. The composition of the intestinal microbiota varies among individuals and throughout development, and is dependent on host and environmental factors. However, although the microbiota is constantly exposed to environmental challenges, its composition and function in an individual are stable against perturbations, as microbial communities are resilient and resistant to change. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and also between the microorganisms and the intestinal interface of the host. The resilience of the healthy microbiota protects us from dysbiosis-related diseases, such as inflammatory bowel disease (IBD) or metabolic disorder. By contrast, a resilient dysbiotic microbiota may cause disease. In this Opinion article, we propose that microbial resilience has a key role in health and disease. We will discuss the concepts and mechanisms of microbial resilience against dietary, antibiotic or bacteriotherapy-induced perturbations and the implications for human health.
601 citations
Authors
Showing all 28103 results
Name | H-index | Papers | Citations |
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Stefan Schreiber | 178 | 1233 | 138528 |
Jun Wang | 166 | 1093 | 141621 |
William J. Sandborn | 162 | 1317 | 108564 |
Jens Nielsen | 149 | 1752 | 104005 |
Tak W. Mak | 148 | 807 | 94871 |
Annette Peters | 138 | 1114 | 101640 |
Severine Vermeire | 134 | 1086 | 76352 |
Peter M. Rothwell | 134 | 779 | 67382 |
Dusan Bruncko | 132 | 1042 | 84709 |
Gideon Bella | 129 | 1301 | 87905 |
Dirk Schadendorf | 127 | 1017 | 105777 |
Neal L. Benowitz | 126 | 792 | 60658 |
Thomas Schwarz | 123 | 701 | 54560 |
Meletios A. Dimopoulos | 122 | 1371 | 71871 |
Christian Weber | 122 | 776 | 53842 |