Institution
Humboldt University of Berlin
Education•Berlin, Germany•
About: Humboldt University of Berlin is a education organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Medicine. The organization has 33671 authors who have published 61781 publications receiving 1908102 citations. The organization is also known as: Humboldt-Universität zu Berlin & Universitas Humboldtiana Berolinensis.
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TL;DR: This work investigates ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue and in cells derived from subsegmental bronchial branches by single nuclei and single cell RNA sequencing, suggesting increased vulnerability for SARS‐CoV‐2 infection.
Abstract: The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.
808 citations
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TL;DR: In this article, two NF-kappaB binding sites in the human cyclin D1 promoter were found to stimulate transcription of cyclin-D1, a key regulator of G1 checkpoint control.
Abstract: Nuclear factor kappa B (NF-kappaB) has been implicated in the regulation of cell proliferation, transformation, and tumor development. We provide evidence for a direct link between NF-kappaB activity and cell cycle regulation. NF-kappaB was found to stimulate transcription of cyclin D1, a key regulator of G1 checkpoint control. Two NF-kappaB binding sites in the human cyclin D1 promoter conferred activation by NF-kappaB as well as by growth factors. Both levels and kinetics of cyclin D1 expression during G1 phase were controlled by NF-kappaB. Moreover, inhibition of NF-kappaB caused a pronounced reduction of serum-induced cyclin D1-associated kinase activity and resulted in delayed phosphorylation of the retinoblastoma protein. Furthermore, NF-kappaB promotes G1-to-S-phase transition in mouse embryonal fibroblasts and in T47D mammary carcinoma cells. Impaired cell cycle progression of T47D cells expressing an NF-kappaB superrepressor (IkappaBalphaDeltaN) could be rescued by ectopic expression of cyclin D1. Thus, NF-kappaB contributes to cell cycle progression, and one of its targets might be cyclin D1.
807 citations
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TL;DR: The authors' data under-score the frequency and severity of coronary and valvular calcifications in dialysis patients, and illustrate the rapid progression of this calcification, drawing attention to hypertension as an important risk factor in this process.
807 citations
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TL;DR: In this paper, a multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Car to develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients.
Abstract: Objective:To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients.Participants:A multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Car
805 citations
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TL;DR: The double cubic lattice method (DCLM) is an accurate and rapid approach for computing numerically molecular surface areas and the volume and compactness of molecular assemblies and for generating dot surfaces, and is the method of choice, especially for large molecular complexes and high point densities.
Abstract: The double cubic lattice method (DCLM) is an accurate and rapid approach for computing numerically molecular surface areas (such as the solvent accessible or van der Waals surface) and the volume and compactness of molecular assemblies and for generating dot surfaces. The algorithm has no special memory requirements and can be easily implemented. The computation speed is extremely high, making interactive calculation of surfaces, volumes, and dot surfaces for systems of 1000 and more atoms possible on single-processor workstations. The algorithm can be easily parallelized. The DCLM is an algorithmic variant of the approach proposed by Shrake and Rupley (J. Mol. Biol., 79, 351–371, 1973). However, the application of two cubic lattices—one for grouping neighboring atomic centers and the other for grouping neighboring surface dots of an atom—results in a drastic reduction of central processing unit (CPU) time consumption by avoiding redundant distance checks. This is most noticeable for compact conformations. For instance, the calculation of the solvent accessible surface area of the crystal conformation of bovine pancreatic trypsin inhibitor (entry 4PTI of the Brookhaven Protein Data Bank, 362-point sphere for all 454 nonhydrogen atoms) takes less than 1 second (on a single R3000 processor of an SGI 4D/480, about 5 MFLOP). The DCLM does not depend on the spherical point distribution applied. The quality of unit sphere tesselations is discussed. We propose new ways of subdivision based on the icosahedron and dodecahedron, which achieve constantly low ratios of longest to shortest arcs over the whole frequency range. The DCLM is the method of choice, especially for large molecular complexes and high point densities. Its speed has been compared to the fastest techniques known to the authors, and it was found to be superior, especially when also taking into account the small memory requirement and the flexibility of the algorithm. The program text may be obtained on request. © 1995 by John Wiley & Sons, Inc.
805 citations
Authors
Showing all 34115 results
Name | H-index | Papers | Citations |
---|---|---|---|
Karl J. Friston | 217 | 1267 | 217169 |
Peer Bork | 206 | 697 | 245427 |
Raymond J. Dolan | 196 | 919 | 138540 |
Stefan Schreiber | 178 | 1233 | 138528 |
Andreas Pfeiffer | 149 | 1756 | 131080 |
Thomas Hebbeker | 148 | 1984 | 114004 |
Thomas Lohse | 148 | 1237 | 101631 |
Jean Bousquet | 145 | 1288 | 96769 |
Hermann Kolanoski | 145 | 1279 | 96152 |
Josh Moss | 139 | 1019 | 89255 |
R. D. Kass | 138 | 1920 | 107907 |
W. Kozanecki | 138 | 1498 | 99758 |
U. Mallik | 137 | 1625 | 97439 |
C. Haber | 135 | 1507 | 98014 |
Christophe Royon | 134 | 1453 | 90249 |